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While the synthesis of nanocrystalline feedstocks in the form of foils, powders, and wires is relatively straightforward, the tendency of nanocrystalline feedstocks to coarsen upon extended exposure to elevated temperatures means that low-temperature and rapid densification techniques are necessary to consolidate these feedstocks into bulk components. A variety of techniques show potential in this respect, such as spark plasma sintering or ultrasonic additive manufacturing, although the synthesis of bulk nanocrystalline components on a commercial scale remains untenable.
0
Metallurgy
Induction heating is a non contact heating process which uses the principle of electromagnetism induction to produce heat in a work-piece. In this case thermal expansion is used in a mechanical application to fit parts over one another, e.g. a bushing can be fitted over a shaft by making its inner diameter slightly smaller than the diameter of the shaft, then heating it until it fits over the shaft, and allowing it to cool after it has been pushed over the shaft, thus achieving a shrink fit. By placing a conductive material into a strong alternating magnetic field, electric current can be made to flow in the metal thereby creating heat due to the IR losses in the material. The current generated flows predominantly in the surface layer. The depth of this layer being dictated by the frequency of the alternating field and the permeability of the material. Induction heaters for shrink fitting fall into two broad categories: * Mains frequency (MF) units using magnetic cores (iron) * Solid state MF and radio frequency (RF) heaters
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Metallurgy
Marion Katherine Blight was born in Watford in 1921. Her mother worked in domestic service while her father was a shop assistant. McQuillan attended Wycombe High School before getting a scholarship to Henrietta Barnett’s School. McQuillan went to University in 1939 where she graduated from Girton College, Cambridge with a degree in metallurgy and natural sciences. She got her first job in 1942 in the Royal Aircraft Establishment Farnborough (RAE) in 1942. McQuillan researched jet engine metals and was a member of the first team to research titanium. In 1946 she travelled through Germany and Austria as member of one of the many teams sent by the British Intelligence Objectives Sub-Committee, collecting technical information from universities, research establishments and factories. She also worked at the Atomic Energy Research Establishment at Harwell, working on some of the early metallurgical problems of nuclear energy. From 1948-1951 she was at the Australian Royal Aircraft Establishment in Melbourne. McQuillan returned to the UK where she began to work for ICI Metals (also known as IMI), in the Titanium Alloy Research Department where, within two years later she was head of the section. With her husband McQuillan published the seminal book “Titanium” in 1956. During the 1960s McQuillan registered 8 titanium alloy patents. In 1967 McQuillan was appointed technical director of the New Metals Division and by 1978 she became the first woman managing director of Imperial Metal Industries subsidiary, Enots.
0
Metallurgy
The Wilfley Table is commonly used for the concentration of heavy minerals from the laboratory up to the industrial scale. It has a traditional shaking (oscillating) table design with a riffled deck. It is one of several brands of wet tables used for the separation and concentration of heavy ore minerals which include the Deister Table and Holman Table, all built to handle either coarse or fine feeds for mineral processing. The Wilfley Table became a design used world-wide due to the fact it significantly increased the recovery of silver, gold and other precious metals. Such was the tables widespread use that it was included in Websters Dictionary, and has been in constant use by miners and metallurgists since its invention.
0
Metallurgy
The mappae clavicula is a medieval Latin text containing manufacturing recipes for crafts materials, including for metals, glass, mosaics, and dyes and tints for materials. The information and style in the recipes is very terse. Each recipe consists of the names of the ingredients and typically about two sentences on combining the ingredients together. A small minority of the recipes go to about six sentences. The text comes with a short preamble, and other than that it is just recipes. The number of recipes was expanded over the course of the medieval centuries, and some medieval copies have deletions as well as additions, so it is better thought of as a family of texts with a largely common core, not a single text. Most of the Mappae Clavicula recipes are also in medieval Latin in a text known as the Compositiones ad Tingenda (English: "Recipes for Coloring (or Tingeing)").
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Metallurgy
Discontinuous recrystallization is heterogeneous; there are distinct nucleation and growth stages. It is common in materials with low stacking-fault energy. Nucleation then occurs, generating new strain-free grains which absorb the pre-existing strained grains. It occurs more easily at grain boundaries, decreasing the grain size and thereby increasing the amount of nucleation sites. This further increases the rate of discontinuous dynamic recrystallization. Discontinuous Dynamic Recrystallization has 5 main characteristics: * Recrystallization does not occur until the threshold strain has been reached * The stress-strain curve may have several peaks – there is not a universal equation * Nucleation generally occurs along pre-existing grain boundaries * Recrystallization rates increase as the initial grain size decreases * There is a steady grain size which is approached as recrystallization proceeds Discontinuous dynamic recrystallization is caused by the interplay of work hardening and recovery. If the annihilation of dislocations is slow relative to the rate at which they are generated, dislocations accumulate. Once critical dislocation density is achieved, nucleation occurs on grain boundaries.  Grain boundary migration, or the atoms transfer from a large pre-existing grain to a smaller nucleus, allows the growth of the new nuclei at the expense of the pre-existing grains. The nucleation can occur through the bulging of existing grain boundaries. A bulge forms if the subgrains abutting a grain boundary are of different sizes, causing a disparity in energy from the two subgrains. If the bulge achieves a critical radius, it will successfully transition to a stable nucleus and continue its growth. This can be modeled using Cahn’s theories pertaining to nucleation and growth. Discontinuous dynamic recrystallization commonly produces a ‘necklace’ microstructure. Since new grain growth is energetically favorable along grain boundaries, new grain formation and bulging preferentially occurs along pre-existing grain boundaries. This generates layers of new, very fine grains along the grain boundary initially leaving the interior of the pre-existing grain unaffected. As the dynamic recrystallization continues, it consumes the unrecrystallized region. As deformation continues, the recrystallization does not maintain coherency between layers of new nuclei, producing a random texture.
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Metallurgy
The lacUV5 promoter is a mutated promoter from the Escherichia coli lac operon which is used in molecular biology to drive gene expression on a plasmid. lacUV5 is very similar to the classical lac promoter, containing just 2 base pair mutations in the -10 hexamer region, compared to the lac promoter. LacUV5 is among the most commonly used promoters in molecular biology because it requires no additional activators and it drives high levels of gene expression. The lacUV5 promoter sequence conforms more closely to the consensus sequence recognized by bacterial sigma factors than the traditional lac promoter does. Due to this, lacUV5 recruits RNA Polymerase more effectively, thus leading to higher transcription of target genes. Additionally, unlike the lac promoter, lacUV5 works independently of activator proteins or other cis regulatory elements (apart from the -10 and -35 promoter regions). While no activators are required, lacUV5 promoter expression can be regulated by the LacI repressor and can be induced with IPTG, which is an effective inducer of protein expression when used in the concentration range of 100 μM to 1.5 mM. Due to this control, the lacUV5 promoter is commonly found on expression plasmids and is used when controllable but high levels of a product are desired. The lacUV5 mutation was first identified in 1970 in a study of lac promoter mutants that produce higher yields. Some of them, including UV5, has lost catabolite repression at the CAP site. Development into cloning vectors is known since 1982, when a UV5-carrying phage known as "λ h80 lacUV5 cI857" has its genome spliced with the HaeIII restriction enzyme to make plasmids carrying the fragment with UV5.
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Gene expression + Signal Transduction
Thermomechanical processing is a metallurgical process that combines mechanical or plastic deformation process like compression or forging, rolling, etc. with thermal processes like heat-treatment, water quenching, heating and cooling at various rates into a single process.
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Metallurgy
Everolimus is the second novel Rapamycin analog. Compared with the parent compound rapamycin, everolimus is more selective for the mTORC1 protein complex, with little impact on the mTORC2 complex. mTORC1 inhibition by everolimus has been shown to normalize tumor blood vessels, to increase tumor-infiltrating lymphocytes, and to improve adoptive cell transfer therapy. From March 30, 2009, to May 5, 2011, the U.S. FDA approved everolimus for the treatment of advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib, subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS), and progressive neuroendocrine tumors of pancreatic origin (PNET). In July and August 2012, two new indications were approved, for advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane, and pediatric and adult patients with SEGA. In 2009 and 2011, it was also approved throughout the European Union for advanced breast cancer, pancreatic neuroendocrine tumours, advanced renal cell carcinoma, and SEGA in patients with tuberous sclerosis.
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Gene expression + Signal Transduction
Karl A. Smith is a metallurgical engineer, academic and author. He is an emeritus Cooperative Learning Professor of Engineering Education at Purdue University's School of Engineering Education, as well as an emeritus Professor of Civil, Environmental, and Geo-Engineering, Morse-Alumni Distinguished University Teaching Professor, and Faculty Member at the Technological Leadership Institute at the University of Minnesota. Smiths work has focused on developing research and innovation capabilities in engineering education, exploring cooperation in learning and design, and managing projects and knowledge. His publications comprise research articles and eight books including Teamwork and Project Management, How to Model it: Problem Solving for the Computer Age and New Paradigms for College Teaching'. He is the recipient of the University of Minnesota Distinguished Alumni Award (2006), an Honorary Doctorate from the Universiti Teknologi Malaysia (2014) along with the Chester F. Carlson Award (2001), the Distinguished Service Award (2006), and the Lifetime Achievement Award (2015), all from the American Society for Engineering Education. Smith is a Fellow of the American Association for the Advancement of Science and the American Society for Engineering Education, where he was inducted into the Hall of Fame in 2023. He served as the Guest Editor of a Special Issue of the Journal of Engineering Education, and as the Editor-in-Chief of Annals of Research on Engineering Education (AREE).
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Metallurgy
As mentioned above, G-proteins may terminate their own activation due to their intrinsic GTP→GDP hydrolysis capability. However, this reaction proceeds at a slow rate (≈0.02 times/sec) and, thus, it would take around 50 seconds for any single G-protein to deactivate if other factors did not come into play. Indeed, there are around 30 isoforms of RGS proteins that, when bound to Gα through their GAP domain, accelerate the hydrolysis rate to ≈30 times/sec. This 1500-fold increase in rate allows for the cell to respond to external signals with high speed, as well as spatial resolution due to limited amount of second messenger that can be generated and limited distance a G-protein can diffuse in 0.03 seconds. For the most part, the RGS proteins are promiscuous in their ability to deactivate G-proteins, while which RGS is involved in a given signaling pathway seems more determined by the tissue and GPCR involved than anything else. In addition, RGS proteins have the additional function of increasing the rate of GTP-GDP exchange at GPCRs, (i.e., as a sort of co-GEF) further contributing to the time resolution of GPCR signaling. In addition, the GPCR may be desensitized itself. This can occur as: # a direct result of ligand occupation, wherein the change in conformation allows recruitment of GPCR-Regulating Kinases (GRKs), which go on to phosphorylate various serine/threonine residues of IL-3 and the C-terminal tail. Upon GRK phosphorylation, the GPCR's affinity for β-arrestin (β-arrestin-1/2 in most tissues) is increased, at which point β-arrestin may bind and act to both sterically hinder G-protein coupling as well as initiate the process of receptor internalization through clathrin-mediated endocytosis. Because only the liganded receptor is desensitized by this mechanism, it is called homologous desensitization # the affinity for β-arrestin may be increased in a ligand occupation and GRK-independent manner through phosphorylation of different ser/thr sites (but also of IL-3 and the C-terminal tail) by PKC and PKA. These phosphorylations are often sufficient to impair G-protein coupling on their own as well. # PKC/PKA may, instead, phosphorylate GRKs, which can also lead to GPCR phosphorylation and β-arrestin binding in an occupation-independent manner. These latter two mechanisms allow for desensitization of one GPCR due to the activities of others, or heterologous desensitization. GRKs may also have GAP domains and so may contribute to inactivation through non-kinase mechanisms as well. A combination of these mechanisms may also occur. Once β-arrestin is bound to a GPCR, it undergoes a conformational change allowing it to serve as a scaffolding protein for an adaptor complex termed AP-2, which in turn recruits another protein called clathrin. If enough receptors in the local area recruit clathrin in this manner, they aggregate and the membrane buds inwardly as a result of interactions between the molecules of clathrin, in a process called opsonization. Once the pit has been pinched off the plasma membrane due to the actions of two other proteins called amphiphysin and dynamin, it is now an endocytic vesicle. At this point, the adapter molecules and clathrin have dissociated, and the receptor is either trafficked back to the plasma membrane or targeted to lysosomes for degradation. At any point in this process, the β-arrestins may also recruit other proteins—such as the non-receptor tyrosine kinase (nRTK), c-SRC—which may activate ERK1/2, or other mitogen-activated protein kinase (MAPK) signaling through, for example, phosphorylation of the small GTPase, Ras, or recruit the proteins of the ERK cascade directly (i.e., Raf-1, MEK, ERK-1/2) at which point signaling is initiated due to their close proximity to one another. Another target of c-SRC are the dynamin molecules involved in endocytosis. Dynamins polymerize around the neck of an incoming vesicle, and their phosphorylation by c-SRC provides the energy necessary for the conformational change allowing the final "pinching off" from the membrane.
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Gene expression + Signal Transduction
SH2 domains, and other binding domains, have been used in protein engineering to create protein assemblies. Protein assemblies are formed when several proteins bind to one another to create a larger structure (called a supramolecular assembly). Using molecular biology techniques, fusion proteins of specific enzymes and SH2 domains have been created, which can bind to each other to form protein assemblies. Since SH2 domains require phosphorylation in order for binding to occur, the use of kinase and phosphatase enzymes gives researchers control over whether protein assemblies will form or not. High affinity engineered SH2 domains have been developed and utilized for protein assembly applications. The goal of most protein assembly formation is to increase the efficiency of metabolic pathways via enzymatic co-localization. Other applications of SH2 domain mediated protein assemblies have been in the formation of high density fractal-like structures, which have extensive molecular trapping properties.
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Gene expression + Signal Transduction
Calthemite coralloids (also known as popcorn), can form on the underside of concrete structures and look very similar to those which occurs in caves. Coralloids can form by a number of different methods in caves, however on concrete the most common form is created when hyperalkaline solution seeps from fine cracks in concrete. Due to solution evaporation, deposition of calcium carbonate occurs before any drop can form. The resulting coralloids are small and chalky with a cauliflower appearance.
0
Metallurgy
The RNA-editing system seen in the animal may have evolved from mononucleotide deaminases, which have led to larger gene families that include the apobec-1 and adar genes. These genes share close identity with the bacterial deaminases involved in nucleotide metabolism. The adenosine deaminase of E. coli cannot deaminate a nucleoside in the RNA; the enzymes reaction pocket is too small for the RNA strand to bind to. However, this active site is widened by amino acid changes in the corresponding human analog genes, APOBEC1 and ADAR', allowing deamination. The gRNA-mediated pan-editing in trypanosome mitochondria, involving templated insertion of U residues, is an entirely different biochemical reaction. The enzymes involved have been shown in other studies to be recruited and adapted from different sources. But the specificity of nucleotide insertion via the interaction between the gRNA and mRNA is similar to the tRNA editing processes in the animal and Acanthamoeba mitochondria. Eukaryotic ribose methylation of rRNAs by guide RNA molecules is a similar form of modification. Thus, RNA editing evolved more than once. Several adaptive rationales for editing have been suggested. Editing is often described as a mechanism of correction or repair to compensate for defects in gene sequences. However, in the case of gRNA-mediated editing, this explanation does not seem possible because if a defect happens first, there is no way to generate an error-free gRNA-encoding region, which presumably arises by duplication of the original gene region. A more plausible alternative for the evolutionary origins of this system is through constructive neutral evolution, where the order of steps is reversed, with the gratuitous capacity for editing preceding the "defect".
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Gene expression + Signal Transduction
Zinc smelting is the process of converting zinc concentrates (ores that contain zinc) into pure zinc. Zinc smelting has historically been more difficult than the smelting of other metals, e.g. iron, because in contrast, zinc has a low boiling point. At temperatures typically used for smelting metals, zinc is a gas that will escape from a furnace with the flue gas and be lost, unless specific measures are taken to prevent it. The most common zinc concentrate processed is zinc sulfide, which is obtained by concentrating sphalerite using the froth flotation method. Secondary (recycled) zinc material, such as zinc oxide, is also processed with the zinc sulfide. Approximately 30% of all zinc produced is from recycled sources.
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Metallurgy
Downregulation of protein kinase A occurs by a feedback mechanism and uses a number of cAMP hydrolyzing phosphodiesterase (PDE) enzymes, which belong to the substrates activated by PKA. Phosphodiesterase quickly converts cAMP to AMP, thus reducing the amount of cAMP that can activate protein kinase A. PKA is also regulated by a complex series of phosphorylation events, which can include modification by autophosphorylation and phosphorylation by regulatory kinases, such as PDK1. Thus, PKA is controlled, in part, by the levels of cAMP. Also, the catalytic subunit itself can be down-regulated by phosphorylation.
1
Gene expression + Signal Transduction
Pharmacologic down-regulation of (mTOR) pathway during chemotherapy in a mouse model prevents activation of primordial follicles, preserves ovarian function, and maintains normal fertility using clinically available inhibitors INK and RAD. In that way, it helps to maintain fertility while undergoing chemotherapy treatments. These mTOR inhibitors, when administered as pretreatment or co-treatment with standard gonadotoxic chemotherapy, helps to maintain ovarian follicles in their primordial state.
1
Gene expression + Signal Transduction
A Lot (formerly Loth) was an old unit of measurement for the relative fineness to gross weight in metallurgy and especially in coinage until the 19th century. A Lot was thus a proportion of the precious metal content in a piece of metal. It was used in the four main monetary systems of Germany: Austrian, South German, North German and Hamburg. The lot was defined as the sixteenth part of a Mark. For example, in silver, the total weight was divided into 16 (proportional) Lots until about 1857, according to which a "12-Lot" silver alloy (750 silver) contained 12/16 = or 75% by weight of silver and 25% of another metal (usually copper). A 14-Lot silver alloy (), on the other hand, corresponded to 875 silver. For refinement, a Lot was further divided into 18 grains. Thus 14 Lots, 4 grains fine then correspond to a fineness of 888.89 ‰ = (14 + 4 / 18) / 16 = (252 + 4)/288, i.e. 256/288 grains. The German proportional measure, the Lot, was finally replaced on 1 January 1888 in the German Empire by the proportional measure, permille (thousandths).
0
Metallurgy
In cardiac muscle, β-catenin forms a complex with N-cadherin at adherens junctions within intercalated disc structures, which are responsible for electrical and mechanical coupling of adjacent cardiac cells. Studies in a model of adult rat ventricular cardiomyocytes have shown that the appearance and distribution of β-catenin is spatio-temporally regulated during the redifferentiation of these cells in culture. Specifically, β-catenin is part of a distinct complex with N-cadherin and alpha-catenin, which is abundant at adherens junctions in early stages following cardiomyocyte isolation for the reformation of cell–cell contacts. It has been shown that β-catenin forms a complex with emerin in cardiomyocytes at adherens junctions within intercalated discs; and this interaction is dependent on the presence of GSK 3-beta phosphorylation sites on β-catenin. Knocking out emerin significantly altered β-catenin localization and the overall intercalated disc architecture, which resembled a dilated cardiomyopathy phenotype. In animal models of cardiac disease, functions of β-catenin have been unveiled. In a guinea pig model of aortic stenosis and left ventricular hypertrophy, β-catenin was shown to change subcellular localization from intercalated discs to the cytosol, despite no change in the overall cellular abundance of β-catenin. vinculin showed a similar profile of change. N-cadherin showed no change, and there was no compensatory upregulation of plakoglobin at intercalated discs in the absence of β-catenin. In a hamster model of cardiomyopathy and heart failure, cell–cell adhesions were irregular and disorganized, and expression levels of adherens junction/intercalated disc and nuclear pools of β-catenin were decreased. These data suggest that a loss of β-catenin may play a role in the diseased intercalated discs that have been associated with cardiac muscle hypertrophy and heart failure. In a rat model of myocardial infarction, adenoviral gene transfer of nonphosphorylatable, constitutively-active β-catenin decreased MI size, activated the cell cycle, and reduced the amount of apoptosis in cardiomyocytes and cardiac myofibroblasts. This finding was coordinate with enhanced expression of pro-survival proteins, survivin and Bcl-2, and vascular endothelial growth factor while promoting the differentiation of cardiac fibroblasts into myofibroblasts. These findings suggest that β-catenin can promote the regeneration and healing process following myocardial infarction. In a spontaneously-hypertensive heart failure rat model, investigators detected a shuttling of β-catenin from the intercalated disc/sarcolemma to the nucleus, evidenced by a reduction of β-catenin expression in the membrane protein fraction and an increase in the nuclear fraction. Additionally, they found a weakening in the association between glycogen synthase kinase-3β and β-catenin, which may indicate altered protein stability. Overall, results suggest that an enhanced nuclear localization of β-catenin may be important in the progression of cardiac hypertrophy. Regarding the mechanistic role of β-catenin in cardiac hypertrophy, transgenic mouse studies have shown somewhat conflicting results regarding whether upregulation of β-catenin is beneficial or detrimental. A recent study using a conditional knockout mouse that either lacked β-catenin altogether or expressed a non-degradable form of β-catenin in cardiomyocytes reconciled a potential reason for these discrepancies. There appears to be strict control over the subcellular localization of β-catenin in cardiac muscle. Mice lacking β-catenin had no overt phenotype in the left ventricular myocardium; however, mice harboring a stabilized form of β-catenin developed dilated cardiomyopathy, suggesting that the temporal regulation of β-catenin by protein degradation mechanisms is critical for normal functioning of β-catenin in cardiac cells. In a mouse model harboring knockout of a desmosomal protein, plakoglobin, implicated in arrhythmogenic right ventricular cardiomyopathy, the stabilization of β-catenin was also enhanced, presumably to compensate for the loss of its plakoglobin homolog. These changes were coordinate with Akt activation and glycogen synthase kinase 3β inhibition, suggesting once again that the abnormal stabilization of β-catenin may be involved in the development of cardiomyopathy. Further studies employing a double knockout of plakoglobin and β-catenin showed that the double knockout developed cardiomyopathy, fibrosis and arrhythmias resulting in sudden cardiac death. Intercalated disc architecture was severely impaired and connexin 43-resident gap junctions were markedly reduced. Electrocardiogram measurements captured spontaneous lethal ventricular arrhythmias in the double transgenic animals, suggesting that the two catenins—β-catenin and plakoglobin—are critical and indispensable for mechanoelectrical coupling in cardiomyocytes.
1
Gene expression + Signal Transduction
Like the major spliceosome, the minor spliceosome had an early origin: several of its characteristic constituents are present in representative organisms from all eukaryotic supergroups for which there is any substantial genome sequence information. In addition, functionally important sequence elements contained within U12-type introns and snRNAs are highly conserved during evolution.
1
Gene expression + Signal Transduction
Methanosaeta harundinacea 6Ac, a methanogenic archaeon, produces carboxylated acyl homoserine lactone compounds that facilitate the transition from growth as short cells to growth as filaments.
1
Gene expression + Signal Transduction
The V Brigade uncovered peculiarities in metal composition during the Palaeo-Metallic epoch at the Allyn-Depe settlement. The VII Brigade, carried out by Kuftin, was of the Namazgadepe explorations, which revealed six phases, sequentially deposited, and referred to as Namazga I to VI. It established the Chalcolithic (Eneolithic) to the late Bronze Age period. Between 1951 and 1961, the VII Brigade explored the Bronze Age site of Altyndepe (which had been discovered earlier by A.A. Semenov in 1929), Iron Age Yaz I complex in Margiana (old delta of the Morghab River, 11 sites at the ancient delta of the Geoksyur oasis, and Bronze Age piedmont sites in the Sumbar Valley with a noteworthy discovery of the Early Bronze Age cemetery of Parkhai II. In the Margiana archaeological expeditions undertaken during the second phase, work was continued at the Auchindepe and Takirbaidepe, which revealed 100 Bronze Age sites and the settlement of Gomur I. Also explored were the sites at the southern and eastern Togolok and Gomur, and in the northern part of Kalleli group sites. The Jeitun Culture of the Kopetdag Neolithic sites were explored from 1963 to 1973. The survey covered Jeitun Culture as a whole, and particular credit is given to the Turkmen archaeologist, O. K. Berdiev who died in an accident at a young age; his 10 years of explorations have been published under the title “The Most Ancient Agriculturalists of Southern Turkmenistan.” Neolithic pediment sites of Jeitun Culture extended from Bami in the west to the Meana Chacha district in the east. In the explorations done at the north mound of Anau, excavation in the Komanov trench at the north end were subject to deep sounding which revealed consecutive layers of buildings. From this, a stratigraphic sequence of developments evolved with "craft production and social stratification".
0
Metallurgy
The alloys of tantalum–tungsten have high corrosion resistance, and refractory properties. The crystalline structure of the material is body-centered cubic with a substitutional solid solution with atoms of tungsten. The alloy also has a high melting point and can reach high elastic modulus and high tensile strength.
0
Metallurgy
To obtain the desired measurement of , it is not sufficient to just measure . The temperature at the reference junctions must be already known. Two strategies are often used here: * "Ice bath" method: The reference junction block is immersed in a semi-frozen bath of distilled water at atmospheric pressure. The precise temperature of the melting point phase transition acts as a natural thermostat, fixing to 0 °C. * Reference junction sensor (known as ""): The reference junction block is allowed to vary in temperature, but the temperature is measured at this block using a separate temperature sensor. This secondary measurement is used to compensate for temperature variation at the junction block. The thermocouple junction is often exposed to extreme environments, while the reference junction is often mounted near the instrument's location. Semiconductor thermometer devices are often used in modern thermocouple instruments. In both cases the value is calculated, then the function is searched for a matching value. The argument where this match occurs is the value of :
0
Metallurgy
Rust is a general name for a complex of oxides and hydroxides of iron, which occur when iron or some alloys that contain iron are exposed to oxygen and moisture for a long period of time. Over time, the oxygen combines with the metal, forming new compounds collectively called rust, in a process called rusting. Rusting is an oxidation reaction specifically occurring with iron. Other metals also corrode via similar oxidation, but such corrosion is not called rusting. The main catalyst for the rusting process is water. Iron or steel structures might appear to be solid, but water molecules can penetrate the microscopic pits and cracks in any exposed metal. The hydrogen atoms present in water molecules can combine with other elements to form acids, which will eventually cause more metal to be exposed. If chloride ions are present, as is the case with saltwater, the corrosion is likely to occur more quickly. Meanwhile, the oxygen atoms combine with metallic atoms to form the destructive oxide compound. These iron compounds are brittle and crumbly and replace strong metallic iron, reducing the strength of the object.
0
Metallurgy
Members of the HNF4 subfamily are nuclear receptors and bind to DNA either as homodimers or RXR heterodimers. * HNF4α/TCF14/MODY1 * HNF4γ
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Gene expression + Signal Transduction
Screening falls under two general categories: dry screening, and wet screening. From these categories, screening separates a flow of material into grades, these grades are then either further processed to an intermediary product or a finished product. Additionally, the machines can be categorized into a moving screen and static screen machines, as well as by whether the screens are horizontal or inclined.
0
Metallurgy
The first step in failure analysis is investigating the failure to collect information. The sequence of steps for information gathering in a failure investigation are: # Collection information about the circumstances surrounding the failure and selection of specimens # Preliminary examination of the failed part (visual examination) and comparison with parts that have not failed # Macroscopic examination and analysis and photographic documentation of specimens (fracture surfaces, secondary cracks, and other surface phenomena) # Microscopic examination and analysis of specimens (fracture surfaces) # Selection and preparation of metallographic sections # Microscopic examination and analysis of prepared metallographic specimens # Nondestructive testing # Destructive/mechanical testing # Determination of failure mechanism # Chemical analysis (bulk, local, surface corrosion products, deposits or coatings) # Identify all possible root causes # Testing most likely possible root causes under simulated service conditions # Analysis of all the evidence, formulation of conclusions, and writing the report including recommendations
0
Metallurgy
In April 1918, after the attack of German-Austrian troops, most of the equipment and materials of the Yuzovsky plant were evacuated to Tsaritsyn (Volgograd), and detachments of workers retreated with the Red Army. On May 24, 1918, the plant was nationalized. In May 1918, during the German occupation, an underground organization of the Russian Communist Party bolsheviks or the RCP(b), led by E. Severyanov, began operating at the plant, and in July 1918 an underground regional committee of six members began operating at the plant. In December 1919, Soviet power was restored in Yuzovka, on January 30, 1920, a workers' board of all enterprises of the former "Novorossiysk Society of Coal, Iron and Rail Production" (headed by M. S. Titov) was created in Yuzovka, and the restoration of the plant began. On July 6, 1921, the first blast furnace was launched again, by the end of 1921, production at the plant was restored. In 1924, the plant was named after Joseph Vissarionovich Stalin. During Industrialization in the Soviet Union, the plant was transformed into a new technical base. During the First Five-Year Plan, mechanization of the mill and a bunker system for blast furnace charging were introduced and technical renovation was initiated; in 1936 the reconstruction of the mill and the construction of the flat furnace mill were completed, the plate and profilerolling mills were mechanized and a new, powerful blooming mill replaced the old rail-rolling mill.
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Metallurgy
EGF; LDLR; LRP1; LRP10; LRP1B; LRP2; LRP4; LRP5; LRP5L; LRP6; LRP8; NID1; NID2; SORL1; VLDLR;
1
Gene expression + Signal Transduction
CeCoIn is a member of a rich family of heavy-fermion compounds. CeIn is heavy-fermion metal with cubic crystal structure that orders antiferromagnetically below 10K. With applying external pressure, antiferromagnetism in CeIn is continuously suppressed, and a superconducting dome emerges in the phase diagram near the antiferromagnetic quantum critical point. CeCoIn has a tetragonal crystal structure, and the unit cell of CeCoIn can be considered as CeIn with an additional CoIn layer per unit cell. Closely related to CeCoIn is the heavy-fermion material CeRhIn, which has the same crystal structure and which orders antiferromagnetically below 4K, but does not become superconducting at ambient pressure. At high pressure CeRhIn becomes superconducting with a maximum T slightly above 2 K at a pressure around 2 GPa, and at the same pressure the Fermi surface of CeRhIn changes suggesting so-called local quantum criticality. Also the compound PuCoGa, which is a superconductor with T approximately 18.5 K and which can be considered an intermediate between heavy-fermion and cuprate superconductors, has the same crystal structure. Growth of single-crystalline CeCoIn has been very successful soon after the discovery of the material, and large single crystals of CeCoIn, such as required for inelastic neutron scattering, have been prepared. (In contrast to some other heavy-fermion compounds where single-crystal growth is more challenging.)
0
Metallurgy
The MyD88-dependent response occurs on dimerization of TLRs, and is used by every TLR except TLR3. Its primary effect is activation of NFκB and Mitogen-activated protein kinase. Ligand binding and conformational change that occurs in the receptor recruits the adaptor protein MyD88, a member of the TIR family. MyD88 then recruits IRAK4, IRAK1 and IRAK2. IRAK kinases then phosphorylate and activate the protein TRAF6, which in turn polyubiquinates the protein TAK1, as well as itself to facilitate binding to IKK-β. On binding, TAK1 phosphorylates IKK-β, which then phosphorylates IκB causing its degradation and allowing NFκB to diffuse into the cell nucleus and activate transcription and consequent induction of inflammatory cytokines.
1
Gene expression + Signal Transduction
The Ellingham curve for the reaction 2C(s) + (g) → 2CO(g) slopes down and falls below the curves for all the metals. Hence, carbon can normally act as a reducing agent for all metal oxides at very high temperatures. But chromium formed at these temperatures reacts with carbon to form its carbide, which gives undesirable properties to the chromium metal obtained. Hence, for high temperature reduction of chromic oxide, carbon cannot be used.
0
Metallurgy
Silicon carbide exists in about 250 crystalline forms. Through inert atmospheric pyrolysis of preceramic polymers, silicon carbide in a glassy amorphous form is also produced. The polymorphism of SiC is characterized by a large family of similar crystalline structures called polytypes. They are variations of the same chemical compound that are identical in two dimensions and differ in the third. Thus, they can be viewed as layers stacked in a certain sequence. Alpha silicon carbide (α-SiC) is the most commonly encountered polymorph, and is formed at temperatures greater than 1700 °C and has a hexagonal crystal structure (similar to Wurtzite). The beta modification (β-SiC), with a zinc blende crystal structure (similar to diamond), is formed at temperatures below 1700 °C. Until recently, the beta form has had relatively few commercial uses, although there is now increasing interest in its use as a support for heterogeneous catalysts, owing to its higher surface area compared to the alpha form. Pure SiC is colorless. The brown to black color of the industrial product results from iron impurities. The rainbow-like luster of the crystals is due to the thin-film interference of a passivation layer of silicon dioxide that forms on the surface. The high sublimation temperature of SiC (approximately 2700 °C) makes it useful for bearings and furnace parts. Silicon carbide does not melt but begins to sublimate near 2700 °C like graphite, having an appreciable vapor pressure near that temp. It is also highly inert chemically, partly due to the formation of a thin passivated layer of SiO2. There is currently much interest in its use as a semiconductor material in electronics, where its high thermal conductivity, high electric field breakdown strength and high maximum current density make it more promising than silicon for high-powered devices. SiC has a very low coefficient of thermal expansion of about 2.3 × 10 K near 300 K (for 4H and 6H SiC) and experiences no phase transitions in the temperature range 5 K to 340 K that would cause discontinuities in the thermal expansion coefficient.
0
Metallurgy
De re metallica (Latin for On the Nature of Metals [Minerals]) is a book in Latin cataloguing the state of the art of mining, refining, and smelting metals, published a year posthumously in 1556 due to a delay in preparing woodcuts for the text. The author was Georg Bauer, whose pen name was the Latinized Georgius Agricola ("Bauer" and "Agricola" being respectively the German and Latin words for "farmer"). The book remained the authoritative text on mining for 180 years after its publication. It was also an important chemistry text for the period and is significant in the history of chemistry. Mining was typically left to professionals, craftsmen and experts who were not eager to share their knowledge. Much experiential knowledge had been accumulated over the course of time. This knowledge was consecutively handed down orally within a small group of technicians and mining overseers. In the Middle Ages these people held the same leading role as the master builders of the great cathedrals, or perhaps also alchemists. It was a small, cosmopolitan elite within which existing knowledge was passed on and further developed but not shared with the outside world. Only a few writers from that time wrote anything about mining itself. Partly, that was because this knowledge was very difficult to access. Most writers also found it simply not worth the effort to write about it. Only in the Renaissance did this perception begin to change. With the improved transport and the invention of the printing press knowledge spread much more easily and faster than before. In 1500, the first printed book dedicated to mining engineering, called the Nützlich Bergbüchleyn ("The Useful Little Mining Book”) by Ulrich Rülein von Calw, was published. The most important works in this genre were, however, the twelve books of De Re Metallica by Georgius Agricola, published in 1556. Agricola had spent nine years in the Bohemian town of Joachimsthal (now Jáchymov in the Czech Republic). After Joachimsthal, he spent the rest of his life in Chemnitz in Saxony, another prominent mining town in the Ore Mountains. The book was greatly influential, and for more than a century after it was published, De Re Metallica remained a standard treatise used throughout Europe. The German mining technology it portrayed was acknowledged as the most advanced at the time, and the metallic wealth produced in German mining districts was the envy of many other European nations. The book was reprinted in a number of Latin editions, as well as in German and Italian translations. Publication in Latin meant that it could be read by any educated European of the time. The 292 superb woodcut illustrations and the detailed descriptions of machinery made it a practical reference for those wishing to replicate the latest in mining technology. The drawings from which the woodcuts were made were done by an artist in Joachimsthal named Blasius Weffring or Basilius Wefring. The woodcuts were then prepared in the Froben publishing house by Hans Rudolf Manuel Deutsch and Zacharias Specklin. In 1912, the first English translation of De Re Metallica was privately published in London by subscription. The translators were Herbert Hoover, a mining engineer (and later President of the United States), and his wife, Lou Henry Hoover, a geologist and Latinist. The translation is notable not only for its clarity of language, but for the extensive footnotes, which detail the classical references to mining and metals. Subsequent translations into other languages, including German, owe much to the Hoover translations, as their footnotes detail their difficulties with Agricola's invention of several hundred Latin expressions to cover Medieval German mining and milling terms that were unknown to classical Latin. The most important translation—outside English—was the one published by the Deutsches Museum in Munich.
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Metallurgy
William H. Peirce (died 1944) was an American civil engineer and metallurgist, who pioneered copper production in the early 20th century. Among his achievements was the , invented with Elias Anton Cappelen Smith.
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Metallurgy
5-Methylcytosine (5-mC) is a methylated form of the DNA base cytosine (see figure). 5-mC is an epigenetic marker found predominantly on cytosines within CpG dinucleotides, which consist of a cytosine is followed by a guanine reading in the 5′ to 3′ direction along the DNA strand (CpG sites). About 28 million CpG dinucleotides occur in the human genome. In most tissues of mammals, on average, 70% to 80% of CpG cytosines are methylated (forming 5-methyl-CpG, or 5-mCpG). Methylated cytosines within CpG sequences often occur in groups, called CpG islands. About 59% of promoter sequences have a CpG island while only about 6% of enhancer sequences have a CpG island. CpG islands constitute regulatory sequences, since if CpG islands are methylated in the promoter of a gene this can reduce or silence gene expression. DNA methylation regulates gene expression through interaction with methyl binding domain (MBD) proteins, such as MeCP2, MBD1 and MBD2. These MBD proteins bind most strongly to highly methylated CpG islands. These MBD proteins have both a methyl-CpG-binding domain and a transcriptional repression domain. They bind to methylated DNA and guide or direct protein complexes with chromatin remodeling and/or histone modifying activity to methylated CpG islands. MBD proteins generally repress local chromatin by means such as catalyzing the introduction of repressive histone marks or creating an overall repressive chromatin environment through nucleosome remodeling and chromatin reorganization. Transcription factors are proteins that bind to specific DNA sequences in order to regulate the expression of a given gene. The binding sequence for a transcription factor in DNA is usually about 10 or 11 nucleotides long. There are approximately 1,400 different transcription factors encoded in the human genome and they constitute about 6% of all human protein coding genes. About 94% of transcription factor binding sites that are associated with signal-responsive genes occur in enhancers while only about 6% of such sites occur in promoters. EGR1 is a transcription factor important for regulation of methylation of CpG islands. An EGR1 transcription factor binding site is frequently located in enhancer or promoter sequences. There are about 12,000 binding sites for EGR1 in the mammalian genome and about half of EGR1 binding sites are located in promoters and half in enhancers. The binding of EGR1 to its target DNA binding site is insensitive to cytosine methylation in the DNA. While only small amounts of EGR1 protein are detectable in cells that are un-stimulated, EGR1 translation into protein at one hour after stimulation is markedly elevated. Expression of EGR1 in various types of cells can be stimulated by growth factors, neurotransmitters, hormones, stress and injury. In the brain, when neurons are activated, EGR1 proteins are upregulated, and they bind to (recruit) pre-existing TET1 enzymes, which are highly expressed in neurons. TET enzymes can catalyze demethylation of 5-methylcytosine. When EGR1 transcription factors bring TET1 enzymes to EGR1 binding sites in promoters, the TET enzymes can demethylate the methylated CpG islands at those promoters. Upon demethylation, these promoters can then initiate transcription of their target genes. Hundreds of genes in neurons are differentially expressed after neuron activation through EGR1 recruitment of TET1 to methylated regulatory sequences in their promoters.
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Gene expression + Signal Transduction
The surface of a metallographic specimen is prepared by various methods of grinding, polishing, and etching. After preparation, it is often analyzed using optical or electron microscopy. Using only metallographic techniques, a skilled technician can identify alloys and predict material properties. Mechanical preparation is the most common preparation method. Successively finer abrasive particles are used to remove material from the sample surface until the desired surface quality is achieved. Many different machines are available for doing this grinding and polishing, which are able to meet different demands for quality, capacity, and reproducibility. A systematic preparation method is the easiest way to achieve the true structure. Sample preparation must therefore pursue rules which are suitable for most materials. Different materials with similar properties (hardness and ductility) will respond alike and thus require the same consumables during preparation. Metallographic specimens are typically "mounted" using a hot compression thermosetting resin. In the past, phenolic thermosetting resins have been used, but modern epoxy is becoming more popular because reduced shrinkage during curing results in a better mount with superior edge retention. A typical mounting cycle will compress the specimen and mounting media to and heat to a temperature of . When specimens are very sensitive to temperature, "cold mounts" may be made with a two-part epoxy resin. Mounting a specimen provides a safe, standardized, and ergonomic way by which to hold a sample during the grinding and polishing operations. After mounting, the specimen is wet ground to reveal the surface of the metal. The specimen is successively ground with finer and finer abrasive media. Silicon carbide abrasive paper was the first method of grinding and is still used today. Many metallographers, however, prefer to use a diamond grit suspension which is dosed onto a reusable fabric pad throughout the polishing process. Diamond grit in suspension might start at 9 micrometres and finish at one micrometre. Generally, polishing with diamond suspension gives finer results than using silicon carbide papers (SiC papers), especially with revealing porosity, which silicon carbide paper sometimes "smear" over. After grinding the specimen, polishing is performed. Typically, a specimen is polished with a slurry of alumina, silica, or diamond on a napless cloth to produce a scratch-free mirror finish, free from smear, drag, or pull-outs and with minimal deformation remaining from the preparation process. After polishing, certain microstructural constituents can be seen with the microscope, e.g., inclusions and nitrides. If the crystal structure is non-cubic (e.g., a metal with a hexagonal-closed packed crystal structure, such as Ti or Zr) the microstructure can be revealed without etching using crossed polarized light (light microscopy). Otherwise, the microstructural constituents of the specimen are revealed by using a suitable chemical or electrolytic etchant. Non-destructive surface analysis techniques can involve applying a thin film or varnish that can be peeled off after drying and examined under a microscope. The technique was developed by Pierre Armand Jacquet and others in 1957.
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Metallurgy
The mechanisms of embrittlement are similar to those of metals. Inorganic glass embrittlement can be manifested via static fatigue. Embrittlement in glasses, such as Pyrex, is a function of humidity. Growth rate of cracks vary linearly with humidity, suggesting a first-order kinetic relationship. The static fatigue of Pyrex by this mechanism requires dissolution to be concentrated at the tip of the crack. If the dissolution is uniform along the crack flat surfaces, the crack tip will be blunted. This blunting can actually increase the fracture strength of the material by 100 times. The embrittlement of SiC/alumina composites serves as an instructive example. The mechanism for this system is primarily the diffusion of oxygen into the material through cracks in the matrix. The oxygen reaches the SiC fibers and produces silicate. Stress concentrates around the newly formed silicate and the fibers strength is degraded. This ultimately leads to fracture at stresses less than the materials typical fracture stress.
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Metallurgy
MCT2 transporters within the peroxisome function to transport pyruvate into the peroxisome where it is reduced by peroxisomal LDH (pLDH) to lactate. In turn, NADH is converted to NAD+, regenerating this necessary component for subsequent β-oxidation. Lactate is then shuttled out of the peroxisome via MCT2, where it is oxidized by cytoplasmic LDH (cLDH) to pyruvate, generating NADH for energy use and completing the cycle (see figure).
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Gene expression + Signal Transduction
One simplified example of a synexpression group is the genes cdc6, cdc3, cdc46, and swi4 in yeast, which are all co-expressed early in the G-1 stage of the cell cycle., These genes share one common cis-regulatory element, called ECB, which serves as a binding site for the MCM1 trans-acting protein. Although these genes are not spatially clustered, co-regulation seems to be achieved via this common cis and trans control mechanism. Most synexpression groups are more complicated than the ECB group in yeast, involving myriad cis and trans control elements.
1
Gene expression + Signal Transduction
The lactate shuttle hypothesis also explains the balance of lactate production in the cytosol, via glycolysis or glycogenolysis, and lactate oxidation in the mitochondria (described below).
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Gene expression + Signal Transduction
Puddling is the process of converting pig iron to bar (wrought) iron in a coal fired reverberatory furnace. It was developed in England during the 1780s. The molten pig iron was stirred in a reverberatory furnace, in an oxidizing environment to burn the carbon, resulting in wrought iron. It was one of the most important processes for making the first appreciable volumes of valuable and useful bar iron (malleable wrought iron) without the use of charcoal. Eventually, the furnace would be used to make small quantities of specialty steels. Though it was not the first process to produce bar iron without charcoal, puddling was by far the most successful, and replaced the earlier potting and stamping processes, as well as the much older charcoal finery and bloomery processes. This enabled a great expansion of iron production to take place in Great Britain, and shortly afterwards, in North America. That expansion constitutes the beginnings of the Industrial Revolution so far as the iron industry is concerned. Most 19th century applications of wrought iron, including the Eiffel Tower, bridges, and the original framework of the Statue of Liberty, used puddled iron.
0
Metallurgy
Iron or steel, when heated to above 460 °C (900 °F), glows with a red color. The color of heated iron changes predictably (due to black-body radiation) from dull red through orange and yellow to white, and can be a useful indicator of its temperature. Good quality iron or steel at and above this temperature becomes increasingly malleable and plastic. Iron or steel having too much sulfur, on the other hand, becomes crumbly and brittle. This is due to the sulfur forming iron sulfide/iron mixtures in the grain boundaries of the metal which have a lower melting point than the steel. When the steel is heated up and worked, the mechanical energy added to the workpiece increases the temperature further. The iron sulfide (FeS) or iron/iron sulfide alloy (which has an even lower melting point) begins to melt, and the steel starts to separate at the grain boundaries. Steelmakers add manganese (Mn) to the steel when it is produced, to form manganese sulfide (MnS). Manganese sulfide inclusions have a higher melting point and do not concentrate at the grain boundaries. Thus, when the steel is later heated up and worked, the melting at the grain boundaries does not occur.
0
Metallurgy
Froth flotation is achieved by mixing chemicals known as collectors with the ore slurry. The collectors adsorb onto the surfaces of the particles of select minerals (usually the valuable mineral that is targeted for concentration), making these minerals hydrophobic. Air is passed through the slurry in a tank known as a flotation cell. The air is broken into tiny bubbles by various mechanisms (depending on the design of the flotation cell), and the now-hydrophobic minerals attach to the bubbles, rising with them to the surface of the flotation cell, where they form a froth. The froth flows over the top edge (or "lip") of the flotation cell and forms the flotation concentrate. Ideally, none of the unwanted mineral particles float, and they remain behind as the flotation tailings. However, the selectivity of the collection mechanism is not perfect. Some unwanted ("gangue") minerals are also carried into the froth, largely by entrainment with the water rising with the bubbles. This is particularly the case for particles less than 10 μm in size. Some of the gangue particles follow the water between the bubbles as it drains back to the underlying pulp. This process can be assisted by the application of sufficient "wash water" to the froth to displace the water entrained with the bubbles and the fine gangue particles brought with them. Column flotation cells, invented in Canada by Boutin and Tremblay in 1961, grew increasingly popular in the 1980s and 1990s as a way of reducing entrainment of fine gangue particles during "cleaning" of flotation concentrates. With heights usually between 6 and 14 meters, they could have froth depths up to 2 m, providing more residence time than conventional cells and more stable froth surfaces that enable better froth washing. Froth flotation efficiency is determined by a series of probabilities: those of particle–bubble contact, particle–bubble attachment, transport between the pulp and the froth, and froth collection into the product launder. In a conventional mechanically agitated cell, the void fraction is low (5–10%) and the bubble size is large (2–3 mm), which results in a low interfacial area with a low probability of particle–bubble contact. In a conventional flotation column, the void fraction is similarly low, and so the probability of particle–bubble contact is increased by increasing the height of the column to provide greater residence time. Traditionally, the ore slurry and the air are introduced separately to the flotation cell (see Figure 2). The Jameson Cell differs from this traditional approach by mixing the slurry with the air in the downcomers. The slurry is introduced at the top of the downcomer as a jet that draws in air through a second pipe to form a stable two-phase mixture (see Figure 3). The plunging slurry jet shears and then entrains the air. The target minerals, with their collector-coated surfaces, attach to the bubbles and this mixture travels down the downcomer, driven by hydrostatic forces, before it is discharged into the tank portion of the Jameson Cell (see Figure 4). The downcomer is designed to provide high-intensity mixing of the air and the slurry to generate a dense foam of fine bubbles and maximise the contact between the target mineral particles and the bubbles. The probability of particle–bubble contact is "virtually 100%" with a slurry residence time in the downcomer of 5–10 seconds. The high probability of particle–bubble contact, and subsequent short residence times (five to ten seconds in the downcomer, allows for a much more compact column design than conventional column flotation cells (see Figure 1). The fine nature of the bubbles (0.3 to 0.5 mm in diameter) gives them enhanced carrying capabilities for fine mineral particles. Fine bubbles also improve the separation of minerals, as they intensify the difference in the flotation kinetics of the valuable minerals from the gangue minerals, thus allowing higher grade concentrates to be produced. The foam in the downcomer is about 50–60% air. Because of this, the pulp is distributed in the form of thin interfacial slurry films between the bubbles, providing an ideal environment for particle–bubble contact. Collection occurs by migration of the particles within the thin films, which are not much thicker than the diameter of the particles. The best collection occurs when the volume of air roughly equals that of the injected slurry. The Cell is operated by initially closing the air inlet at the top of the downcomer and feeding the flotation pulp in through the nozzle. The air in the downcomer is entrained in the pulp, creating a partial vacuum that draws pulp from the tank up into the downcomer. The pulp level quickly reaches the nozzle, which is at a level above that of the liquid level in the tank. This creates a hydrostatic head in the downcomer, meaning that the pressure inside the top of the downcomer is lower than the atmospheric pressure. When the inlet is opened, air is drawn into the top space of the downcomer by this lower pressure, where it too is entrained into the downcomer contents by the plunging jet. At the same time, a downward flow is established in the pulp in the downcomer that is sufficient to counter the buoyancy of the bubbles, and the aerated pulp discharges into the tank. Once in the tank, the wider cross sectional area of the tank reduces the downward superficial velocity of the mixture, allowing mineral-laden bubbles to disengage from the liquid and rise to the surface as they would in a conventional cell, where they form the froth. The velocity of the mixture discharging into the tank, and the large density differential between it and the remainder of the pulp in the tank, results in recirculating fluid patterns that keep the particles in the tank in suspension without requiring mechanical agitation. The purpose of the tank is simply for bubble–pulp separation, so the volume of the tank is small compared with alternative technologies. The froth that forms at the top of the tank flows over its lip to be collected. This froth can be "washed" by a light flow of water, if desired. The bubbles flowing over the lip of the cell are smaller in diameter than those that flow over the lip of conventional flotation columns. The non-floating tailings are discharged through a hole in the bottom of the tank. The Cell has no moving parts and no requirement for compressed air or sparging mechanisms. This results in lower power consumption than the equivalent mechanical or column flotation cells. Maintenance costs are also lower because the only wearing part is the slurry lens used to create the jet in the downcomer.
0
Metallurgy
The three related TET genes, TET1, TET2 and TET3 code respectively for three related mammalian proteins TET1, TET2, and TET3. All three proteins possess 5mC oxidase activity, but they differ in terms of domain architecture. TET proteins are large (~180- to 230-kDa) multidomain enzymes. All TET proteins contain a conserved double-stranded β-helix (DSBH) domain, a cysteine-rich domain, and binding sites for the cofactors Fe(II) and 2-oxoglutarate (2-OG) that together form the core catalytic region in the C terminus. In addition to their catalytic domain, full-length TET1 and TET3 proteins have an N-terminal CXXC zinc finger domain that can bind DNA. The TET2 protein lacks a CXXC domain, but the IDAX gene, that's a neighbor of the TET2 gene, encodes a CXXC4 protein. IDAX is thought to play a role in regulating TET2 activity by facilitating its recruitment to unmethylated CpGs.
1
Gene expression + Signal Transduction
mTOR promotes the protein synthesis required for synaptic plasticity. Studies in cell cultures and hippocampal slices indicate that mTOR inhibition reduces long-term potentiation. mTOR activation can protect against certain neurodegeneration associated with certain disease conditions. On the other hand, promotion of autophagy by mTOR inhibition may reduce cognitive decline associated with neurodegeneration. Moderate reduction of mTOR activity by 25-30% has been shown to improve brain function, suggesting that the relation between mTOR and cognition is optimized with intermediate doses (2.24 mg/kg/day in mice, human equivalent about 0.19 mg/kg/day), where very high or very low doses impair cognition. Reduction of the inflammatory cytokine Interleukin 1 beta (IL-1β) in mice by mTOR inhibition (with rapamycin in doses of 20 mg/kg/day, human equivalent about 1.6 mg/kg/day) has been shown to enhance learning and memory. Although IL-1β is required for memory, IL-1β normally increases with age, impairing cognitive function.
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Gene expression + Signal Transduction
*Erosion corrosion *Pitting corrosion Oxygen pitting *Hydrogen embrittlement *Hydrogen-induced cracking (ASM term) *Corrosion embrittlement (ASM term) *Hydrogen disintegration (NACE term) *Hydrogen-assisted cracking (ASM term) *Hydrogen blistering *Corrosion
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Metallurgy
It had long been thought that the sigma factor obligatorily leaves the core enzyme once it has initiated transcription, allowing it to link to another core enzyme and initiate transcription at another site. Thus, the sigma factor would cycle from one core to another. However, fluorescence resonance energy transfer was used to show that the sigma factor does not obligatorily leave the core. Instead, it changes its binding with the core during initiation and elongation. Therefore, the sigma factor cycles between a strongly bound state during initiation and a weakly bound state during elongation.
1
Gene expression + Signal Transduction
Bacterial initiation factor 1 associates with the 30S ribosomal subunit in the A site and prevents an aminoacyl-tRNA from entering. It modulates IF2 binding to the ribosome by increasing its affinity. It may also prevent the 50S subunit from binding, stopping the formation of the 70S subunit. It also contains a β-domain fold common for nucleic acid-binding proteins. It is a homolog of eIF1A. Initiation factor IF-1 is the smallest translation factor at only 8.2kDa. Beyond blocking the A-site, it affects the dynamics of ribosome association and dissociation. IF-1 enhances dissociation with IF-3, likely by inducing conformational changes in the 30S subunit. It also increases the binding affinity of IF-2 to the 30S subunit, possibly by altering the subunit configuration. Though IF-1 occupies the A-site, it does so in a way that is distinct from tRNA binding. Structural studies show IF-1 inserts a loop into the minor groove of helix 44 of 16S rRNA, flipping out bases A1492 and A1493. This insertion repositions nucleotides of helix 44, transmitting a conformational change over a 70Å distance and rotating the head of the 30S subunit. IF-1 mutants can exhibit cold-sensitive phenotypes, indicating a role for the factor in cold shock adaptation. Certain mutations also lead to o of genes at low temperatures, suggesting IF-1 is involved in gene regulation. IF-1 actively modifies ribosome structure and dynamics during initiation, in addition to just blocking the A-site.
1
Gene expression + Signal Transduction
Because of the widespread use and importance of iron and steel products, the prevention or slowing of rust is the basis of major economic activities in a number of specialized technologies. A brief overview of methods is presented here; for detailed coverage, see the cross-referenced articles. Rust is permeable to air and water, therefore the interior metallic iron beneath a rust layer continues to corrode. Rust prevention thus requires coatings that preclude rust formation.
0
Metallurgy
The formation of new blood capillaries is an important component of pathological tissue repair in response to ischemia. The angiogenic process is complex and involves endothelial cell (EC) movement and proliferation. SFRP1 has been shown to have a role in new vascularization after an ischemic event and as a potent angiogenic factor. In vitro SFRP1 modulated the EC angiogenic response (migration, differentiation) and in vivo SFRP1 stimulated neovascularization in plug or tumor models. The directed movements of EC during de novo vessel formation are coordinated through cellular adhesion mechanisms, cytoskeletal reorganization and by association with elevated expression of angiogenic factors such as, the key factor, vascular endothelial growth factor. The regulation of the EC cytoskeleton is critical to EC spreading and motility. SFRP1 was found to have a major role in mediating EC spreading by regulating reorganization of the actin network and focal contact formations. In vivo data supports a critical role for SFRP1 in ischemia-induced angiogenesis in adults. Using adenovirus-expressing SFRP1, impaired the canonical Wnt/Fzd pathway in the early phase of ischemia and as a result reduced vascular cell proliferation and delayed vessel formation. When SFRP1 was induced specifically in ECs along the kinetics of ischemia repair, a biphasic response was seen: a delay in capillary formation until day 15 and then an increase in vascular formation at day 25. This indicates that SFRP1 can fine tune the outcome of Wnt/Fzd signaling at different steps in the course of neovessel formation.
1
Gene expression + Signal Transduction
The Ruhr Valley provided an excellent location for the German iron and steel industry because of the availability of raw materials, coal, transport, a skilled labor force, nearby markets, and an entrepreneurial spirit that led to the creation of many firms, often in close conjunction with coal mines. By 1850 the Ruhr had 50 iron works with 2,813 full-time employees. The first modern furnace was built in 1849. The unification of Germany in 1871 gave further impetus to rapid growth, as the German Empire started to catch up with Britain. From 1880 to World War I, the industry of the Ruhr area consisted of numerous enterprises, each working on a separate level of production. Mixed enterprises could unite all levels of production through vertical integration, thus lowering production costs. Technological progress brought new advantages as well. These developments set the stage for the creation of combined business concerns. The leading firm was Friedrich Krupp AG run by the Krupp family. Many diverse, large-scale family firms such as Krupps reorganized in order to adapt to the changing conditions and meet the economic depression of the 1870s, which reduced the earnings in the German iron and steel industry. Krupp reformed his accounting system to better manage his growing empire, adding a specialized bureau of calculation as well as a bureau for the control of times and wages. The rival firm GHH quickly followed, as did Thyssen AG, which had been founded by August Thyssen in 1867. Germany became Europes leading steel-producing nation in the late 19th century, thanks in large part to the protection from American and British competition afforded by tariffs and cartels. By 1913 American and German exports dominated the world steel market, and Britain slipped to third place. German steel production grew explosively from 1 million metric tons in 1885 to 10 million in 1905 and peaked at 19 million in 1918. In the 1920s Germany produced about 15 million tons, but output plunged to 6 million in 1933. Under Nazi rule, steel output peaked at 22 million tons in 1940, then dipped to 18 million in 1944 under Allied bombing. The merger of four major firms into the German Steel Trust (Vereinigte Stahlwerke) in 1926 was modeled on the U.S. Steel corporation in the U.S. The goal was to move beyond the limitations of the old cartel system by incorporating advances simultaneously inside a single corporation. The new company emphasized rationalization of management structures and modernization of the technology; it employed a multi-divisional structure and used return on investment as its measure of success. It represented the "Americanization" of the German steel industry because its internal structure, management methods, use of technology, and emphasis on mass production. The chief difference was that consumer capitalism as an industrial strategy did not seem plausible to German steel industrialists. In iron and steel and other industries, German firms avoided cut-throat competition and instead relied on trade associations. Germany was a world leader because of its prevailing "corporatist mentality", its strong bureaucratic tradition, and the encouragement of the government. These associations regulated competition and allowed small firms to function in the shadow of much larger companies. With the need to rebuild the bombed-out infrastructure after the Second World War, Marshall Plan (1948–51) enabled West Germany to rebuild and modernize its mills. It produced 3 million tons of steel in 1947, 12 million in 1950, 34 million in 1960 and 46 million in 1970. East Germany produced about a tenth as much.
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Metallurgy
Signal transducing histidine kinases are the key elements in two-component signal transduction systems. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation, and CheA, which plays a central role in the chemotaxis system. Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate to water. The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily. HKs can be roughly divided into two classes: orthodox and hybrid kinases. Most orthodox HKs, typified by the E. coli EnvZ protein, function as periplasmic membrane receptors and have a signal peptide and transmembrane segment(s) that separate the protein into a periplasmic N-terminal sensing domain and a highly conserved cytoplasmic C-terminal kinase core. Members of this family, however, have an integral membrane sensor domain. Not all orthodox kinases are membrane bound, e.g., the nitrogen regulatory kinase NtrB (GlnL) is a soluble cytoplasmic HK. Hybrid kinases contain multiple phosphodonor and phosphoacceptor sites and use multi-step phospho-relay schemes instead of promoting a single phosphoryl transfer. In addition to the sensor domain and kinase core, they contain a CheY-like receiver domain and a His-containing phosphotransfer (HPt) domain.
1
Gene expression + Signal Transduction
β-Catenin also acts as a morphogen in later stages of embryonic development. Together with TGF-β, an important role of β-catenin is to induce a morphogenic change in epithelial cells. It induces them to abandon their tight adhesion and assume a more mobile and loosely associated mesenchymal phenotype. During this process, epithelial cells lose expression of proteins like E-cadherin, Zonula occludens 1 (ZO1), and cytokeratin. At the same time they turn on the expression of vimentin, alpha smooth muscle actin (ACTA2), and fibroblast-specific protein 1 (FSP1). They also produce extracellular matrix components, such as type I collagen and fibronectin. Aberrant activation of the Wnt pathway has been implicated in pathological processes such as fibrosis and cancer. In cardiac muscle development, β-catenin performs a biphasic role. Initially, the activation of Wnt/β-catenin is essential for committing mesenchymal cells to a cardiac lineage; however, in later stages of development, the downregulation of β-catenin is required.
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Gene expression + Signal Transduction
Individual transmembrane adenylyl cyclase isoforms have been linked to numerous physiological functions. Soluble adenylyl cyclase (sAC, AC10) has a critical role in sperm motility. Adenylyl cyclase has been implicated in memory formation, functioning as a coincidence detector.
1
Gene expression + Signal Transduction
In order to maintain the solution electroneutrality inside the pit populated by cations released by oxidation in the anodic zone (e.g., in case of steel), anions need to migrate inside the narrow pit. It is worth to notice that the electromobilities of thiosulfate () and chloride () anions are the highest after these of and ions in aqueous solution. Moreover, the molar conductivity of thiosulfate ions is even higher than that of chloride ions because they are twice negatively charged (weak base reluctant to accept a proton). In capillary electrophoresis, thiosulfate moves faster than chloride and eluates before this latter. The high electromobility of both anions could also be one of the many factors explaining their harmful impact for pitting corrosion when compared with other much less damaging ion species such as and .
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Metallurgy
Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can be programmed by the nucleotide sequence of the mRNA and is sometimes affected by the secondary, 3-dimensional mRNA structure. It has been described mainly in viruses (especially retroviruses), retrotransposons and bacterial insertion elements, and also in some cellular genes. Small molecules, proteins, and nucleic acids have also been found to stimulate levels of frameshifting. In December 2023, it was reported that in vitro-transcribed (IVT) mRNAs in response to BNT162b2 (Pfizer–BioNTech) anti-COVID-19 vaccine caused ribosomal frameshifting.
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Gene expression + Signal Transduction
There are several challenges associated with gene silencing therapies, including delivery and specificity for targeted cells. For instance, for treatment of neurodegenerative disorders, molecules for a prospective gene silencing therapy must be delivered to the brain. The blood–brain barrier makes it difficult to deliver molecules into the brain through the bloodstream by preventing the passage of the majority of molecules that are injected or absorbed into the blood. Thus, researchers have found that they must directly inject the molecules or implant pumps that push them into the brain. Once inside the brain, however, the molecules must move inside of the targeted cells. In order to efficiently deliver siRNA molecules into the cells, viral vectors can be used. Nevertheless, this method of delivery can also be problematic as it can elicit an immune response against the molecules. In addition to delivery, specificity has also been found to be an issue in gene silencing. Both antisense oligonucleotides and siRNA molecules can potentially bind to the wrong mRNA molecule. Thus, researchers are searching for more efficient methods to deliver and develop specific gene silencing therapeutics that are still safe and effective.
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Gene expression + Signal Transduction
Scrap metal is delivered to a scrap bay, located next to the melt shop. Scrap generally comes in two main grades: shred (whitegoods, cars and other objects made of similar light-gauge steel) and heavy melt (large slabs and beams), along with some direct reduced iron (DRI) or pig iron for chemical balance. Some furnaces melt almost 100% DRI. The scrap is loaded into large buckets called baskets, with "clamshell" doors for a base. Care is taken to layer the scrap in the basket to ensure good furnace operation; heavy melt is placed on top of a light layer of protective shred, on top of which is placed more shred. These layers should be present in the furnace after charging. After loading, the basket may pass to a scrap pre-heater, which uses hot furnace off-gases to heat the scrap and recover energy, increasing plant efficiency. The scrap basket is then taken to the melt shop, the roof is swung off the furnace, and the furnace is charged with scrap from the basket. Charging is one of the more dangerous operations for the EAF operators. A lot of potential energy is released by the tonnes of falling metal; any liquid metal in the furnace is often displaced upwards and outwards by the solid scrap, and the grease and dust on the scrap is ignited if the furnace is hot, resulting in a fireball erupting. In some twin-shell furnaces, the scrap is charged into the second shell while the first is being melted down, and pre-heated with off-gas from the active shell. Other operations are continuous charging—pre-heating scrap on a conveyor belt, which then discharges the scrap into the furnace proper, or charging the scrap from a shaft set above the furnace, with off-gases directed through the shaft. Other furnaces can be charged with hot (molten) metal from other operations. After charging, the roof is swung back over the furnace and meltdown commences. The electrodes are lowered onto the scrap, an arc is struck and the electrodes are then set to bore into the layer of shred at the top of the furnace. Lower voltages are selected for this first part of the operation to protect the roof and walls from excessive heat and damage from the arcs. Once the electrodes have reached the heavy melt at the base of the furnace and the arcs are shielded by the scrap, the voltage can be increased and the electrodes raised slightly, lengthening the arcs and increasing power to the melt. This enables a molten pool to form more rapidly, reducing tap-to-tap times. Oxygen is blown into the scrap, combusting or cutting the steel, and extra chemical heat is provided by wall-mounted oxygen-fuel burners. Both processes accelerate scrap meltdown. Supersonic nozzles enable oxygen jets to penetrate foaming slag and reach the liquid bath. An important part of steelmaking is the formation of slag, which floats on the surface of the molten steel. Slag usually consists of metal oxides, and acts as a destination for oxidised impurities, as a thermal blanket (stopping excessive heat loss) and helping to reduce erosion of the refractory lining. For a furnace with basic refractories, which includes most carbon steel-producing furnaces, the usual slag formers are calcium oxide (CaO, in the form of burnt lime) and magnesium oxide (MgO, in the form of dolomite and magnesite). These slag formers are either charged with the scrap, or blown into the furnace during meltdown. Another major component of EAF slag is iron oxide from steel combusting with the injected oxygen. Later in the heat, carbon (in the form of coke or coal) is injected into this slag layer, reacting with the iron oxide to form metallic iron and carbon monoxide gas, which then causes the slag to foam, allowing greater thermal efficiency, and better arc stability and electrical efficiency. The slag blanket also covers the arcs, preventing damage to the furnace roof and sidewalls from radiant heat. Once the initial scrap charge has been melted down, another bucket of scrap can be charged into the furnace, although EAF development is moving towards single-charge designs. The scrap-charging and meltdown process can be repeated as many times as necessary to reach the required heat weight - the number of charges is dependent on the density of scrap; lower-density scrap means more charges. After all scrap charges have completely melted, refining operations take place to check and correct the steel chemistry and superheat the melt above its freezing temperature in preparation for tapping. More slag formers are introduced and more oxygen is blown into the bath, burning out impurities such as silicon, sulfur, phosphorus, aluminium, manganese, and calcium, and removing their oxides to the slag. Removal of carbon takes place after these elements have burnt out first, as they have a greater affinity for oxygen. Metals that have a poorer affinity for oxygen than iron, such as nickel and copper, cannot be removed through oxidation and must be controlled through scrap chemistry alone, such as introducing the direct reduced iron and pig iron mentioned earlier. A foaming slag is maintained throughout, and often overflows the furnace to pour out of the slag door into the slag pit. Temperature sampling and chemical sampling take place via automatic lances. Oxygen and carbon can be automatically measured via special probes that dip into the steel, but for all other elements, a "chill" sample — a small, solidified sample of the steel — is analysed on an arc-emission spectrometer. Once the temperature and chemistry are correct, the steel is tapped out into a preheated ladle through tilting the furnace. For plain-carbon steel furnaces, as soon as slag is detected during tapping the furnace is rapidly tilted back towards the deslagging side, minimising slag carryover into the ladle. For some special steel grades, including stainless steel, the slag is poured into the ladle as well, to be treated at the ladle furnace to recover valuable alloying elements. During tapping some alloy additions are introduced into the metal stream, and more fluxes such as lime are added on top of the ladle to begin building a new slag layer. Often, a few tonnes of liquid steel and slag is left in the furnace in order to form a "hot heel", which helps preheat the next charge of scrap and accelerate its meltdown. During and after tapping, the furnace is "turned around": the slag door is cleaned of solidified slag, the visible refractories are inspected and water-cooled components checked for leaks, and electrodes are inspected for damage or lengthened through the addition of new segments. The taphole is filled with sand at the completion of tapping. For a 90-tonne, medium-power furnace, the whole process will usually take about 60–70 minutes from the tapping of one heat to the tapping of the next (the tap-to-tap time). The furnace is completely emptied of steel and slag on a regular basis so that an inspection of the refractories can be made and larger repairs made if necessary. As the refractories are often made from calcined carbonates, they are extremely susceptible to hydration from water, so any suspected leaks from water-cooled components are treated extremely seriously, beyond the immediate concern of potential steam explosions. Excessive refractory wear can lead to breakouts, where the liquid metal and slag penetrate the refractory and furnace shell and escape into the surrounding areas.
0
Metallurgy
*Prastarika: metal trader *Sulbhadhatusastra: science of metals *panchaloha, sarva loha: the five base metals (tin, lead, iron, copper, silver)
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Metallurgy
Directing edits to correct mutated sequences was first proposed and demonstrated in 1995. This initial work used synthetic RNA antisense oligonucleotides complementary to a pre-mature stop codon mutation in a dystrophin sequence to activate A-to-I editing of the stop codon to a read through codon in a model xenopus cell system. While this also led to nearby inadvertent A-to-I transitions, A to I (read as G) transitions can correct all three stop codons, but cannot create a stop codon. Therefore, the changes led >25% correction of the targeted stop codon with read through to a downstream luciferase reporter sequence. Follow on work by Rosenthal achieved editing of mutated mRNA sequence in mammalian cell culture by directing an oligonucleotide linked to a cytidine deaminase to correct a mutated cystic fibrosis sequence. More recently, CRISPR-Cas13 fused to deaminases has been employed to direct mRNA editing. In 2022, therapeutic RNA editing for Cas7-11 was reported. It enables sufficiently targeted cuts and an early version of it was used for in vitro editing in 2021.
1
Gene expression + Signal Transduction
Dideoxynucleotides are used in sequencing. These nucleoside triphosphates possess a non-canonical sugar, dideoxyribose, which lacks the 3 hydroxyl group normally present in DNA and therefore cannot bond with the next base. The lack of the 3 hydroxyl group terminates the chain reaction as the DNA polymerases mistake it for a regular deoxyribonucleotide. Another chain-terminating analogue that lacks a 3' hydroxyl and mimics adenosine is called cordycepin. Cordycepin is an anticancer drug that targets RNA replication. Another analogue in sequencing is a nucleobase analogue, 7-deaza-GTP and is used to sequence CG rich regions, instead 7-deaza-ATP is called tubercidin, an antibiotic.
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Gene expression + Signal Transduction
Lightning strike protection minimizes damage to buildings during lightning terminations. This is usually accomplished by providing multiple interconnected pathways of low electrical impedance to the ground. Copper and its alloys are the most common materials used in residential lightning protections, however in industrial, chemically corrosive environments, the copper may need to be clad in tin. Copper effectively facilitates the transmission of lightning energy to the ground because of its excellent electrical conductivity. Also, it bends easily compared to other conductor materials. When copper roofing, gutters, and rain leaders are electrically bonded to an earth termination facility, a pathway of low electrical impedance to ground is provided, however without dedicated conduction pathways to concentrate the discharge channel, a disperse energized surface may not be the most desirable. Because copper has a higher electrical conductivity than aluminium and its impedance during a lightning termination is less, copper allows for the use of less cross-sectional surface area per linear length, in its woven wires pathway than does aluminum. Also, aluminium cannot be used in poured concrete or for any component underground due to its galvanic properties. To be effective, lightning protection systems generally maximize the surface area contact between the conductors and the earth through a ground grid of varying designs. To supplement grounding grids in low-conductivity earth, such as sand or rock, long, hollow copper tubes filled with metallic salts are available. These salts leach through holes in the tube, making the surrounding soil more conductive as well as increasing the overall surface area which decreases effective resistance. Copper roofs may be used as part of a lightning protection scheme where the copper skin, gutters and rainwater pipes can be linked and bonded to an earth termination facility. The thickness of copper specified for roofing materials is usually adequate for lightning protection. A dedicated lightning protection system may be recommended to adequate lightning protection with an installed copper roof system. The system would include air terminals and intercepting conductors on the roof, a system of ground electrodes, and a system of down-conductors connecting the roof and ground components. It is recommended that the copper roof be bonded to the system of conductors. Bonding ensures that the conductors and roof remain at equipotential and reduce side flashing and possible roof damage.
0
Metallurgy
In order for long-term potentiation (LTP) to occur, there must be stimulation of NMDA receptors, which causes AMPA receptors to be inserted postsynaptically. PI3K binds to AMPA receptors in a conserved region to orient the receptors in the membrane, specifically at the GluR subunit. PI3K activity increases in response to calcium ions and CaM. Additionally, AKT localizes PtdIns-3Ps in the post synapse, which recruits docking proteins such as tSNARE and Vam7. This directly leads to the docking of AMPA in the post synapse. mTOR activated p70S6K and inactivated 4EBP1 which changes gene expression to allow LTP to occur. Long-term fear conditioning training was affected in rats but there was no effect in short term conditioning. Specifically, amygdala fear conditioning was lost. This is a type of trace conditioning which is a form of learning that requires association of a conditioned stimulus with an unconditioned stimulus. This effect was lost in PI3K knockdowns and increased in PI3K overexpressions.
1
Gene expression + Signal Transduction
In 1821, the German physicist Thomas Johann Seebeck discovered that a magnetic needle held near a circuit made up of two dissimilar metals got deflected when one of the dissimilar metal junctions was heated. At the time, Seebeck referred to this consequence as thermo-magnetism. The magnetic field he observed was later shown to be due to thermo-electric current. In practical use, the voltage generated at a single junction of two different types of wire is what is of interest as this can be used to measure temperature at very high and low temperatures. The magnitude of the voltage depends on the types of wire being used. Generally, the voltage is in the microvolt range and care must be taken to obtain a usable measurement. Although very little current flows, power can be generated by a single thermocouple junction. Power generation using multiple thermocouples, as in a thermopile, is common. The standard configuration for thermocouple usage is shown in the figure. Briefly, the desired temperature T is obtained using three inputs—the characteristic function E(T) of the thermocouple, the measured voltage V, and the reference junctions temperature T'. The solution to the equation E(T) = V + E(T) yields T. These details are often hidden from the user since the reference junction block (with T thermometer), voltmeter, and equation solver are combined into a single product.
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Metallurgy
During the development of B cells, the immunoglobulin gene undergoes sequences of rearrangements that lead to formation of the antibody repertoire. For example, in the lymphoid cell, a partial rearrangement of the heavy-chain gene occurs which is followed by complete rearrangement of heavy-chain gene. Here at this stage, Pre-B cell, mμ heavy chain and surrogate light chain are formed. The final rearrangement of the light chain gene generates immature B cell and mIgM. The process explained here occurs only in the absence of the antigen. The mature B cell formed as RNA processing changes leaves the bone marrow and is stimulated by the antigen then differentiated into IgM -secreted plasma cells. Also at first, the mature B cell expresses membrane-bound IgD and IgM. These two classes could switch to secretory IgD and IgM during the processing of mRNAs. Finally, further class switching follows as the cell keep dividing and differentiating. For instance, IgM switches to IgG which switches to IgA that eventually switches to IgE
1
Gene expression + Signal Transduction
The function of the active zone is to ensure that neurotransmitters can be reliably released in a specific location of a neuron and only released when the neuron fires an action potential. As an action potential propagates down an axon it reaches the axon terminal called the presynaptic bouton. In the presynaptic bouton, the action potential activates calcium channels (VDCCs) that cause a local influx of calcium. The increase in calcium is detected by proteins in the active zone and forces vesicles containing neurotransmitter to fuse with the membrane. This fusion of the vesicles with the membrane releases the neurotransmitters into the synaptic cleft (space between the presynaptic bouton and the postsynaptic membrane). The neurotransmitters then diffuse across the cleft and bind to ligand gated ion channels and G-protein coupled receptors on the postsynaptic membrane. The binding of neurotransmitters to the postsynaptic receptors then induces a change in the postsynaptic neuron. The process of releasing neurotransmitters and binding to the postsynaptic receptors to cause a change in the postsynaptic neuron is called neurotransmission.
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Gene expression + Signal Transduction
Historically, small muffle ovens were often used for a second firing of porcelain at a relatively low temperature to fix overglaze enamels; these tend to be called muffle kilns. The pigments for most enamel colours discoloured at the high temperatures required for the body and glaze of the porcelain. They were used for painted enamels on metal for the same reason. Like other types of muffle furnaces, the design isolates the objects from the flames producing the heat (with electricity this is not so important). For historical overglaze enamels the kiln was generally far smaller than that for the main firing, and produced firing temperatures in the approximate range of 750 to 950 °C, depending on the colours used. Typically, wares were fired for between five and twelve hours and then cooled over twelve hours.
0
Metallurgy
South American metal working seems to have developed in the Andean region of modern Peru, Bolivia, Ecuador, Chile, and Argentina with gold and native copper being hammered and shaped into intricate objects, particularly ornaments. Recent finds date the earliest gold work to 2155–1936 BCE. and the earliest copper work to 1432–1132 BCE. Ice core studies in Bolivia suggest copper smelting may have begun as early as 700 BCE, over 2700 years ago. By 1410–1090 BCE, gilding was practiced in coastal Peru. Further evidence for this type of metal work comes from the sites at Waywaka (near Andahuaylas in southern Peru), Chavín and Kotosh, and it seems to have been spread throughout Andean societies by the Early horizon (1000–200 BCE). Unlike other metallurgy traditions where metals gained importance through practical use in weaponry and everyday utensils, metals in South America (and later Central America) were mainly valued as adornments and status objects. Though also functional objects were produced, even in the metallurgically advanced Andean cultures of the Inca era stone tools were never completely replaced by bronze items in everyday life. During the Early horizon, advances in metal working produced spectacular and characteristic Andean gold objects made by the joining of smaller metal sheets, and also gold-silver alloy appeared. Two traditions seem to have developed alongside each other – one in northern Peru and Ecuador, and another in the Altiplano region of southern Peru, Bolivia and Chile. There is evidence for smelting of copper sulphide in the Altiplano region around the Early horizon. Evidence for this comes from copper slag recovered at several sites, with the ore itself possibly coming from the south Chilean-Bolivian border. Near Puma Punku, Bolivia, and at three additional sites in Peru and Bolivia, portable smelting kilns were used to cast I-shaped "cramps" (fasteners) in place, to join large stone blocks during construction. Their chemical analysis shows The estimated date of these pours lies between 800 and 500 BCE. Evidence for fully developed smelting, however, only appears with the Moche culture (northern coast, 200 BCE – 600 CE). The ores were extracted from shallow deposits in the Andean foothills. They were probably smelted nearby, as pictorially depicted on the metal artifacts themselves and on ceramic vessels. Smelting was done in adobe brick furnaces with at least three blow pipes to provide the air flow needed to reach the high temperatures. The resulting ingots would then have been moved to coastal centers for shaping in specialised workshops. Two workshops found and studied near the administrative sections of their towns, again showing the prestige of metal. Analysis of a Moche statue composed of numerous thin metal layers revealed complex plating and gilding involving a combination of immersion in acidic solutions and the application of extreme heat. The objects themselves were still mainly adornments, now often being attached to beads. In fact, in the Lambayeque and Chimu cultures (750–1400 CE), a wide range of functional metal items were produced such as bowls, plates, drinking vessels, boxes, plates, models, scales and especially beakers (acquillas), but mostly for ceremonial or elite use. Some functional objects were fashioned, but they were elaborately decorated and often found in high-status burials, seemingly still used more for symbolic than for practical purposes. The appearance of gold or silver seems to have been important, with a high number of gilded or silvered objects as well as the appearance of Tumbaga, a alloy of copper and gold, and sometimes also silver. Arsenic bronze was also smelted from sulphidic ores, a practice either independently developed or learned from the southern tradition. The earliest known powder metallurgy, and earliest working of platinum in the world, was apparently developed by the cultures of Esmeraldas (northwest Ecuador) before the Spanish conquest Beginning with the La Tolita culture (600 BCE – 200 CE), Ecuadorian cultures mastered the soldering of platinum grains through alloying with copper, gold and silver, producing platinum-surfaced rings, handles, ornaments and utensils. This technology was eventually noticed and adopted by the Spanish . Coastal communities of Atacama Desert, as exemplified by those near Tocopilla, produced their own metal objects for practical use in the 900–1400 CE period. Metallurgy gradually spread north into Colombia, Panama and Costa Rica, reaching Guatemala and Belize by 800 CE. By , depletion gilding was developed by the Nahuange culture of Colombia to produce ornamental variations such as rose gold. Muisca goldworking, from modern Colombia, made a wide variety of small ornamental and religious objects from about 600 CE onwards. The gold Muisca raft is probably the best-known single object. This is in the Gold Museum, Bogotá, the largest of the six "gold museums" owned by the Central Bank of Colombia displaying gold from the Muisca and other pre-Columbian cultures in the country.
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Metallurgy
The technique was developed in Wallonia in present-day Belgium during the Middle Ages. The Walloon method consisted of making pig iron in a blast furnace, followed by refining it in a finery forge. The process was devised in the Liège region, and spread into France and thence from the Pays de Bray to England before the end of the 15th century. Louis de Geer took it to Roslagen in Sweden in the early 17th century, where he employed Walloon ironmakers. Iron made there by this method was known in England as oregrounds iron.
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Metallurgy
cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase A (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids Three alternatively spliced transcript variants encoding the same protein have been observed.
1
Gene expression + Signal Transduction
Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the CTCF gene. CTCF is involved in many cellular processes, including transcriptional regulation, insulator activity, V(D)J recombination and regulation of chromatin architecture.
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Gene expression + Signal Transduction
This category groups pages related to the spliceosome, which is a loose conglomerate of protein and RNA responsible for the correct splicing of mRNA.
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Gene expression + Signal Transduction
Transient liquid phase diffusion bonding (TLPDB) is a joining process that has been applied for bonding many metallic and ceramic systems which cannot be bonded by conventional fusion welding techniques. The bonding process produces joints with a uniform composition profile, tolerant of surface oxides and geometrical defects. The bonding technique has been exploited in a wide range of applications, from the production and repair of turbine engines in the aerospace industry, to nuclear power plants, and in making connections to integrated circuit dies as a part of the microelectronics industry.
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Metallurgy
Introns were first discovered in protein-coding genes of adenovirus, and were subsequently identified in genes encoding transfer RNA and ribosomal RNA genes. Introns are now known to occur within a wide variety of genes throughout organisms, bacteria, and viruses within all of the biological kingdoms. The fact that genes were split or interrupted by introns was discovered independently in 1977 by Phillip Allen Sharp and Richard J. Roberts, for which they shared the Nobel Prize in Physiology or Medicine in 1993. The term intron was introduced by American biochemist Walter Gilbert: The term intron also refers to intracistron, i.e., an additional piece of DNA that arises within a cistron. Although introns are sometimes called intervening sequences, the term "intervening sequence" can refer to any of several families of internal nucleic acid sequences that are not present in the final gene product, including inteins, untranslated regions (UTR), and nucleotides removed by RNA editing, in addition to introns.
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Gene expression + Signal Transduction
According to some serotonin was "named for its source (sero-) and ability to modify smooth muscle tone (tonin)" an effect that may be dependent (some controversy exists) upon serotonylation. The term serotonylation was created in 2003 by Diego J. Walther and colleagues of the Max Planck Institute for Molecular Genetics in a paper in the journal Cell.
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Gene expression + Signal Transduction
*Gamma (γ): This is the matrix phase. While Co-based superalloys are less-used commercially, alloying elements include C, Cr, W, Ni, Ti, Al, Ir, and Ta. As in stainless steels, Chromium is used (occasionally up to 20 wt.%) to improve resistance to oxidation and corrosion via the formation of a CrO passive layer, which is critical for use in gas turbines, but also provides solid-solution strengthening due to the mismatch in the atomic radii of Co and Cr, and precipitation hardening due to the formation of MC-type carbides. * Gamma Prime (γ): Constitutes the precipitate used to strengthen the alloy. It is usually close-packed with a L1 structure of CoTi or FCC CoTa, though both W and Al integrate into these cuboidal precipitates. Ta, Nb, and Ti integrate into the γ phase and are stabilize it at high temperatures. * Carbide Phases: Carbides strengthen the alloy through precipitation hardening but decrease low-temperature ductility. * Topologically Close-Packed (TCP) phases may appear in some Co-based superalloys, but embrittle the alloy and are thus undesirable.
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Metallurgy
Von Stahel und Eysen (English: On Steel and Iron) is the first printed book on metallurgy, published in 1532 by several publishers: Kunegunde Hergot in Nuremberg, Melchior Sachs in Erfurt, and Peter Jordan in Mainz. It has been suggested that Hergot was probably the first to publish the text, as the material seems to come from Nuremberg: its material on tempering and quenching is similar to the short treatise on hardening iron beginning Von dem herten. Nu spricht meister Alkaym in the late fourteenth- or early fifteenth-century Nuremberg manuscript Nürnberger Handschrift GNM 3227a. About half the text is on how to harden iron and steel through tempering and quenching, mentioning water, but also a range of recipes of varying degrees of elaborateness. The recipe take clarified honey, fresh urine of a he-goat, alum, borax, olive oil, and salt; mix everything well together and quench therein might, through the urea content of the urine (HNCONH), have helped to produce nitrated, case-hardened iron. Less likely to have been efficacious is: take varnish, dragons blood, horn scrapings, half as much salt, juice made from earthworms, radish juice, tallow, and vervain and quench therein. It is also very advantageous in hardening if a piece that is to be hardened is first thoroughly cleaned and well polished'. A modern commentator on some of the more outlandish techniques in the book noted: "There isn't really much to say...except that perhaps it was meant to trip up rivals. However, this may not be the case because similar instructions were circulated in 1708 in Nuremberg." The text also includes techniques for colouring, soldering, and etching. Etching was quite a new technology at the time, and Von Stahel und Eysen provides the first attested recipes.
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Metallurgy
In response to these market changes Eric Duckworth initiated changes of policy. Fulmer sought to extend its services to include the full range from R&D and testing to small scale manufacture, to extend its area of expertise to cover a wider range of materials and to develop new markets. It sought to collaborate with or to acquire organisations with complementary skills and facilities. The aim was to be able to offer to industrial companies a comprehensive service in all aspects of materials technology. Fulmer also changed its policy on intellectual property. Previously patents were applied for as part of sponsored projects so that all rights belonged to the sponsor. Beginning in 1970, the policy also included the patenting of worthwhile ideas developed in-house before applying for sponsorship so that Fulmer could retain rights and benefit from subsequent exploitation. Another new approach was to launch projects in which a number of clients jointly sponsored a development (multi-client projects). There was also a change of management style. Early in his career Eric Duckworth had spent ten years at the Glacier Metal Company at the time when the Glacier Project - a pioneering new approach to management-staff relations - was being developed there by Wilfred (later Lord) Brown, the managing director, and Elliott Jaques of the Tavistock Institute of Human Relations. When he joined Fulmer Eric Duckworth introduced a style of management heavily influenced by his experience of the Glacier Project. Over time this evolved into an open style with features such as a company council with representatives from all staff, regular management briefing of staff and transparent grading and pay scales against which individual staff were appraised annually. The grading system enabled parity of career progression between managers and people who focussed on developing their technical expertise.
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Metallurgy
With the appearance of the first factories in the Urals and the establishment of production and economic relations between the authorities and the owners, pronounced features of a subsistence economy appeared: everything necessary to ensure production was prepared and carried out at the factories on their own. Mining factories had their own landholdings, mines, quarries, forestry, stable yards, hayfields, marinas, courts, mills, and various auxiliary workshops. Such industrial and economic complexes were called mining districts and were legally described in the Mountain Regulations of 1806. The first mining plants of the Urals were fortified settlements with defensive structures to protect them from the raids of the Bashkirs. In total, about 250-260 mining plants of various specializations were built in the Urals and the Kama region: iron foundries, copper smelting, iron-making and processing plants. In total, there were about 500 mining plants in Russia. The first Ural ironworks of the 17th century did not have blast furnaces and were small forges of several smelting furnaces. Such factories include Nitsynsky (founded in 1630), Krasnoborsky (1640), Tumashevsky (1669), Dalmatovsky Monastery Zhelezenskoye settlement (1683, the Kamensky iron foundry was founded on the site of the plant) and the plant in Aramashevskaya Sloboda (1654). The first full-fledged mining plants in the Urals were the Nevyansky and Kamensky plants, founded in 1699-1700 and equipped with blast furnaces, the last mining plant was Ivano-Pavlovsky, launched in 1875. Later, metallurgical plants and mills were already under construction. Actually, the beginning of the history of the mining industry in the Urals is considered to be January 1697, when Governor D. M. Protasyev reported to Moscow about the discovery of iron ore on the Tagil and Neyva rivers. The iron obtained from this ore was studied by Moscow gunsmiths and the Tula blacksmith N. D. Antufiev (Demidov) and was given a high appraisal. On May 10 and June 15, 1697, decrees were issued for the construction of the first Ural factories. And the date of birth of Ural metallurgy is considered to be 1701 when blast-furnace plants were launched and produced the first cast iron. A specific feature of the Ural mining plants was the obligatory presence of a dam and a pond, which ensured the operation of factory mechanisms through water wheels. Therefore, mining plants were built in close proximity to ore deposits and the river. In a drought, when the water level in the navigable river decreased, the passage of ships was ensured by the synchronous discharge of water from several factory ponds located on the tributaries. The supply of charcoal was provided by the vast forest dachas assigned to the factories. The length of the dams of large factories reached 200–300 m and more (the largest dam of the Byngovsky plant was 695 m long), the width was 30–40 m, and the height was 6–10 m. Due to the climatic conditions of the Urals, it was necessary to maintain a large volume of water in the pond in order to avoid it freezing in the winter. The complete dependence of factories on the availability of water in the ponds led to frequent shutdowns of enterprises or their individual shops for a period of up to 200 days a year. To increase the water pressure, various methods were used: connecting ponds through channels with lakes or other ponds, replenishing ponds from high-mountain reservoirs through gutters. Another difference from European dams was the presence of pine or larch log cabins with valves to regulate the water level in the pond. A wide (up to 10 m and more) slot or "Veshnyak" served to let in excess water during spring floods or in summer after heavy rains. A narrower (about 2 m wide) working slot was intended to supply water to a water conduit - a wooden trough, which was laid along the entire length of the plant's territory and through which water was supplied by a system of wooden pipes and gutters to the impellers of numerous plant mechanisms. The dams of large factories had several slots. All production buildings were located along the working slots. At the same time, industries that required more energy to drive mechanisms were located closer to the dam. Directly behind the dam there was usually a blast-furnace shop, behind it - blast factories, further along the trough there were drilling, stacking, steel, armature and auxiliary factories. The blast furnace was connected to the dam by a bridge across which ore, coal and fluxes were delivered. Almost all the Ural mining plants of the 18th century had two blast furnaces in their composition; in the future, the number of furnaces could increase. Pig iron, as a rule, was sent to a blast factory, where it was processed into blast iron and pounded with hammers. At large factories, the number of hammers reached 8-13. As a rule, the factory office, the manor house, the houses of the employees of the plant administration, and the church were located on the square in front of the plant. Subsequently, with the expansion of factories, such a layout became environmental stress on factory settlements, which gradually grew into cities. Factory ponds, where industrial waste was dumped, were at the same time a source of drinking water, which contributed to the spread of all kinds of illnesses. The plants located close to each other were eventually united by one settlement: Verkh-Neyvinsky and Nizhny-Verkhneyvinsky plants in Verkh-Neyvinsky, Yekaterinburg and Verkh-Isetsky plants in Yekaterinburg, and others. The management of state-owned factories was carried out on the military settlements model. Mining superiors, who received the title of generals, were appointed by the authorities. The plant was provided with a military garrison, which partly supported the convoy with products. The work was led by mining officers and craftsmen, who were replaced on average every five years. In 1834, state-owned factories were legally equated with military organizations and their workers with soldiers. The management of private factories was carried out by the factory owners under the supervision of the state. The presence of one owner of factories in different regions contributed to the exchange of experience and technologies between enterprises. In literature, over time, the term "mining district" became more widely used meaning a historically established complex of enterprises with lands and forests belonging to it, pits, mines, and a mining population living on its territory. Since the beginning of the 20th century, the term "mining plant" is practically not used.
0
Metallurgy
* Bacteria: The code is used in Entomoplasmatales and Mycoplasmatales (Bove et al. 1989). The situation in the Acholeplasmatales is unclear. Based on a study of ribosomal protein genes, it had been concluded that UGA does not code for tryptophan in plant-pathogenic mycoplasma-like organisms (MLO) and the Acholeplasmataceae (Lim and Sears, 1992) and there seems to be only a single tRNA-CCA for tryptophan in Acholeplasma laidlawii (Tanaka et al. 1989). In contrast, in a study of codon usage in Phytoplasmas, it was found that 30 out of 78 open reading frames analysed translated better with this code (UGA for tryptophan) than with the bacterial, archaeal and plant plastid code while the remainder showed no differences between the two codes (Melamed et al. 2003). In addition, the coding reassignment of UGA Stop → Trp can be found in an alpha-proteobacterial symbiont of cicadas: Candidatus Hodgkinia cicadicola (McCutcheon et al. 2009). Mycoplasma pneumoniae also uses the codon UGA to code for tryptophan rather than using it as a stop codon. * Fungi: Emericella nidulans, Neurospora crassa, Podospora anserina, Acremonium (Fox, 1987), Candida parapsilosis (Guelin et al., 1991), Trichophyton rubrum (de Bievre and Dujon, 1992), Dekkera/Brettanomyces, Eeniella (Hoeben et al., 1993), and probably Ascobolus immersus, Aspergillus amstelodami, Claviceps purpureaand Cochliobolus heterostrophus. * Protists: the red algae of Gigartinales (Boyen et al. 1994), the protozoa Trypanosoma brucei, Leishmania tarentolae, Paramecium tetraurelia, Tetrahymena pyriformis and probably Plasmodium gallinaceum (Aldritt et al., 1989), and the stramenopile Cafileria marina. * Metazoa: Coelenterata (Ctenophora and Cnidaria). * Other: this code is also used for the kinetoplast DNA (maxicircles, minicircles). Kinetoplasts are modified mitochondria (or their parts).
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Gene expression + Signal Transduction
Signaling Gateway Molecule Pages is a database containing "essential information on more than 8000 mammalian proteins (Mouse and Human) involved in cellular signaling." The content of molecule pages is authored by invited experts and is peer-reviewed. The published pages are citable by digital object identifiers (DOIs). All data in the Molecule Pages are freely available to the public. Data can be exported to PDF, XML, BioPAX/SBPAX and SBML. MIRIAM Registry Details.
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Gene expression + Signal Transduction
Neural stem cells (NSCs) in the brain must find a balance between maintaining their multipotency by self renewing and proliferating as opposed to differentiating and becoming quiescent. The PI3K/AKT pathway is crucial in this decision making process. NSCs are able to sense and respond to changes in the brain or throughout the organism. When blood glucose levels are elevated acutely, insulin is released from the pancreas. Activation of insulin receptors activates the PI3K/AKT pathway, which promotes proliferation. In this way, when there is high glucose and abundant energy in the organism, the PI3K/AKT pathway is activated and NSCs tend to proliferate. When there are low amounts of available energy, the PI3K/AKT pathway is less active and cells adopt a quiescent state. This occurs, in part, when AKT phosphorylates FOXO, keeping FOXO in the cytoplasm. FOXO, when dephosphorylated, can enter the nucleus and work as a transcription factor to promote the expression of various tumor suppressors such as p27 and p21. These tumor suppressors push the NSC to enter quiescence. FOXO knockouts lose the ability for cells to enter a quiescent state as well as cells losing their neural stem cell character, possibly entering a cancer like state.
1
Gene expression + Signal Transduction
Various methods are used to prevent and protect against corrosion, such as cathodic protection, selection and injection of chemicals such as corrosion inhibitors or other ways to prevent corrosion. However, in order to see the results of these methods and how effective these measures are, corrosion monitoring should be done and, if necessary, corrosion protection methods should be modified or optimized based on the results obtained from corrosion monitoring. In many industries, preventive measures are used to protect against corrosion, but obviously without knowing the results of these measures, protection is a chance, that is, either full protection will not be done or in case of excessive protection, it will waste capital and resources.
0
Metallurgy
In the phosphatidylinositol signal pathway, the extracellular signal molecule binds with the G-protein receptor (G) on the cell surface and activates phospholipase C, which is located on the plasma membrane. The lipase hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds with the IP3 receptor in the membrane of the smooth endoplasmic reticulum and mitochondria to open Ca channels. DAG helps activate protein kinase C (PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses. The effects of Ca are also remarkable: it cooperates with DAG in activating PKC and can activate the CaM kinase pathway, in which calcium-modulated protein calmodulin (CaM) binds Ca, undergoes a change in conformation, and activates CaM kinase II, which has unique ability to increase its binding affinity to CaM by autophosphorylation, making CaM unavailable for the activation of other enzymes. The kinase then phosphorylates target enzymes, regulating their activities. The two signal pathways are connected together by Ca-CaM, which is also a regulatory subunit of adenylyl cyclase and phosphodiesterase in the cAMP signal pathway.
1
Gene expression + Signal Transduction
Transfer RNA (tRNA) helps decode a messenger RNA sequence into a protein. They function at specific sites within the ribosome during translation (the process going from code to protein). Within the mRNA molecule we have three nucleotides in length codons. These codons all have a unique universal code which represents a particular amino acid. tRNAs can be classified as an adaptor molecule, being typically 76 to 90 nucleotides in length.
1
Gene expression + Signal Transduction
This book describes separating silver from copper or iron. This is achieved by adding large amounts of lead at a temperature just above the melting point of lead. The lead will liquate out with the silver. This process will need to be repeated several times. The lead and silver can be separated by cupellation.
0
Metallurgy
George Warren Hammond (April 4, 1833 – January 6, 1908) was an American businessman. Camp Hammond, in Yarmouth, Maine, is named for him. He was also one of its architects. Built in , it was placed on the National Register of Historic Places in 1979. Hammond was also co-owner of Forest Paper Company, which was the largest paper mill in the world at the time of his death. The mill was also known as a pioneer in the processing of soda pulp.
0
Metallurgy
The retinoblastoma protein is involved in the growth and development of mammalian hair cells of the cochlea, and appears to be related to the cells' inability to regenerate. Embryonic hair cells require pRb, among other important proteins, to exit the cell-cycle and stop dividing, which allows maturation of the auditory system. Once wild-type mammals have reached adulthood, their cochlear hair cells become incapable of proliferation. In studies where the gene for pRb is deleted in mice cochlea, hair cells continue to proliferate in early adulthood. Though this may seem to be a positive development, pRb-knockdown mice tend to develop severe hearing loss due to degeneration of the organ of Corti. For this reason, pRb seems to be instrumental for completing the development of mammalian hair cells and keeping them alive. However, it is clear that without pRb, hair cells have the ability to proliferate, which is why pRb is known as a tumor suppressor. Temporarily and precisely turning off pRb in adult mammals with damaged hair cells may lead to propagation and therefore successful regeneration. Suppressing function of the retinoblastoma protein in the adult rat cochlea has been found to cause proliferation of supporting cells and hair cells. pRb can be downregulated by activating the sonic hedgehog pathway, which phosphorylates the proteins and reduces gene transcription.
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Gene expression + Signal Transduction
The next major change in shutter hardware coincided with the American Civil War era. Heavy presses and punches were in use in factories around the country and a maturing rail transportation system opened inland areas for the products of the factories. Iron was the norm up until that time – steel had been expensive to produce. Hardware makers were quick to take advantage of this new material. They produced the first of the "butt" and "H" or "Parliament" style lift-off hinges. Quick and easy to produce and strong enough to hold heavy shutters, they found favor in the new construction of the period. Around 1880 the first examples of "New York" style hardware appeared. Plate steel elements were assembled by unskilled labor in sprawling factories. This hardware style evolved into the many imported forms seen today. It provided the ability to surface mount hinges and tie the wooden elements of the shutters together, and also allowed for smaller and less expensive window and shutter elements. About this time the first commercially produced "S" style tie-backs were seen – manufactured by Stanley Works in Connecticut. Historically an "S" is a very difficult form to forge. Stanley forged the first simple styles for commercial consumption but it wasn't until the 1930s that they started to stamp them.
0
Metallurgy
The first iron-cased and metal-cylinder rockets (Mysorean rockets) were developed by the Mysorean army of the South Indian Kingdom of Mysore in the 1780s. The Mysoreans successfully used these iron-cased rockets against the Presidency armies of the East India Company during the Anglo-Mysore Wars.
0
Metallurgy
By using the S&S algorithm, mutations and genes that cause many different forms of cancer have been discovered. For example, genes causing commonly occurring cancers including breast cancer, ovarian cancer, colorectal cancer, leukemia, head and neck cancers, prostate cancer, retinoblastoma, squamous cell carcinoma, gastrointestinal cancer, melanoma, liver cancer, Lynch syndrome, skin cancer, and neurofibromatosis have been found. In addition, splicing mutations in genes causing less commonly known cancers including gastric cancer, gangliogliomas, Li-Fraumeni syndrome, Loeys–Dietz syndrome, Osteochondromas (bone tumor), Nevoid basal cell carcinoma syndrome, and Pheochromocytomas have been identified. Specific mutations in different splice sites in various genes causing breast cancer (e.g., BRCA1, PALB2), ovarian cancer (e.g., SLC9A3R1, COL7A1, HSD17B7), colon cancer (e.g., APC, MLH1, DPYD), colorectal cancer (e.g., COL3A1, APC, HLA-A), skin cancer (e.g., COL17A1, XPA, POLH), and Fanconi anemia (e.g., FANC, FANA) have been uncovered. The mutations in the donor and acceptor splice sites in different genes causing a variety of cancers that have been identified by S&S are shown in Table 1.
1
Gene expression + Signal Transduction
The first time that A15 structure was observed was in 1931 when an electrolytically deposited layer of tungsten was examined. Discussion of whether the β-tungsten structure is an allotrope of tungsten or the structure of a tungsten suboxide was long-standing, but since the 1950s there has been many publications showing that the material is a true allotrope of tungsten. The first intermetallic compound discovered with typical AB composition was chromium silicide CrSi, discovered in 1933. Several other compounds with A15 structure were discovered in following years. No large interest existed in research on those compounds. This changed with the discovery that vanadium silicide VSi showed superconductivity at around 17 K in 1953. In following years, several other AB superconductors were found. Niobium-germanium held the record for the highest temperature of 23.2 K from 1973 until the discovery of the cuprate superconductors in 1986. It took time for the method to produce wires from the very brittle A15 phase materials to be established. This method is still complicated. Though some A15 phase materials can withstand higher magnetic field intensity and have higher critical temperatures than the NbZr and NbTi alloys, NbTi is still used for most applications due to easier manufacturing. NbSn is used for some high field applications, for example high-end MRI scanners and NMR spectrometers. A relaxed form of the Voronoi diagram of the A15 phase seems to have the least surface area among all the possible partitions of three-dimensional Euclidean space in regions of equal volume. This partition, also known as the Weaire–Phelan structure, is often present in clathrate hydrates.
0
Metallurgy
There are numerous cell signalling pathways that exhibit cross-talk with the PI3K pathway, potentially allowing cancer cells to escape inhibition of PI3K. As such, inhibition of the PI3K pathway alongside other targets could offer a synergistic response, such as that seen with PI3K and MEK co-targeted inhibition in lung cancer cells. More recently, co-targeting the PI3K pathway with PIM kinases has been suggested, with numerous pre-clinical studies suggesting the potential benefit of this approach. Development of panels of cell lines that are resistant to inhibition of the PI3K pathway may lead to the identification of future co-targets, and better understanding of which pathways may compensate for loss of PI3K signalling following drug treatment. Combined PI3K inhibition with more traditional therapies such as chemotherapy may also offer improved response over inhibition of PI3K alone.
1
Gene expression + Signal Transduction
NANOG is highly expressed in cancer stem cells and may thus function as an oncogene to promote carcinogenesis. High expression of NANOG correlates with poor survival in cancer patients. Recent research has shown that the localization of NANOG and other transcription factors have potential consequences on cellular function. Experimental evidence has shown that the level of NANOG p8 expression is elevated specially in cancer cells, which mean that NANOG p8 gene is a critical member in (CSCs) Cancer stem cells, so knocking it down could reduce the cancer malignancy.
1
Gene expression + Signal Transduction
;Chemical shrinkage (self-desiccation) The cement hydration process consumes water molecules. The sum of the volumes of the hydration products present in the hardened cement paste is smaller than the sum of the volumes of the reacting mineral phases present in the cement clinker. Therefore, the volume of the fresh and very young concrete undergoes a contraction due to the hydration reaction: it is what is called "chemical shrinkage" or "self-desiccation". It is not a problem as long as the very fresh concrete is still in a liquid, or a sufficiently plastic, state and can easily accommodate volume changes (contraction). ;Plastic shrinkage Later in the setting phase, when the fresh concrete becomes more viscous and starts to harden, water loss due to unwanted evaporation can cause "plastic shrinkage". This occur when concrete is placed under hot conditions, e.g. in the summer and not sufficiently protected against evaporation. Cracks often develop above reinforcement bars because the contraction of concrete is locally restrained at this level and the still setting and weakly resistant concrete cannot freely shrink. ;Cracks due to a poor curing (loss of water at early age) The curing of concrete when it continues to harden after its initial setting and progressively develops its mechanical strength is a critical phase to avoid unwanted cracks in concrete. Depending on the temperature (summer or winter conditions) and thus on the cement hydration kinetics controlling the setting and hardening rate of concrete, curing time can require a few days only (summer) or up to two weeks (winter). It is then capital to avoid losses of water by evaporation because water is still necessary for continuing the slow cement hydration. Water loss at this stage aggravates concrete shrinkage and can cause unacceptable cracks to develop in concrete. Cracks form in case of a too short, or too poor, curing when young concrete has not yet developed a sufficient early strength to withstand tensile stress caused by undesirable and premature drying. Cracks development occurs when early-age concrete is insufficiently protected against desiccation and too much water evaporates with heat because of unfavorable meteorological conditions: e.g, high temperature, direct solar insolation, dry air, low relative humidity, and high wind speed during summer, or in hot conditions. Curing is intended to maintain moist conditions at the surface of concrete. It can be done by letting the formworks in place for a longer time, or by applying a hydrophobic thin film of an oily product (curing compound) at the concrete surface (e.g., for large slabs or rafts) to minimize water evaporation. ;Drying shrinkage After sufficient setting and hardening of concrete (after 28 days), the progressive loss of capillary water is also responsible for the "drying shrinkage". It is a continuous and long-term process occurring later during the concrete life when under dry conditions the larger pores of concrete are no longer completely saturated by water. ;Thermal cracks When concrete is subject to an excessive temperature increase during its setting and hardening as in massive concrete structures from where cement hydration heat cannot easily escape (semi-adiabatic conditions), the temperature gradients and the differential volume changes can also cause the formation of thermal cracks and fissures. To minimize them a slowly-setting cement (CEM III, with blast furnace slags) is preferred to a quickly setting cement (CEM I: Portland cement). Pouring concrete under colder conditions (e.g., during the night, or in the winter), or using cold water and ice mixed with cooled aggregates to prepare concrete, may also contribute to minimize thermal cracks.
0
Metallurgy
Usually, a set of individually designed oligonucleotides is made on automated solid-phase synthesizers, purified and then connected by specific annealing and standard ligation or polymerase reactions. To improve specificity of oligonucleotide annealing, the synthesis step relies on a set of thermostable DNA ligase and polymerase enzymes. To date, several methods for gene synthesis have been described, such as the ligation of phosphorylated overlapping oligonucleotides, the Fok I method and a modified form of ligase chain reaction for gene synthesis. Additionally, several PCR assembly approaches have been described. They usually employ oligonucleotides of 40-50 nucleotides length that overlap each other. These oligonucleotides are designed to cover most of the sequence of both strands, and the full-length molecule is generated progressively by overlap extension (OE) PCR, thermodynamically balanced inside-out (TBIO) PCR or combined approaches. The most commonly synthesized genes range in size from 600 to 1,200 bp although much longer genes have been made by connecting previously assembled fragments of under 1,000 bp. In this size range it is necessary to test several candidate clones confirming the sequence of the cloned synthetic gene by automated sequencing methods.
1
Gene expression + Signal Transduction
The docking of IP to its receptor, which is called the inositol trisphosphate receptor (InsP3R), was first studied using deletion mutagenesis in the early 1990s. Studies focused on the N-terminus side of the IP receptor. In 1997 researchers localized the region of the IP receptor involved with binding of IP to between amino acid residues 226 and 578 in 1997. Considering that IP is a negatively charged molecule, positively charged amino acids such as arginine and lysine were believed to be involved. Two arginine residues at position 265 and 511 and one lysine residue at position 508 were found to be key in IP docking. Using a modified form of IP, it was discovered that all three phosphate groups interact with the receptor, but not equally. Phosphates at the 4th and 5th positions interact more extensively than the phosphate at the 1st position and the hydroxyl group at the 6th position of the inositol ring.
1
Gene expression + Signal Transduction
From the medieval period, an indirect process began to replace the direct reduction in bloomeries. This used a blast furnace to make pig iron, which then had to undergo a further process to make forgeable bar iron. Processes for the second stage include fining in a finery forge. In the 13th century during the High Middle Ages the blast furnace was introduced by China who had been using it since as early as 200 b.c during the Qin dynasty. [https://www.britannica.com/summary/blast-furnace#:~:text=Blast%20furnaces%20were%20used%20in,century%2C%20replacing%20the%20bloomery%20process.] Puddling was also introduced in the Industrial Revolution. Both processes are now obsolete, and wrought iron is now rarely made. Instead, mild steel is produced from a Bessemer converter or by other means including smelting reduction processes such as the Corex Process.
0
Metallurgy