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The isomerization of uridine to pseudoridine is the second most common rRNA modification. These pseudoridines are also introduced by the same classes of snoRNPs that participate in methylation. Psuedouridine synthases are the major participating enzymes in the reaction. The H/ACA box snoRNPs introduce guide sequences that are about 14-15 nucleotides long. Pseudouridylation is triggered in numerous places of rRNAs at once to preserve the thermal stability of RNA. Pseudouridine allows for increased hydrogen bonding and alters translation in rRNA and tRNA. It alters translation by increasing the affinity of the ribosome subunit to specific mRNAs. Base Editing: Base editing is the third major class of rRNA modification, specifically in eukaryotes. There are 8 categories of base edits that can occur at the gap between the small and large ribosomal subunits. RNA methyltransferases are the enzymes that introduce base methylation. Acetyltransferases are the enzymes responsible for acetylation of cytosine in rRNA. Base methylation plays a role in translation. These base modifications all work in conjunction with the two other main classes of modification to contribute to RNA structural stability. An example of this occurs in N7-methylation, which increases the nucleotide's charge to increase ionic interactions of proteins attaching to the RNA before translation.

Gene expression + Signal Transduction

The majority of observed interactions between promoters and enhancers do not cross TAD boundaries. Removing a TAD boundary (for example, using CRISPR to delete the relevant region of the genome) can allow new promoter-enhancer contacts to form. This can affect gene expression nearby - such misregulation has been shown to cause limb malformations (e.g. polydactyly) in humans and mice. Computer simulations have shown that transcription-induced supercoiling of chromatin fibres can explain how TADs are formed and how they can assure very efficient interactions between enhancers and their cognate promoters located in the same TAD.

Gene expression + Signal Transduction

Biological crosstalk refers to instances in which one or more components of one signal transduction pathway affects another. This can be achieved through a number of ways with the most common form being crosstalk between proteins of signaling cascades. In these signal transduction pathways, there are often shared components that can interact with either pathway. A more complex instance of crosstalk can be observed with transmembrane crosstalk between the extracellular matrix (ECM) and the cytoskeleton.

Gene expression + Signal Transduction

The FSHR become desensitized when exposed to FSH for some time. A key reaction of this downregulation is the phosphorylation of the intracellular (or cytoplasmic) receptor domain by protein kinases. This process uncouples Gs protein from the FSHR. Another way to desensitize is to uncouple the regulatory and catalytic units of the cAMP system.

Gene expression + Signal Transduction

Serious galvanic corrosion has been reported on the latest US Navy attack littoral combat vessel the USS Independence caused by steel water jet propulsion systems attached to an aluminium hull. Without electrical isolation between the steel and aluminium, the aluminium hull acts as an anode to the stainless steel, resulting in aggressive galvanic corrosion.

Metallurgy

The discovery that the β chemokines RANTES, MIP (macrophage inflammatory proteins) 1α and 1β (now known as CCL5, CCL3 and CCL4 respectively) suppress HIV-1 provided the initial connection and indicated that these molecules might control infection as part of immune responses in vivo, and that sustained delivery of such inhibitors have the capacity of long-term infection control. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection.

Gene expression + Signal Transduction

An improvement on vibration, vibratory, and linear screeners, a tumbler screener uses elliptical action which aids in screening of even very fine material. As like panning for gold, the fine particles tend to stay towards the center and the larger go to the outside. It allows for segregation and unloads the screen surface so that it can effectively do its job. With the addition of multiple decks and ball cleaning decks, even difficult products can be screened at high capacity to very fine separations.

Metallurgy

The slow block to polyspermy in the sea urchin is mediated by the PIP secondary messenger system. Activation of the binding receptors activates PLC, which cleaves PIP in the egg plasma membrane, releasing IP into the egg cell cytoplasm. IP diffuses to the ER, where it opens Ca channels.

Gene expression + Signal Transduction

Genes encoding the MuvB complex were originally identified from loss-of-function mutation studies in C. elegans. When mutated, these genes produced worms with multiple vulva-like organs, hence the name ‘Muv’. Three classes of Muv genes were classified, with class B genes encoding homologues of mammalian RB, E2F, and DP1, and others such as LIN-54, LIN-37, LIN-7 and LIN-52, whose functions were not yet understood. Studies in Drosophila melanogaster ovarian follicle cells identified a protein complex that bound to repeatedly amplifying chorion genes. The complex included genes that had close homology with the MuvB genes such as Mip130, Mip120 and Mip40. These Mip genes were identified as homologues of the MuvB genes LIN9, LIN54, and LIN37 respectively. Further studies in the fly embryo nuclear extracts confirmed the coexistence of these proteins with others such as the RB homologues Rbf1 and Rbf2, and others like E2f and Dp. The protein complex was thus termed as the Drosophila RBF, E2f2 and Mip (dREAM) complex. Disruption of the dREAM complex through RNAi knockdown of the components of dREAM complex led to higher expression of E2f regulated genes that are typically silenced, implicating dREAM’s role in gene down-regulation. Later in Drosophila melanogaster, there was also found a testis-specific paralog of the Myb-MuvB/DREAM complex known as tMAC (testis-specific meiotic arrest complex), which is involved in meiotic arrest. A protein complex similar to dREAM was subsequently identified in C. elegans extract containing DP, RB, and MuvB, and was named as DRM. This complex included mammalian homologues of RB and DP, and other members of the MuvB complex. The mammalian DREAM complex was identified following immunoprecipitation of p130 with mass-spectrometry analysis. The results showed that p130 was associated with E2F4, E2F5, the dimerization partner DP, and LIN9, LIN54, LIN37, LIN52, and RBBP4 that make up the MuvB complex. Immunoprecipitation of MuvB factors also revealed association of BMYB. Subsequent immunoprecipitation with BMYB yielded all the MuvB core proteins, but not other members of the DREAM complex – p130, p107, E2F4/5 and DP. This indicated that MuvB associated with BMYB to form the BMYB-MuvB complex or with p130/p107, E2F4/5 and DP to form the DREAM complex. The DREAM complex was found prevalent in quiescent or starved cells, and the BMYB-MuvB complex was found in actively dividing cells, hinting at separate functionalities of these two complexes. MuvB-like complexes were also recently discovered in Arabidoposis that include E2F and MYB orthologs combined with LIN9 and LIN54 orthologs.

Gene expression + Signal Transduction

Underwater corrosion engineers apply the same principals used in underground corrosion control but use specially trained and certified scuba divers for condition assessment, and corrosion control system installation and commissioning. The main difference being in the type of reference cells used to collect voltage readings. Corrosion of piles and the legs of oil and gas rigs are of particular concern. This includes rigs in the North Sea off the coast of the United Kingdom and the Gulf of Mexico.

Metallurgy

Metal whiskering is a crystalline metallurgical phenomenon involving the spontaneous growth of tiny, filiform hairs from a metallic surface. The effect is primarily seen on elemental metals but also occurs with alloys. The mechanism behind metal whisker growth is not well understood, but seems to be encouraged by compressive mechanical stresses including: * energy gained due to electrostatic polarization of metal filaments in the electric field, * residual stresses caused by electroplating, * mechanically induced stresses, * stresses induced by diffusion of different metals, * thermally induced stresses, and * strain gradients in materials. Metal whiskers differ from metallic dendrites in several respects: dendrites are fern-shaped and grow across the surface of the metal, while metal whiskers are hair-like and project normal to the surface. Dendrite growth requires moisture capable of dissolving the metal into a solution of metal ions, which are then redistributed by electromigration in the presence of an electromagnetic field. While the precise mechanism for whisker formation remains unknown, it is known that whisker formation does not require either dissolution of the metal or the presence of an electromagnetic field.

Metallurgy

The RNA polymerase holoenzyme binds to a promoter of an exposed DNA strand and begins to synthesize the new strand of RNA. The double helix DNA is unwound and a short nucleotide sequence is accessible on each strand. The transcription bubble is a region of unpaired bases on one of the exposed DNA strands. The starting transcription point is determined by the place where the holoenzyme binds to a promoter. The DNA is unwound and single-stranded at the start site. The DNA promoter interaction is interrupted as the RNA polymerase moves down the template DNA strand and the sigma factor is released. The σ factor is required for the initiation but not for the remaining steps of the DNA transcription. Once the σ factor dissociates from the RNA polymerase, the transcription continues. About 10 synthesized nucleotides of a new RNA strand are required for this to proceed to the elongation step. The process of transcribing during elongation is very fast. Elongation takes place until the RNA polymerase comes across a termination signal (terminator) which arrests the process and causes the release of both the DNA template and the new RNA molecule. The DNA usually encodes the termination signal.

Gene expression + Signal Transduction

* CDC14s: CDC14A, CDC14B, CDC14C, CDKN3 * Phosphatase and tensin homologs: PTEN * slingshot: SSH1, SSH2, SSH3

Gene expression + Signal Transduction

Pressureless sintering is the sintering of a powder compact (sometimes at very high temperatures, depending on the powder) without applied pressure. This avoids density variations in the final component, which occurs with more traditional hot pressing methods. The powder compact (if a ceramic) can be created by slip casting, injection moulding, and cold isostatic pressing. After presintering, the final green compact can be machined to its final shape before being sintered. Three different heating schedules can be performed with pressureless sintering: constant-rate of heating (CRH), rate-controlled sintering (RCS), and two-step sintering (TSS). The microstructure and grain size of the ceramics may vary depending on the material and method used. Constant-rate of heating (CRH), also known as temperature-controlled sintering, consists of heating the green compact at a constant rate up to the sintering temperature. Experiments with zirconia have been performed to optimize the sintering temperature and sintering rate for CRH method. Results showed that the grain sizes were identical when the samples were sintered to the same density, proving that grain size is a function of specimen density rather than CRH temperature mode. In rate-controlled sintering (RCS), the densification rate in the open-porosity phase is lower than in the CRH method. By definition, the relative density, ρ, in the open-porosity phase is lower than 90%. Although this should prevent separation of pores from grain boundaries, it has been proven statistically that RCS did not produce smaller grain sizes than CRH for alumina, zirconia, and ceria samples. Two-step sintering (TSS) uses two different sintering temperatures. The first sintering temperature should guarantee a relative density higher than 75% of theoretical sample density. This will remove supercritical pores from the body. The sample will then be cooled down and held at the second sintering temperature until densification is completed. Grains of cubic zirconia and cubic strontium titanate were significantly refined by TSS compared to CRH. However, the grain size changes in other ceramic materials, like tetragonal zirconia and hexagonal alumina, were not statistically significant.

Metallurgy

DNA methylation in cancer plays a variety of roles, helping to change the healthy cells by regulation of gene expression to a cancer cells or a diseased cells disease pattern. One of the most widely studied DNA methylation dysregulation is the promoter hypermethylation where the CPGs islands in the promoter regions are methylated contributing or causing genes to be silenced. All mammalian cells descended from a fertilized egg (a zygote) share a common DNA sequence (except for new mutations in some lineages). However, during development and formation of different tissues epigenetic factors change. The changes include histone modifications, CpG island methylations and chromatin reorganizations which can cause the stable silencing or activation of particular genes. Once differentiated tissues are formed, CpG island methylation is generally stably inherited from one cell division to the next through the DNA methylation maintenance machinery. In cancer, a number of mutational changes are found in protein coding genes. Colorectal cancers typically have 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations that silence protein expression in the genes affected. However, transcriptional silencing may be more important than mutation in causing gene silencing in progression to cancer. In colorectal cancers about 600 to 800 genes are transcriptionally silenced, compared to adjacent normal-appearing tissues, by CpG island methylation. Such CpG island methylation has also been described in glioblastoma and mesothelioma. Transcriptional repression in cancer can also occur by other epigenetic mechanisms, such as altered expression of microRNAs.

Gene expression + Signal Transduction

In tissues, many different cell types interact with one another. In the brain, for example, neurons, astrocytes, and oligodendrocytes (specialized cells of the neural tissue, each with specific functions) interact with one another as well as with cells that comprise blood vessels. All these different cell types may interact with all others by the production of ligands that may activate receptors on the cell surface of other cell types. Understanding the way these different cell types interact with one another will allow to predict ways of activating eNSCs. For example, because eNSCs are found in close proximity with blood vessels, it has been hypothesized that signals (e.g., ligands) from cells comprising the blood vessel act on receptors found on the cell surface of eNSCs. Endogenous neural stem cells are often in close physical proximity to blood vessels. Signals from blood vessels regulate their interaction with stem cells and contribute to the cytoarchitecture of the tissue. The STAT3-Ser/Hes3 signaling axis operating in Hes3+ cells is a convergence point for several of these signals (e.g. Delta4, Angiopoietin 2). Hes3, in turn, by regulating the expression of Shh and potentially other factors, can also exert an effect on blood vessels and other cells comprising their microenvironment.

Gene expression + Signal Transduction

Nod factors are potentially recognized by plant receptors made of two histidine kinases with extracellular LysM domain, which have been identified in L. japonicus, soybean, and M. truncatula . Binding of Nod factors to these receptors depolarizes the plasma membrane of root hairs via an influx of Ca which induce the expression of early nodulin (ENOD) genes and swelling of the root hairs. In M. truncatula, the signal transduction initiates by the activation of dmi1, dmi2, and dmi3 which lead to the deformation of root hairs, early nodulin expression, cortical cell division and bacterial infection. Additionally, nsp and hcl genes are recruited later and aid in the process of early nodulation expression, cortical cell division, and infection. Genes dmi1, dmi2, and dmi3 have also been found to aid in the establishment of interactions between M. truncatula and arbuscular mycorrhiza, indicating that the two very different symbioses may share some common mechanisms. The end result is the nodule, the structure in which nitrogen is fixed. Nod factors act by inducing changes in gene expression in the legume, most notable the nodulin genes, which are needed for nodule organogenesis.

Gene expression + Signal Transduction

The Forest of Dean and nearby areas were an ancient source of iron ore and charcoal. There is evidence of early mining and smelting, and there were many sites consisting of groups of forges. The site of Ariconium was on the rise of a hill, where airflow is increased due to the terrain. This favoured the establishment of bloomeries, an ancient process that produced imperfect iron, together with cinders, dirt, and unreduced oxide. A Roman contribution was the use of bellows, causing an air blast that was hotter and produced better but unforgeable iron, requiring a further refining by reheating, and using a great deal of charcoal. The cinder refuse or scoriae was dumped in great piles at such sites.

Metallurgy

As a hydrogen storage alloy, LaNi can absorb hydrogen to form the hydride LaNiH (x≈6) when the pressure is slightly high and the temperature is low, or when the pressure decreases or the temperature increases, hydrogen can be released to form repeated absorption and release of hydrogen. But for the dehydrogenation process, because it is an endothermic reaction, in order to enable the reaction to proceed, the necessary energy must be added, otherwise the reaction will stop due to the decrease in temperature.

Metallurgy

Manufacturing processes have five main variables: the workpiece, the tool, the machine tool, the environment, and process variables. All of these variables can affect the surface integrity of the workpiece by producing: *High temperatures involved in various machining processes *Plastic deformation in the workpiece (residual stresses) *Surface geometry (roughness, cracks, distortion) *Chemical reactions, especially between the tool and the workpiece

Metallurgy

The story of ledeburite begins in the late 19th century when Adolf Ledebur, a pioneering German metallurgist, embarked on a journey to unravel the complexities of steel microstructures. In 1882, Ledebur identified a distinct microconstituent in high-carbon steels, characterized by its unique lamellar structure. This discovery marked the birth of ledeburite, named in honor of the scientist whose keen observations laid the foundation for understanding the intricate world within steel.

Metallurgy

Cast iron has been found in China dating to the 5th century BC, but the earliest extant blast furnaces in China date to the 1st century AD and in the West from the High Middle Ages. They spread from the region around Namur in Wallonia (Belgium) in the late 15th century, being introduced to England in 1491. The fuel used in these was invariably charcoal. The successful substitution of coke for charcoal is widely attributed to English inventor Abraham Darby in 1709. The efficiency of the process was further enhanced by the practice of preheating the combustion air (hot blast), patented by Scottish inventor James Beaumont Neilson in 1828.

Metallurgy

mTOR signaling intersects with Alzheimer's disease (AD) pathology in several aspects, suggesting its potential role as a contributor to disease progression. In general, findings demonstrate mTOR signaling hyperactivity in AD brains. For example, postmortem studies of human AD brain reveal dysregulation in PTEN, Akt, S6K, and mTOR. mTOR signaling appears to be closely related to the presence of soluble amyloid beta (Aβ) and tau proteins, which aggregate and form two hallmarks of the disease, Aβ plaques and neurofibrillary tangles, respectively. In vitro studies have shown Aβ to be an activator of the PI3K/AKT pathway, which in turn activates mTOR. In addition, applying Aβ to N2K cells increases the expression of p70S6K, a downstream target of mTOR known to have higher expression in neurons that eventually develop neurofibrillary tangles. Chinese hamster ovary cells transfected with the 7PA2 familial AD mutation also exhibit increased mTOR activity compared to controls, and the hyperactivity is blocked using a gamma-secretase inhibitor. These in vitro studies suggest that increasing Aβ concentrations increases mTOR signaling; however, significantly large, cytotoxic Aβ concentrations are thought to decrease mTOR signaling. Consistent with data observed in vitro, mTOR activity and activated p70S6K have been shown to be significantly increased in the cortex and hippocampus of animal models of AD compared to controls. Pharmacologic or genetic removal of the Aβ in animal models of AD eliminates the disruption in normal mTOR activity, pointing to the direct involvement of Aβ in mTOR signaling. In addition, by injecting Aβ oligomers into the hippocampi of normal mice, mTOR hyperactivity is observed. Cognitive impairments characteristic of AD appear to be mediated by the phosphorylation of PRAS-40, which detaches from and allows for the mTOR hyperactivity when it is phosphorylated; inhibiting PRAS-40 phosphorylation prevents Aβ-induced mTOR hyperactivity. Given these findings, the mTOR signaling pathway appears to be one mechanism of Aβ-induced toxicity in AD. The hyperphosphorylation of tau proteins into neurofibrillary tangles is one hallmark of AD. p70S6K activation has been shown to promote tangle formation as well as mTOR hyperactivity through increased phosphorylation and reduced dephosphorylation. It has also been proposed that mTOR contributes to tau pathology by increasing the translation of tau and other proteins. Synaptic plasticity is a key contributor to learning and memory, two processes that are severely impaired in AD patients. Translational control, or the maintenance of protein homeostasis, has been shown to be essential for neural plasticity and is regulated by mTOR. Both protein over- and under-production via mTOR activity seem to contribute to impaired learning and memory. Furthermore, given that deficits resulting from mTOR overactivity can be alleviated through treatment with rapamycin, it is possible that mTOR plays an important role in affecting cognitive functioning through synaptic plasticity. Further evidence for mTOR activity in neurodegeneration comes from recent findings demonstrating that eIF2α-P, an upstream target of the mTOR pathway, mediates cell death in prion diseases through sustained translational inhibition. Some evidence points to mTORs role in reduced Aβ clearance as well. mTOR is a negative regulator of autophagy; therefore, hyperactivity in mTOR signaling should reduce Aβ clearance in the AD brain. Disruptions in autophagy may be a potential source of pathogenesis in protein misfolding diseases, including AD. Studies using mouse models of Huntingtons disease demonstrate that treatment with rapamycin facilitates the clearance of huntingtin aggregates. Perhaps the same treatment may be useful in clearing Aβ deposits as well.

Gene expression + Signal Transduction

Previous reports have identified as many as eight splice variants, which are translated into seven isoforms of the protein. Apoptosis-inducing Fas receptor is dubbed isoform 1 and is a type 1 transmembrane protein. Many of the other isoforms are rare haplotypes that are usually associated with a state of disease. However, two isoforms, the apoptosis-inducing membrane-bound form and the soluble form, are normal products whose production via alternative splicing is regulated by the cytotoxic RNA binding protein TIA1. The mature Fas protein has 319 amino acids, has a predicted molecular weight of 48 kilodaltons and is divided into three domains: an extracellular domain, a transmembrane domain, and a cytoplasmic domain. The extracellular domain has 157 amino acids and is rich in cysteine residues. The transmembrane and cytoplasmic domains have 17 and 145 amino acids respectively. Exons 1 through 5 encode the extracellular region. Exon 6 encodes the transmembrane region. Exons 7-9 encode the intracellular region.

Gene expression + Signal Transduction

Williams was born in Tonypandy, Wales, the son of a coal miner. In 1944, he won a scholarship to study at the University of Bristol, where he earned a bachelors degree in 1948 and later a Master of Science in physics. In working to earn his masters degree, he studied stereo micro-radiography at the University of Chicago, under the direction of Cyril Stanley Smith. Around the same time, he also took up a position as a metallurgist with the Revere Copper Company in Rome, New York. In 1960, Williams earned his doctorate from the University of Toronto.

Metallurgy

In order to infect a cell, the envelope glycoprotein GP120 of the HIV virus interacts with CD4 (acting as the primary receptor) and a co-receptor: either CCR5 or CXCR4. This binding results in membrane fusion and the subsequent intracellular signaling that facilitates viral invasion. In approximately half of all HIV cases, the viruses using the CCR5 co-receptor seem to favor immediate infection and transmission while those using the CXCR4 receptor do not present until later in the immunologically suppressed stage of the disease. The virus will often switch from using CCR5 to CXCR4 during the course of the infection, which serves as an indicator for the progression of the disease. Recent evidence suggests that some forms of HIV also use the large integrin a4b7 receptor to facilitate increased binding efficiency in mucosal tissues.

Gene expression + Signal Transduction

Here is a summary of the sequence of events that take place in synaptic transmission from a presynaptic neuron to a postsynaptic cell. Each step is explained in more detail below. Note that with the exception of the final step, the entire process may run only a few hundred microseconds, in the fastest synapses. #The process begins with a wave of electrochemical excitation called an action potential traveling along the membrane of the presynaptic cell, until it reaches the synapse. #The electrical depolarization of the membrane at the synapse causes channels to open that are permeable to calcium ions. #Calcium ions flow through the presynaptic membrane, rapidly increasing the calcium concentration in the interior. #The high calcium concentration activates a set of calcium-sensitive proteins attached to vesicles that contain a neurotransmitter chemical. #These proteins change shape, causing the membranes of some "docked" vesicles to fuse with the membrane of the presynaptic cell, thereby opening the vesicles and dumping their neurotransmitter contents into the synaptic cleft, the narrow space between the membranes of the pre- and postsynaptic cells. #The neurotransmitter diffuses within the cleft. Some of it escapes, but some of it binds to chemical receptor molecules located on the membrane of the postsynaptic cell. #The binding of neurotransmitter causes the receptor molecule to be activated in some way. Several types of activation are possible, as described in more detail below. In any case, this is the key step by which the synaptic process affects the behavior of the postsynaptic cell. #Due to thermal vibration, the motion of atoms, vibrating about their equilibrium positions in a crystalline solid, neurotransmitter molecules eventually break loose from the receptors and drift away. #The neurotransmitter is either reabsorbed by the presynaptic cell, and then repackaged for future release, or else it is broken down metabolically.

Gene expression + Signal Transduction

Presence of un-phosphorylated pRb drives cell cycle exit and maintains senescence. At the end of mitosis, PP1 dephosphorylates hyper-phosphorylated pRb directly to its un-phosphorylated state. Furthermore, when cycling C2C12 myoblast cells differentiated (by being placed into a differentiation medium), only un-phosphorylated pRb was present. Additionally, these cells had a markedly decreased growth rate and concentration of DNA replication factors (suggesting G0 arrest). This function of un-phosphorylated pRb gives rise to a hypothesis for the lack of cell cycle control in cancerous cells: Deregulation of Cyclin D - Cdk 4/6 phosphorylates un-phosphorylated pRb in senescent cells to mono-phosphorylated pRb, causing them to enter G1. The mechanism of the switch for Cyclin E activation is not known, but one hypothesis is that it is a metabolic sensor. Mono-phosphorylated pRb induces an increase in metabolism, so the accumulation of mono-phosphorylated pRb in previously G0 cells then causes hyper-phosphorylation and mitotic entry. Since any un-phosphorylated pRb is immediately phosphorylated, the cell is then unable to exit the cell cycle, resulting in continuous division. DNA damage to G0 cells activates Cyclin D - Cdk 4/6, resulting in mono-phosphorylation of un-phosphorylated pRb. Then, active mono-phosphorylated pRb causes repression of E2F-targeted genes specifically. Therefore, mono-phosphorylated pRb is thought to play an active role in DNA damage response, so that E2F gene repression occurs until the damage is fixed and the cell can pass the restriction point. As a side note, the discovery that damages causes Cyclin D - Cdk 4/6 activation even in G0 cells should be kept in mind when patients are treated with both DNA damaging chemotherapy and Cyclin D - Cdk 4/6 inhibitors.

Gene expression + Signal Transduction

The hatched areas in the figure represent the amount of solute in the solid and liquid. Considering that the total amount of solute in the system must be conserved, the areas are set equal as follows: Since the partition coefficient (related to solute distribution) is : (determined from the phase diagram) and mass must be conserved the mass balance may be rewritten as Using the boundary condition : at the following integration may be performed: Integrating results in the Scheil-Gulliver equation for composition of the liquid during solidification: or for the composition of the solid:

Metallurgy

is a traditional Japanese chemical compound used in the niiro process for artificially inducing patination in decorative non-ferrous metals, especially several copper alloys, with the results being metals of the irogane class. These "colour metals," virtually unknown outside Japan until the late 19th century, have achieved some popularity in craft circles in other parts of the world since then.

Metallurgy

The Mark III design encompassed the greatest improvement in the technology since its commercialisation. The focus was to make the technology more robust and easier to use in operations. The total redesign of the downcomer assembly allowed it to be isolated and unblocked much more easily compared to the Mark II design. The Mark III design also saw slurry flow per downcomer to be increased from 60 m/h to 75–85 m/h using larger orifice sizes in the slurry lenses. The Mark III Cell was introduced in 2000. It included the following improvements: * a new slurry lens orifice design (see Figures 7 and 8) * a new design downcomer and nozzle * a new design flat plate bubble dispersers * a stainless steel adjustable above and in-froth wash water system (see Figure 9) * automated air and wash water flow control * air-isolating slurry-eliminating valves ("AISE valves") * a bottom-fed new slurry distributor. The earlier models of the Jameson Cell used orifice plates to generate the downcomer jet. The new slurry lens design had a smooth, shallow entry angle that created an optimum flow regime over the ceramic, reducing wear and extending its life. The shape resulted in a decrease in power consumption by the feed slurry pump by up to 10% and resulted in better jet formation that improved air entrainment. For coal applications, the wash water addition system was changed from a tray to stainless-steel circular rings attached to a manual lifting system. This allowed the flexibility of an easy transition from above-froth wash water addition to the in-froth addition that might be necessary for high concentrate-grade operations. For metals applications, new design wash water trays consisting of removable rubber mats for easy maintenance were used. The AISE valves were developed to prevent solids being sucked back into the air lines when individual downcomers become blocked. Solids depositing in the air lines and their build up in the air distributor decreases flotation performance as it prevents air from being efficiently entrained in the downcomers.

Metallurgy

The MODAL strategy defines overlap sequences known as "linkers" to reduce the amount of customisation that needs to be done with each DNA fragment. The linkers were designed using the [https://omictools.com/r2odna-designer-tool R2oDNA Designer] software and the overlap regions were designed to be 45 bp long to be compatible with Gibson assembly and other overlap assembly methods. To attach these linkers to the parts to be assembled, PCR is carried using part-specific primers containing 15 bp prefix and suffix adaptor sequences. The linkers are then attached to the adaptor sequences via a second PCR reaction. To position the DNA fragments, the same linker will be attached to the suffix of the desired upstream fragment and the prefix of the desired downstream fragments. Once the linkers are attached, Gibson assembly, CPEC, or the other overlap assembly methods can all be used to assemble the DNA fragments in the desired order.

Gene expression + Signal Transduction

When (p)ppGpp is absent, pathogenicity is compromised for reasons that vary with the organism studied. Deleting relA and spoT genes, but not relA alone, gave a (p)ppGpp state that resulted in strong attenuation in mice and noninvasiveness in vitro. Vaccine tests reveal that 30 days after single immunization with the (p)ppGpp strain, mice were protected from challenge with wild-type Salmonella at a dose 10-fold above the established LD.

Gene expression + Signal Transduction

There are several ways of reducing and preventing this form of corrosion. * Electrically insulate the two metals from each other. If they are not in electrical contact, no galvanic coupling will occur. This can be achieved by using non-conductive materials between metals of different electropotential. Piping can be isolated with a spool of pipe made of plastic materials, or made of metal material internally coated or lined. It is important that the spool be a sufficient length to be effective. For reasons of safety, this should not be attempted where an electrical earthing system uses the pipework for its ground or has equipotential bonding. * Metal boats connected to a shore line electrical power feed will normally have to have the hull connected to earth for safety reasons. However the end of that earth connection is likely to be a copper rod buried within the marina, resulting in a steel-copper "battery" of about 0.5 V. Additionally, the hull of each boat is connected to the hull of all other boats, resulting in further "batteries" between propellers (which may be made of bronze) and steel hulls, which may cause corrosion of the expensive propellers. For such cases, the use of a galvanic isolator is essential, typically two semiconductor diodes in series, in parallel with two diodes conducting in the opposite direction (antiparallel). This device is inserted in the protective earth connection between the hull and the shoreline protective conductor. This prevents any current in the protective conductor while the applied voltage is less than 1.4 V (i.e. 0.7 V per diode), but allows a full current in the case of an electrical fault. There will still be a very minor leakage of current through the diodes, which may result in slightly faster corrosion than normal. * Ensure there is no contact with an electrolyte. This can be done by using water-repellent compounds such as greases, or by coating the metals with an impermeable protective layer, such as a suitable paint, varnish, or plastic. If it is not possible to coat both, the coating should be applied to the more noble, the material with higher potential. This is advisable because if the coating is applied only on the more active material, in case of damage to the coating there will be a large cathode area and a very small anode area, and for the exposed anodic area the corrosion rate will be correspondingly high. * Using antioxidant paste is beneficial for preventing corrosion between copper and aluminium electrical connections. The paste consists of a lower nobility metal than aluminium or copper. * Choose metals that have similar electropotentials. The more closely matched the individual potentials, the smaller the potential difference and hence the smaller the galvanic current. Using the same metal for all construction is the easiest way of matching potentials. * Electroplating or other plating can also help. This tends to use more noble metals that resist corrosion better. Chrome, nickel, silver and gold can all be used. Galvanizing with zinc protects the steel base metal by sacrificial anodic action. * Cathodic protection uses one or more sacrificial anodes made of a metal which is more active than the protected metal. Alloys of metals commonly used for sacrificial anodes include zinc, magnesium, and aluminium. This approach is commonplace in water heaters and many buried or immersed metallic structures. * Cathodic protection can also be applied by connecting a direct current (DC) electrical power supply to oppose the corrosive galvanic current. (See .)

Metallurgy

Ceramography is the art and science of preparation, examination and evaluation of ceramic microstructures. Ceramography can be thought of as the metallography of ceramics. The microstructure is the structure level of approximately 0.1 to 100 µm, between the minimum wavelength of visible light and the resolution limit of the naked eye. The microstructure includes most grains, secondary phases, grain boundaries, pores, micro-cracks and hardness microindentations. Most bulk mechanical, optical, thermal, electrical and magnetic properties are significantly affected by the microstructure. The fabrication method and process conditions are generally indicated by the microstructure. The root cause of many ceramic failures is evident in the microstructure. Ceramography is part of the broader field of materialography, which includes all the microscopic techniques of material analysis, such as metallography, petrography and plastography. Ceramography is usually reserved for high-performance ceramics for industrial applications, such as 85–99.9% alumina (AlO) in Fig. 1, zirconia (ZrO), silicon carbide (SiC), silicon nitride (SiN), and ceramic-matrix composites. It is seldom used on whiteware ceramics such as sanitaryware, wall tiles and dishware.

Metallurgy

Calcium is a necessary ion in the formation of the mitotic spindle. Without the mitotic spindle, cellular division cannot occur. Although young leaves have a higher need for calcium, older leaves contain higher amounts of calcium because calcium is relatively immobile through the plant. It is not transported through the phloem because it can bind with other nutrient ions and precipitate out of liquid solutions.

Gene expression + Signal Transduction

The mineralization of copper is restricted to a few areas in western, central and southern Africa, and some have the richest deposits of copper in the world. In the west, copper has only been found in the arid regions of the Sahel and southern Sahara. The main sources of copper are: # Akjoujt in Mauritania # Nioro du Sahel to Sirakoro in Northern Mali # The Aïr Massif near Azelik and Agadez in Niger There are not any known mines in tropical West Africa, however copper and lead workings have been in the Benue Trough in southeastern Nigeria. With the exception of a few areas near Kilembe in Uganda and Rwanda, there are no sources of copper in East Africa. The largest concentration of copper found in Africa is the Lufilian Arc. It is an eight hundred kilometer crescent shaped belt, which extends from the Copperbelt in Zambia to the southern Shaba Province in Congo.

Metallurgy

Genes with uninterrupted coding sequences that are thousands of bases long - up to 90,000 bases - that occur in many bacterial organisms were practically impossible to have occurred. However, the bacterial genes could have originated from split genes by losing introns, the only proposed way to arrive at long coding sequences. It is also a better way than by increasing the lengths of ORFs from short random ORFs to long ORFs by specifically removing the stop codons by mutation. According to the split gene theory, this process of intron loss could have happened from prebiotic random DNA. These contiguously coding genes could be tightly organized in the bacterial genomes without any introns and be more streamlined. According to Senapathy, the nuclear boundary that was required for a cell containing split genes would not be required for a cell containing only uninterrupted genes. Thus, the bacterial cells did not develop a nucleus. Based on split gene theory, the eukaryotic genomes and bacterial genomes could have independently originated from the split genes in primordial random DNA sequences.

Gene expression + Signal Transduction

POSCO, one of the world's biggest steel production companies, in 1986, initiated a founding of a science and technology university in the city of Pohang, about 200 miles southeast of Seoul, the capital city of Korea. Pohang University of Science and Technology (POSTECH) has now become one of the top research universities in Asia. GIFT was founded to provide an academic environment for education and research on ferrous materials.

Metallurgy

In the human genome, STAT6 protein is encoded by the STAT6 gene, located on the chromosome 12q13.3-q14.1. The gene encompasses over 19 kb and consists of 23 exons. STAT6 shares structural similarity with the other STAT proteins and is composed of the N-terminal domain, DNA binding domain, SH3- like domain, SH2 domain and transactivation domain (TAD). STAT proteins are activated by the Janus family (JAKs) tyrosine kinases in response to cytokine exposure. STAT6 is activated by cytokines interleukin-4 (IL-4), and interleukin-13 (IL-13) with their receptors that both contain the α subunit of the IL-4 receptor (IL-4Rα). Tyrosine phosporylation of STAT6 after stimulation by IL-4 results in the formation of STAT6 homodimers that bind specific DNA elements via a DNA-binding domain.

Gene expression + Signal Transduction

A dendrite in metallurgy is a characteristic tree-like structure of crystals growing as molten metal solidifies, the shape produced by faster growth along energetically favourable crystallographic directions. This dendritic growth has large consequences in regard to material properties.

Metallurgy

Commonly referred to as STD (Submarine Tailings Disposal) or DSTD (Deep Sea Tailings Disposal). Tailings can be conveyed using a pipeline then discharged so as to eventually descend into the depths. Practically, it is not an ideal method, as the close proximity to off-shelf depths is rare. When STD is used, the depth of discharge is often what would be considered shallow, and extensive damage to the seafloor can result due to covering by the tailings product. It is also critical to control the density and temperature of the tailings product, to prevent it from travelling long distances, or even floating to the surface. This method is used by the gold mine on Lihir Island; its waste disposal has been viewed by environmentalists as highly damaging, while the owners claim that it is not harmful.

Metallurgy

bHLH transcription factors have been shown to have a wide array of functions in developmental processes. More precisely, they have critical roles in the control of cellular differentiation, proliferation and regulation of oncogenesis. To date, 242 eukaryotic proteins belonging to the HLH superfamily have been reported. They have varied expression patterns in all eukaryotes from yeast to humans. Structurally, bHLH proteins are characterised by a “highly conserved domain containing a stretch of basic amino acids adjacent to two amphipathic α-helices separated by a loop”. These helices have important functional properties, forming part of the DNA binding and transcription activating domains. With respect to scleraxis, the bHLH region spans amino acid residues 78 to 131. A proline rich region is also predicted to lie between residues 161–170. A stretch of basic residues, which aids in DNA binding, is found closer to the N terminal end of scleraxis. HLH proteins that lack this basic domain have been shown to negatively regulate the activities of bHLH proteins and are called inhibitors of differentiation (Id). Basic HLH proteins function normally as dimers and bind to a specific hexanucleotide DNA sequence (CAANTG) known as an E-box thus switching on the expression of various genes involved in cellular development and survival.

Gene expression + Signal Transduction

The 3′-untranslated region plays a crucial role in gene expression by influencing the localization, stability, export, and translation efficiency of an mRNA. It contains various sequences that are involved in gene expression, including microRNA response elements (MREs), AU-rich elements (AREs), and the poly(A) tail. In addition, the structural characteristics of the 3′-UTR as well as its use of alternative polyadenylation play a role in gene expression.

Gene expression + Signal Transduction

An alloy is a mixture of chemical elements, which forms an impure substance (admixture) that retains the characteristics of a metal. An alloy is distinct from an impure metal in that, with an alloy, the added elements are well controlled to produce desirable properties, while impure metals such as wrought iron are less controlled, but are often considered useful. Alloys are made by mixing two or more elements, at least one of which is a metal. This is usually called the primary metal or the base metal, and the name of this metal may also be the name of the alloy. The other constituents may or may not be metals but, when mixed with the molten base, they will be soluble and dissolve into the mixture. The mechanical properties of alloys will often be quite different from those of its individual constituents. A metal that is normally very soft (malleable), such as aluminium, can be altered by alloying it with another soft metal, such as copper. Although both metals are very soft and ductile, the resulting aluminium alloy will have much greater strength. Adding a small amount of non-metallic carbon to iron trades its great ductility for the greater strength of an alloy called steel. Due to its very-high strength, but still substantial toughness, and its ability to be greatly altered by heat treatment, steel is one of the most useful and common alloys in modern use. By adding chromium to steel, its resistance to corrosion can be enhanced, creating stainless steel, while adding silicon will alter its electrical characteristics, producing silicon steel. Like oil and water, a molten metal may not always mix with another element. For example, pure iron is almost completely insoluble with copper. Even when the constituents are soluble, each will usually have a saturation point, beyond which no more of the constituent can be added. Iron, for example, can hold a maximum of 6.67% carbon. Although the elements of an alloy usually must be soluble in the liquid state, they may not always be soluble in the solid state. If the metals remain soluble when solid, the alloy forms a solid solution, becoming a homogeneous structure consisting of identical crystals, called a phase. If as the mixture cools the constituents become insoluble, they may separate to form two or more different types of crystals, creating a heterogeneous microstructure of different phases, some with more of one constituent than the other. However, in other alloys, the insoluble elements may not separate until after crystallization occurs. If cooled very quickly, they first crystallize as a homogeneous phase, but they are supersaturated with the secondary constituents. As time passes, the atoms of these supersaturated alloys can separate from the crystal lattice, becoming more stable, and forming a second phase that serves to reinforce the crystals internally. Some alloys, such as electrum—an alloy of silver and gold—occur naturally. Meteorites are sometimes made of naturally occurring alloys of iron and nickel, but are not native to the Earth. One of the first alloys made by humans was bronze, which is a mixture of the metals tin and copper. Bronze was an extremely useful alloy to the ancients, because it is much stronger and harder than either of its components. Steel was another common alloy. However, in ancient times, it could only be created as an accidental byproduct from the heating of iron ore in fires (smelting) during the manufacture of iron. Other ancient alloys include pewter, brass and pig iron. In the modern age, steel can be created in many forms. Carbon steel can be made by varying only the carbon content, producing soft alloys like mild steel or hard alloys like spring steel. Alloy steels can be made by adding other elements, such as chromium, molybdenum, vanadium or nickel, resulting in alloys such as high-speed steel or tool steel. Small amounts of manganese are usually alloyed with most modern steels because of its ability to remove unwanted impurities, like phosphorus, sulfur and oxygen, which can have detrimental effects on the alloy. However, most alloys were not created until the 1900s, such as various aluminium, titanium, nickel, and magnesium alloys. Some modern superalloys, such as incoloy, inconel, and hastelloy, may consist of a multitude of different elements. An alloy is technically an impure metal, but when referring to alloys, the term impurities usually denotes undesirable elements. Such impurities are introduced from the base metals and alloying elements, but are removed during processing. For instance, sulfur is a common impurity in steel. Sulfur combines readily with iron to form iron sulfide, which is very brittle, creating weak spots in the steel. Lithium, sodium and calcium are common impurities in aluminium alloys, which can have adverse effects on the structural integrity of castings. Conversely, otherwise pure-metals that contain unwanted impurities are often called "impure metals" and are not usually referred to as alloys. Oxygen, present in the air, readily combines with most metals to form metal oxides; especially at higher temperatures encountered during alloying. Great care is often taken during the alloying process to remove excess impurities, using fluxes, chemical additives, or other methods of extractive metallurgy.

Metallurgy

Huntington's disease occurs when the cytosolic protein Huntingtin (Htt) has an additional 35 glutamine residues added to its amino terminal region. This modified form of Htt is called Htt. Htt makes Type 1 IP receptors more sensitive to IP, which leads to the release of too much Ca from the ER. The release of Ca from the ER causes an increase in the cytosolic and mitochondrial concentrations of Ca. This increase in Ca is thought to be the cause of GABAergic MSN degradation.

Gene expression + Signal Transduction

eIF4F is important for recruiting the small ribosomal subunit (40S) to the 5' cap of mRNAs during cap-dependent translation initiation. Components of the complex are also involved in cap-independent translation initiation; for instance, certain viral proteases cleave eIF4G to remove the eIF4E-binding region, thus inhibiting cap-dependent translation.

Gene expression + Signal Transduction

The suppressor of cytokine signaling 1 has been shown to interact with: * Tax, * CD117, * Colony stimulating factor 1 receptor * Growth hormone receptor, * IRS2, * Janus kinase 2, and * TEC.

Gene expression + Signal Transduction

* [https://web.archive.org/web/20071209060605/http://cus.cam.ac.uk/~jld1/lists/ Cambridge University Officers]

Metallurgy

Nuclear DNA is normally tightly wrapped around histones rendering the DNA inaccessible to the general transcription machinery and hence this tight association prevents transcription of DNA. At physiological pH, the phosphate component of the DNA backbone is deprotonated which gives DNA a net negative charge. Histones are rich in lysine residues which at physiological pH are protonated and therefore positively charged. The electrostatic attraction between these opposite charges is largely responsible for the tight binding of DNA to histones. Many coactivator proteins have intrinsic histone acetyltransferase (HAT) catalytic activity or recruit other proteins with this activity to promoters. These HAT proteins are able to acetylate the amine group in the sidechain of histone lysine residues which makes lysine much less basic, not protonated at physiological pH, and therefore neutralizes the positive charges in the histone proteins. This charge neutralization weakens the binding of DNA to histones causing the DNA to unwind from the histone proteins and thereby significantly increases the rate of transcription of this DNA. Many corepressors can recruit histone deacetylase (HDAC) enzymes to promoters. These enzymes catalyze the hydrolysis of acetylated lysine residues restoring the positive charge to histone proteins and hence the tie between histone and DNA. PELP-1 can act as a transcriptional corepressor for transcription factors in the nuclear receptor family such as glucocorticoid receptors.

Gene expression + Signal Transduction

Scaffolds localize the signaling reaction to a specific area in the cell, a process that could be important for the local production of signaling intermediates. A particular example of this process is the scaffold, A-kinase anchor proteins (AKAPs), which target cyclic AMP-dependent protein kinase (PKA) to various sites in the cell. This localization is able to locally regulate PKA and results in the local phosphorylation by PKA of its substrates.

Gene expression + Signal Transduction

In metals and minerals, grains are ordered structures in different crystal orientations. Subgrains are defined as grains that are oriented at a < 10–15 degree angle at the grain boundary, making it a low-angle grain boundary (LAGB). Due to the relationship between the energy versus the number of dislocations at the grain boundary, there is a driving force for fewer high-angle grain boundaries (HAGB) to form and grow instead of a higher number of LAGB. The energetics of the transformation depend on the interfacial energy at the boundaries, the lattice geometry (atomic and planar spacing, structure [i.e. FCC/BCC/HCP] of the material, and the degrees of freedom of the grains involved (misorientation, inclination). The recrystallized material has less total grain boundary area, which means that failure via brittle fracture along the grain boundary is less probable.

Metallurgy

Alfred G. Gilman and Martin Rodbell received the 1994 Nobel Prize in Medicine and Physiology for the discovery of the G Protein System.

Gene expression + Signal Transduction

Bronze disease is an irreversible and nearly inexorable corrosion process that occurs when chlorides come into contact with bronze or other copper-bearing alloys. It can occur as both a dark green coating, or as a much lighter whitish fuzzy or furry green coating. It is not a bacterial infection, but the result of a chemical reaction with the chlorides that usually occurs due to contamination of the bronze object by saltwater or from burial in specific types of soil where chloride salts are present. If not treated, complete destruction of the affected artifact is possible. Treatment is very difficult, costly and not always effective. Transfer of chlorides from the contaminated artefact to other artefacts can spread the condition.

Metallurgy

Receptor desensitization is mediated through a combination phosphorylation, β-arr binding, and endocytosis as described above. Downregulation occurs when endocytosed receptor is embedded in an endosome that is trafficked to merge with an organelle called a lysosome. Because lysosomal membranes are rich in proton pumps, their interiors have low pH (≈4.8 vs. the pH≈7.2 cytosol), which acts to denature the GPCRs. In addition, lysosomes contain many degradative enzymes, including proteases, which can function only at such low pH, and so the peptide bonds joining the residues of the GPCR together may be cleaved. Whether or not a given receptor is trafficked to a lysosome, detained in endosomes, or trafficked back to the plasma membrane depends on a variety of factors, including receptor type and magnitude of the signal. GPCR regulation is additionally mediated by gene transcription factors. These factors can increase or decrease gene transcription and thus increase or decrease the generation of new receptors (up- or down-regulation) that travel to the cell membrane.

Gene expression + Signal Transduction

According to structural and functional similarity, many local hormones fall into either the gastrin or the secretin family.

Gene expression + Signal Transduction

In the Copper Country region of the Upper Peninsula of Michigan, the rock was reduced to fragments because further crushing would not result in enough additional copper recovery to be economical. The sand was then usually disposed near the mill. As mills often relied on steam power to operate and water for some of the processing methods, they were built on the shore of lakes and rivers. The stamp sand was thus dumped into the water, sometimes growing deep enough to create entirely new land. Stamp sand discarded into the water was sometimes reclaimed with dredges to be re-stamped when more efficient stamping technology was developed (for example, Quincy Dredge Number Two). Stamp sand may be hazardous to human health, since it contains trace amounts of harmful heavy metals (such as arsenic). For this reason, land created from stamp sand may be poisonous to plant life, and can pollute nearby water as well. For example, aquatic life in the Keweenaw Waterway, near the Keweenaw copper mines of Michigan, has declined significantly near stamp sand deposits, while the waterway is reasonably healthy in other areas. Several stamp sand dumps have been designated as Superfund sites to remove or contain the sands. Some stamp sand land has been covered with clean fill dirt and used for housing developments. The coarseness of the sand has led to its use in place of (or in combination with) road salt in some areas, such as the Copper Country of Michigan. Typically, only stamp sand which has not been chemically processed is used, due to environmental concerns. In addition, some companies have developed methods to reprocess stamp sands to reclaim their small mineral content.

Metallurgy

In materials science and soil mechanics, a slip line field or slip line field theory is a technique often used to analyze the stresses and forces involved in the major deformation of metals or soils. In essence, in some problems including plane strain and plane stress elastic-plastic problems, elastic part of the material prevent unrestrained plastic flow but in many metal-forming processes, such as rolling, drawing, gorging, etc., large unrestricted plastic flows occur except for many small elastic zones. In effect we are concerned with a rigid-plastic material under condition of plane strain. it turns out that the simplest way of solving stress equations is to express them in terms of a coordinate system that is along potential slip (or failure) surfaces. It is for this reason that this type of analysis is termed slip line analysis or the theory of slip line fields in the literature.

Metallurgy

The lost-wax method is well documented in ancient Indian literary sources. The Shilpa Shastras, a text from the Gupta Period (–550 AD), contains detailed information about casting images in metal. The 5th-century AD Vishnusamhita, an appendix to the Vishnu Purana, refers directly to the modeling of wax for making metal objects in chapter XIV: "if an image is to be made of metal, it must first be made of wax." Chapter 68 of the ancient Sanskrit text Mānasāra Silpa details casting idols in wax and is entitled Maduchchhista Vidhānam, or the "lost wax method". The 12th century text Mānasollāsa, allegedly written by King Someshvara III of the Western Chalukya Empire, also provides detail about lost-wax and other casting processes. In a 16th-century treatise, the Uttarabhaga of the Śilparatna written by Srïkumāra, verses 32 to 52 of Chapter 2 ("Linga Lakshanam"), give detailed instructions on making a hollow casting.

Metallurgy

The silver-stained spots on the microarray are clearly visible. By using a transmission microarray scanner, the signals are transformed into digital values which are finally available as an image file.

Gene expression + Signal Transduction

At the beginning of the 20th century, the entire Russian industry was in a deep crisis, the consequences of which affected the factories of the Urals until 1909. In 1909, the Ural iron and steel plants smelted 34.7 million tons of iron, which is 30.9% less than in 1900. During the crisis years, the share of finished iron increased, new markets were searched for, syndicates and associations were created to fight the competition of factories in Southern Russia. To a lesser extent, the crisis affected the copper smelting industry, thanks to continued demand and an increase in customs duties on copper imports. In the first decade of the 20th century, small technically backward factories with worn-out equipment, which had become unprofitable, were closed. Of the 111 metallurgical plants operating in the Urals in 1900, 35 plants were shut down by 1913. In conditions of tough competition, factories were forced to modernize: blast furnaces with a lightweight casing were erected, hot blast was introduced everywhere, steam engines and ore preparation for smelting, furnaces and puddling furnaces were replaced by open-hearth furnaces, more powerful rolling mills were built, and factories received electricity. In the mountainous districts, the optimization and reorganization of capacities were carried out: the final processing was concentrated, as a rule, at the main plant of the district, the rest of the factories provided supplies of iron. During the Russo-Japanese War, the Izhevsk, Perm, and Zlatoust arms factories sharply increased the production of guns, rifles, and shells. In 1908, the construction of the Porogi electrometallurgical plant for the production of ferroalloys, and one of the first hydroelectric power plants in Russia to provide the plant with electricity began. Until 1931, the plant was the only producer of ferroalloys in the country. In 1910, an industrial boom began, which continued until the First World War. From 1910 to 1913, the production of iron increased to 55.3 million poods (by 29.9%), finished metal products - up to 40.8 million poods (by 9.6%). But the share of the Ural factories in the all-Russian iron smelting fell to 21.6%. Commercial banks actively invested in the development of the metallurgy of the Urals. The most important role in the Urals was played by the Azov-Don Commercial Bank, Saint Petersburg International Commercial Bank, and Russo-Asiatic Bank. The volume of investments at the turn of the 20th century was estimated at 10.8 million rubles. Modernization and reconstruction of mountain districts continued. In 1911, a new blast furnace with a volume of 150 m³ and an open-hearth furnace with a capacity of 25 tons were launched at the Nizhniy Tagil plant; two Bessemer converters and two new blast furnaces were installed at the Nizhnesaldinsky plant. The Votkinsk plant was reconstructed for the production of steam locomotives and river vessels. The factories that produced weapons were reconstructed and switched over to the production of civilian products. Also in the pre-war years, the concentration of production at large factories increased: in 1914, out of 49 Ural plants, 16 had the productivity of more than 1 million poods of iron per year and produced 65% of the total volume, including 5 factories with a capacity of more than 2 million poods of iron per year. Nadezhdinsky, Nizhnesaldinsky, Zlatoustovsky, Chusovskoy, and Votkinsky produced 36.1% of the total volume. Copper smelters of the Urals at the beginning of the 20th century mastered pyrite smelting, which made it possible to process poor sulfur ores. In the pre-war years, the Nizhnekyshtymsky Copper Electrolytic Plant, the Karabashsky, and Kalatinsky plants were launched. Through syndicates formed, British companies owned 65.5% of the copper mined in the Urals. The gold-platinum mining industry underwent mechanization. The first Dutch dredges appeared in 1900 at the Neozhidany Mine on the Is River. By 1913, the number of dredges in the Urals reached 50, they ensured the extraction of 20% of gold and 50% of platinum. Until 1913, the average production of gold in the Urals was 550-650 poods per year, while the average production of platinum was 300-350 poods per year.

Metallurgy

The transcriptional regulation of the genome is controlled primarily at the preinitiation stage by binding of the core transcriptional machinery proteins (namely, RNA polymerase, transcription factors, and activators and repressors) to the core promoter sequence on the coding region of the DNA. However, DNA is tightly packaged in the nucleus with the help of packaging proteins, chiefly histone proteins to form repeating units of nucleosomes which further bundle together to form condensed chromatin structure. Such condensed structure occludes many DNA regulatory regions, not allowing them to interact with transcriptional machinery proteins and regulate gene expression. To overcome this issue and allow dynamic access to condensed DNA, a process known as chromatin remodeling alters nucleosome architecture to expose or hide regions of DNA for transcriptional regulation. By definition, chromatin remodeling is the enzyme-assisted process to facilitate access of nucleosomal DNA by remodeling the structure, composition and positioning of nucleosomes.

Gene expression + Signal Transduction

Though there are many methods to detect protein–protein interactions, the majority of these methods—such as co-immunoprecipitation, fluorescence resonance energy transfer (FRET) and dual polarisation interferometry—are not screening approaches.

Gene expression + Signal Transduction

Karat is a variant of carat. First attested in English in the mid-15th century, the word carat came from Middle French , in turn derived either from Italian or Medieval Latin . These were borrowed into Medieval Europe from the Arabic meaning "fruit of the carob tree", also "weight of 5 grains", () and was a unit of mass though it was probably not used to measure gold in classical times. The Arabic term ultimately originates from the Greek () meaning carob seed (literally "small horn") (diminutive of – , "horn"). In 309 CE, Roman Emperor Constantine I began to mint a new gold coin solidus that was of a libra (Roman pound) of gold equal to a mass of 24 siliquae, where each siliqua (or carat) was of a libra. This is believed to be the origin of the value of the karat.

Metallurgy

The Jameson Cell is used to recover the organic solvent in solvent extraction – electrowinning plants from both the electrolyte and raffinate streams. Contamination of the electrolyte increases operating costs and reduces the quality of the copper product. Any solvent remaining in the raffinate stream represents a loss of solvent and hence an increase in operating costs. Major users of the Cell in SX–EW plants include Freeport McMoRan at its Morenci operations, BHP Billiton at its Olympic Dam operations and Grupo México at its Cananea and La Caridad operations. In all, Xstrata Technology reports 41 SX–EW applications. Recent developments in the Cell design for SX–EW applications include large, flat-bottomed cell design to allow it to sit on the ground and large (500 mm diameter) downcomers that can have multiple liquor (there being no slurry in SX–EW applications) lenses fitted to each downcomer. The biggest operating Cell is at the Olympic Dam operations, treating 3000 m/h of raffinate.

Metallurgy

Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). It functions as a transcription factor downstream of type I interferons. STAT2 sequence identity between mouse and human is only 68%.

Gene expression + Signal Transduction

The importance of tin to the success of Bronze Age cultures and the scarcity of the resource offers a glimpse into that time periods trade and cultural interactions, and has therefore been the focus of intense archaeological studies. However, a number of problems have plagued the study of ancient tin such as the limited archaeological remains of placer mining, the destruction of ancient mines by modern mining operations, and the poor preservation of pure tin objects due to tin disease or tin pest'. These problems are compounded by the difficulty in provenancing tin objects and ores to their geological deposits using isotopic or trace element analyses. Current archaeological debate is concerned with the origins of tin in the earliest Bronze Age cultures of the Near East.

Metallurgy

There are many ways to install screen media into a screen box deck (shaker deck). Also, the type of attachment system has an influence on the dimensions of the media.

Metallurgy

Dross is a mass of solid impurities floating on a molten metal or dispersed in the metal, such as in wrought iron. It forms on the surface of low-melting-point metals such as tin, lead, zinc or aluminium or alloys by oxidation of the metal. For higher melting point metals and alloys such as steel and silver, oxidized impurities melt and float making them easy to pour off. With wrought iron, hammering and later rolling remove some dross. With tin and lead the dross can be removed by adding sodium hydroxide pellets, which dissolve the oxides and form a slag. If floating, dross can also be skimmed off. Dross, as a solid, is distinguished from slag, which is a liquid. Dross product is not entirely waste material; for example, aluminium dross can be recycled and is also used in secondary steelmaking for slag deoxidation.

Metallurgy

* NSD1 () * PELP-1 (proline, glutamic acid and leucine rich protein 1) * RIP140 (receptor-interacting protein 140) * YAP * WWTR1 (TAZ)

Gene expression + Signal Transduction

Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the TRIM24 gene.

Gene expression + Signal Transduction

The earliest smelted iron object from Europe is a knife blade from the Catacomb culture in present day Ukraine, dated to c. 2500 BC. During most of the Middle and Late Bronze Age in Europe, iron was present, though scarce. It was used for personal ornaments and small knives, for repairs on bronzes, and for bimetallic items. Early smelted iron finds from central Europe include an iron knife or sickle from Ganovce in Slovakia, possibly dating from the 18th century BC, an iron ring from Vorwohlde in Germany dating from circa the 15th century BC, and an iron chisel from Heegermühle in Germany dating from circa 1000 BC. Iron metallurgy began to be practised in Scandinavia during the later Bronze Age from at least the 9th century BC. In the 11th century BC iron swords replaced bronze swords in Southern Europe, especially in Greece, and in the 10th century BC iron became the prevailing metal in use. In the Carpathian Basin there is a significant increase in iron finds dating from the 10th century BC onwards, with some finds possibly dating as early as the 12th century BC. Iron swords have been found in central Europe dating from the 10th century BC, however the Iron Age began in earnest with the Hallstatt culture from 800 BC. From 500 BC the La Tène culture saw a significant increase in iron production, with iron metallurgy also becoming common in southern Scandinavia. North of Sweden saw steel manufacturing dating back to around 0 AD through the eastern-western migration of hunter-gatherers in the Cap of the North. The spread of ironworking in Central and Western Europe is associated with Celtic expansion. Celtic smiths produced steel from circa 800 BC as part of the production of swords, and the production of high-carbon steel is attested in Britain after circa 490 BC. By the 1st century BC, Noric steel was famous for its quality and sought-after by the Roman military. The annual iron output of the Roman Empire is estimated at 84,750 t.

Metallurgy

ASM International, formerly known as the American Society for Metals, is an association of materials-centric engineers and scientists. As the charitable arm of ASM, the ASM Materials Education Foundation also operates ASM Materials Camp in the summers for high school students and teachers. These camps are intended to educate the public about the materials field, and encourage young people to pursue careers in materials science and engineering.

Metallurgy

Protein production is the biotechnological process of generating a specific protein. It is typically achieved by the manipulation of gene expression in an organism such that it expresses large amounts of a recombinant gene. This includes the transcription of the recombinant DNA to messenger RNA (mRNA), the translation of mRNA into polypeptide chains, which are ultimately folded into functional proteins and may be targeted to specific subcellular or extracellular locations. Protein production systems (also known as expression systems) are used in the life sciences, biotechnology, and medicine. Molecular biology research uses numerous proteins and enzymes, many of which are from expression systems; particularly DNA polymerase for PCR, reverse transcriptase for RNA analysis, restriction endonucleases for cloning, and to make proteins that are screened in drug discovery as biological targets or as potential drugs themselves. There are also significant applications for expression systems in industrial fermentation, notably the production of biopharmaceuticals such as human insulin to treat diabetes, and to manufacture enzymes.

Gene expression + Signal Transduction

Formation of the Pol I preinitiation complex requires the binding of selective factor 1 (SL1 or TIF-IB) to the core element of the rDNA promoter. SL1 is a complex composed of TBP and at least three TBP-associated factors (TAFs). For basal levels of transcription, only SL1 and the initiation-competent form of Pol I (Pol Iβ), characterized by RRN3 binding, are required. For activated transcription levels, UBTF (UBF) is also required. UBTF binds as a dimer to both the upstream control element (UCE) and core element of the rDNA promoter, bending the DNA to form an enhanceosome. SL1 has been found to stabilize the binding of UBTF to the rDNA promoter. The subunits of the Pol I PIC differ between organisms.

Gene expression + Signal Transduction

Different grains and their orientations can be observed using scanning electron microscope (SEM) techniques such as electron backscatter diffraction (EBSD) or polarized optical microscopy (POM). Samples are initially cold- or hot-rolled to introduce a high degree of dislocation density, and then deformed at different strain rates so that dynamic recrystallization occurs. The deformation may be in the form of compression, tension, or torsion. The grains elongate in the direction of applied stress and the misorientation angle of subgrain boundaries increases.

Metallurgy

Several species of fungi can be used for bioleaching. Fungi can be grown on many different substrates, such as electronic scrap, catalytic converters, and fly ash from municipal waste incineration. Experiments have shown that two fungal strains (Aspergillus niger, Penicillium simplicissimum) were able to mobilize Cu and Sn by 65%, and Al, Ni, Pb, and Zn by more than 95%. Aspergillus niger can produce some organic acids such as citric acid. This form of leaching does not rely on microbial oxidation of metal but rather uses microbial metabolism as source of acids that directly dissolve the metal.

Metallurgy

This process was developed by the National Smelting Company at Avonmouth Docks, England, in order to increase production, increase efficiency, and decrease labour and maintenance costs. L. J. Derham proposed using a spray of molten lead droplets to rapidly cool and absorb the zinc vapour, despite the high concentration of carbon dioxide. The mixture is then cooled, where the zinc separates from the lead. The first plant using this design opened up in 1950. One of the advantages of this process is that it can co-produce lead bullion and copper dross. In 1990, it accounted for 12% of the world's zinc production. The process starts by charging solid sinter and heated coke into the top of the blast furnace. Preheated air at is blown into the bottom of the furnace. Zinc vapour and sulfides leave through the top and enter the condenser. Slag and lead collect at the bottom of the furnace and are tapped off regularly. The zinc is scrubbed from the vapour in the condenser via liquid lead. The liquid zinc is separated from the lead in the cooling circuit. Approximately of lead are required each year for this process, however this process recovers 25% more lead from the starting ores than other processes.

Metallurgy

Santiago Ramón y Cajal proposed that neurons are not continuous throughout the body, yet still communicate with each other, an idea known as the neuron doctrine. The word "synapse" was introduced in 1897 by the English neurophysiologist Charles Sherrington in Michael Fosters Textbook of Physiology. Sherrington struggled to find a good term that emphasized a union between two separate elements, and the actual term "synapse" was suggested by the English classical scholar Arthur Woollgar Verrall, a friend of Foster. The word was derived from the Greek synapsis (), meaning "conjunction", which in turn derives from synaptein (), from syn () "together" and haptein' () "to fasten". However, while the synaptic gap remained a theoretical construct, and was sometimes reported as a discontinuity between contiguous axonal terminations and dendrites or cell bodies, histological methods using the best light microscopes of the day could not visually resolve their separation which is now known to be about 20 nm. It needed the electron microscope in the 1950s to show the finer structure of the synapse with its separate, parallel pre- and postsynaptic membranes and processes, and the cleft between the two.

Gene expression + Signal Transduction

Continuous dynamic recrystallization is common in materials with high stacking-fault energies. It occurs when low angle grain boundaries form and evolve into high angle boundaries, forming new grains in the process. For continuous dynamic recrystallization there is no clear distinction between nucleation and growth phases of the new grains. Continuous Dynamic Recrystallization has 4 main characteristics: * As strain increases, stress increases * As strain increases, subgrain boundary misorientation increases * As low angle grain boundaries evolve into high angle grain boundaries, the misorientation increases homogeneously * As deformation increases, crystallite size decreases There are three main mechanisms of continuous dynamic recrystallization: First, continuous dynamic recrystallization can occur when low angle grain boundaries are assembled from dislocations formed within the grain. When the material is subjected to continued stress, the misorientation angle increases until the critical angle is achieved, creating a high angle grain boundary. This evolution can be promoted by the pinning of subgrain boundaries. Second, continuous dynamic recrystallization can occur through subgrain rotation recrystallization; subgrains rotate increasing the misorientation angle. Once the misorientation angle exceeds the critical angle, the former subgrains qualify as independent grains. Third, continuous dynamic recrystallization can occur due to deformation caused by microshear bands. Subgrains are assembled by dislocations within the grain formed during work hardening. If microshear bands are formed within the grain, the stress they introduce rapidly increases the misorientation of low angle grain boundaries, transforming them into high angle grain boundaries. However, the impact of microshear bands are localized, so this mechanism preferentially impacts regions which deform heterogeneously, such as microshear bands or areas near pre-existing grain boundaries. As recrystallization proceeds, it spreads out from these zones, generating a homogenous, equiaxed microstructure.

Metallurgy

When referring to a promoter some authors actually mean promoter + operator; i.e., the lac promoter is IPTG inducible, meaning that besides the lac promoter, the lac operon is also present. If the lac operator were not present the IPTG would not have an inducible effect. Another example is the Tac-Promoter system (Ptac). Notice how tac is written as a tac promoter, while in fact tac is actually both a promoter and an operator.

Gene expression + Signal Transduction

In welding, equivalent carbon content (C.E) is used to understand how the different alloying elements affect hardness of the steel being welded. This is then directly related to hydrogen-induced cold cracking, which is the most common weld defect for steel, thus it is most commonly used to determine weldability. Higher concentrations of carbon and other alloying elements such as manganese, chromium, silicon, molybdenum, vanadium, copper, and nickel tend to increase hardness and decrease weldability. Each of these elements tends to influence the hardness and weldability of the steel to different magnitudes, however, making a method of comparison necessary to judge the difference in hardness between two alloys made of different alloying elements. There are two commonly used formulas for calculating the equivalent carbon content. One is from the American Welding Society (AWS) and recommended for structural steels and the other is the formula based on the International Institute of Welding (IIW). The AWS states that for an equivalent carbon content above 0.40% there is a potential for cracking in the heat-affected zone (HAZ) on flame cut edges and welds. However, structural engineering standards rarely use CE, but rather limit the maximum percentage of certain alloying elements. This practice started before the CE concept existed, so just continues to be used. This has led to issues because certain high strength steels are now being used that have a CE higher than 0.50% that have brittle failures. The other and most popular formula is the Dearden and O'Neill formula, which was adopted by IIW in 1967. This formula has been found suitable for predicting hardenability in a large range of commonly used plain carbon and carbon-manganese steels, but not to microalloyed high-strength low-alloy steels or low-alloy Cr-Mo steels. The formula is defined as follows: For this equation the weldability based on a range of CE values can be defined as follows: The Japanese Welding Engineering Society adopted the critical metal parameter (Pcm) for weld cracking, which was based on the work from Ito and Bessyo, is: If some of the values are not available, the following formula is sometimes used: The carbon equivalent is a measure of the tendency of the weld to form martensite on cooling and to suffer brittle fracture. When the carbon equivalent is between 0.40 and 0.60 weld preheat may be necessary. When the carbon equivalent is above 0.60, preheat is necessary, postheat may be necessary. The following carbon equivalent formula is used to determine if a spot weld will fail in high-strength low-alloy steel due to excessive hardenability: Where UTS is the ultimate tensile strength in ksi and h is the strip thickness in inches. A CE value of 0.3 or less is considered safe. A special carbon equivalent was developed by Yurioka, which could determine the critical time in seconds Δt for the formation of martensitic in the Heat Affected Zone (HAZ) in low-carbon alloy steels. The equation is given as: where: Then the critical time length in seconds Δt can be determined as follows:

Metallurgy

The most elaborately accurate, but totally destructive, precious metal assay is fire assay. (It may also be called by the critical cupellation step that separates precious metal from lead.) If performed on bullion to international standards, the method can be accurate on gold metal to 1 part in 10,000. If performed on ore materials using fusion followed by cupellation separation, detection may be in parts per billion. However, accuracy on ore material is typically limited to 3 to 5% of reported value. Although time-consuming, the method is the accepted standard applied for valuing gold ore as well as gold and silver bullion at major refineries and gold mining companies. In the case of fire assaying of gold and platinum ores, the lengthy time required to carry out an assay is generally offset by carrying out large numbers of assays simultaneously, and a typical laboratory will be equipped with several fusion and cupellation furnaces, each capable of taking multiple samples, so that several hundred analyses per day can be carried out. The principal advantage of fire assay is that large samples can be used, and these increase the accuracy in analyzing low-yield ores in the <1g/T range of concentration. Fusion: the process requires a self-generating reducing atmosphere, and so the crushed ore sample is mixed with fluxes and a carbon source (e.g. coal dust, ground charcoal, flour, etc.) mixed with powdered lead oxide (litharge) in a refractory crucible. In general, multiple crucibles will be placed inside an electric furnace fitted with silicon carbide heating elements, and heated to between 1,000 and 1,200 °C. The temperature required, and the type of flux used, are dependent on the composition of the rock in which the precious metals are concentrated, and in many laboratories an empirical approach based on long experience is used. A complex reaction takes place, whereby the carbon source reduces the lead oxide to lead, which alloys with the precious metals: at the same time, the fluxes combine with the crushed rock, reducing its melting point and forming a glassy slag. When fusion is complete, the sample is tipped into a mold (usually iron) where the slag floats to the top, and the lead, now alloyed with the precious metals, sinks to the bottom, forming a button. After solidification, the samples are knocked out, and the lead bullets recovered for cupellation, or for analysis by other means. Method details for various fire assay procedures vary, but concentration and separation chemistry typically comply with traditions set by Bugby or Shepard & Dietrich in the early 20th century. Method advancements since that time primarily automate material handling and final finish measurements (i.e., instrument finish rather than physical gold product weighing). Arguably, even these texts are largely an extension of traditions that were detailed in De re metallica by Agricola in 1556. Variation from skills taught in modern standard adaptations of fire assay methodology should be viewed with caution. The standard traditions have a long history of reliability; "special" new methods frequently associate with reduced assay accuracy and fraud. Cupellation: the lead bullets are placed in porous crucibles (cupels) of bone ash or magnesium oxide and heated in air to about 1,000 °C. This is usually carried out in a muffle furnace, containing a refractory muffle (usually nitride-bonded silicon carbide) heated externally by silicon carbide heating elements. A flow of air through the muffle assists oxidation of the lead, and carries the fumes for safe collection outside the furnace unit. The lead melts and oxidises to lead oxide, which in turn melts and is drawn into the pores of the cupel by capillary attraction. The precious metals remain in the base of the cupel as a prill which is sent for final analysis of precious metal content. In the bullion fire assay process, a sample from the article is wrapped in a lead foil with copper and silver. The wrapped sample, along with prepared control samples, heated at 1,650 °F (or 898.9 °C; temperature varies with exact method) in a cupel made of compressed bone ash or magnesium oxide powder. Base metals oxidize and absorb into the cupel. The product of this cupellation (doré) is flattened and treated in nitric acid to remove silver. Precision weighing of metal content of samples and process controls (proofs) at each process stage is the basis of the extreme method precision. European assayers follow bullion traditions based in hallmarking regulations. Reputable North American bullion assayers conform closely to [http://www.astm.org/Standards/E1335.htm ASTM method E1335-04e1]. Only bullion methods validated and traceable to accepted international standards obtain genuine accuracies of 1 part in 10,000. Cupellation alone can only remove a limited quantity of impurities from a sample. Fire assay, as applied to ores, concentrates, or less pure metals, adds a fusion or scorification step before cupellation.

Metallurgy

Whether or not a given individuals brain can deal effectively with stress, and thus their susceptibility to depression, depends on the β-catenin in each persons brain, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published November 12, 2014, in the journal Nature. Higher β-catenin signaling increases behavioral flexibility, whereas defective β-catenin signaling leads to depression and reduced stress management.

Gene expression + Signal Transduction

In 2008, Place et al. identified targets for miRNA miR-373 on the promoters of several human genes and found that introduction of miR-373 mimics into human cells induced the expression of its predicted target genes. This study provided the first example that RNAa could be mediated by naturally occurring non-coding RNA (ncRNA). In 2011, Huang et al. further demonstrated in mouse cells that endogenous RNAa mediated by miRNAs functions in a physiological context and is possibly exploited by cancer cells to gain a growth advantage. Since then, a number of miRNAs have been shown to upregulate gene expression by targeting gene promoters or enhancers, thereby, exerting important biological roles. A good example is miR-551b-3p which is overexpressed in ovarian cancer due to amplification. By targeting the promoter of STAT3 to increase its transcription, miR-551b-3p confers to ovarian cancer cells resistance to apoptosis and a proliferative advantage. In C. elegans hypodermal seam cells, the transcription of lin-4 miRNA is positively regulated by lin-4 itself which binds to a conserved lin-4 complementary element in its promoter, constituting a positive autoregulatory loop. In C. elegans, Argonaute CSR-1 interacts with 22G small RNAs derived from RNA-dependent RNA polymerase and antisense to germline-expressed transcripts to protect these mRNAs from Piwi-piRNA mediated silencing via promoting epigenetic activation. It is currently unknown how widespread gene regulation by endogenous RNAa is in mammalian cells. Studies have shown that both miRNAs and Ago proteins (Ago1) bind to numerous sites in human genome, especially promoter regions, to exert a largely positive effect on gene transcription.

Gene expression + Signal Transduction

Currently, receptor modulators are categorized in the Agonist, Partial Agonist, Selective Tissue Modulators, Antagonist, and Inverse Agonist categories in terms of the effect they cause. They are further divided into Orthosteric or Allosteric Modulators according to how they effect said result. Typically, a chemical acts in an agonist fashion whenever it instigates or else facilitates a particular reaction by binding to a particular receptor. In contract, a chemical acts as an antagonist whenever binding to a particular receptor blocks or inhibits a particular response. Between these endpoints exists a gradient defined by a number of variables. One example is Selective Tissue Modulators, which mean a given ligand can behave differently according to the tissue type it is in. As for orthosteric and allosteric modulation, this describes the manner in which the ligand binds to the receptor in question: if it binds directly to the prescribed binding site of a receptor, the ligand is orthosteric in this instance; if the ligand alters the receptor by interacting with it at any place other than a binding site, allosteric interaction occurred. Note that a drug's categorization does not dictate how another drug of the same family could be categorized or whether the same drug may also function in another category. An example is found in medications used to treat opioid addiction, with methadone, buprenorphine, naloxone, and naltrexone all in separate categories or in more than one simultaneously. In addition, depending on the cell type, the specific effect, whether agonist, antagonist, inverse agonist, etc., could have a unique specific effect. An example is seen in insulin, under "Receptor Agonists," as it interacts with multiple different cell types as an agonist, but incites multiple and different responses in both.

Gene expression + Signal Transduction

The mouse sperm genome is 80–90% methylated at its CpG sites in DNA, amounting to about 20 million methylated sites. After fertilization, early in the first day of embryogenesis, the paternal chromosomes are almost completely demethylated in six hours by an active TET-dependent process, before DNA replication begins (blue line in Figure). Demethylation of the maternal genome occurs by a different process. In the mature oocyte, about 40% of its CpG sites in DNA are methylated. In the pre-implantation embryo up to the blastocyst stage (see Figure), the only methyltransferase present is an isoform of DNMT1 designated DNMT1o. It appears that demethylation of the maternal chromosomes largely takes place by blockage of the methylating enzyme DNMT1o from entering the nucleus except briefly at the 8 cell stage (see DNA demethylation). The maternal-origin DNA thus undergoes passive demethylation by dilution of the methylated maternal DNA during replication (red line in Figure). The morula (at the 16 cell stage), has only a small amount of DNA methylation (black line in Figure).

Gene expression + Signal Transduction

The die casting process forces molten metal under high pressure into mold cavities (which are machined into dies). Most die castings are made from nonferrous metals, specifically zinc, copper, and aluminium-based alloys, but ferrous metal die castings are possible. The die casting method is especially suited for applications where many small to medium-sized parts are needed with good detail, a fine surface quality and dimensional consistency.

Metallurgy

The Polycomb-group (PcG) regulatory complexes are known for their influence in the epigenetic regulation of stem cells, especially in hematopoietic stem cells. The Polycomb Repressive Complex 1 (PRC 1) is directly involved in the process of hematopoiesis, and functions together with, for example, the PcG gene “Bmi1”. Studies in mice indicate that organisms with mutated “Bmi1” demonstrate deficient mitochondrial functioning, and also hindered the ability of hematopoietic cells to self-renew. Likewise, mutations in PRC2 genes were related to hematological conditions such as acute lymphoblastic leukemia (ALL), which is a form of leukemia. Hence, Polycomb-group genes and proteins are involved in the proper maintenance of hematopoiesis in the body.

Gene expression + Signal Transduction

Ceramic microstructures are most often analyzed by reflected visible-light microscopy in brightfield. Darkfield is used in limited circumstances, e.g., to reveal cracks. Polarized transmitted light is used with thin sections, where the contrast between grains comes from birefringence. Very fine microstructures may require the higher magnification and resolution of a scanning electron microscope (SEM) or confocal laser scanning microscope (CLSM). The cathodoluminescence microscope (CLM) is useful for distinguishing phases of refractories. The transmission electron microscope (TEM) and scanning acoustic microscope (SAM) have specialty applications in ceramography. Ceramography is often done qualitatively, for comparison of the microstructure of a component to a standard for quality control or failure analysis purposes. Three common quantitative analyses of microstructures are grain size, second-phase content and porosity. Microstructures are measured by the principles of stereology, in which three-dimensional objects are evaluated in 2-D by projections or cross-sections. Microstructures exhibiting heterogeneous grain sizes, with certain grains growing very large, occur in diverse ceramic systems and this phenomenon is known as abnormal grain growth or AGG. The occurrence of AGG has consequences, positive or negative, on mechanical and chemical properties of ceramics and its identification is often the goal of ceramographic analysis. Grain size can be measured by the line-fraction or area-fraction methods of ASTM E112. In the line-fraction methods, a statistical grain size is calculated from the number of grains or grain boundaries intersecting a line of known length or circle of known circumference. In the area-fraction method, the grain size is calculated from the number of grains inside a known area. In each case, the measurement is affected by secondary phases, porosity, preferred orientation, exponential distribution of sizes, and non-equiaxed grains. Image analysis can measure the shape factors of individual grains by ASTM E1382. Second-phase content and porosity are measured the same way in a microstructure, such as ASTM E562. Procedure E562 is a point-fraction method based on the stereological principle of point fraction = volume fraction, i.e., P = V. Second-phase content in ceramics, such as carbide whiskers in an oxide matrix, is usually expressed as a mass fraction. Volume fractions can be converted to mass fractions if the density of each phase is known. Image analysis can measure porosity, pore-size distribution and volume fractions of secondary phases by ASTM E1245. Porosity measurements do not require etching. Multi-phase microstructures do not require etching if the contrast between phases is adequate, as is usually the case. Grain size, porosity and second-phase content have all been correlated with ceramic properties such as mechanical strength σ by the Hall–Petch equation. Hardness, toughness, dielectric constant and many other properties are microstructure-dependent.

Metallurgy

The ISASMELT process began with the invention in 1973 of the Sirosmelt lance by Drs Bill Denholm and John Floyd at the CSIRO. The lance was developed as a result of investigations into improved tin-smelting processes, in which it was found that the use of a top-entry submerged lance would result in greater heat transfer and mass transfer efficiencies. The idea of top-entry submerged lances goes back to at least 1902, when such a system was attempted in Clichy, France. However, early attempts failed because of the short lives of the lances on submersion in the bath. The Mitsubishi copper smelting process is one alternative approach, wherein lances are used in a furnace, but they are not submerged into the bath. Instead, they blow oxygen-enriched air onto the surface of the slag (top jetting). Similarly, a water-cooled, top-jetting lance was the basis of the LD (Linz-Donawitz) steelmaking process. This does not produce the same intensity of mixing in the bath as a submerged lance. The CSIRO scientists first tried developing a submerged lance system using a water-cooled lance, but moved to an air-cooled system because "scale up of the water-cooled lance would have been problematic". Introducing any water to a system involving molten metals and slags can result in catastrophic explosions, such as that in the Scunthorpe Steelworks in November 1975 in which 11 men lost their lives. The inclusion of the swirlers in the Sirosmelt lance and forming a splash coating of slag on the lance were the major innovations that led to the successful development of submerged lance smelting. From 1973, the CSIRO scientists began a series of trials using the Sirosmelt lance to recover metals from industrial slags in Australia, including lead softener slag at the Broken Hill Associated Smelters in Port Pirie (1973), tin slag from Associated Tin Smelters in Sydney (1974), copper converter slag at the Electrolytic Refining and Smelting ("ER&S") Port Kembla plant (1975) and copper anode furnace slag at Copper Refineries Limited (another subsidiary of MIM Holdings) in Townsville (1976) and of copper converter slag in Mount Isa (1977). The work then proceeded to smelting tin concentrates (1975) and then sulfidic tin concentrates (1977). MIM and ER&S jointly funded the 1975 Port Kembla converter slag treatment trials and MIM's involvement continued with the slag treatment work in Townsville and Mount Isa. In parallel with the copper slag treatment work, the CSIRO was continuing to work in tin smelting. Projects included a five tonne ("t") plant for recovering tin from slag being installed at Associated Tin Smelters in 1978, and the first sulfidic smelting test work being done in collaboration with Aberfoyle Limited, in which tin was fumed from pyritic tin ore and from mixed tin and copper concentrates. Aberfoyle was investigating the possibility of using the Sirosmelt lance approach to improve the recovery of tin from complex ores, such as its mine at Cleveland, Tasmania, and the Queen Hill ore zone near Zeehan in Tasmania. The Aberfoyle work led to the construction and operation in late 1980 of a four t/h tin matte fuming pilot plant at the Western Mining Corporation's Kalgoorlie Nickel Smelter, located to the south of Kalgoorlie, Western Australia.

Metallurgy

The notions that not all enhancers are transcribed at the same time and that eRNA transcription correlates with enhancer-specific activity support the idea that individual eRNAs carry distinct and relevant biological functions. However, there is still no consensus on the functional significance of eRNAs. Furthermore, eRNAs can easily be degraded through exosomes and nonsense-mediated decay, which limits their potential as important transcriptional regulators. To date, four main models of eRNA function have been proposed, each supported by different lines of experimental evidence.

Gene expression + Signal Transduction

Edward W Davis of the University of Minnesota is credited for devising the process of pelletizing iron ore. Pelletizing iron ore is undertaken due to the excellent physical and metallurgical properties of iron ore pellets. Iron ore pellets are spheres of typically to be used as raw material for blast furnaces. They typically contain 64–72% Fe and various additional material adjusting the chemical composition and the metallurgic properties of the pellets. Typically limestone, dolomite and olivine is added and Bentonite is used as binder. The process of pelletizing combines mixing of the raw material, forming the pellet and a thermal treatment baking the soft raw pellet to hard spheres. The raw material is rolled into a ball, then fired in a kiln or in travelling grate to sinter the particles into a hard sphere. The configuration of iron ore pellets as packed spheres in the blast furnace allows air to flow between the pellets, decreasing the resistance to the air that flows up through the layers of material during the smelting. The configuration of iron ore powder in a blast furnace is more tightly-packed and restricts the air flow. This is the reason that iron ore is preferred in the form of pellets rather than in the form of finer particles. The quality of the iron ore pellets depends on different factors, which include feed particle size, amount of water used, disc rotating speed, inclination angle of the disc bottom, residence time in the disc as well as the quality and quantity of the binder(s) used.

Metallurgy

Apoptosis triggered by FasR-Fas ligand binding plays a fundamental role in the regulation of the immune system. Its functions include: *T-cell homeostasis: the activation of T-cells leads to their expression of the Fas ligand. T cells are initially resistant to Fas-mediated apoptosis during clonal expansion, but become progressively more sensitive the longer they are activated, ultimately resulting in activation-induced cell death (AICD). This process is needed to prevent an excessive immune response and eliminate autoreactive T-cells. Humans and mice with deleterious mutations of Fas or Fas ligand develop an accumulation of aberrant T-cells, leading to lymphadenopathy, splenomegaly, and lupus erythematosus. *Cytotoxic T-cell activity: Fas-induced apoptosis and the perforin pathway are the two main mechanisms by which cytotoxic T lymphocytes induce cell death in cells expressing foreign antigens. *Immune privilege: Cells in immune privileged areas such as the cornea or testes express Fas ligand and induce the apoptosis of infiltrating lymphocytes. It is one of many mechanisms the body employs in the establishment and maintenance of immune privilege. *Maternal tolerance: Fas ligand may be instrumental in the prevention of leukocyte trafficking between the mother and the fetus, although no pregnancy defects have yet been attributed to a faulty Fas-Fas ligand system. *Tumor counterattack: Tumors may over-express Fas ligand and induce the apoptosis of infiltrating lymphocytes, allowing the tumor to escape the effects of an immune response. The up-regulation of Fas ligand often occurs following chemotherapy, from which the tumor cells have attained apoptosis resistance.

Gene expression + Signal Transduction

The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the SLC18A2 gene. SLC18A2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, SLC18A2 function is also necessary for the vesicular release of the neurotransmitter GABA.

Gene expression + Signal Transduction

The effectiveness of a medium to adsorb to a particle is influenced by the relationship between the surfaces of both materials. There are multiple factors that affect the efficiency of adsorption in chemical, thermodynamic, and physical domains. These factors can range from surface energy and polarity to the shape, size, and roughness of the particle. In froth flotation, adsorption is a strong consequence of surface energy, since the small particles have a high surface area to size ratio, resulting in higher energy surfaces to form attractions with adsorbates. The air bubbles must selectively adhere to the desired minerals to elevate them to the surface of the slurry while wetting the other minerals and leaving them in the aqueous slurry medium. Particles that can be easily wetted by water are called hydrophilic, while particles that are not easily wetted by water are called hydrophobic. Hydrophobic particles have a tendency to form a separate phase in aqueous media. In froth flotation the effectiveness of an air bubble to adhere to a particle is based on how hydrophobic the particle is. Hydrophobic particles have an affinity to air bubbles, leading to adsorption. The bubble-particle combinations are elevated to the froth zone driven by buoyancy forces. The attachment of the bubbles to the particles is determined by the interfacial energies of between the solid, liquid, and vapor phases, as modeled by the Young/Dupre Equation. The interfacial energies can be based on the natural structure of the materials, or the addition of chemical treatments can improve energy compatibility. Collectors are the main additives used to improve particle surfaces. They function as surfactants to selectively isolate and aid adsorption between the particles of interest and bubbles rising through the slurry. Common collectors used in flotation are anionic sulfur ligands, which have a bifunctional structure with an ionic portion which shares attraction with metals, and a hydrophobic portion such as a long hydrocarbon tail. These collectors coat a particle's surface with a monolayer of non-polar substance to aid separation from the aqueous phase by decreasing the adsorbed particle solubility in water. The adsorbed ligands can form micelles around the particles and form small-particle colloids improving stability and phase separation further.

Metallurgy

The Historical Metallurgy Society is a British learned society providing an international forum for exchange of information and research in historical metallurgy. It was founded as the Historical Metallurgy Group in 1963. All aspects of the history of metals and associated materials are covered from prehistory to the present, from processes and production through technology and economics to archaeology and conservation. The Historical Metallurgy Society origins were partly a response to the damage and destruction of many historically important metallurgical sites. Conservation, research and protection remain important parts of the society’s role. Each year the society holds a two-day conference (usually in the United Kingdom) with a program of papers covering a particular area of metallurgical interest. In addition to this, it also runs other day meetings. The Historical Metallurgy Society publishes Historical Metallurgy an internationally recognised peer-reviewed journal, published annually in two parts. The society also issues a newsletter The Crucible three times a year, and has published edited collections based on the papers given at several of its conferences in an Occasional Papers series. The Historical Metallurgy Society is a company limited by guarantee (no. 1442508) and a registered charity (no. 279314).

Metallurgy

Fougèrite is a relatively recently described naturally occurring green rust mineral. It is the archetype of the fougèrite group in the larger hydrotalcite supergroup of naturally occurring layered double hydroxides. The structure is based on brucite-like layers containing Fe and Fe cations, O and OH anions, with loosely bound [CO] groups and HO molecules between the layers. Fougèrite crystallizes in trigonal system. The ideal formula for fougèrite is [FeFe(OH)][CO]·3HO. Higher degrees of oxidation produce the other members of the fougèrite group, namely trébeurdenite, [FeFeO(OH)][CO]·3HO and mössbauerite, [FeO(OH)][CO]·3HO. Fougèrite was first found in forested soils near Fougères, Brittany, France, and recognised as a valid mineral species by the International Mineralogical Association in 2002. It is blue-green to bluish-gray in colour, and resembles clay minerals in habit, forming hexagonal platelets of submicron diameter. In this environment, it is intimately intergrown with trébeurdenite, to give varying overall ratios of Fe:Fe. The existence of two intergrown fixed-composition phases has been demonstrated by Mössbauer spectroscopy. The mineral is unstable in air, and decomposes by oxidation, dehydration and decarbonation, to ferrihydrite, and ultimately to lepidocrocite or goethite, FeO(OH).

Metallurgy

In eukaryotes mRNA molecules form circular structures due to an interaction between the eIF4E and poly(A)-binding protein, which both bind to eIF4G, forming an mRNA-protein-mRNA bridge. Circularization is thought to promote cycling of ribosomes on the mRNA leading to time-efficient translation, and may also function to ensure only intact mRNA are translated (partially degraded mRNA characteristically have no m7G cap, or no poly-A tail). Other mechanisms for circularization exist, particularly in virus mRNA. Poliovirus mRNA uses a cloverleaf section towards its 5 end to bind PCBP2, which binds poly(A)-binding protein, forming the familiar mRNA-protein-mRNA circle. Barley yellow dwarf virus has binding between mRNA segments on its 5 end and 3' end (called kissing stem loops), circularizing the mRNA without any proteins involved. RNA virus genomes (the + strands of which are translated as mRNA) are also commonly circularized. During genome replication the circularization acts to enhance genome replication speeds, cycling viral RNA-dependent RNA polymerase much the same as the ribosome is hypothesized to cycle.

Gene expression + Signal Transduction

In molecular biology, extracellular signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway. The term, "extracellular signal-regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase (MAPK), but has more recently been adopted for a specific subset of the mammalian MAPK family. In the MAPK/ERK pathway, Ras activates c-Raf, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals. ERKs are known to activate many transcription factors, such as ELK1, and some downstream protein kinases. Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf, and receptors such as HER2.

Gene expression + Signal Transduction