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Heterosynaptic plasticity (or also heterotropic modulation) is a change in synaptic strength that results from the activity of other neurons. Again, the plasticity can alter the number of vesicles or their replenishment rate or the relationship between calcium and vesicle release. Additionally, it could directly affect calcium influx. Heterosynaptic plasticity can also be postsynaptic in nature, affecting receptor sensitivity.
One example is again neurons of the sympathetic nervous system, which release noradrenaline, which, in addition, generates an inhibitory effect on presynaptic terminals of neurons of the parasympathetic nervous system. | 1 | Gene expression + Signal Transduction |
At the beginning of the twentieth century, as steel production became more dependent on the use of electric arc furnace technology in mini-mill environments, the convenient transportation of scrap metal became a competitive advantage of manufacturers, so the availability of geographical resources was no longer the most significant driving force for iron-and-steel production growth. The Birmingham area began to invest in building the earliest mini-mills, and continued to have a strong foundry emphasis, attracting many large cast-iron pipe producers, such as American Cast Iron Pipe Company. Headquartered in Birmingham in 1905, American Cast Iron Pipe Company, with its 2,100 acre site and 2,400 employees at its operations, became the worlds largest iron pipe casting plant. With advanced expertise and the latest technological innovations, Birmingham furnaces produced millions of tons of pig iron from 1990s to 1970s. A half of the produced pig iron was used for steel production, and the other half was sold as foundry iron. This trend reflected that the regions iron ore was of poor quality, so manufacturers had difficulties in extracting it. This is a geological factor that limited the further development of Alabama's iron and steel industry, despite the help of advanced technology and innovative smelting practices. | 0 | Metallurgy |
In materials science, grain-boundary strengthening (or Hall–Petch strengthening) is a method of strengthening materials by changing their average crystallite (grain) size. It is based on the observation that grain boundaries are insurmountable borders for dislocations and that the number of dislocations within a grain has an effect on how stress builds up in the adjacent grain, which will eventually activate dislocation sources and thus enabling deformation in the neighbouring grain as well. By changing grain size, one can influence the number of dislocations piled up at the grain boundary and yield strength. For example, heat treatment after plastic deformation and changing the rate of solidification are ways to alter grain size. | 0 | Metallurgy |
Proteins are the product of a gene that are formed from translation of a mature mRNA molecule. Proteins contain 4 elements in regards to their structure: primary, secondary, tertiary and quaternary. The linear amino acid sequence is also known as the primary structure. Hydrogen bonding between the amino acids of the primary structure results in the formation of alpha helices or beta sheets. These stable foldings are the secondary structure. The particular combination of the primary and secondary structures form the tertiary structure of a polypeptide. The quaternary structure refers to the way multiple chains of polypeptides fold together. | 1 | Gene expression + Signal Transduction |
A position of a codon is said to be a n-fold degenerate site if only n of four possible nucleotides (A, C, G, T) at this position specify the same amino acid. A nucleotide substitution at a 4-fold degenerate site is always a synonymous mutation with no change on the amino acid.
A less degenerate site would produce a nonsynonymous mutation on some of the substitutions. An example (and the only) 3-fold degenerate site is the third position of an isoleucine codon. AUU, AUC, or AUA all encode isoleucine, but AUG encodes methionine. In computation, this position is often treated as a twofold degenerate site.
A position is said to be non-degenerate if any mutation at this position changes the amino acid. For example, all three positions of methionines AUG are non-degenerate, because the only codon coding for methionine is AUG. The same goes for tryptophans UGG.
There are three amino acids encoded by six different codons: serine, leucine, and arginine. Only two amino acids are specified by a single codon each. One of these is the amino-acid methionine, specified by the codon AUG, which also specifies the start of translation; the other is tryptophan, specified by the codon UGG. | 1 | Gene expression + Signal Transduction |
Sintering or frittage is the process of compacting and forming a solid mass of material by pressure or heat without melting it to the point of liquefaction. Sintering happens as part of a manufacturing process used with metals, ceramics, plastics, and other materials. The nanoparticles in the sintered material diffuse across the boundaries of the particles, fusing the particles together and creating a solid piece.
Since the sintering temperature does not have to reach the melting point of the material, sintering is often chosen as the shaping process for materials with extremely high melting points, such as tungsten and molybdenum. The study of sintering in metallurgical powder-related processes is known as powder metallurgy.
An example of sintering can be observed when ice cubes in a glass of water adhere to each other, which is driven by the temperature difference between the water and the ice. Examples of pressure-driven sintering are the compacting of snowfall to a glacier, or the formation of a hard snowball by pressing loose snow together.
The material produced by sintering is called sinter. The word sinter comes from the Middle High German , a cognate of English cinder. | 0 | Metallurgy |
HACNS1 (also known as CENTG2 and located in the Human Accelerated Region 2) is a gene enhancer "that may have contributed to the evolution of the uniquely opposable human thumb, and possibly also modifications in the ankle or foot that allow humans to walk on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human genome, HACNS1 has undergone the most change during the evolution of humans following the split with the ancestors of chimpanzees. | 1 | Gene expression + Signal Transduction |
β-Catenin has a central role in directing several developmental processes, as it can directly bind transcription factors and be regulated by a diffusible extracellular substance: Wnt. It acts upon early embryos to induce entire body regions, as well as individual cells in later stages of development. It also regulates physiological regeneration processes. | 1 | Gene expression + Signal Transduction |
The most common standard in Europe is ISO 9454-1 (also known as DIN EN 29454-1).
This standard specifies each flux by a four-character code: flux type, base, activator, and form. The form is often omitted.
Therefore, 1.1.2 means rosin flux with halides. | 0 | Metallurgy |
Most class III adenylyl cyclases are transmembrane proteins with 12 transmembrane segments. The protein is organized with 6 transmembrane segments, then the C1 cytoplasmic domain, then another 6 membrane segments, and then a second cytoplasmic domain called C2. The important parts for function are the N-terminus and the C1 and C2 regions. The C1a and C2a subdomains are homologous and form an intramolecular dimer that forms the active site. In Mycobacterium tuberculosis and many other bacterial cases, the AC-III polypeptide is only half as long, comprising one 6-transmembrane domain followed by a cytoplasmic domain, but two of these form a functional homodimer that resembles the mammalian architecture with two active sites. In non-animal class III ACs, the catalytic cytoplasmic domain is seen associated with other (not necessarily transmembrane) domains.
Class III adenylyl cyclase domains can be further divided into four subfamilies, termed class IIIa through IIId. Animal membrane-bound ACs belong to class IIIa. | 1 | Gene expression + Signal Transduction |
A wide variety of algorithms have been developed to facilitate detection of promoters in genomic sequence, and promoter prediction is a common element of many gene prediction methods. A promoter region is located before the -35 and -10 Consensus sequences. The closer the promoter region is to the consensus sequences the more often transcription of that gene will take place. There is not a set pattern for promoter regions as there are for consensus sequences. | 1 | Gene expression + Signal Transduction |
It was established by the decree of Peter the Great to process the local copper deposits. The Polevskoy Plant was named after the local river Polevaya. The plant became the basis for the settlement which later grew into the town of Polevskoy.
The place for a new plant was chosen by Vasily Tatishchev. Georg Wilhelm de Gennin was in charge of the construction. The Plant became active in 1724. The copper was branded with the symbol of the Roman goddess Venus. The Venus symbol (♀), which represents copper as a chemical element, is now displayed in the Polevskoy town coat of arms.
In 1757 the Polevskoy Plant was purchased by the Ural merchant Alexei Turchaninov along with the Seversky Pipe Plant. Along with the Seversky and Sysertsky Plants, the Polevskoy Plant represented the Sysert Mining District. It was extremely profitable. Turchaninov's descendants managed the plant til 1912. For a long time the main ore supplier for the plant was the Gumyoshevsky mine, called "The Copper Mountain" by the local populace. However in the 19th century the Gumyoshevsky mine was exhausted. After it was shut down in 1870, the Polevskoy Copper Smelting Plant was reorganized to the iron plant. In this capacity the plant stayed active until 1923, but then shut down due to the lack of prospects. | 0 | Metallurgy |
As hormones are defined functionally, not structurally, they may have diverse chemical structures. Hormones occur in multicellular organisms (plants, animals, fungi, brown algae, and red algae). These compounds occur also in unicellular organisms, and may act as signaling molecules however there is no agreement that these molecules can be called hormones. | 1 | Gene expression + Signal Transduction |
mRNA binding allows repression of protein translation through direct blocking, degradation or cleavage of mRNA. Certain mRNA binding mechanisms have high specificity, which can act as a form of the intrinsic immune response during certain viral infections. Certain segmented RNA viruses can also regulate viral gene expression through RNA binding of another genome segment, however, the details of this mechanism are still unclear.
Specific examples include:
* RNA binding protein
* siRNA
* miRNA
* piRNA | 1 | Gene expression + Signal Transduction |
In metallurgy, materials science and structural geology, subgrain rotation recrystallization is recognized as an important mechanism for dynamic recrystallisation. It involves the rotation of initially low-angle sub-grain boundaries until the mismatch between the crystal lattices across the boundary is sufficient for them to be regarded as grain boundaries. This mechanism has been recognized in many minerals (including quartz, calcite, olivine, pyroxenes, micas, feldspars, halite, garnets and zircons) and in metals (various magnesium, aluminium and nickel alloys). | 0 | Metallurgy |
Growth factor and clotting factors are paracrine signaling agents. The local action of growth factor signaling plays an especially important role in the development of tissues. Also, retinoic acid, the active form of vitamin A, functions in a paracrine fashion to regulate gene expression during embryonic development in higher animals.
In insects, Allatostatin controls growth through paracrine action on the corpora allata.
In mature organisms, paracrine signaling is involved in responses to allergens, tissue repair, the formation of scar tissue, and blood clotting. Histamine is a paracrine that is released by immune cells in the bronchial tree. Histamine causes the smooth muscle cells of the bronchi to constrict, narrowing the airways. | 1 | Gene expression + Signal Transduction |
The first known use of metals in the Southern Levant is during the Chalcolithic period (end of 5th–most of the 4th millennium BCE). More than 500 metal objects were found, mainly in hoards, burials, and habitation
remains. Most of the metals originate from sites in the southern part of Israel and Jordan; very rarely do they occur beyond the center of Israel and north of Wadi Qana. The metal findings from this period were separated into three groups; most of them belong to the following first two groups:
Prestige/cult-elaborated and complex-shaped objects made of copper (Cu) alloyed (a deliberate
choice of complex minerals that could be reduced to a mixture of metals with specific recognizable
and desirable properties, totally different from unalloyed copper) with distinct amounts of antimony
(Sb) or nickel (Ni) and arsenic (As). They were cast using a “lost wax” technique into single closed clay moulds and then polished into their final shining gray or gold-like colors depending on the amount of antimony or nickel and arsenic in the copper. The Nahal Mishmar hoard was the biggest hoard (416 metal objects comprising mainly artistically complex-shaped objects), found hidden in a cave by Nahal Mishmar, Judean Desert, Israel.
They were wrapped in a straw mat (e.g., Shalev; Tadmor). Carbon-14 dating of the reed mat in which the objects were wrapped suggests that it dates to at least 3500 B.C.
The origin of the complex source material for the production of these objects is currently unknown. The nearest suitable ore is in Trans-Caucasus and Azerbaijan — more than 1500 km from the finding sites of the objects. Several clay and stone cores and clay
mould remains were petrographically analyzed and the results point to a possible local
production in the area of the Judean Desert, within the metals distribution zone in Israel, which is concentrated mainly in the southern part of the country: between Giv’at Oranit and Wadi Qana (east of
modern Tel Aviv) in the north and the Be’er Sheva valley sites in the south. Currently, no production
remains or production sites of these prestige/cult objects were found.
Unalloyed copper tools comprising mainly relatively thick- and short-bladed objects (axes, adzes,
and chisels) and points (awls and/or drills) made from a smelted copper ore, cast into an open mould and then hammered and annealed into their final shape. The copper tools were produced in the Chalcolithic villages on the banks of the Be’er Sheva valley where slag fragments, clay crucibles, some possible furnace lining pieces, copper prills, and amorphous lumps were found, in addition to high-grade carbonated copper ore (cuprite). The ore was collected and selected in the area of Feinan in Trans-Jordan and transported to northern Negev villages some 150 km to the north, to be smelted for the local production of these copper objects.
A third group of eight gold (Au) and electrum (Au + up to 30% Ag) solid rings was found in Wadi Qanah cave.
This unique find, with no dated parallels, is attributed by the excavators to the Chalcolithic period based on local stratigraphic and geological evidence and 14C dating of ground samples from the vicinity of the finds in the cave. Surface analyses of these objects revealed a surface
gold enrichment caused by the depletion of silver and the copper traces. This effect could be caused naturally by deposition but could have been achieved intentionally at the time of production in
order to achieve a yellow color for the electrum rings rich in silver, as well. During the Chalcolithic
(copper and stone) era at least two, if not three distinct industries of different metals were operating
and their products were found in the Southern Levant. | 0 | Metallurgy |
NASA used additive manufacturing to synthesize an alloy they termed GRX-810, which survived temperatures over . The alloy also featured improved strength, malleability, and durability. The printer dispersed oxide particles uniformly throughout the metal matrix. The alloy was identified using 30 simulations of thermodynamic modeling. | 0 | Metallurgy |
The deepest gold mines of the Ancient world were found in the Maski region in Karnataka. There were ancient silver mines in northwest India. Dated to the middle of the 1st millennium BCE. gold and silver were also used for making utensils for the royal family and nobilities.the royal family wore costly fabrics that were made from gold and silver thin fibres embroidered or woven into fabrics or dress. | 0 | Metallurgy |
Calcineurin along with NFAT, may improve the function of diabetics' pancreatic beta cells. Thus tacrolimus contributes to the frequent development of new diabetes following renal transplantation.
Calcineurin/NFAT signaling is required for perinatal lung maturation and function. | 1 | Gene expression + Signal Transduction |
Ferrous metallurgy is the metallurgy of iron and its alloys. The earliest surviving prehistoric iron artifacts, from the 4th millennium BC in Egypt, were made from meteoritic iron-nickel. It is not known when or where the smelting of iron from ores began, but by the end of the 2nd millennium BC iron was being produced from iron ores in the region from Greece to India, and sub-Saharan Africa. The use of wrought iron (worked iron) was known by the 1st millennium BC, and its spread defined the Iron Age. During the medieval period, smiths in Europe found a way of producing wrought iron from cast iron, in this context known as pig iron, using finery forges. All these processes required charcoal as fuel.
By the 4th century BC southern India had started exporting wootz steel, with a carbon content between pig iron and wrought iron, to ancient China, Africa, the Middle East, and Europe. Archaeological evidence of cast iron appears in 5th-century BC China. New methods of producing it by carburizing bars of iron in the cementation process were devised in the 17th century. During the Industrial Revolution, new methods of producing bar iron by substituting coke for charcoal emerged, and these were later applied to produce steel, ushering in a new era of greatly increased use of iron and steel that some contemporaries described as a new "Iron Age".
In the late 1850s Henry Bessemer invented a new steelmaking process which involved blowing air through molten pig-iron to burn off carbon, and so producing mild steel. This and other 19th-century and later steel-making processes have displaced wrought iron. Today, wrought iron is no longer produced on a commercial scale, having been displaced by the functionally equivalent mild or low-carbon steel. | 0 | Metallurgy |
Prehistoric links between Mesoamerica and the Andes have been suggested on several occasions. Early Mesoamerican and Ecuadorian pottery style show some similarities, both in technique and motifs. Likewise, similarities in early burial styles (so-called "shaft tombs") present in Ecuador and western Mesoamerica have been pointed out. Even the origins of the Purépecha people in Michoacán have been suggested as lying in South America. However, none of these proposals are widely accepted by specialists. More widely accepted is the influence of South American metallurgy on Mesoamerica.
South American metallurgy itself can be divided into two traditions: one in Peru, southern Ecuador, and Bolivia, which used copper, tin, silver, gold, and arsenic in various alloys with a variety of uses; and a second in Colombia and southern Central America, the so-called Intermediate Area, which relied on gold and copper for largely artistic rather than utilitarian purposes. The metallurgical tradition of western Mesoamerica, though geographically closer to the Intermediate Zone, is much closer in form and function to the southern Ecuadorian tradition. The form and method of creating interlocking metal rings is identical in the two traditions, and even their archaeological context (placed around the cranium in burials) is remarkably similar. Fish-hooks, needles, and tweezers, also appear in both traditions. However, the wax-casting tradition of the Intermediate Area, which spread to other parts of Mesoamerica, also proved influential in the western Mesoamerican context, such as in the creation of copper-gold alloy bells. | 0 | Metallurgy |
Although traditionally thought to form at compositions XYZ and XYZ, studies published after 2015 have discovered and reliably predicted Heusler compounds with atypical compositions such as XYZ and XYZ. Besides these ternary compositions, quaternary Heusler compositions called the double Half-Heusler XYYZ (e.g. TiFeNiSb) and triple Half-Heusler XXYZ (for e.g. MgVNiSb) have also been discovered. These "off-stoichiometric" (that is, differing from the well-known XYZ and XYZ compositions) Heuslers are mostly semiconductors in the low temperature T = 0 K limit. The stable compositions and corresponding electrical properties for these compounds can be quite sensitive to temperature and their order-disorder transition temperatures often occur below room-temperatures. Large amounts of defects at the atomic scale in off-stoichiometric Heuslers helps them achieve very low thermal conductivities and make them favorable for thermoelectric applications. The XYZ semiconducting composition is stabilized by the transition metal X playing a dual role (electron donor as well as acceptor) in the structure. | 0 | Metallurgy |
WECs are sub-surface white cracks networks within local microstructural changes that are characterised by a changed microstructure known as white etching area (WEA). The term "white etching" refers to the white appearance of the altered microstructure of a polished and etched steel sample in the affected areas. The WEA is formed by amorphisation (phase transformation) of the martensitic microstructure due to friction at the crack faces during over-rolling, and these areas appear white under an optical microscope due to their low-etching response to the etchant. The microstructure of WECs consists of ultra-fine, nano-crystalline, carbide-free ferrite, or ferrite with a very fine distribution of carbide particles that exhibits a high degree of crystallographic misorientation.
WEC propagation is mostly transgranular and does not follow a certain cleavage plane.
Researchers observed three distinct types of microstructural alterations near the generated cracks: uniform white etching areas (WEAs), thin elongated regions of dark etching areas (DEA), and mixed regions comprising both light and dark etching areas with some misshaped carbides. During repeated stress cycles, the position of the crack constantly shifts, leaving behind an area of intense plastic deformation composed of ferritic, martensite, austenite (due to austenitization) and carbides. nano-grains, i.e., WEAs. The microscopic displacement of the crack plane in a single stress cycle accumulates to form micron-sized WEAs during repeated stress cycles. After the initial development of a fatigue crack around inclusions, the faces of the crack rub against each other during cycles of compressive stress. This results in the creation of WEAs through localised intense plastic deformation. It also causes partial bonding of the opposing crack faces and material transfer between them. Consequently, the WEC reopens at a slightly different location compared to its previous position during the release of stress.
Furthermore, it has been acknowledged that WEA is one of the phases that arise from different processes and is generally observed as a result of a phase transformation in rolling contact fatigue. WEA is harder than the matrix and . Additionally, WECs are caused by stresses higher than anticipated and occur due to bearing rolling contact fatigue as well as accelerated rolling contact fatigue.
WECs in bearings are accompanied with a white etching matter (WEM). WEM forms asymmetrically along WECs. There is no significant microstructural differences between the untransformed material adjacent to cracking and the parent material although WEM exhibits variable carbon content and increased hardness compared to the parent material. A study in 2019 suggests that WEM may initiate ahead of the crack, challenging the conventional crack-rubbing mechanism. | 0 | Metallurgy |
A bacterial initiation factor (IF) is a protein that stabilizes the initiation complex for polypeptide translation.
Translation initiation is essential to protein synthesis and regulates mRNA translation fidelity and efficiency in bacteria. The 30S ribosomal subunit, initiator tRNA, and mRNA form an initiation complex for elongation. This complex process requires three essential protein factors in bacteria – IF1, IF2, and IF3. These factors bind to the 30S subunit and promote correct initiation codon selection on the mRNA. IF1, the smallest factor at 8.2 kDa, blocks elongator tRNA binding at the A-site. IF2 is the major component that transports initiator tRNA to the P-site. IF3 checks P-site codon-anticodon pairing and rejects incorrect initiation complexes.
The orderly mechanism of initiation starts with IF3 attaching to the 30S subunit and changing its shape. IF1 joins next, followed by mRNA binding, and starts codon-P-site interaction. IF2 enters with the initiator tRNA and places it on the start codon. GTP hydrolysis by IF2 releases it and IF3, enabling 50S subunit joining. The coordinated binding and activities of IF1, IF2, and IF3 are essential for the rapid and precise translation initiation in bacteria. They facilitate start codon selection and assemble an active, protein-synthesis-ready 70S ribosome. | 1 | Gene expression + Signal Transduction |
Değirmentepe or Değirmentepe Hüyük is an archaeological site which is located at 50 km north of the river Euphrates and at 24 km in the northeast of Malatya province in eastern Anatolia. It is now submerged in the reservoir area of the Karakaya and Atatürk dams. Rescue excavations were undertaken in under the supervision of Ufuk Esin of Istanbul University and interrupted in by flooding of the dams.
Four archaeological layers whose dates are determined by techniques such as C14 and traces of fusion have been discovered in this mound:
# Middle Ages (late Roman-Byzantine period)
# Iron Age (1000 BC)
# Bronze Age ancient I (Karaz or Khirbet Kerak culture, end of 4th millennium-beginning of 3rd millennium BCE)
# Chalcolithic Age (Ubaid period, second half of Vth millennium BCE.)
The Chalcolithic Değirmentepe level of Ubaid-4 of the second half of the Vth millennium BCE, of which the sites of Tülintepe, Seyh Hüyük and Kurban Hüyük are contemporary, contain skeletons of adolescents with skull deformed. The remains of this cultural phase belonging to the Chalcolithic are relatively well preserved. However, serious damage caused by occasional flooding of the Euphrates did occur, especially on architectural structures and the cemetery. Cranial deformities are not observed on human remains discovered and identified in Iron Age periods and medieval levels from Değrentepe.
The Chalcolithic period of this ancient village is characterized by rectangular mud brick houses that communicate with each other. We see the appearance of domestic animals such as dogs, sheeps, goats, pigs and Bovinae than at the beginning of the Chalcolithic. barley, wheat, oats, and peas were the most commonly cultivated plants.
Many potteries characteristic of Ubaid culture have been found at the site. Archaeologists have discovered 450 sealings there which indicate intensive commercial activities, and production management. | 0 | Metallurgy |
Iron smelting was unknown in pre-Columbian America.
Excavations at LAnse aux Meadows, Newfoundland, have found considerable evidence for the processing of bog iron and the production of iron in a bloomery by the Norse. The cluster of Viking Age (–1022 AD) at LAnse aux Meadows are situated on a raised marine terrace, between a sedge peat bog and the ocean. Estimates from the smaller amount of slag recovered archaeologically suggest 15 kg of slag was produced during what appears to have been a single smelting attempt. By comparing the iron content of the primary bog iron ore found in the purpose built furnace hut with the iron remaining in that slag, an estimated 3 kg iron bloom was produced. At a yield of at best 20% from what is a good iron rich ore, this suggests the workers processing the ore had not been particularly skilled. This supports the idea that iron processing knowledge was widespread and not restricted to major centers of trade and commerce. Archaeologists also found 98 nail, and importantly, ship rivet fragments, at the site as well as considerable evidence for woodworking – which points to boat or possibly ship repairs being undertaken at the site. (An important consideration remains that a potential 3 kg raw bloom most certainly does not make enough refined bar to manufacture the 3 kg of recovered nails and rivets.)
In the Spanish colonization of the Americas, bloomeries or "Catalan forges" were part of "self-sufficiency" at some of the missions, , and . As part of the Franciscan Spanish missions in Alta California, the "Catalan forges" at Mission San Juan Capistrano from the 1790s are the oldest existing facilities of their kind in the present day state of California. The bloomeries sign proclaims the site as being "part of Orange Countys first industrial complex".
The archaeology at Jamestown Virginia (circa 1610–1615) had recovered the remains of a simple short-shaft bloomery furnace, likely intended as yet another "resource test" like the one in Vinland much earlier. The English settlers of the Thirteen Colonies were prevented by law from manufacture; for a time, the British sought to situate most of the skilled artisanry at domestic locations. In fact, this was one of the problems that led to the revolution. The Falling Creek Ironworks was the first in the United States. The Neabsco Iron Works is an example of the early Virginian effort to form a workable American industry.
The earliest iron forge in colonial Pennsylvania was Thomas Rutter's bloomery near Pottstown, founded in 1716. In the Adirondacks, New York, new bloomeries using the hot blast technique were built in the 19th century. | 0 | Metallurgy |
The fraction of tailings to ore can range from 90 to 98% for some copper ores to 20–50% of the other (less valuable) minerals. The rejected minerals and rocks liberated through mining and processing have the potential to damage the environment by releasing toxic metals (arsenic and mercury being two major culprits), by acid drainage (usually by microbial action on sulfide ores), or by damaging aquatic wildlife that rely on clear water (vs suspensions).
Tailings ponds can also be a source of acid drainage, leading to the need for permanent monitoring and treatment of water passing through the tailings dam; the cost of mine cleanup has typically been 10 times that of mining industry estimates when acid drainage was involved. | 0 | Metallurgy |
Recent work has investigated the role of enhancers in morphological changes in threespine stickleback fish. Sticklebacks exist in both marine and freshwater environments, but sticklebacks in many freshwater populations have completely lost their pelvic fins (appendages homologous to the posterior limb of tetrapods).<br> Pitx1 is a homeobox gene involved in posterior limb development in vertebrates. Preliminary genetic analyses indicated that changes in the expression of this gene were responsible for pelvic reduction in sticklebacks. Fish expressing only the freshwater allele of Pitx1 do not have pelvic spines, whereas fish expressing a marine allele retain pelvic spines. A more thorough characterization showed that a 500 base pair enhancer sequence is responsible for turning on Pitx1 expression in the posterior fin bud. This enhancer is located near a chromosomal fragile site—a sequence of DNA that is likely to be broken and thus more likely to be mutated as a result of imprecise DNA repair. This fragile site has caused repeated, independent losses of the enhancer responsible for driving Pitx1 expression in the pelvic spines in isolated freshwater population, and without this enhancer, freshwater fish fail to develop pelvic spines. | 1 | Gene expression + Signal Transduction |
In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication. | 1 | Gene expression + Signal Transduction |
The choice of metallic substrate is determined by the dimensional, mechanical and corrosion resistance properties required of the coated product in use. The most common metallic substrates that are organically coated are:
* Hot dip galvanised steel (HDG) which consists of a cold reduced steel substrate onto which a layer of zinc is coated via a hot dip process to impart enhanced corrosion properties onto the base steel.
* Galvanized mild steel (GMS) can be used as balustrade and handrail of staircase, pipe, etc.
* Other zinc-based alloys are coated onto steel and used as a substrate for coil coating, giving different properties. They give improved corrosion resistance in particular conditions.
* Electro-galvanised (EG) coated steel consists of a cold reduced substrate onto which a layer of zinc is coated by an electrolytic process.
* Cold reduced steel (CR) without any zinc coating
* Wrought aluminium alloys
* Many other substrates are organically coated: zinc/iron, stainless steel, tinplate, brass, zinc and copper. | 0 | Metallurgy |
C/EBP proteins interact with the CCAAT (cytosine-cytosine-adenosine-adenosine-thymidine) box motif, which is present in several gene promoters. They are characterized by a highly conserved basic-leucine zipper (bZIP) domain at the C-terminus. This domain is involved in dimerization and DNA binding, as are other transcription factors of the leucine zipper domain-containing family (c-Fos and c-jun). The bZIP domain structure of C/EBPs is composed of an α-helix that forms a "coiled coil" structure when it dimerizes. Members of the C/EBP family can form homodimers or heterodimers with other C/EBPs and with other transcription factors, which may or may not contain the leucine zipper domain. The dimerization is necessary to enable C/EBPs to bind specifically to DNA through a palindromic sequence in the major groove of the DNA. C/EBP proteins also contain activation domains at the N-terminus and regulatory domains.
These proteins are found in hepatocytes, adipocytes, hematopoietic cells, spleen, kidney, brain, and many other organs. C/EBP proteins are involved in different cellular responses, such as in the control of cellular proliferation, growth and differentiation, in metabolism, and in immunity. Nearly all the members of the C/EBP family can induce transcription through their activation domains by interacting with components of the basal transcription apparatus. (C/EBPγ is an exception that lacks a functional transcriptional activation domain.) Their expression is regulated at multiple levels, including through hormones, mitogens, cytokines, nutrients, and other factors.
This protein is expressed in the mammalian nervous system and plays a significant role in the development and function of nerve cells. C/EBPβ plays a role in neuronal differentiation, in learning, in memory processes, in glial and neuronal cell functions, and in neurotrophic factor expression. | 1 | Gene expression + Signal Transduction |
In materials science, critical resolved shear stress (CRSS) is the component of shear stress, resolved in the direction of slip, necessary to initiate slip in a grain. Resolved shear stress (RSS) is the shear component of an applied tensile or compressive stress resolved along a slip plane that is other than perpendicular or parallel to the stress axis. The RSS is related to the applied stress by a geometrical factor, , typically the Schmid factor:
where is the magnitude of the applied tensile stress, is the angle between the normal of the slip plane and the direction of the applied force, and is the angle between the slip direction and the direction of the applied force. The Schmid factor is most applicable to FCC single-crystal metals, but for polycrystal metals the Taylor factor has been shown to be more accurate. The CRSS is the value of resolved shear stress at which yielding of the grain occurs, marking the onset of plastic deformation. CRSS, therefore, is a material property and is not dependent on the applied load or grain orientation. The CRSS is related to the observed yield strength of the material by the maximum value of the Schmid factor:
CRSS is a constant for crystal families. Hexagonal close-packed crystals, for example, have three main families - basal, prismatic, and pyramidal - with different values for the critical resolved shear stress. | 0 | Metallurgy |
In anti-tank warfare, spalling through mechanical stress is an intended effect of high-explosive squash head (HESH) anti-tank shells and many other munitions, which may not be powerful enough to pierce the armour of a target. The relatively soft warhead, containing or made of plastic explosive, flattens against the armour plating on tanks and other armoured fighting vehicles (AFVs) and explodes, creating a shock wave that travels through the armour as a compression wave and is reflected at the free surface as a tensile wave breaking (tensile stress/strain fracture) the metal on the inside. The resulting spall is dangerous to crew and equipment, and may result in a partial or complete disablement of a vehicle and/or its crew. Many AFVs are equipped with spall liners inside their armour for protection.
A kinetic energy penetrator, if it can defeat the armour, generally causes spalling within the target as well, which helps to destroy or disable the vehicle and its crew.
An early example of anti-tank weapon intentionally designed to cause spallation instead of penetration is the wz. 35 anti-tank rifle. | 0 | Metallurgy |
Direct reduction processes can be divided roughly into two categories: gas-based and coal-based. In both cases, the objective of the process is to remove the oxygen contained in various forms of iron ore (sized ore, concentrates, pellets, mill scale, furnace dust, etc.) in order to convert the ore to metallic iron, without melting it (below ).
The direct reduction process is comparatively energy efficient. Steel made using DRI requires significantly less fuel, in that a traditional blast furnace is not needed. DRI is most commonly made into steel using electric arc furnaces to take advantage of the heat produced by the DRI product. | 0 | Metallurgy |
The Blepharisma nuclear code (translation table 15) is a genetic code found in the nuclei of Blepharisma. | 1 | Gene expression + Signal Transduction |
The glycoprotein consists of a homodimer of 180 kDA stabilized by intermolecular disulfide bonds. It has a large extracellular domain of about 561 amino acids, a hydrophobic transmembrane domain and a short cytoplasmic tail domain composed of 45 amino acids. The 260 amino acid region closest to the extracellular membrane is referred to as the ZP domain (or, more correctly, ZP module). The outermost extracellular region is termed as the orphan domain (or, more correctly, orphan region (OR)) and it is the part that binds ligands such as BMP-9.
There are two isoforms of endoglin created by alternative splicing: the long isoform (L-endoglin) and the short isoform (S-endoglin). However, the L-isoform is expressed to a greater extent than the S-isoform. A soluble form of endoglin can be produced by the proteolytic cleaving action of metalloproteinase MMP-14 in the extracellular domain near the membrane.
It has been found on endothelial cells in all tissues, activated macrophages, activated monocytes, lymphoblasts fibroblasts, and smooth muscle cells. Endoglin was first identified using monoclonal antibody (mAb) 44G4 but more mAbs against endoglin have been discovered, giving more ways to identify it in tissues.
It is suggested that endoglin has 5 potential N-linked glycosylation sites in the N-terminal domain (of which N102 was experimentally observed in the crystal structure of the orphan region ()) and an O-glycan domain near the membrane domain that is rich in Serine and Threonine. The cytoplasmic tail contains a PDZ-binding motif that allows it to bind to PDZ containing proteins and interact with them. It contains an Arginine-Glycine-Aspartic Acid (RGD) tripeptide sequence that enables cellular adhesion, through the binding of integrins or other RGD binding receptors that are present in the extracellular matrix (ECM). This RGD sequence on endoglin is the first RGD sequence identified on endothelial tissue.
X-ray crystallographic structures of human endoglin () and its complex with ligand BMP-9 () revealed that the orphan region of the protein (residues E26-S337) consists of two domains (OR1 and OR2, corresponding to residues E36-T46 + T200-C330 and residues S47-R199, respectively) with a new fold resulting from gene duplication and circular permutation. The ZP module (residues P338-G581), whose ZP-N and ZP-C moieties (residues T349-L443 and N444-S576, respectively) are closely packed against each other, mediates the homodimerization of endoglin by forming an intermolecular disulfide bond that involves cysteine 516. Together with a second intermolecular disulfide, involving cysteine 582, this generates a molecular clamp that secures the ligand via interaction of two copies of OR1 with the knuckle regions of homodimeric BMP-9. In addition to rationalizing a large number of HHT1 mutations, the crystal structure of endoglin shows that the epitope of anti-ENG monoclonal antibody TRC105 overlaps with the binding site for BMP-9. | 1 | Gene expression + Signal Transduction |
These adenylyl cyclases are toxins secreted by pathogenic bacteria such as Bacillus anthracis, Bordetella pertussis, Pseudomonas aeruginosa, and Vibrio vulnificus during infections. These bacteria also secrete proteins that enable the AC-II to enter host cells, where the exogenous AC activity undermines normal cellular processes. The genes for Class II ACs are known as cyaA, one of which is anthrax toxin. Several crystal structures are known for AC-II enzymes. | 1 | Gene expression + Signal Transduction |
Under the split gene theory, an exon is defined by an ORF. It requires a mechanism to recognize an ORF to have originated. As an ORF is defined by a contiguous coding sequence bounded by stop codons, these stop codon ends had to be recognized by the exon-intron gene recognition system. This system could have defined the exons by the presence of a stop codon at the ends of ORFs, which should be included within the ends of the introns and eliminated by the splicing process. Thus, the introns should contain a stop codon at their ends, which would be part of the splice junction sequences.
If this hypothesis was true, the split genes of today's living organisms should contain stop codons exactly at the ends of introns. When Senapathy tested this hypothesis in the splice junctions of eukaryotic genes, he found that the vast majority of splice junctions did contain a stop codon at the end of each intron, outside of the exons. In fact, these stop codons were found to form the “canonical” GT:AG splicing sequence, with the three stop codons occurring as part of the strong consensus signals. Thus, the basic split gene theory for the origin of introns and the split gene structure led to the understanding that the splice junctions originated from the stop codons.
Sequence data for only about 1,000 exon-intron junctions were available when Senapathy thought about this question. He took the data for 1,030 splice junction sequences (donors and acceptors) and counted the codons occurring at
each of the 7- base positions in the donor signal sequence [CAG:GTGAGT] and each of the possible 2-base positions in the acceptor signal [CAG:G] from the GenBank database. He found that the stop codons occurred at high frequency only at the 5th base position in the donor signal and the first base position in the acceptor signal. These positions are the* start of the intron (in fact, one base after the start) and at the end of the intron, as Senapathy had predicted. The codon counts at only these positions are shown. Even when the codons at these positions were not stop
codons, 70% of them began with the first two bases of the stop codons TA and TG [TAT = 75; TAC = 59; TGT = 70].
All three stop codons (TGA, TAA and TAG) were found after one base (G) at the start of introns. These stop codons are shown in the consensus canonical donor splice junction as AG:GT(A/G)GGT, wherein the TAA and TGA are the stop codons, and the additional TAG is also present at this position. Besides the codon CAG, only TAG, which is a stop codon, was found at the ends of introns. The canonical acceptor splice junction is shown as (C/T)AG:GT, in which TAG is the stop codon. These consensus sequences clearly show the presence of the stop codons at the ends of introns bordering the exons in all eukaryotic genes, thus providing a strong corroboration for the split gene theory. Nirenberg again stated that these observations fully supported the split gene theory for the origin of splice junction sequences from stop codons.
Soon after the discovery of introns by Philip Sharp and Richard Roberts, it became known that mutations within splice junctions could lead to diseases. Senapathy showed that mutations in the stop codon bases (canonical bases) caused more diseases than the mutations in non-canonical bases. | 1 | Gene expression + Signal Transduction |
Two groups of well-known mimicking molecules include halogenated furanones, which mimic AHL molecules, and synthetic Al peptides (AIPs), which mimic naturally occurring AIPs. These groups inhibit receptors from binding substrate or decrease the concentration of receptors in the cell. Furanones have also been found to act on AHL-dependant transcriptional activity, whereby the half life of the autoinducer-binding LuxR protein is significantly shortened. | 1 | Gene expression + Signal Transduction |
Casting processes simulation uses numerical methods to calculate cast component quality considering mold filling, solidification and cooling, and provides a quantitative prediction of casting mechanical properties, thermal stresses and distortion. Simulation accurately describes a cast component's quality up-front before production starts. The casting rigging can be designed with respect to the required component properties. This has benefits beyond a reduction in pre-production sampling, as the precise layout of the complete casting system also leads to energy, material, and tooling savings.
The software supports the user in component design, the determination of melting practice and casting methoding through to pattern and mold making, heat treatment, and finishing. This saves costs along the entire casting manufacturing route.
Casting process simulation was initially developed at universities starting from the early 70s, mainly in Europe and in the U.S., and is regarded as the most important innovation in casting technology over the last 50 years. Since the late 80s, commercial programs are available which make it possible for foundries to gain new insight into what is happening inside the mold or die during the casting process. | 0 | Metallurgy |
The carboxy-terminal domain is also the binding site of the cap-synthesizing and cap-binding complex. In eukaryotes, after transcription of the 5 end of an RNA transcript, the cap-synthesizing complex on the CTD will remove the gamma-phosphate from the 5-phosphate and attach a GMP, forming a 5,5-triphosphate linkage. The synthesizing complex falls off and the cap then binds to the cap-binding complex (CBC), which is bound to the CTD.
The 5'cap of eukaryotic RNA transcripts is important for binding of the mRNA transcript to the ribosome during translation, to the CTD of RNAP, and prevents RNA degradation. | 1 | Gene expression + Signal Transduction |
Zinc pest (from German Zinkpest "zinc plague"), also known as zinc rot and zamak rot, is a destructive, intercrystalline corrosion process of zinc alloys containing lead impurities. While impurities of the alloy are the primary cause of the problem, environmental conditions such as high humidity (greater than 65%) may accelerate the process.
It was first discovered to be a problem in 1923, and primarily affects die-cast zinc articles that were manufactured during the 1920s through 1950s. The New Jersey Zinc Company developed zamak alloys in 1929 using 99.99% pure zinc metal to avoid the problem, and articles made after 1960 are usually considered free of the risk of zinc pest since the use of purer materials and more controlled manufacturing conditions make zinc pest degradation unlikely.
Affected objects may show surface irregularities such as small cracks and fractures, blisters or pitting. Over time, the material slowly expands, cracking, buckling and warping in an irreversible process that makes the object exceedingly brittle and prone to fracture, and can eventually shatter the object, destroying it altogether. Due to the expansion process, attached normal material may also be damaged. The occurrence and severity of zinc pest in articles made of susceptible zinc alloys depends both on the concentration of lead impurities in the metal and on the storage conditions of the article in the ensuing decades. Zinc pest is dreaded by collectors of vintage die-cast model trains, toys, or radios, because rare or otherwise valuable items can inescapably be rendered worthless as the process of zinc pest destroys them. Because castings of the same object were usually made from various batches of metal over the production process, some examples of a given toy or model may survive today completely unaffected, while other identical examples may have completely disintegrated. It has also affected carburetors, hubcaps, door handles and automobile trim on cars of the 1920s and 1930s.
Since the 1940s, some model railroad hobbyists have claimed, with varying degrees of success, that a method of "pickling" zinc alloy parts by soaking them in vinegar or oxalic acid solution for several minutes before painting and assembling them could prevent or delay the effects of zinc pest.
Engine parts of older vehicles or airplanes, and military medals made of zinc alloys, may also be affected. In addition, the post-1982 copper-plated zinc Lincoln cents have been known to be affected.
Zinc pest is not related to tin pest, and is also different from a superficial white corrosion oxidation process ("Weissrost") that affects some zinc articles. | 0 | Metallurgy |
Metal sulfides (e.g., pyrite FeS, arsenopyrite FeAsS, chalcopyrite CuFeS) are normally processed by chemical oxidation either in aqueous media or at high temperatures. In fact, most base metals, e.g., aluminium, chromium, must be (electro)chemically reduced at high temperatures by which the process entails a high energy demand, and sometimes large volumes of aqueous waste is generated. In aqueous media chalcopyrite, for instance, is more difficult to dissolve chemically than covellite and chalcocite due to surface effects (formation of polysulfide species,). The presence of Cl ions has been suggested to alter the morphology of any sulfide surface formed, allowing the sulfide mineral to leach more easily by preventing passivation. DESs provide a high Cl ion concentration and low water content, whilst reducing the need for either high additional salt or acid concentrations, circumventing most oxide chemistry. Thus, the electrodissolution of sulfide minerals has demonstrated promising results in DES media in absence of passivation layers, with the release into the solution of metal ions which could be recovered from solution.
During extraction of copper from copper sulfide minerals with Ethaline, chalcocite (CuS) and covellite (CuS) produce a yellow solution, indicating that [CuCl] complex are formed. Meanwhile, in the solution formed from chalcopyrite, Cu and Cu species co-exist in solution due to the generation of reducing Fe species at the cathode. The best selective recovery of copper (>97 %) from chalcopyrite can be obtained with a mixed DES of 20 wt.% ChCl-oxalic acid and 80 wt.% Ethaline. | 0 | Metallurgy |
Recovery of metals from oxide matrixes is generally carried out using mineral acids. However, electrochemical dissolution of metal oxides in DES can allow to enhance the dissolution up to more than 10 000 times in pH neutral solutions.
Studies have shown that ionic oxides such as ZnO tend to have high solubility in ChCl:malonic acid, ChCl:urea and Ethaline, which can resemble the solubilities in aqueous acidic solutions, e.g., HCl. Covalent oxides such as TiO, however, exhibits almost no solubility. The electrochemical dissolution of metal oxides is strongly dependent on the proton activity from the HBD, i.e. capability of the protons to act as oxygen acceptors, and on the temperature. It has been reported that eutectic ionic fluids of lower pH-values, such as ChCl:oxalic acid and ChCl:lactic acid, allow a better solubility than that of higher pH (e.g., ChCl:acetic acid). Hence, different solubilities can be obtained by using, for instance, different carboxylic acids as HBD. | 0 | Metallurgy |
CK1ε and CK1δ are essential in the genetic transcription-translation (and post-translation) feedback loops that generate circadian rhythm in mammals.
The previously-characterized CK1ε isoform was first implicated as a clock gene when its Drosophila homolog, double-time (Doubletime (gene)), was discovered in 1998. Double-time is 86% identical to human CK1ε. Kloss et al and Price et al showed that mutations in double-time altered circadian rhythm. They found two DBT mutants that had abnormal free-running periods and one that was pupal-lethal but resulted in accumulations of hypophosphorylated PER protein. Since then, double-time's protein product DBT has been well characterized for its role in phosphorylating PER, the protein product of clock gene period in Drosophila, and its mammalian homologs appear to play a similar role.
In 2021, scientists reported the development of a light-responsive days-lasting modulator of circadian rhythms of tissues via Ck1 inhibition. Such modulators may be useful for chronobiology research and repair of organs that are "out of sync". | 1 | Gene expression + Signal Transduction |
Pioneer factors can also affect transcription and differentiation through the control of DNA methylation. Pioneer factors that bind to CpG islands and cytosine residues block access to methyltransferases. Many eukaryotic cells have CpG islands in their promoters that can be modified by methylation having adverse effects on their ability to control transcription. This phenomenon is also present in promoters without CpG islands where single cytosine residues are protected from methylation until further cell differentiation. An example is FoxD3 preventing methylation of a cytosine residue in Alb1 enhancer, acting as a place holder for FoxA1 later in hepatic as well as in CpG islands of genes in chronic lymphocytic leukemia. For stable control of methylation state the cytosine residues are covered during mitosis, unlike most other transcription factors, to prevent methylation. Studies have shown that during mitosis 15% of all interphase FoxA1 binding sites were bound. The protection of cytosine methylation can be quickly removed allowing for rapid induction when a signal is present. | 1 | Gene expression + Signal Transduction |
In mining, tailings or tails are the materials left over after the process of separating the valuable fraction from the uneconomic fraction (gangue) of an ore. Tailings are different from overburden, which is the waste rock or other material that overlies an ore or mineral body and is displaced during mining without being processed.
The extraction of minerals from ore can be done two ways: placer mining, which uses water and gravity to concentrate the valuable minerals, or hard rock mining, which pulverizes the rock containing the ore and then relies on chemical reactions to concentrate the sought-after material. In the latter, the extraction of minerals from ore requires comminution, i.e., grinding the ore into fine particles to facilitate extraction of the target element(s). Because of this comminution, tailings consist of a slurry of fine particles, ranging from the size of a grain of sand to a few micrometres. Mine tailings are usually produced from the mill in slurry form, which is a mixture of fine mineral particles and water.
Tailings are likely to be dangerous sources of toxic chemicals such as heavy metals, sulfides and radioactive content. These chemicals are especially dangerous when stored in water in ponds behind tailings dams. These ponds are also vulnerable to major breaches or leaks from the dams, causing environmental disasters, such as the Mount Polley disaster in British Columbia. Because of these and other environmental concerns such as groundwater leakage, toxic emissions and bird death, tailing piles and ponds have received more scrutiny, especially in first world countries, but the first UN-level standard for tailing management was only established 2020.
There are a wide range of methods for recovering economic value, containing or otherwise mitigating the impacts of tailings. However, internationally, these practices are poor, sometimes violating human rights. | 0 | Metallurgy |
Clinical and translational data suggest that sensitive tumor types, with adequate parameters and functional apoptosis pathways, might not need high doses of mTOR inhibitors to trigger apoptosis. In most cases, cancer cells might only be partially sensitive to mTOR inhibitors due to redundant signal transduction or lack of functional apoptosis signaling pathways. In situations like this, high doses of mTOR inhibitors might be required. In a recent study of patients with Renal cell carcinoma, resistance to Temsirolimus was associated with low levels of p-AKT and p-S6K1, that play the key role in mTOR activation. These data strongly suggests number of tumors with an activated PI3K/AKT/mTOR signaling pathway that does not respond to mTOR inhibitors. For future studies, it is recommended to exclude patients with low or negative p-AKT levels from trials with mTOR inhibitors.
Current data is insufficient to predict sensitivity of tumors to rapamycin. However, the existing data allows us to characterize tumors that might not respond to rapalogs. | 1 | Gene expression + Signal Transduction |
Reverberatory furnaces are long furnaces that can treat wet, dry, or roasted concentrate. Most of the reverberatory furnaces used in the latter years treated roasted concentrate because putting dry feed materials into the reverberatory furnace is more energy efficient, and because the elimination of some of the sulfur in the roaster results in higher matte grades.
The reverberatory furnace feed is added to the furnace through feed holes along the sides of the furnace, and the solid charge is melted. Additional silica is normally added to help form the slag. The furnace is fired with burners using pulverized coal, fuel oil or natural gas
Reverberatory furnaces can additionally be fed with molten slag from the later converting stage to recover the contained copper and other materials with a high copper content.
Because the reverberatory furnace bath is quiescent, very little oxidation of the feed occurs (and thus very little sulfur is eliminated from the concentrate). It is essentially a melting process. Consequently, wet-charged reverberatory furnaces have less copper in their matte product than calcine-charged furnaces, and they also have lower copper losses to slag. Gill quotes a copper in slag value of 0.23% for a wet-charged reverberatory furnace vs 0.37% for a calcine-charged furnace.
In the case of calcine-charged furnaces, a significant portion of the sulfur has been eliminated during the roasting stage, and the calcine consists of a mixture of copper and iron oxides and sulfides. The reverberatory furnace acts to allow these species to approach chemical equilibrium at the furnace operating temperature (approximately 1600 °C at the burner end of the furnace and about 1200 °C at the flue end; the matte is about 1100 °C and the slag is about 1195 °C). In this equilibration process, oxygen associated with copper compounds exchanges with sulfur associated with iron compounds, increasing the iron oxide content of the furnace, and the iron oxides interact with silica and other oxide materials to form the slag.
The main equilibration reaction is:
:CuO + FeS → CuS + FeO
The slag and the matte form distinct layers that can be removed from the furnace as separate streams. The slag layer is periodically allowed to flow through a hole in the wall of the furnace above the height of the matte layer. The matte is removed by draining it through a hole into ladles for it to be carried by crane to the converters. This draining process is known as tapping the furnace. The matte taphole is normally a hole through a water-cooled copper block that prevents erosion of the refractory bricks lining the furnace. When the removal of the matte or slag is complete, the hole is normally plugged with clay, which is removed when the furnace is ready to be tapped again.
Reverberatory furnaces were often used to treat molten converter slag to recover contained copper. This would be poured into the furnaces from ladles carried by cranes. However, the converter slag is high in magnetite and some of this magnetite would precipitate from the converter slag (due to its higher melting point), forming an accretion on the hearth of the reverberatory furnace and necessitating shut downs of the furnace to remove the accretion. This accretion formation limits the quantity of converter slag that can be treated in a reverberatory furnace.
While reverberatory furnaces have very low copper losses to slag, they are not very energy-efficient and the low concentrations of sulfur dioxide in their off-gases make its capture uneconomic. Consequently, smelter operators devoted a lot of money in the 1970s and 1980s to developing new, more efficient copper smelting processes. In addition, flash smelting technologies had been developed in earlier years and began to replace reverberatory furnaces. By 2002, 20 of the 30 reverberatory furnaces still operating in 1994 had been shut down. | 0 | Metallurgy |
Homeobox protein NANOG (hNanog) is a transcriptional factor that helps embryonic stem cells (ESCs) maintain pluripotency by suppressing cell determination factors. hNanog is encoded in humans by the NANOG gene. Several types of cancer are associated with NANOG. | 1 | Gene expression + Signal Transduction |
Anaerobic oxidation of iron and steel commonly finds place in oxygen-depleted environments, such as in permanently water-saturated soils, peat bogs or wetlands in which archaeological iron artefacts are often found.
Anaerobic oxidation of carbon steel of canisters and overpacks is also expected to occur in deep geological formations in which high-level radioactive waste and spent fuels should be ultimately disposed. Nowadays, in the frame of the corrosion studies related to HLW disposal, anaerobic corrosion of steel is receiving a renewed and continued attention. Indeed, it is essential to understand this process to guarantee the total containment of HLW waste in an engineered barrier during the first centuries or millennia when the radiotoxicity of the waste is high and when it emits a significant quantity of heat.
The question is also relevant for the corrosion of the reinforcement bars (rebars) in concrete (Aligizaki et al., 2000). This deals then with the service life of concrete structures, amongst others the near-surface vaults intended for hosting low-level radioactive waste. | 0 | Metallurgy |
RopB transcriptional regulator, also known as RopB/Rgg transcriptional regulator is a transcriptional regulator protein that regulates expression of the extracellularly secreted cysteine protease streptococcal pyrogenic exotoxin B (speB) [See Also: erythrogenic toxins] which is an important virulence factor of Streptococcus pyogenes and is responsible for the dissemination of a host of infectious diseases including strep throat, impetigo, streptococcal toxic shock syndrome, necrotizing fasciitis, and scarlet fever. Functional studies suggest that the ropB multigene regulon is responsible for not only global regulation of virulence but also a wide range of functions from stress response, metabolic function, and two-component signaling. Structural studies implicate ropB's regulatory action being reliant on a complex interaction involving quorum sensing with the leaderless peptide signal speB-inducing peptide (SIP) acting in conjunction with a pH sensitive histidine switch.
See Photo: | 1 | Gene expression + Signal Transduction |
Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the targeted removal or inactivation of a specific gene within an organism's genome. This can be done through a variety of methods, including homologous recombination, CRISPR-Cas9, and TALENs.
One of the main advantages of gene knockouts is that they allow researchers to study the function of a specific gene in vivo, and to understand the role of the gene in normal development and physiology as well as in the pathology of diseases. By studying the phenotype of the organism with the knocked out gene, researchers can gain insights into the biological processes that the gene is involved in.
There are two main types of gene knockouts: complete and conditional. A complete gene knockout permanently inactivates the gene, while a conditional gene knockout allows for the gene to be turned off and on at specific times or in specific tissues. Conditional knockouts are particularly useful for studying developmental processes and for understanding the role of a gene in specific cell types or tissues.
Gene knockouts have been widely used in many different organisms, including bacteria, yeast, fruit flies, zebrafish, and mice. In mice, gene knockouts are commonly used to study the function of specific genes in development, physiology, and cancer research.
The use of gene knockouts in mouse models has been particularly valuable in the study of human diseases. For example, gene knockouts in mice have been used to study the role of specific genes in cancer, neurological disorders, immune disorders, and metabolic disorders.
However, gene knockouts also have some limitations. For example, the loss of a single gene may not fully mimic the effects of a genetic disorder, and the knockouts may have unintended effects on other genes or pathways. Additionally, gene knockouts are not always a good model for human disease as the mouse genome is not identical to the human genome, and mouse physiology is different from human physiology.
The KO technique is essentially the opposite of a gene knock-in. Knocking out two genes simultaneously in an organism is known as a double knockout (DKO). Similarly the terms triple knockout (TKO) and quadruple knockouts (QKO) are used to describe three or four knocked out genes, respectively. However, one needs to distinguish between heterozygous and homozygous KOs. In the former, only one of two gene copies (alleles) is knocked out, in the latter both are knocked out. | 1 | Gene expression + Signal Transduction |
Freeze–thaw weathering is caused by moisture freezing inside cracks in rock. Upon freezing its volume expands, causing large forces which cracks spall off the outer surface. As this cycle repeats the outer surface repeatedly undergoes spalling, resulting in weathering.
Some stone and masonry surfaces used as building surfaces will absorb moisture at their surface. If exposed to severe freezing conditions, the surface may flake off due to the expansion of the water. This effect can also be seen in terracotta surfaces (even if glazed) if there is an entrance for water at the edges. | 0 | Metallurgy |
Spatiotemporal gene expression is the activation of genes within specific tissues of an organism at specific times during development. Gene activation patterns vary widely in complexity. Some are straightforward and static, such as the pattern of tubulin, which is expressed in all cells at all times in life. Some, on the other hand, are extraordinarily intricate and difficult to predict and model, with expression fluctuating wildly from minute to minute or from cell to cell. Spatiotemporal variation plays a key role in generating the diversity of cell types found in developed organisms; since the identity of a cell is specified by the collection of genes actively expressed within that cell, if gene expression was uniform spatially and temporally, there could be at most one kind of cell.
Consider the gene wingless, a member of the wnt family of genes. In the early embryonic development of the model organism Drosophila melanogaster, or fruit fly, wingless is expressed across almost the entire embryo in alternating stripes three cells separated. This pattern is lost by the time the organism develops into a larva, but wingless is still expressed in a variety of tissues such as the wing imaginal discs, patches of tissue that will develop into the adult wings. The spatiotemporal pattern of wingless gene expression is determined by a network of regulatory interactions consisting of the effects of many different genes such as even-skipped and Krüppel.
What causes spatial and temporal differences in the expression of a single gene? Because current expression patterns depend strictly on previous expression patterns, there is a regressive problem of explaining what caused the first differences in gene expression. The process by which uniform gene expression becomes spatially and temporally differential is known as symmetry breaking. For example, in the case of embryonic Drosophila development, the genes nanos and bicoid are asymmetrically expressed in the oocyte because maternal cells deposit messenger RNA (mRNA) for these genes in the poles of the egg before it is laid. | 1 | Gene expression + Signal Transduction |
The HMG proteins are subdivided into 3 superfamilies each containing a characteristic functional domain:
* HMGA – contains an AT-hook domain
** HMGA1
** HMGA2
* HMGB – contains a HMG-box domain
** HMGB1
** HMGB2
** HMGB3
** HMGB4
* HMGN – contains a nucleosomal binding domain
** HMGN1
** HMGN2
** HMGN3
** HMGN4
** HMGN5
Proteins containing any of these embedded in their sequence are known as HMG motif proteins.
HMG-box proteins are found in a variety of eukaryotic organisms.
They were originally isolated from mammalian cells, and named according to their electrophoretic mobility in polyacrylamide gels. | 1 | Gene expression + Signal Transduction |
Corrosion in Ballast Tanks is the deterioration process where the surface of a ballast tank progresses from microblistering, to hydroscaletric electration, and finally to cracking of the tank steel itself.
::“Effective corrosion control in segregated water ballast spaces is probably the single most important feature, next to the integrity of the initial design, in determining the ship’s effective life span and structural reliability,” said Alan Gavin, Germanischer Lloyd's Principal surveyor.
Throughout the years the merchant fleet has become increasingly aware of the importance of avoiding corrosion in ballast tanks. | 0 | Metallurgy |
Heavy chain contains similar gene segments such as VH, JH and CH, but also has another gene segment called D (diversity). Unlike the light chain multigene family, VDJ gene segments code for the variable region of the heavy chain. The rearrangement and reorganization of gene segments in this multigene family is more complex . The rearranging and joining of segments produced different end products because these are carried out by different RNA processes. The same reason is why the IgM and IgG are generates at the time. | 1 | Gene expression + Signal Transduction |
Chromatin remodeling plays a central role in the regulation of gene expression by providing the transcription machinery with dynamic access to an otherwise tightly packaged genome. Further, nucleosome movement by chromatin remodelers is essential to several important biological processes, including chromosome assembly and segregation, DNA replication and repair, embryonic development and pluripotency, and cell-cycle progression. Deregulation of chromatin remodeling causes loss of transcriptional regulation at these critical check-points required for proper cellular functions, and thus causes various disease syndromes, including cancer. | 1 | Gene expression + Signal Transduction |
Due to the biological complexity of gene expression, the considerations of experimental design that are discussed in the expression profiling article are of critical importance if statistically and biologically valid conclusions are to be drawn from the data.
There are three main elements to consider when designing a microarray experiment. First, replication of the biological samples is essential for drawing conclusions from the experiment. Second, technical replicates (e.g. two RNA samples obtained from each experimental unit) may help to quantitate precision. The biological replicates include independent RNA extractions. Technical replicates may be two aliquots of the same extraction. Third, spots of each cDNA clone or oligonucleotide are present as replicates (at least duplicates) on the microarray slide, to provide a measure of technical precision in each hybridization. It is critical that information about the sample preparation and handling is discussed, in order to help identify the independent units in the experiment and to avoid inflated estimates of statistical significance. | 1 | Gene expression + Signal Transduction |
DNA repair genes are frequently repressed in cancers due to hypermethylation of CpG islands within their promoters. In head and neck squamous cell carcinomas at least 15 DNA repair genes have frequently hypermethylated promoters; these genes are XRCC1, MLH3, PMS1, RAD51B, XRCC3, RAD54B, BRCA1, SHFM1, GEN1, FANCE, FAAP20, SPRTN, SETMAR, HUS1, and PER1. About seventeen types of cancer are frequently deficient in one or more DNA repair genes due to hypermethylation of their promoters. As summarized in one review article, promoter hypermethylation of the DNA repair gene MGMT occurs in 93% of bladder cancers, 88% of stomach cancers, 74% of thyroid cancers, 40%-90% of colorectal cancers and 50% of brain cancers. Promoter hypermethylation of LIG4 occurs in 82% of colorectal cancers. This review article also indicates promoter hypermethylation of NEIL1 occurs in 62% of head and neck cancers and in 42% of non-small-cell lung cancers; promoter hypermetylation of ATM occurs in 47% of non-small-cell lung cancers; promoter hypermethylation of MLH1 occurs in 48% of squamous cell carcinomas; and promoter hypermethylation of FANCB occurs in 46% of head and neck cancers.
On the other hand, the promoters of two genes, PARP1 and FEN1, were hypomethylated and these genes were over-expressed in numerous cancers. PARP1 and FEN1 are essential genes in the error-prone and mutagenic DNA repair pathway microhomology-mediated end joining. If this pathway is over-expressed, the excess mutations it causes can lead to cancer. PARP1 is over-expressed in tyrosine kinase-activated leukemias, in neuroblastoma, in testicular and other germ cell tumors, and in Ewing's sarcoma, FEN1 is over-expressed in the majority of cancers of the breast, prostate, stomach, neuroblastomas, pancreatic, and lung.
DNA damage appears to be the primary underlying cause of cancer. If accurate DNA repair is deficient, DNA damages tend to accumulate. Such excess DNA damage can increase mutational errors during DNA replication due to error-prone translesion synthesis. Excess DNA damage can also increase epigenetic alterations due to errors during DNA repair. Such mutations and epigenetic alterations can give rise to cancer (see malignant neoplasms). Thus, CpG island hyper/hypo-methylation in the promoters of DNA repair genes are likely central to progression to cancer. | 1 | Gene expression + Signal Transduction |
When stored in air, it forms a yellow potassium superoxide coating and may ignite. This superoxide reacts explosively with water and organics. NaK is not dense enough to sink in most hydrocarbons, but will sink in lighter mineral oil. It is unsafe to store in this manner if the superoxide has formed. A large explosion took place at the Oak Ridge Y-12 facility on December 8, 1999, when NaK cleaned up after an accidental spill and inappropriately treated with mineral oil was scratched with a metal tool. The liquid alloy also attacks PTFE ("Teflon"). | 0 | Metallurgy |
Signal peptides are extremely heterogeneous, many prokaryotic and eukaryotic ones are functionally interchangeable within or between species and all determine protein secretion efficiency. | 1 | Gene expression + Signal Transduction |
Atmospheric corrosion generally refers to general corrosion in a non-specific environment. Prevention of atmospheric corrosion is typically handled by use of materials selection and coatings specifications. The use of zinc coatings also known as galvanization on steel structures is a form of cathodic protection where the zinc acts as a sacrificial anode and also a form of coating. Small scratches are expected to occur in the galvanized coating over time. The zinc being more active in the galvanic series corrodes in preference to the underlying steel and the corrosion products fil the scratch preventing further corrosion. As long as the scratches are fine, condensation moisture should not corrode the underlying steel as long as both the zinc and steel are in contact. As long as there is moisture, the zinc corrodes and eventually disappears. Impressed current cathodic protection is also used. | 0 | Metallurgy |
The rust resistance of EPS-processed steel strip is superior to that of acid pickled steel strip primarily because acid pickling imposes a corrosion "penalty" on the steel which EPS processing does not. This penalty is a result of chemical reactions that occur after acid pickling and serve as a catalyst for oxidation. The primary pickling agent is hydrochloric acid (HCl). Although the steel strip is thoroughly rinsed with clean water after immersion in the HCl bath, some residual amount of chlorine (Cl) remains on the surface of the strip. Chlorine reacts very readily with oxygen to form chlorides, so the free Cl acts as something of a "magnet" for oxygen. This mechanism makes acid-pickled steel more prone to picking up oxygen, whereas there is no comparable mechanism at work with EPS mechanical pickling.
In addition to the free Cl, compounds known as "chloride salts" remain on the surface of acid pickled steel in trace amounts, even after rinsing. Chloride salts react rapidly with moisture and accelerate oxidation of iron on the steel's surface. To prevent oxidation of the iron in the acid pickled strip, a thin film of oil is applied to the surface to serve as a barrier between the free Cl, chloride salts and oxygen. No such protective barrier is needed for EPS-processed steel, as no free Cl or chloride salts are present.
However, an additive is used in the EPS slurry blast carrier liquid to reduce the "smut" that would otherwise remain on the surface and dull the appearance of EPS-processed strip. This additive contains a rust inhibitor, a residual amount of which remains on the surface even after rinsing. It is believed that the presence of the rust inhibitor adds to the overall EPS-processed strip's ability to resist rusting. The additive has been demonstrated to have no impact on paint performance. | 0 | Metallurgy |
There is varying impact on local corrosion noted from biofilms formed of diverse microbial communities. For instance, when isolating a sample of biofilm from a pipe within the first week of growth, the corrosion of the pipe accelerated, yet by the end of a month, the same biofilm began to act as a protective layer for the pipe. Variation between corrosion in similar environments might be attributed to the local bacterial communities. Biofilms further mediate corrosion by altering the electrochemical processes at the interface of the underlying substrate. | 0 | Metallurgy |
The inhabitants of Ban Na Di were casting bronze from to 200 AD, using the lost-wax technique to manufacture bangles. Bangles made by the lost-wax process are characteristic of northeast Thailand. Some of the bangles from Ban Na Di revealed a dark grey substance between the central clay core and the metal, which on analysis was identified as an unrefined form of insect wax. It is likely that decorative items, like bracelets and rings, were made by cire perdue at Non Nok Tha and Ban Chiang. There are technological and material parallels between northeast Thailand and Vietnam concerning the lost-wax technique. The sites exhibiting artifacts made by the lost-mould process in Vietnam, such as the Dong Son drums, come from the Dong Son, and Phung Nguyen cultures, such as one sickle and the figure of a seated individual from Go Mun (near Phung Nguyen, the Bac Bo Region), dating to the Go Mun phase (end of the General B period, up until the 7th century BC). | 0 | Metallurgy |
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-terminus (or occasionally nonclassically at the C-terminus or internally) of most newly synthesized proteins that are destined toward the secretory pathway.
These proteins include those that reside either inside certain organelles (the endoplasmic reticulum, Golgi or endosomes), secreted from the cell, or inserted into most cellular membranes. Although most type I membrane-bound proteins have signal peptides, most type II and multi-spanning membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which biochemically resembles a signal sequence except that it is not cleaved. They are a kind of target peptide. | 1 | Gene expression + Signal Transduction |
Vacuum arc remelting (VAR) is a secondary melting process for production of metal ingots with elevated chemical and mechanical homogeneity for highly demanding applications. The VAR process has revolutionized the specialty traditional metallurgical techniques industry, and has made possible tightly-controlled materials used in biomedical, aviation and aerospace. | 0 | Metallurgy |
The first commercial primary-lead ISASMELT furnace was installed at the Yunnan Chihong Zinc and Germanium Company Limited (YCZG) greenfield zinc and lead smelting complex at Qujing in Yunnan Province in China. This furnace was part of a plant consisting of the ISASMELT furnace and a blast furnace specially designed to treat high-lead ISASMELT slag. The ISASMELT furnace was designed to produce both the slag and lead bullion, with about 40% of the lead in the concentrate being converted to lead bullion in the ISASMELT furnace.
The ISASMELT–blast furnace combination was designed to treat 160,000 t/y of lead concentrate.
The second commercial primary-lead ISASMELT furnace was commissioned at Kazzinc's smelting complex at Ust-Kamenogorsk in Kazakhstan in 2012. It is designed to treat 300,000 t/y of lead concentrate, again using an ISASMELT–blast furnace combination.
YCZG is constructing another lead ISASMELT at a new greenfield smelter in Huize in China, and this is due to be commissioned in 2013.
In June 2017, Glencore announced that Nyrstar NV had acquired an Isasmelt licence for its new Ausmelt furnace in Port Pirie. As part of the agreement, Nyrstar engaged training and ramp-up support services for the Ausmelt furnace and blast furnace by personnel from Glencore's Kazzinc operations in Kazakhstan. This involved training Nyrstar personnel at Ust-Kamenogorsk operations and site support by Kazzinc personnel during the commissioning and ramp-up stages of the Ausmelt plant. | 0 | Metallurgy |
The BASIC assembly strategy was developed in 2015 and sought to address the limitations of previous assembly techniques, incorporating six key concepts from them: standard reusable parts; single-tier format (all parts are in the same format and are assembled using the same process); idempotent cloning; parallel (multipart) DNA assembly; size independence; automatability.
DNA parts and linker design
The DNA parts are designed and cloned into storage plasmids, with the part flanked by an integrated prefix (iP) and an integrated suffix (iS) sequence. The iP and iS sequences contain inward facing BsaI restriction sites, which contain overhangs complementary to the BASIC linkers. Like in MODAL, the 7 standard linkers used in BASIC were designed with the R2oDNA Designer software, and screened to ensure that they do not contain sequences with homology to chassis genomes, and that they do not contain unwanted sequences like secondary structure sequences, restriction sites or ribosomal binding sites. Each linker sequence is split into two halves, each with a 4 bp overhang complementary to the BsaI restriction site, a 12 bp double stranded sequence and sharing a 21 bp overlap sequence with the other half. The half that is will bind to the upstream DNA part is known as the suffix linker part (e.g. L1S) and the half that binds to the downstream part is known as the prefix linker part (e.g. L1P). These linkers form the basis of assembling the DNA parts together.
Besides directing the order of assembly, the standard BASIC linkers can also be modified to carry out other functions. To allow for idempotent assembly, linkers were also designed with additional methylated iP and iS sequences inserted to protect them from being recognised by BsaI. This methylation is lost following transformation and in vivo plasmid replication, and the plasmids can be extracted, purified, and used for further reactions.
Because the linker sequence are relatively long (45bp for a standard linker), there is an opportunity to incorporate functional DNA sequences to reduce the number of DNA parts needed during assembly. The BASIC assembly standard provides several linkers embedded with RBS of different strengths. Similarly to facilitate the construction of fusion proteins containing multiple protein domains, several fusion linkers were also designed to allow for full read-through of the DNA construct. These fusion linkers code for a 15 amino acid glycine and serine polypeptide, which is an ideal linker peptide for fusion proteins with multiple domains.
Assembly
There are three main steps in the assembly of the final construct.
# First, the DNA parts are excised from the storage plasmid, giving a DNA fragment with BsaI overhangs on the 3 and 5 end.
# Next, each linker part is attached to its respective DNA part by incubating with T4 DNA ligase. Each DNA part will have a suffix and prefix linker part from two different linkers to direct the order of assembly. For example, the first part in the sequence will have L1P and L2S, while the second part will have L2P and L3S attached. The linker parts can be changed to change the sequence of assembly.
# Finally, the parts with the attached linkers are assembled into a plasmid by incubating at 50 °C. The 21 bp overhangs of the P and S linkers anneal and the final construct can be transformed into bacteria cells for cloning. The single stranded nicks are repaired in vivo following transformation, producing a stable final construct cloned into plasmids. | 1 | Gene expression + Signal Transduction |
Although an attenuation mechanism that involves translation while transcription is ongoing, like to the mechanism for the trp operon (and some other amino acid biosynthetic operons), would not work in eukaryotes, there is evidence for attenuation in Eukaryotes. Research conducted on microRNA processing provides evidence of eukaryotic attenuation; after co-transcriptional endonucleolitical cleavage by Drosha 5->3 exonuclease XRN2 may terminate further transcription by torpedo mechanism. | 1 | Gene expression + Signal Transduction |
Incidental decarburization can be detrimental to surface properties in products (where carbon content is desirable) when done during heat treatment or after rolling or forging, because the material is only affected to a certain depth according to the temperature and duration of heating. This can be prevented by using an inert or reduced-pressure atmosphere, applying resistive heating for a short duration, by limiting the time that the material is submitted to a high heat, as it is done in a walking-beam furnace, or through restorative carburization, which uses a hydrocarbon atmosphere to transfer carbon into the surface of the material during annealing. The decarburized surface of the material can also be removed by grinding. | 0 | Metallurgy |
The Lamberhurst Foundry is believed to have been the maker in 1710–14 of some of the earliest cast-iron railings produced in England, which they made for St Paul's Cathedral, despite the objections of Christopher Wren, who did not want a fence around the Cathedral at all, and said that if there had to be one it should be of wrought rather than cast iron. The railings surrounded the cathedral, including seven gates. It weighed two hundred tons and cost six pence a pound. The total cost was £11,202. No further railings are known to have been cast in the Weald. Other early uses of cast iron railings were at Cambridge Senate House and at St Martin-in-the-Fields, London. | 0 | Metallurgy |
Changes in promoter sequences are critical in evolution as indicated by the relatively stable number of genes in many lineages. For instance, most vertebrates have roughly the same number of protein-coding genes (about 20,000) which are often highly conserved in sequence, hence much of evolutionary change must come from changes in gene expression. | 1 | Gene expression + Signal Transduction |
Since the ERK signaling pathway is involved in both physiological and pathological cell proliferation, it is natural that ERK1/2 inhibitors would represent a desirable class of antineoplastic agents. Indeed, many of the proto-oncogenic "driver" mutations are tied to ERK1/2 signaling, such as constitutively active (mutant) receptor tyrosine kinases, Ras or Raf proteins. Although no MKK1/2 or ERK1/2 inhibitors were developed for clinical use, kinase inhibitors that also inhibit Raf kinases (e.g. Sorafenib) are successful antineoplastic agents against various types of cancer. MEK inhibitor cobimetinib has been investigated in pre-clinical lung cancer models in combination with inhibition of the PI3K pathway, where the two drugs lead to a synergistic response.
JNK kinases are implicated in the development of insulin resistance in obese individuals as well as neurotransmitter excitotoxicity after ischaemic conditions. Inhibition of JNK1 ameliorates insulin resistance in certain animal models. Mice that were genetically engineered to lack a functional JNK3 gene - the major isoform in brain – display enhanced ischemic tolerance and stroke recovery. Although small-molecule JNK inhibitors are under development, none of them proved to be effective in human tests yet. A peptide-based JNK inhibitor (AM-111, a retro-inverse D-motif peptide from JIP1, formerly known as XG-102) is also under clinical development for sensorineural hearing loss.
p38 was once believed to be a perfect target for anti-inflammatory drugs. Yet the failure of more than a dozen chemically different compounds in the clinical phase suggests that p38 kinases might be poor therapeutic targets in autoimmune diseases. Many of these compounds were found to be hepatotoxic to various degree and tolerance to the anti-inflammatory effect developed within weeks. An alternative approach is to evaluate the potential for targeting upstream MAPKs, such as ASK1. Studies in animal models of inflammatory arthritis have yielded promising results, and ASK1 has recently been found to be unique amongst the MAPKs in that it is inducible by inflammatory cytokines such as TNF-α. | 1 | Gene expression + Signal Transduction |
Biogenic sulfide corrosion is a bacterially mediated process of forming hydrogen sulfide gas and the subsequent conversion to sulfuric acid that attacks concrete and steel within wastewater environments. The hydrogen sulfide gas is biochemically oxidized in the presence of moisture to form sulfuric acid. The effect of sulfuric acid on concrete and steel surfaces exposed to severe wastewater environments can be devastating. In the USA alone, corrosion is causing sewer asset losses estimated at $14 billion per year. This cost is expected to increase as the aging infrastructure continues to fail. | 0 | Metallurgy |
The 3′-UTR often contains microRNA response elements (MREs), which are sequences to which miRNAs bind. miRNAs are short, non-coding RNA molecules capable of binding to mRNA transcripts and regulating their expression. One miRNA mechanism involves partial base pairing of the 5' seed sequence of an miRNA to an MRE within the 3′-UTR of an mRNA; this binding then causes translational repression. | 1 | Gene expression + Signal Transduction |
This gene contains a single nucleotide polymorphism that causes an amino acid substitution within the 11 of 12 ankyrin repeats of ANKK1 (Glu713Lys of 765 residues). This polymorphism, which is commonly referred to Taq1A, was previously believed to be located in the promoter region of the DRD2 gene, since the polymorphism is proximal to the DRD2 gene and can influence DRD2 receptor expression. It is now known to be located in the coding region of the ANKK1 gene which controls the synthesis of dopamine in the brain. The A1 allele is associated with increased activity of striatal L-amino acid decarboxylase. | 1 | Gene expression + Signal Transduction |
Over-activation of mTOR signaling significantly contributes to the initiation and development of tumors and mTOR activity was found to be deregulated in many types of cancer including breast, prostate, lung, melanoma, bladder, brain, and renal carcinomas. Reasons for constitutive activation are several. Among the most common are mutations in tumor suppressor PTEN gene. PTEN phosphatase negatively affects mTOR signalling through interfering with the effect of PI3K, an upstream effector of mTOR. Additionally, mTOR activity is deregulated in many cancers as a result of increased activity of PI3K or Akt. Similarly, overexpression of downstream mTOR effectors 4E-BP1, S6K1, S6K2 and eIF4E leads to poor cancer prognosis. Also, mutations in TSC proteins that inhibit the activity of mTOR may lead to a condition named tuberous sclerosis complex, which exhibits as benign lesions and increases the risk of renal cell carcinoma.
Increasing mTOR activity was shown to drive cell cycle progression and increase cell proliferation mainly due to its effect on protein synthesis. Moreover, active mTOR supports tumor growth also indirectly by inhibiting autophagy. Constitutively activated mTOR functions in supplying carcinoma cells with oxygen and nutrients by increasing the translation of HIF1A and supporting angiogenesis. mTOR also aids in another metabolic adaptation of cancerous cells to support their increased growth rate—activation of glycolytic metabolism. Akt2, a substrate of mTOR, specifically of mTORC2, upregulates expression of the glycolytic enzyme PKM2 thus contributing to the Warburg effect. | 1 | Gene expression + Signal Transduction |
The Sawmill is run by a D-3000 Cat diesel engine, Hawthorne Machinery in San Diego provided the cylinder liners. The Sawmill was re-assembled and improved following a donation from the Pederson Brothers who had operated it in the Big Bear area years ago. This is likely the only Sawmill that can be seen operating in San Diego County. | 0 | Metallurgy |
Electroforming is a metal forming process in which parts are fabricated through electrodeposition on a model, known in the industry as a mandrel. Conductive (metallic) mandrels are treated to create a mechanical parting layer, or are chemically passivated to limit electroform adhesion to the mandrel and thereby allow its subsequent separation. Non-conductive (glass, silicon, plastic) mandrels require the deposition of a conductive layer prior to electrodeposition. Such layers can be deposited chemically, or using vacuum deposition techniques (e.g., gold sputtering). The outer surface of the mandrel forms the inner surface of the form.
The process involves passing direct current through an electrolyte containing salts of the metal being electroformed. The anode is the solid metal being electroformed, and the cathode is the mandrel, onto which the electroform gets plated (deposited). The process continues until the required electroform thickness is achieved. The mandrel is then either separated intact, melted away, or chemically dissolved.
The surface of the finished part that was in intimate contact with the mandrel is replicated in fine detail with respect to the original, and is not subject to the shrinkage that would normally be experienced in a foundry cast metal object, or the tool marks of a milled part. The solution side of the part is less well defined, and that loss of definition increases with thickness of the deposit. In extreme cases, where a thickness of several millimetres is required, there is preferential build-up of material on sharp outside edges and corners. This tendency can be reduced by shielding, or a process known as periodic reverse, where the electroforming current is reversed for short periods and the excess is preferentially dissolved electrochemically. The finished form can either be the finished part, or can be used in a subsequent process to produce a positive of the original mandrel shape, such as with vinyl records or CD and DVD stamper manufacture.
In recent years, due to its ability to replicate a mandrel surface with practically no loss of fidelity, electroforming has taken on new importance in the fabrication of micro and nano-scale metallic devices and in producing precision injection molds with micro- and nano-scale features for production of non-metallic micro-molded objects. | 0 | Metallurgy |
The cyanide remaining in tails streams from gold plants is potentially hazardous. Therefore, some operations process the cyanide-containing waste streams in a detoxification step. This step lowers the concentrations of these cyanide compounds. The INCO-licensed process and the Caro's acid process oxidise the cyanide to cyanate, which is not as toxic as the cyanide ion, and which can then react to form carbonates and ammonia:
: + [O] →
The Inco process can typically lower cyanide concentrations to below 50 mg/L, whereas the Caros acid process can lower cyanide levels to between 10 and 50 mg/L, with the lower concentrations achievable in solution streams rather than slurries. Caros acid – peroxomonosulfuric acid (HSO) - converts cyanide to cyanate. Cyanate then hydrolyses to ammonium and carbonate ions. The Caros acid process is able to achieve discharge levels of Weak Acid Dissociable" (WAD) cyanide below 50 mg/L, which is generally suitable for discharge to tailings. Hydrogen peroxide and basic chlorination can also be used to oxidize cyanide, although these approaches are less common. Typically, this process blows compressed air through the tailings while adding sodium metabisulfite, which releases SO. Lime is added to maintain the pH at around 8.5, and copper sulfate is added as a catalyst if there is insufficient copper in the ore extract. This procedure can reduce concentrations of WAD cyanide to below the 10 ppm mandated by the EUs Mining Waste Directive. This level compares to the 66-81 ppm free cyanide and 500-1000 ppm total cyanide in the pond at Baia Mare. Remaining free cyanide degrades in the pond, while cyanate ions hydrolyse to ammonium. Studies show that residual cyanide trapped in the gold-mine tailings causes persistent release of toxic metals (e.g. mercury ) into the groundwater and surface water systems. | 0 | Metallurgy |
There are currently three methods in use that involve precisely targeting a DNA sequence in order to introduce a double-stranded break. Once this occurs, the cell's repair mechanisms will attempt to repair this double stranded break, often through non-homologous end joining (NHEJ), which involves directly ligating the two cut ends together. This may be done imperfectly, therefore sometimes causing insertions or deletions of base pairs, which cause frameshift mutations. These mutations can render the gene in which they occur nonfunctional, thus creating a knockout of that gene. This process is more efficient than homologous recombination, and therefore can be more easily used to create biallelic knockouts. | 1 | Gene expression + Signal Transduction |
Bronze Age goldwork is marked by an elegant simplicity of design and fine execution, with decoration usually restricted to relatively simple geometric patterns such as parallel lines, chevron, zig-zag and circular patterns, often extremely small and perfectly executed, especially in Ireland, as can be seen by enlarging the lunula and Irish bracelet illustrated. The objects are nearly all pieces of jewellery, and include clothes-fasteners (somewhat like large one-piece cuff-links), torcs, bracelets, gold lunulae, smaller ornaments that were perhaps worn in the ear, nose or hair, or on clothing as brooches, and a range of thin disc or plaques probably sewn to clothing or worn in the hair. The ends of objects that are essentially bars bent into a round shape often thicken before ending in a flat or concave face, as for example in the Milton Keynes Hoard. The thickening is typically slight in torcs and bracelets, but extreme in clothes fasteners and ear decorations. Tightly wound spirals in pairs are popular, as they were on the continent. | 0 | Metallurgy |
There are two main groups of paired receptors, distinguished by extracellular regions containing immunoglobulin or C-type lectin domains. Nomenclature within these families is complex and has changed over time as new members were identified. In general, the example of the LILR family applies; genes designated A represent the inhibitory receptor and genes designated B represent the activating receptor. | 1 | Gene expression + Signal Transduction |
In case of the fungus Neurospora crassa, the circadian clock is controlled by two light-sensitive domains, known as the white-collar-complex (WCC) and the LOV domain vivid (VVD-LOV). WCC is primarily responsible for the light-induced transcription on the control-gene frequency (FRQ) under day-light conditions, which drives the expression of VVD-LOV and governs the negative feedback loop onto the circadian clock. By contrast, the role of VVD-LOV is mainly modulatory and does not directly affect FRQ. | 1 | Gene expression + Signal Transduction |
Ellingham diagrams are a particular graphical form of the principle that the thermodynamic feasibility of a reaction depends on the sign of ΔG, the Gibbs free energy change, which is equal to ΔH − TΔS, where ΔH is the enthalpy change and ΔS is the entropy change.
The Ellingham diagram plots the Gibbs free energy change (ΔG) for each oxidation reaction as a function of temperature. For comparison of different reactions, all values of ΔG refer to the reaction of the same quantity of oxygen, chosen as one mole O ( mol ) by some authors and one mole by others. The diagram shown refers to 1 mole , so that e.g. the line for the oxidation of chromium shows ΔG for the reaction Cr(s) + (g) → (s), which is of the molar Gibbs energy of formation ΔG°(, s).
In the temperature ranges commonly used, the metal and the oxide are in a condensed state (solid or liquid), and oxygen is a gas with a much larger molar entropy. For the oxidation of each metal, the dominant contribution to the entropy change (ΔS) is the removal of mol , so that ΔS is negative and roughly equal for all metals. The slope of the plots is therefore positive for all metals, with ΔG always becoming more negative with lower temperature, and the lines for all the metal oxides are approximately parallel. Since these reactions are exothermic, they always become feasible at lower temperatures. At a sufficiently high temperature, the sign of ΔG may invert (becoming positive) and the oxide can spontaneously reduce to the metal, as shown for Ag and Cu.
For oxidation of carbon, the red line is for the formation of CO: C(s) + (g) → CO(g) with an increase in the number of moles of gas, leading to a positive ΔS and a negative slope. The blue line for the formation of is approximately horizontal, since the reaction C(s) + (g) → (g) leaves the number of moles of gas unchanged so that ΔS is small.
As with any chemical reaction prediction based on purely thermodynamic grounds, a spontaneous reaction may be very slow if one or more stages in the reaction pathway have very high activation energies E.
If two metals are present, two equilibria have to be considered. The oxide with the more negative ΔG will be formed and the other oxide will be reduced. | 0 | Metallurgy |
The locus of enterocyte effacement-encoded regulator (Ler) is a regulatory protein that controls bacterial pathogenicity of enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC). More specifically, Ler regulates the locus of enterocyte effacement (LEE) pathogenicity island genes, which are responsible for creating intestinal attachment and effacing lesions and subsequent diarrhea: LEE1, LEE2, and LEE3. LEE1, 2, and 3 carry the information necessary for a type III secretion system. The transcript encoding the Ler protein is the open reading frame 1 on the LEE1 operon.
The mechanism of Ler regulation involves competition with histone-like nucleoid structuring protein (H-NS), a negative regulator of the LEE pathogenicity island. Ler is regulated by many factors such as plasmid encoded regulator (Per), integration host factor, Fis, BipA, a positive regulatory loop involving GrlA, and quorum sensing mediated by luxS.
__TOC__ | 1 | Gene expression + Signal Transduction |
Metal dusting is "a catastrophic form of corrosion that occurs when susceptible materials are exposed to environments with high carbon activities." The corrosion manifests itself as a break-up of bulk metal to metal powder. The suspected mechanism is firstly the deposition of a graphite layer on the surface of the metal, usually from carbon monoxide (CO) in the vapour phase. This graphite layer is then thought to form metastable MC species (where M is the metal), which migrate away from the metal surface. However, in some regimes no MC species are observed indicating a direct transfer of metal atoms into the graphite layer.
The temperatures normally associated with metal dusting are high (300–850 °C). From a general understanding of chemistry, it can be deduced that at lower temperatures, the rate of reaction to form the metastable MC species is too low to be significant, and at much higher temperatures the graphite layer is unstable and so CO deposition does not occur (at least to any appreciable degree).
Very briefly, there are several proposed methods for prevention or reduction of metal dusting; the most common seem to be aluminide coatings, alloying with copper and addition of steam.
There is a significant amount of literature in existence that describes proposed mechanisms, prevention methods etc. There is also a good summary of metal dusting and some prevention methods in Corrosion by Carbon and Nitrogen - Metal Dusting, Carburisation and Nitridation | 0 | Metallurgy |
Establishing body axes is a critical step in animal development. During mouse embryonic development, Nodal, a transforming growth factor-beta superfamily ligand, is a key gene involved in patterning both the anterior-posterior axis and the left-right axis of the early embryo. The Nodal gene contains two enhancers: the Proximal Epiblast Enhancer (PEE) and the Asymmetric Enhancer (ASE). The PEE is upstream of the Nodal gene and drives Nodal expression in the portion of the primitive streak that will differentiate into the node (also referred to as the primitive node). The PEE turns on Nodal expression in response to a combination of Wnt signaling plus a second, unknown signal; thus, a member of the LEF/TCF transcription factor family likely binds to a TCF binding site in the cells in the node. Diffusion of Nodal away from the node forms a gradient which then patterns the extending anterior-posterior axis of the embryo. The ASE is an intronic enhancer bound by the fork head domain transcription factor Fox1. Early in development, Fox1-driven Nodal expression establishes the visceral endoderm. Later in development, Fox1 binding to the ASE drives Nodal expression on the left side of the lateral plate mesoderm, thus establishing left-right asymmetry necessary for asymmetric organ development in the mesoderm.
Establishing three germ layers during gastrulation is another critical step in animal development. Each of the three germ layers has unique patterns of gene expression that promote their differentiation and development. The endoderm is specified early in development by Gata4 expression, and Gata4 goes on to direct gut morphogenesis later. Gata4 expression is controlled in the early embryo by an intronic enhancer that binds another forkhead domain transcription factor, FoxA2. Initially the enhancer drives broad gene expression throughout the embryo, but the expression quickly becomes restricted to the endoderm, suggesting that other repressors may be involved in its restriction. Late in development, the same enhancer restricts expression to the tissues that will become the stomach and pancreas. An additional enhancer is responsible for maintaining Gata4 expression in the endoderm during the intermediate stages of gut development. | 1 | Gene expression + Signal Transduction |
Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty acids. They constitute about 0.25% of phospholipids in the bilayer. | 1 | Gene expression + Signal Transduction |
The type of growth factor signaling can effect whether or not NSCs differentiate into motor neurons or not. Priming a media with FGF2 lowers the activity of the PI3K/AKT pathway, which activates GSK3β. This increases expression of HB9. Directly inhibiting PI3K in NSCs leads to a population of cells that are purely HB9+ and differentiate at an elevated efficiency into motor neurons. Grafting these cells into different parts of rats generates motor neurons regardless of the transplanted cells' microenvironment. Following injury, neural stem cells enter a repair phase and express high levels of PI3K to enhance proliferation. This is better for survival of the neurons as a whole but is at the expense of generating motor neurons. Therefore, it can be difficult for injured motor neurons to recover their ability. It is the purpose of modern research to generate neural stem cells that can proliferate but still differentiate into motor neurons. Lowering the effect of the PI3K pathway and increasing the effect of GSK3β and HB9 in NSCs is a potential way of generating these cells. | 1 | Gene expression + Signal Transduction |
DNA-directed RNA interference (ddRNAi) is a gene-silencing technique that utilizes DNA constructs to activate an animal cell's endogenous RNA interference (RNAi) pathways. DNA constructs are designed to express self-complementary double-stranded RNAs, typically short-hairpin RNAs, that bring about the silencing of a target gene or genes once processed. Any RNA, including endogenous messenger RNA (mRNAs) or viral RNAs, can be silenced by designing constructs to express double-stranded RNA complementary to the desired mRNA target.
This mechanism has been demonstrated to work as a novel therapeutic technique to silence disease-causing genes across a range of disease models, including viral diseases such as HIV, hepatitis B or hepatitis C, or diseases associated with altered expression of endogenous genes such as drug-resistant lung cancer, neuropathic pain, advanced cancer, and retinitis pigmentosa. | 1 | Gene expression + Signal Transduction |
(AD 900–1450)
Utilitarian and ceremonial objects; Objects of personal adornment'
#Atotonilco, Hidalgo
#Calixtlahuaca, Mexico
#Tenayuca, Mexico
#Tenochitlan, Distrito Federal (D.F.)
#Teotihuacan, Mexico
#Texcoco, Mexico | 0 | Metallurgy |
Bounded by impoundments (an impoundment is a dam), these dams typically use "local materials" including the tailings themselves, and may be considered embankment dams. Traditionally, the only option for tailings storage was to contain the tailings slurry with locally available earthen materials. This slurry is a dilute stream of the tailings solids within water that was sent to the tailings storage area. The modern tailings designer has a range of tailings products to choose from depending upon how much water is removed from the slurry prior to discharge. It is increasingly common for tailings storage facilities to require special barriers like Bituminous Geomembranes (BGMs) to contain liquid tailings slurries and prevent impact to the surrounding environment. The removal of water not only can create a better storage system in some cases (e.g. dry stacking, see below) but can also assist in water recovery which is a major issue as many mines are in arid regions. In a 1994 description of tailings impoundments, however, the U.S. EPA stated that dewatering methods may be prohibitively expensive except in special circumstances. Subaqueous storage of tailings has also been used.
Tailing ponds are areas of refused mining tailings where the waterborne refuse material is pumped into a pond to allow the sedimentation (meaning separation) of solids from the water. The pond is generally impounded with a dam, and known as tailings impoundments or tailings dams. It was estimated in 2000 that there were about 3,500 active tailings impoundments in the world. The ponded water is of some benefit as it minimizes fine tailings from being transported by wind into populated areas where the toxic chemicals could be potentially hazardous to human health; however, it is also harmful to the environment. Tailing ponds are often somewhat dangerous because they attract wildlife such as waterfowl or caribou as they appear to be a natural pond, but they can be highly toxic and harmful to the health of these animals. Tailings ponds are used to store the waste made from separating minerals from rocks, or the slurry produced from tar sands mining. Tailings are sometimes mixed with other materials such as bentonite to form a thicker slurry that slows the release of impacted water to the environment.
There are many different subsets of this method, including valley impoundments, ring dikes, in-pit impoundments, and specially dug pits. The most common is the valley pond, which takes advantage of the natural topographical depression in the ground. Large earthen dams may be constructed and then filled with the tailings. Exhausted open pit mines may be refilled with tailings. In all instances, due consideration must be made to contamination of the underlying water table, amongst other issues. Dewatering is an important part of pond storage, as the tailings are added to the storage facility the water is removed – usually by draining into decant tower structures. The water removed can thus be reused in the processing cycle. Once a storage facility is filled and completed, the surface can be covered with topsoil and revegetation commenced. However, unless a non-permeable capping method is used, water that infiltrates into the storage facility will have to be continually pumped out into the future. | 0 | Metallurgy |
The first serious attempt at providing a physical explanation of the material removal during electric discharge machining is perhaps that of Van Dijck. Van Dijck presented a thermal model together with a computational simulation to explain the phenomena between the electrodes during electric discharge machining. However, as Van Dijck himself admitted in his study, the number of assumptions made to overcome the lack of experimental data at that time was quite significant.
Further models of what occurs during electric discharge machining in terms of heat transfer were developed in the late eighties and early nineties. It resulted in three scholarly papers: the first presenting a thermal model of material removal on the cathode, the second presenting a thermal model for the erosion occurring on the anode and the third introducing a model describing the plasma channel formed during the passage of the discharge current through the dielectric liquid. Validation of these models is supported by experimental data provided by AGIE.
These models give the most authoritative support for the claim that EDM is a thermal process, removing material from the two electrodes because of melting or vaporization, along with pressure dynamics established in the spark-gap by the collapsing of the plasma channel. However, for small discharge energies the models are inadequate to explain the experimental data. All these models hinge on a number of assumptions from such disparate research areas as submarine explosions, discharges in gases, and failure of transformers, so it is not surprising that alternative models have been proposed more recently in the literature trying to explain the EDM process.
Among these, the model from Singh and Ghosh reconnects the removal of material from the electrode to the presence of an electrical force on the surface of the electrode that could mechanically remove material and create the craters. This would be possible because the material on the surface has altered mechanical properties due to an increased temperature caused by the passage of electric current. The authors' simulations showed how they might explain EDM better than a thermal model (melting or evaporation), especially for small discharge energies, which are typically used in μ-EDM and in finishing operations.
Given the many available models, it appears that the material removal mechanism in EDM is not yet well understood and that further investigation is necessary to clarify it, especially considering the lack of experimental scientific evidence to build and validate the current EDM models. This explains an increased current research effort in related experimental techniques. | 0 | Metallurgy |
Under the light microscope, eyespots appear as dark, orange-reddish spots or stigmata. They get their color from carotenoid pigments contained in bodies called pigment granules. The photoreceptors are found in the plasma membrane overlaying the pigmented bodies.
The eyespot apparatus of Euglena comprises the paraflagellar body connecting the eyespot to the flagellum. In electron microscopy, the eyespot apparatus appears as a highly ordered lamellar structure formed by membranous rods in a helical arrangement.
In Chlamydomonas, the eyespot is part of the chloroplast and takes on the appearance of a membranous sandwich structure. It is assembled from chloroplast membranes (outer, inner, and thylakoid membranes) and carotenoid-filled granules overlaid by plasma membrane. The stacks of granules act as a quarter-wave plate, reflecting incoming photons back to the overlying photoreceptors, while shielding the photoreceptors from light coming from other directions. It disassembles during cell division and reforms in the daughter cells in an asymmetric fashion in relation to the cytoskeleton. This asymmetric positioning of the eyespot in the cell is essential for proper phototaxis. | 1 | Gene expression + Signal Transduction |
The discovery of mTOR was made in 1994 while investigating the mechanism of action of its inhibitor, rapamycin. Rapamycin was first discovered in 1975 in a soil sample from Easter Island of South Pacific, also known as Rapa Nui, from where its name is derived. Rapamycin is a macrolide, produced by the microorganism Streptomyces hygroscopicus and showed antifungal properties. Shortly after its discovery, immunosuppressive properties were detected, which later led to the establishment of rapamycin as an immunosuppressant. In the 1980s, rapamycin was also found to have anticancer activity although the exact mechanism of action remained unknown until many years later.
In the 1990s there was a dramatic change in this field due to studies on the mechanism of action of rapamycin and the identification of the drug target. It was found that rapamycin inhibited cellular proliferation and cell cycle progression. Research on mTOR inhibition has been a growing branch in science and has promising results. | 1 | Gene expression + Signal Transduction |