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pRb has the ability to reversibly inhibit DNA replication through transcriptional repression of DNA replication factors. pRb is able to bind to transcription factors in the E2F family and thereby inhibit their function. When pRb is chronically activated, it leads to the downregulation of the necessary DNA replication factors. Within 72–96 hours of active pRb induction in A2-4 cells, the target DNA replication factor proteins—MCMs, RPA34, DBF4, RFCp37, and RFCp140—all showed decreased levels. Along with decreased levels, there was a simultaneous and expected inhibition of DNA replication in these cells. This process, however, is reversible. Following induced knockout of pRb, cells treated with cisplatin, a DNA-damaging agent, were able to continue proliferating, without cell cycle arrest, suggesting pRb plays an important role in triggering chronic S-phase arrest in response to genotoxic stress.
One such example of E2F-regulated genes repressed by pRb are cyclin E and cyclin A. Both of these cyclins are able to bind to Cdk2 and facilitate entry into the S phase of the cell cycle. Through the repression of expression of cyclin E and cyclin A, pRb is able to inhibit the G1/S transition. | 1 | Gene expression + Signal Transduction |
Due to their high reactivity, most metals were not discovered until the 19th century. A method for extracting aluminium from bauxite was proposed by Humphry Davy in 1807, using an electric arc. Although his attempts were unsuccessful, by 1855 the first sales of pure aluminium reached the market. However, as extractive metallurgy was still in its infancy, most aluminium extraction-processes produced unintended alloys contaminated with other elements found in the ore; the most abundant of which was copper. These aluminium-copper alloys (at the time termed "aluminum bronze") preceded pure aluminium, offering greater strength and hardness over the soft, pure metal, and to a slight degree were found to be heat treatable. However, due to their softness and limited hardenability these alloys found little practical use, and were more of a novelty, until the Wright brothers used an aluminium alloy to construct the first airplane engine in 1903. During the time between 1865 and 1910, processes for extracting many other metals were discovered, such as chromium, vanadium, tungsten, iridium, cobalt, and molybdenum, and various alloys were developed.
Prior to 1910, research mainly consisted of private individuals tinkering in their own laboratories. However, as the aircraft and automotive industries began growing, research into alloys became an industrial effort in the years following 1910, as new magnesium alloys were developed for pistons and wheels in cars, and pot metal for levers and knobs, and aluminium alloys developed for airframes and aircraft skins were put into use. | 0 | Metallurgy |
Classified as an orphan disease, there is currently no therapy for OPMD, caused by a mutation in the poly(A) binding protein nuclear 1 (PABPN1) gene. Silencing the mutant gene using DDRNAI offers a potential therapeutic approach. | 1 | Gene expression + Signal Transduction |
In genetics, an enhancer is a short (50–1500 bp) region of DNA that can be bound by proteins (activators) to increase the likelihood that transcription of a particular gene will occur. These proteins are usually referred to as transcription factors. Enhancers are cis-acting. They can be located up to 1 Mbp (1,000,000 bp) away from the gene, upstream or downstream from the start site. There are hundreds of thousands of enhancers in the human genome. They are found in both prokaryotes and eukaryotes.
The first discovery of a eukaryotic enhancer was in the immunoglobulin heavy chain gene in 1983. This enhancer, located in the large intron, provided an explanation for the transcriptional activation of rearranged Vh gene promoters while unrearranged Vh promoters remained inactive. Lately, enhancers have been shown to be involved in certain medical conditions, for example, myelosuppression. Since 2022, scientists have used artificial intelligence to design synthetic enhancers and applied them in animal systems, first in a cell line, and one year later also in vivo. | 1 | Gene expression + Signal Transduction |
Archaeal transcription is the process in which a segment of archaeal DNA is copied into a newly synthesized strand of RNA using the sole Pol II-like RNA polymerase (RNAP). The process occurs in three main steps: initiation, elongation, and termination; and the end result is a strand of RNA that is complementary to a single strand of DNA. A number of transcription factors govern this process with homologs in both bacteria and eukaryotes, with the core machinery more similar to eukaryotic transcription.
Because archaea lack a membrane-enclosed nucleus like bacteria do, transcription and translation can happen at the same time on a newly-generated piece of mRNA. Operons are widespread in archaea. | 1 | Gene expression + Signal Transduction |
An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. | 1 | Gene expression + Signal Transduction |
Lead-Bismuth Eutectic or LBE is a eutectic alloy of lead (44.5 at%) and bismuth (55.5 at%) used as a coolant in some nuclear reactors, and is a proposed coolant for the lead-cooled fast reactor, part of the Generation IV reactor initiative.
It has a melting point of 123.5 °C/254.3 °F (pure lead melts at 327 °C/621 °F, pure bismuth at 271 °C/520 °F) and a boiling point of 1,670 °C/3,038 °F.
Lead-bismuth alloys with between 30% and 75% bismuth all have melting points below 200 °C/392 °F.
Alloys with between 48% and 63% bismuth have melting points below 150 °C/302 °F.
While lead expands slightly on melting and bismuth contracts slightly on melting, LBE has negligible change in volume on melting. | 0 | Metallurgy |
mTOR integrates the input from upstream pathways, including insulin, growth factors (such as IGF-1 and IGF-2), and amino acids. mTOR also senses cellular nutrient, oxygen, and energy levels. The mTOR pathway is a central regulator of mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain, and is dysregulated in human diseases, such as diabetes, obesity, depression, and certain cancers. Rapamycin inhibits mTOR by associating with its intracellular receptor FKBP12. The FKBP12–rapamycin complex binds directly to the FKBP12-Rapamycin Binding (FRB) domain of mTOR, inhibiting its activity. | 1 | Gene expression + Signal Transduction |
The Graduate Institute of Ferrous Technology has nine laboratories with key areas of expertise:
* [https://web.archive.org/web/20110728031933/http://www.postech.ac.kr/mse/axal/ Alternative Technology Lab]:
**Continuous casting-related innovation
**Texture control
**Alternative alloying and processing
* [https://web.archive.org/web/20100325004541/http://controllab.postech.ac.kr/ Control and Automation Lab]:
**Computer control system
**Process automation
**Control theory & Applications
**Measurement
* [http://gift.webteem.co.kr/jdboard/club/main.php?page=club&code=csl&group_a=csl Clean Steel Lab]:
**Thermochemistry
**Physico-chemical properties
**Fluid dynamics
**Solidification and casting
* Environmental Metallurgy Lab:
**Reduction of CO emission
**Improvement of energy efficiency
**Gas alloying technology
* [http://cml.postech.ac.kr/ Computational Metallurgy Lab]:
**Classical modeling and experiments
**Phase field modeling and experiments
**First principle calculation, quantum mechanical modeling
* Microstructure Control Lab:
**Phase transformation / electron microscopy
**Microscopic deformation behavior
**Toughness enhancement via microstructure control
**Innovative processing (e.g., twin-roll casting)
* Materials Design Lab:
**[http://www.worldsteel.org/?action=storypages&id=242 Automotive Steels], Galvanized/Galvannealed Products
**Electrical Steels
**Stainless steels
**Steel grades related to power generation
* [http://mml.postech.ac.kr/ Materials Mechanics Lab]:
**Net Shape Forming (sheet forming, other forming)
**Performance in service (fracture, crashworthiness, fatigue)
* [http://sel.postech.ac.kr/ Surface Engineering Lab]:
**Composite coatings
** Corrosion mechanism & lifetime prediction
**Corrosion resistant alloy design
**Metallic coatings | 0 | Metallurgy |
In humans endoglin may be involved in the autosomal dominant disorder known as hereditary hemorrhagic telangiectasia (HHT) type 1. HHT is actually the first human disease linked to the TGF beta receptor complex. This condition leads to frequent nose bleeds, telangiectases on skin and mucosa and may cause arteriovenous malformations in different organs including brain, lung, and liver. | 1 | Gene expression + Signal Transduction |
Western Asia has very little tin ore; the few sources that have recently been found are too insignificant to have played a major role during most of ancient history. However, it is possible that they were exploited at the start of the Bronze Age and are responsible for the development of early bronze manufacturing technology. Kestel, in Southern Turkey, is the site of an ancient cassiterite mine that was used from 3250 to 1800 BC. It contains miles of tunnels, some only large enough for a child. A grave with children who were probably workers has been found. It was abandoned, with crucibles and other tools left at the site.
While there are a few sources of cassiterite in Central Asia, namely in Uzbekistan, Tajikistan, and Afghanistan, that show signs of having been exploited starting around 2000 BC, archaeologists disagree about whether they were significant sources of tin for the earliest Bronze Age cultures of the Middle East.
In Northern Asia the only tin deposits considered exploitable by ancient peoples occur in the far eastern region of Siberia. This source of tin appears to have been exploited by the Eurasian Steppe people known as the Seima-Turbino culture around 2000 BC as well as by northern Chinese cultures around the same time.
Eastern Asia has a number of small cassiterite deposits along the Yellow River which were exploited by the earliest Chinese Bronze Age culture of Erlitou and the Shang dynasty (2500 to 1800 BC). However, the richest deposits for the region, and indeed the world, lie in Southeastern Asia, stretching from Yunnan in China to the Malay Peninsula. The deposits in Yunnan were not mined until around 700 BC, but by the Han dynasty had become the main source of tin in China according to historical texts of the Han, Jin, Tang, and Song dynasties. Other cultures of Southeast Asia exploited the abundant cassiterite resources sometime between the third and second millennia BC, but due to the lack of archaeological work in the region little else is known about tin exploitation during ancient times in that part of the world.
Tin was used in the Indian subcontinent starting between 1500 and 1000 BC. While India does have some small scattered deposits of tin, they were not a major source of tin for Indian Bronze Age cultures as shown by their dependence on imported tin. | 0 | Metallurgy |
A classical view of PIC formation at the promoter involves the following steps:
* TATA binding protein (TBP, a subunit of TFIID) binds the promoter, creating a sharp bend in the promoter DNA.
** Animals have some TBP-related factors (TRF; TBPL1/TBPL2). They can replace TBP in some special contexts.
* TBP recruits TFIIA, then TFIIB, to the promoter.
* TFIIB recruits RNA polymerase II and TFIIF to the promoter.
* TFIIE joins the growing complex and recruits TFIIH which has protein kinase activity (phosphorylates RNA polymerase II within the CTD) and DNA helicase activity (unwinds DNA at promoter). It also recruits nucleotide-excision repair proteins.
* Subunits within TFIIH that have ATPase and helicase activity create negative superhelical tension in the DNA.
* Negative superhelical tension causes approximately one turn of DNA to unwind and form the transcription bubble.
* The template strand of the transcription bubble engages with the RNA polymerase II active site.
* RNA synthesis begins.
* After synthesis of ~10 nucleotides of RNA, and an obligatory phase of several abortive transcription cycles, RNA polymerase II escapes the promoter region to transcribe the remainder of the gene.
An alternative hypothesis of PIC assembly postulates the recruitment of a pre-assembled "RNA polymerase II holoenzyme" directly to the promoter (composed of all, or nearly all GTFs and RNA polymerase II and regulatory complexes), in a manner similar to the bacterial RNA polymerase (RNAP). | 1 | Gene expression + Signal Transduction |
The Mixtec civilization have long been thought to be the dominant goldsmiths of post-classic Mesoamerica. A large number of gold artifacts found in central and southern Mexico have been attributed to the Mixtec. | 0 | Metallurgy |
A variation of the Washoe process was developed in the Reese River mining district around Austin, Nevada. The Washoe process was found not to work well for ores with arsenic or antimony sulfides, or with galena or sphalerite. In 1869, Carl A. Stetefeldt of Reno found that roasting the ore with salt converted the silver sulfides to silver chlorides, which could then be recovered in amalgamation pans. The process was introduced in the Reese River District in 1879, with great success.
Other silver-mining districts using the Reese River process included Georgetown, Colorado, Caribou, Colorado, and Silver Cliff, Colorado. | 0 | Metallurgy |
Thermocouples are suitable for measuring over a large temperature range, from −270 up to 3000 °C (for a short time, in inert atmosphere). Applications include temperature measurement for kilns, gas turbine exhaust, diesel engines, other industrial processes and fog machines. They are less suitable for applications where smaller temperature differences need to be measured with high accuracy, for example the range 0–100 °C with 0.1 °C accuracy. For such applications thermistors, silicon bandgap temperature sensors and resistance thermometers are more suitable. | 0 | Metallurgy |
Iron is usually found as iron ore on Earth, except for one deposit of native iron in Greenland, which was used by the Inuit. Native copper, however, was found worldwide, along with silver, gold, and platinum, which were also used to make tools, jewelry, and other objects since Neolithic times. Copper was the hardest of these metals, and the most widely distributed. It became one of the most important metals to the ancients. Around 10,000 years ago in the highlands of Anatolia (Turkey), humans learned to smelt metals such as copper and tin from ore. Around 2500 BC, people began alloying the two metals to form bronze, which was much harder than its ingredients. Tin was rare, however, being found mostly in Great Britain. In the Middle East, people began alloying copper with zinc to form brass. Ancient civilizations took into account the mixture and the various properties it produced, such as hardness, toughness and melting point, under various conditions of temperature and work hardening, developing much of the information contained in modern alloy phase diagrams. For example, arrowheads from the Chinese Qin dynasty (around 200 BC) were often constructed with a hard bronze-head, but a softer bronze-tang, combining the alloys to prevent both dulling and breaking during use. | 0 | Metallurgy |
Long intergenic Non-coding RNA (LincRNA) is defined as RNA transcripts that are longer than 200 nucleotides. These RNAs must not have open reading frames that encode proteins. The term “intergenic” refers to the identification of these transcripts from regions of the genome that do not contain protein-encoding genes. LncRNAs also contain promoter - or enhancer-associated RNAs that are gene proximal and can be either in the sense or antisense orientation. | 1 | Gene expression + Signal Transduction |
According to some scholars, lost-wax casting was used in China already during the Spring and Autumn period (770 – 476 BCE), although this is often disputed.
The lost-wax method is used in most parts of the world. As the name suggests, the lost-wax method is to use wax as a mold, and heat it to melt the wax mold and lose it, thereby casting bronze ware, making the model (the outer layer of the wax model is coated with mud), lost-wax (heating to make the wax flow out), pouring copper liquid to fill the cavity left by the wax model, etc.
The development and spread of the lost-wax method in the West has never stopped, but the main bronze casting method in the Bronze Age in China is the section mold process. When the lost-wax method was introduced into China is also a topic of academic discussion. But there is no doubt that the lost-wax method already existed in China during the Spring and Autumn Period. In 1978, the Bronze Zun-Pan unearthed from the tomb of Marquis Yi of Zeng in Leigudun, Suixian County, Hubei Province, used a mixed process of section mold method and lost-wax method. | 0 | Metallurgy |
When in biotic conditions, anaerobic corrosion can be facilitated by the metabolic activity of microorganisms in the surrounding environment. This process is known as microbiologically-influenced corrosion or bacterial anaerobic corrosion. Most notably, the production of dissolved sulfides by sulfate-reducing bacteria (SRB) react with solid metals and hydrogen ions to form metal sulfides in a redox reaction. | 0 | Metallurgy |
Enzyme induction is a process in which a molecule (e.g. a drug) induces (i.e. initiates or enhances) the expression of an enzyme.
Enzyme inhibition can refer to
* the inhibition of the expression of the enzyme by another molecule
* interference at the enzyme-level, basically with how the enzyme works. This can be competitive inhibition, uncompetitive inhibition, non-competitive inhibition or partially competitive inhibition.
If the molecule induces enzymes that are responsible for its own metabolism, this is called auto-induction (or auto-inhibition if there is inhibition). These processes are particular forms of gene expression regulation.
These terms are of particular interest to pharmacology, and more specifically to drug metabolism and drug interactions. They also apply to molecular biology. | 1 | Gene expression + Signal Transduction |
Expression systems using either S. cerevisiae or Pichia pastoris allow stable and lasting production of proteins that are processed similarly to mammalian cells, at high yield, in chemically defined media of proteins. | 1 | Gene expression + Signal Transduction |
In the case of antiques, a range of views are held on the value of patination and its replacement if damaged, known as repatination.
Preserving a piece's look and character is important and removal or reduction may dramatically reduce its value. If patination has flaked off, repatination may be recommended. Appraiser Reyne Haines notes that a repatinated metal piece will be worth more than one with major imperfections in the patina, but less than a piece still with its original finish. | 0 | Metallurgy |
Flakes and shatter cracks are internal fissures seen in large forgings. Hydrogen picked up during melting and casting segregates at internal voids and discontinuities and produces these defects during forging. Fish-eyes are bright patches named for their appearance seen on fracture surfaces, generally of weldments. Hydrogen enters the metal during fusion-welding and produces this defect during subsequent stressing. Steel containment vessels exposed to extremely high hydrogen pressures develop small fissures or micro perforations through which fluids may leak. | 0 | Metallurgy |
Members of the MAPK family can be found in every eukaryotic organism examined so far. In particular, both classical and atypical MAP kinases can be traced back to the root of the radiation of major eukaryotic groups. Terrestrial plants contain four groups of classical MAPKs (MAPK-A, MAPK-B, MAPK-C and MAPK-D) that are involved in response to myriads of abiotic stresses. However, none of these groups can be directly equated to the clusters of classical MAPKs found in opisthokonts (fungi and animals). In the latter, the major subgroups of classical MAPKs form the ERK/Fus3-like branch (that is further sub-divided in metazoans into ERK1/2 and ERK5 subgroups), and the p38/Hog1-like kinases (that has also split into the p38 and the JNK subgroups in multicellular animals). In addition, there are several MAPKs in both fungi and animals, whose origins are less clear, either due to high divergence (e.g. NLK), or due to possibly being an early offshoot to the entire MAPK family (ERK3, ERK4, ERK7). In vertebrates, due to the twin whole genome duplications after the cephalochordate/vertebrate split, there are several paralogs in every group. Thus ERK1 and ERK2 both correspond to the Drosophila kinase rolled, JNK1, JNK2 and JNK3 are all orthologous to the gene basket in Drosophila. Although among the p38 group, p38 alpha and beta are clearly paralogous pairs, and so are p38 gamma and delta in vertebrates, the timing of the base split is less clear, given that many metazoans already possess multiple p38 homologs (there are three p38-type kinases in Drosophila, Mpk2(p38a), p38b and p38c). The single ERK5 protein appears to fill a very specialized role (essential for vascular development in vertebrates) wherever it is present. This lineage has been deleted in protostomes, together with its upstream pathway components (MEKK2/3, MKK5), although they are clearly present in cnidarians, sponges and even in certain unicellular organisms (e.g. the choanoflagellate Monosiga brevicollis) closely related to the origins of multicellular animals.
The split between classical and some atypical MAP kinases happened quite early. This is suggested not just by the high divergence between extant genes, but also recent discoveries of atypical MAPKs in primitive, basal eukaryotes. The genome sequencing of Giardia lamblia revealed the presence of two MAPK genes, one of them similar to the already-well-known mammalian MAPKs (ERKs, p38s, etc.), the other one showing similarities to the mammalian ERK7 protein. The situation is similar in the multicellular amoeba Dictyostelium discoideum, where the ddERK1 protein appears to be a classical MAPK, while ddERK2 more closely resembles our ERK7 and ERK3/4 proteins. Atypical MAPKs can also be found in higher plants, although they are poorly known. Similar to the situation in mammals, most aspects of atypical MAPKs are uncharacterized due to the lack of research focus on this area. | 1 | Gene expression + Signal Transduction |
The Institute had its genesis in 1893 with the formation in Adelaide of the Australasian Institute of Mining Engineers drawing its inspiration from the success of the American Institute of Mining Engineers, and some impetus from the Mine Managers Association of Broken Hill. Office-holders were equally from South Australia and "The Hill", where the Institute established its headquarters.
This approach to the foundation of a federal organization was welcomed in mining districts of other Australian colonies. and branches were formed in Broken Hill, the Thames Goldfield (New Zealand), Ballarat, and elsewhere. Succeeding annual conferences were held at Ballarat, Hobart, Broken Hill and other mining centres. The 1926 conference was held in Otago, New Zealand.
In 1896 its headquarters were removed from Broken Hill to Melbourne, and in June 1919 adopted its present name.
In 1954 the institute applied for a royal charter, granted 1955.
The AusIMM represents more than 15 500 members drawn from all sections of the industry and supported by a network of branches and societies in Australasia and internationally. | 0 | Metallurgy |
In addition to containing MREs, the 3′-UTR also often contains AU-rich elements (AREs), which are 50 to 150 bp in length and usually include many copies of the sequence AUUUA. ARE binding proteins (ARE-BPs) bind to AU-rich elements in a manner that is dependent upon tissue type, cell type, timing, cellular localization, and environment. In response to different intracellular and extracellular signals, ARE-BPs can promote mRNA decay, affect mRNA stability, or activate translation. This mechanism of gene regulation is involved in cell growth, cellular differentiation, and adaptation to external stimuli. It therefore acts on transcripts encoding cytokines, growth factors, tumor suppressors, proto-oncogenes, cyclins, enzymes, transcription factors, receptors, and membrane proteins. | 1 | Gene expression + Signal Transduction |
Flotation is used for the purification of potassium chloride from sodium chloride and clay minerals. The crushed mineral is suspended in brine in the presence of fatty ammonium salts. Because the ammonium head group and K have very similar ionic radii (ca. 0.135, 0.143 nm respectively), the ammonium centers exchange for the surface potassium sites on the particles of KCl, but not on the NaCl particles. The long alkyl chains then confer Hydrophobicity to the particles, which enable them to form foams. | 0 | Metallurgy |
The transcription factor NF-κB regulates various genes that play essential roles in signaling, stress responses, cell growth and apoptosis. The temporal control of NF-κB activation by the degradation and synthesis of its inhibitor isoforms, I-κBα, -β, - ε has been computationally modeled. The model suggested that I-κBα results in robust negative feedback that leads to a fast turn off of NF-κB response. On the other hand, the oscillatory potential and stabilization of NF-κB during long stimulations has been shown to be reduced by I-κBβ and –ε.
The outgrowth and progression is of limb organogenesis is controlled by self-regulatory, robust signalling system that involves interlinked feedback mechanisms instead of independent morphogen signals. The studies on morphogenesis of limb buds have been focused on one particular axis of limb bud. However it has long been noted that zone of polarizing activity (ZPA) requires maintenance of apical ectodermal ridge (AER). The dependence of ZPA on ARE indicates the linkage between them. Three phases have been observed during the interplay between ARE and ZPA. Initiation phase involves the Grem1 expression in a fast initiator loop (~2h loop time) due to upregulation by BMP4. The Shh signalling is activated independently of GREM1 and AER-FGFs. Propagation phase involves the control of distal progression during limb bud development. Finally termination of signalling system due to the widening gap between ZPA-SHH signalling and the Grem1 expression domain. In mouse limb patterning, limb development is regulated by linking a fast GREM1 module to the slower SSH/FGF epithelial-mesenchymal feedback loop.
Circadian rhythms, which regulate physiology and behavior in organisms, are dependent upon a system of interlinked feedback mechanisms as well. In mammals, this process is driven by the suprachiasmatic nuclei (SCN) in the hypothalamus, composed of the two negative feedback loops Per-Cry and Clock-Bmal. Transcription of the period (Per) and cryptochrome (Cry) genes cannot proceed until CLOCK and BMAL1 have dimerized and bound to the E-box element, a process initiated by CREB-binding protein (CPB). Once bound to the E-box elements of per and cry, successful production of mRNA transcripts occurs and the proteins PER and CRY are synthesized. PER and CRY then dimerize and repress the transcription of the gene Rev-Erb, the protein product of which, REV-ERB, represses transcription of Bmal. The repression of BMAL in vivo prevents the transactivation of Per-Cry, thereby completing the cycle in just over 24 hours. | 1 | Gene expression + Signal Transduction |
Downregulation refers to the decrease in the number of receptor sites. This can be accomplished by metabolizing bound FSHR sites. The bound FSH-receptor complex is brought by lateral migration to a "coated pit," where such units are concentrated and then stabilized by a framework of clathrins. A pinched-off coated pit is internalized and degraded by lysosomes. Proteins may be metabolized or the receptor can be recycled. Use of long-acting agonists will downregulate the receptor population. | 1 | Gene expression + Signal Transduction |
The word intron is derived from the terms intragenic region, and intracistron, that is, a segment of DNA that is located between two exons of a gene. The term intron refers to both the DNA sequence within a gene and the corresponding sequence in the unprocessed RNA transcript. As part of the RNA processing pathway, introns are removed by RNA splicing either shortly after or concurrent with transcription. Introns are found in the genes of most organisms and many viruses. They can be located in a wide range of genes, including those that generate proteins, ribosomal RNA (rRNA), and transfer RNA (tRNA).
Within introns, a donor site (5 end of the intron), a branch site (near the 3 end of the intron) and an acceptor site (3 end of the intron) are required for splicing. The splice donor site includes an almost invariant sequence GU at the 5 end of the intron, within a larger, less highly conserved region. The splice acceptor site at the 3 end of the intron terminates the intron with an almost invariant AG sequence. Upstream (5-ward) from the AG there is a region high in pyrimidines (C and U), or polypyrimidine tract. Further upstream from the polypyrimidine tract is the branchpoint, which includes an adenine nucleotide involved in lariat formation. The consensus sequence for an intron (in IUPAC nucleic acid notation) is: G-G-[cut]-G-U-R-A-G-U (donor site) ... intron sequence ... Y-U-R-A-C (branch sequence 20-50 nucleotides upstream of acceptor site) ... Y-rich-N-C-A-G-[cut]-G (acceptor site). However, it is noted that the specific sequence of intronic splicing elements and the number of nucleotides between the branchpoint and the nearest 3’ acceptor site affect splice site selection. Also, point mutations in the underlying DNA or errors during transcription can activate a cryptic splice site in part of the transcript that usually is not spliced. This results in a mature messenger RNA with a missing section of an exon. In this way, a point mutation, which might otherwise affect only a single amino acid, can manifest as a deletion or truncation in the final protein. | 1 | Gene expression + Signal Transduction |
Photoreceptor proteins typically consist of a protein attached to a non-protein chromophore (sometimes referred as photopigment, even so photopigment may also refer to the photoreceptor as a whole). The chromophore reacts to light via photoisomerization or photoreduction, thus initiating a change of the receptor protein which triggers a signal transduction cascade. Chromophores found in photoreceptors include retinal (retinylidene proteins, for example rhodopsin in animals), flavin (flavoproteins, for example cryptochrome in plants and animals) and bilin (biliproteins, for example phytochrome in plants). The plant protein UVR8 is exceptional amongst photoreceptors in that it contains no external chromophore. Instead, UVR8 absorbs light through tryptophan residues within its protein coding sequence. | 1 | Gene expression + Signal Transduction |
Ligands of the sigma-2 receptor are exogenous and internalized by endocytosis, and can act as either agonists or antagonists. They can typically be classified into four groups, which are structurally related. It is not entirely understood how binding to the sigma-2 receptor occurs. Proposed models commonly include one small and one bulky hydrophobic pocket, electrostatic hydrogen interactions, and less commonly a third hydrophobic pocket.
A study of the four groups has revealed that a basic nitrogen and at least one hydrophobic moiety is needed to bind a sigma-2 receptor. In addition, there are molecular characteristics that increase the selectivity for sigma-2 receptors, which include bulky hydrophobic regions, nitrogen-carboxylic interaction, and additional basic nitrogens.
Since its discovery in 1990, the sigma-2 receptor has been considered an orphan receptor; however, in 2021 20S-hydroxycholesterol was identified as the putative endogenous ligand. | 1 | Gene expression + Signal Transduction |
For many ores (e.g. those of Cu, Mo, W, Ni), the collectors are anionic sulfur ligands. Particularly popular for sulfide minerals are xanthate salts, including potassium amyl xanthate (PAX), potassium isobutyl xanthate (PIBX), potassium ethyl xanthate (KEX), sodium isobutyl xanthate (SIBX), sodium isopropyl xanthate (SIPX), sodium ethyl xanthate (SEX). Related collectors include related sulfur-based ligands: dithiophosphates, dithiocarbamates. Still other classes of collectors include the thiourea thiocarbanilide. Fatty acid carboxylates, alkyl sulfates, and alkyl sulfonates have also been used for oxide minerals.
For some minerals (e.g., sylvinite for KCl), fatty amines are used as collectors. | 0 | Metallurgy |
Anodizing is an electrolytic passivation process used to increase the thickness of the natural oxide layer on the surface of metal parts.
The process is called anodizing because the part to be treated forms the anode electrode of an electrolytic cell. Anodizing increases resistance to corrosion and wear, and provides better adhesion for paint primers and glues than bare metal does. Anodic films can also be used for several cosmetic effects, either with thick porous coatings that can absorb dyes or with thin transparent coatings that add reflected light wave interference effects.
Anodizing is also used to prevent galling of threaded components and to make dielectric films for electrolytic capacitors. Anodic films are most commonly applied to protect aluminium alloys, although processes also exist for titanium, zinc, magnesium, niobium, zirconium, hafnium, and tantalum. Iron or carbon steel metal exfoliates when oxidized under neutral or alkaline micro-electrolytic conditions; i.e., the iron oxide (actually ferric hydroxide or hydrated iron oxide, also known as rust) forms by anoxic anodic pits and large cathodic surface, these pits concentrate anions such as sulfate and chloride accelerating the underlying metal to corrosion. Carbon flakes or nodules in iron or steel with high carbon content (high-carbon steel, cast iron) may cause an electrolytic potential and interfere with coating or plating. Ferrous metals are commonly anodized electrolytically in nitric acid or by treatment with red fuming nitric acid to form hard black Iron(II,III) oxide. This oxide remains conformal even when plated on wiring and the wiring is bent.
Anodizing changes the microscopic texture of the surface and the crystal structure of the metal near the surface. Thick coatings are normally porous, so a sealing process is often needed to achieve corrosion resistance. Anodized aluminium surfaces, for example, are harder than aluminium but have low to moderate wear resistance that can be improved with increasing thickness or by applying suitable sealing substances. Anodic films are generally much stronger and more adherent than most types of paint and metal plating, but also more brittle. This makes them less likely to crack and peel from ageing and wear, but more susceptible to cracking from thermal stress. | 0 | Metallurgy |
Metal recovery is the final step in a hydrometallurgical process, in which metals suitable for sale as raw materials are produced. Sometimes, however, further refining is needed to produce ultra-high purity metals. The main types of metal recovery processes are electrolysis, gaseous reduction, and precipitation. For example, a major target of hydrometallurgy is copper, which is conveniently obtained by electrolysis. Cu ions are reduced to Cu metal at low potentials, leaving behind contaminating metal ions such as Fe and Zn. | 0 | Metallurgy |
Galvanized steel can last for many decades if other supplementary measures are maintained, such as paint coatings and additional sacrificial anodes. Corrosion in non-salty environments is caused mainly by levels of sulfur dioxide in the air. | 0 | Metallurgy |
Flocculation is used in biotechnology applications in conjunction with microfiltration to improve the efficiency of biological feeds. The addition of synthetic flocculants to the bioreactor can increase the average particle size making microfiltration more efficient. When flocculants are not added, cakes form and accumulate causing low cell viability. Positively charged flocculants work better than negatively charged ones since the cells are generally negatively charged. | 0 | Metallurgy |
In genetics, an expressed sequence tag (EST) is a short sub-sequence of a cDNA sequence. ESTs may be used to identify gene transcripts, and were instrumental in gene discovery and in gene-sequence determination. The identification of ESTs has proceeded rapidly, with approximately 74.2 million ESTs now available in public databases (e.g. GenBank 1 January 2013, all species). EST approaches have largely been superseded by whole genome and transcriptome sequencing and metagenome sequencing.
An EST results from one-shot sequencing of a cloned cDNA. The cDNAs used for EST generation are typically individual clones from a cDNA library. The resulting sequence is a relatively low-quality fragment whose length is limited by current technology to approximately 500 to 800 nucleotides. Because these clones consist of DNA that is complementary to mRNA, the ESTs represent portions of expressed genes. They may be represented in databases as either cDNA/mRNA sequence or as the reverse complement of the mRNA, the template strand.
One can map ESTs to specific chromosome locations using physical mapping techniques, such as radiation hybrid mapping, HAPPY mapping, or FISH. Alternatively, if the genome of the organism that originated the EST has been sequenced, one can align the EST sequence to that genome using a computer.
The current understanding of the human set of genes () includes the existence of thousands of genes based solely on EST evidence. In this respect, ESTs have become a tool to refine the predicted transcripts for those genes, which leads to the prediction of their protein products and ultimately of their function. Moreover, the situation in which those ESTs are obtained (tissue, organ, disease state - e.g. cancer) gives information on the conditions in which the corresponding gene is acting. ESTs contain enough information to permit the design of precise probes for DNA microarrays that then can be used to determine gene expression profiles.
Some authors use the term "EST" to describe genes for which little or no further information exists besides the tag. | 1 | Gene expression + Signal Transduction |
The development process is modeled as the development of gene expression states. The gene expression pattern at time is defined as the initial expression state. The interactions among genes change the expression states during the development process. This process is modeled by the following differential equations
where τ) represents the expression state of at time . It is determined by a filter function σ. represents the weighted sum of regulatory effects () of all genes on gene at time . In the original Wagner model, the filter function is a step function
In other variants, the filter function is implemented as a sigmoidal function
In this way, the expression states will acquire a continuous distribution. The gene expression will reach the final state if it reaches a stable pattern. | 1 | Gene expression + Signal Transduction |
Activation of PKC-θ by diacylglycerol may cause insulin resistance in muscle by decreasing IRS1-associated PI3K activity. Similarly, activation of PKCε by diacyglycerol may cause insulin resistance in the liver. | 1 | Gene expression + Signal Transduction |
Neurons from several brain regions, such as the neocortex, substantia nigra, and hippocampus have been found to contain autapses.
Autapses have been observed to be relatively more abundant in GABAergic basket and dendrite-targeting cells of the cat visual cortex compared to spiny stellate, double bouquet, and pyramidal cells, suggesting that the degree of neuron self-innervation is cell-specific. Additionally, dendrite-targeting cell autapses were, on average, further from the soma compared to basket cell autapses.
80% of layer V pyramidal neurons in developing rat neocortices contained autaptic connections, which were located more so on basal dendrites and apical oblique dendrites rather than main apical dendrites. The dendritic positions of synaptic connections of the same cell type were similar to those of autapses, suggesting that autaptic and synaptic networks share a common mechanism of formation. | 1 | Gene expression + Signal Transduction |
Sociedad Española de Construcciones Electromecánicas (abbreviated as SECEM), colloquially known as "electro", was a Spanish company in the non-ferrous metals industry that operated between 1917 and 1978. Throughout its existence it was one of the most important Spanish companies in the copper sector, having its main activity in Córdoba. Among its products were copper products, brass, electrical transformers, etc. | 0 | Metallurgy |
As part of the Synthetic Yeast 2.0 project, various research groups around the world have participated in a project to synthesise synthetic yeast genomes, and through this process, optimise the genome of the model organism Saccharomyces cerevisiae. The Yeast 2.0 project applied various DNA assembly methods that have been discussed above, and in March 2014, Jef Boeke of the Langone Medical Centre at New York University, revealed that his team had synthesized chromosome III of S. cerevisiae. The procedure involved replacing the genes in the original chromosome with synthetic versions and the finished synthetic chromosome was then integrated into a yeast cell. It required designing and creating 273,871 base pairs of DNA – fewer than the 316,667 pairs in the original chromosome. In March 2017, the synthesis of 6 of the 16 chromosomes had been completed, with synthesis of the others still ongoing. | 1 | Gene expression + Signal Transduction |
The tripartite motif is always present at the N-terminus of the TRIM proteins. The TRIM motif includes the following three domains:
* (1) a RING finger domain
* (2) one or two B-box zinc finger domains
** when only one B-box is present, it is always a type-2 B-box
** when two B-boxes are present the type-1 B-Box always precedes the type-2 B-Box
* (3) coiled coil region
The C-terminus of TRIM proteins contain either:
* Group 1 proteins: a C-terminal domain selected from the following list:
** NHL and IGFLMN domains, either in association or alone
** PHD domain associated with a bromodomain
** MATH domain (in e.g., TRIM37)
** ARF domain (in e.g., TRIM23)
** EXOIII domain (in e.g., TRIM19) or
* Group 2 proteins: a SPRY C-terminal domain
**e.g. TRIM21 | 1 | Gene expression + Signal Transduction |
Ler positively regulates the LEE genes by competition with its homolog, H-NS. H-NS silences LEE genes via rigid filament structures bound to the DNA that Ler disrupts and replaces through unknown mechanisms. Though little is known of the mechanism of Ler regulation, Ler interacts with DNA in specific ways. Ler binds DNA non-cooperatively, bends DNA in low concentrations, stiffens it in high concentration, and forms toroidal nucleoprotein complexes along DNA in vivo. | 1 | Gene expression + Signal Transduction |
Chemotaxis receptors are expressed in the surface membrane with diverse dynamics, some of them have long-term characteristics as they are determined genetically, others have short-term moiety as their assembly is induced ad hoc in the presence of the ligand. The diverse feature of the chemotaxis receptors and ligands provides the possibility to select chemotactic responder cells with a simple chemotaxis assay. By chemotactic selection we can determine whether a still not characterized molecule acts via the long- or the short-term receptor pathway. Recent results proved that chemokines (e.g. IL-8, RANTES) are working on long-term chemotaxis receptors, while vasoactive peptides (e.g. endothelin) act more on the short-term ones. Term chemotactic selection is also used to design a technique which separates eukaryotic or prokaryotic cells upon their chemotactic responsiveness to selector ligands. | 1 | Gene expression + Signal Transduction |
The light chain gene has three gene segments. These include: the light chain variable region (V), joining region (J), and constant region (C) gene segments. The variable region of light is therefore encoded by the rearrangement of VJ segments. The light chain can be either kappa,κ or lambda,λ. This process takes place at the level of mRNAs processing. Random rearrangements and recombinations of the gene segments at DNA level to form one kappa or lambda light chain occurs in an orderly fashion. As a result, "a functional variable region gene of a light chain contains two coding segments that are separated by a non-coding DNA sequence in unrearranged germ-line DNA" (Barbara et al., 2007). | 1 | Gene expression + Signal Transduction |
In December 2021, the FDA came up with a draft guidance for the use of ASO drug products. This draft guidance was directed towards sponsor-investigators who are developing individualized investigational antisense oligonucleotides (ASO) drug products for severely debilitating or life threatening diseases. Severely debilitating corresponds to a disease or condition that causes major irreversible morbidity. However, life-threatening is defined as the disease or condition has a likelihood of death unless the course of treatment leads to an endpoint of survival. Usually individuals that have a severely debilitating life threatening disease don't have any alternative treatment options, and their diseases will be rapidly progressing, leading to an early death and/or devastating or irreversible morbidity within a short time frame without treatment.
Drug development is usually targeted for a large number of individuals, in this case that is not possible because of the specificity of the mechanism of action of the ASO combined with the rarity of the treatment-amenable patient population. Under FDA regulations, a protocol under which an individual ASO product is administered to a human subject must be reviewed and approved by an institutional review board (IRB) before it can be administered to human subjects. When the individual is a child, additional safeguards need to be identified in order to prevent any developmental issues from occurring that may affect the life of the individual. The sponsor-investigator needs to get informed consent from the individual or from the person who is responsible for the individual. The consent needs to include a description of reasonably foreseeable risks or discomforts as part of the use of the ASO drug. The sponsor also needs to get individuals clinical and genetic diagnosis to confirm that the ASO will be beneficial. The analysis may be through gene sequencing, enzymatic analysis, biochemical testing, imaging evaluations. All results need to be included in the application. Also the sponsor needs to include evidence that establishes the role of the gene variant targeted by the ASO drug. The sponsor/investigator need to also provide evidence that the identified gene variant or variants are unique to the individual.
The guidance suggests that the starting dose should be based on available non-clinical data that has been collected from model organisms or in vitro studies and should be in correlation with other ASO drug product dosing information that is available. At the starting dose, pharmacological effects are expected. Furthermore, It is advised that a dosing escalation method be utilized. This includes the step of escalating the dodge from its initial dose based on pharmacodynamic effects and/or trial participants' response to the ASO.
In addition, protocols submitted to the FDA need to have a clear dosing plan and justification for selecting the starting dose, dosing interval, and plan for dose escalation or dose reduction based on clinical pharmacodynamic effects of the drug on the individual. Also all anticipated outcomes should be included in the drug plan when submitted to the FDA. It is extremely important for the investigators to monitor the patient closely during dose escalation. During the escalation period, adequate time should be provided in order to see therapeutic results. It is advised that the investigator not make concurrent changes to the dosing interval along with the dose without justification. The submitted plan should include a de-escalation/discontinuation plan if toxicity is observed. All drug administration needs to take place in an inpatient setting just to get a grasp of the adverse effects the drug may have. Once drug toxicity, beneficiancy and adverse effects are identified, the drug can be administered in an outpatient manner as long as the same concentration of drug is administered. | 1 | Gene expression + Signal Transduction |
While yeasts have only a single CaM gene, plants and vertebrates contain an evolutionarily conserved form of CaM genes. The difference between plants and animals in Ca signaling is that the plants contain an extended family of the CaM in addition to the evolutionarily conserved form. Calmodulins play an essential role in plant development and adaptation to environmental stimuli.
Calcium plays a key role in the structural integrity of the cell wall and the membrane system of the cell. However, high calcium levels can be toxic to a plant's cellular energy metabolism and, hence, the Ca concentration in the cytosol is maintained at a submicromolar level by removing the cytosolic Ca to either the apoplast or the lumen of the intracellular organelles. Ca pulses created due to increased influx and efflux act as cellular signals in response to external stimuli such as hormones, light, gravity, abiotic stress factors and also interactions with pathogens. | 1 | Gene expression + Signal Transduction |
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP or Ins3P or IP is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC).
Together with diacylglycerol (DAG), IP is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals. | 1 | Gene expression + Signal Transduction |
Rgg-like transcriptional regulators can be found in a variety of gram-positive bacteria Where ropB regulates speB protease production in S. pyogenes, a roughly equivalent secretory control mechanism can be seen in Rggs regulation of gtfG glucosyltransferase production in S. gordonii, in the manner in which gadR regulates acid resistance in Lactococcus lactis, how lasX regulates expression of lantibiotic lactocin S in Lactobacillus sakei, and MutRs regulation of mutacin in S. mutans Sequentially, these genes are all localized contiguously to their respective subject of regulation and share promoters localized contiguously to inverted repeat regions. | 1 | Gene expression + Signal Transduction |
The Imd pathway bears a number of similarities to mammalian TNFR signalling, though many of the intracellular regulatory proteins of Imd signalling also bear homology to different signalling cascades of human Toll-like receptors. | 1 | Gene expression + Signal Transduction |
Take samples from the chamber and let them dry in the room air. An initial assessment is made before any corrosion products are removed. When the tested parts are cleaned, the evaluation criteria must be taken into account.
Possible characteristics for evaluation: appearance after the test, appearance after removal of the corrosion products, number and size of imperfections, time to first corrosion, loss of mass.
The results are described in a test report. | 0 | Metallurgy |
Fulmer was a pioneer of Contract R&D in the UK. During its forty five years it provided technical solutions and research results as well as testing and consultancy for hundreds of companies and national and international agencies across the whole field of materials technology and related areas of physics and chemistry. Many papers were published in learned journals and books and many patents were granted to Fulmer authors.
Fulmer sponsored the further education of its technicians and helped many young graduates in metallurgy, physics and other sciences on the road to successful careers. In the 1970s and 80s Fulmer undertook curriculum development projects in Berkshire and Buckinghamshire primary and secondary schools. It thus introduced many young people to engineering, to problem solving methods and to working in teams.[49] A senior staff member joined the Berkshire education advisory service from Fulmer to continue and extend work of this kind.
Among the companies and organizations that owe their origins to Fulmer are:
* Applied Microengineering Limited. In-situ aligned wafer bonding machines and services
* Archer Technicoat Limited. Chemical vapour deposition and infiltration; manufacture and supply of related equipment
* Building Investigation and Testing Services Limited
* Chemlab Technology (Singapore) Pte Ltd. Set up in 1982 as a joint venture between Fulmer and Chemlab International (Singapore) Pte Ltd.
* Hansford Sensors Limited. Manufacture and supply of vibration measurement equipment
* IPH Fulmer Rope Tension Meters
* JRD Fluorochemicals Limited
* M4 Technologies Ltd – a Nottingham University spin-out. Research, consultancy and technology transfer services in the fields of materials and surface engineering, metallurgy, manufacturing and project management.
* Phoenix Scientific Industries Limited. Gas atomization for the production of metal powders; manufacture and supply of related equipment
* Questans Limited. Software development and consultancy specializing in thesaurus management and R&D management. Traded until December 2007
* Quo-tec Limited. Consultancy on the management of innovation. Sold in 2003 to CSIR (South Africa).
* the Technical Service Centre of The Pakistan Standards and Quality Control Authority (PSQCA).
* USL Ultrasonic Sciences. A major supplier to industry of automated and semi-automated ultrasonic testing systems and instruments, worldwide. | 0 | Metallurgy |
Carcinoembryonic antigen cell adhesion molecule-1 (Caecam1) is an immunoglobulin-like co-receptor that aids in cell adhesion in epithelial, endothelial and hematopoietic cells, and plays a vital role during vascularization and angiogenesis by binding vascular endothelial growth factor (VEGF).
Angiogenesis is important in embryonic development but it is also a fundamental process of tumor growth. Deletion of the gene in Caecam1-/- mice results in a reduction of the abnormal vascularization seen in cancer and lowered nitric oxide production, suggesting a therapeutic possibility through targeting of this gene. The neuropilin co-receptor family mediates binding of VEGF in conjunction with the VEGFR1/VEGFR2 and Plexin signaling receptors, and therefore also plays a role in tumor vascular development.
CD109 acts as a negative regulator of the tumor growth factor β (TGF-β) receptor. Upon binding TGF-β, the receptor is internalized via endocytosis through CD109's action which lowers signal transmission into the cell. In this case, the co-receptor is functioning in a critical regulatory manner to reduce signals that instruct the cell to grow and migrate – the hallmarks of cancer. In conjunction, the LRP co-receptor family also mediates binding of TGF-β with a variety of membrane receptors.
Interleukins 1, 2, and 5 all rely on interleukin co-receptors to bind to the primary interleukin receptors.
Syndecans 1 and 4 have been implicated in a variety of cancer types including cervical, breast, lung, and colon cancer, and abnormal expression levels have been associated with poorer prognosis. | 1 | Gene expression + Signal Transduction |
Mill scale is sought after by select abstract expressionist artists as its effect on steel can cause unpredicted and seemingly random abstract organic visual effects. Although the majority of mill scale is removed from steel during its passage through scale breaker rolls during manufacturing, smaller structurally inconsequential residue can be visible. Leveraging this processing vestige by accelerating its corrosive effects through the metallurgical use of phosphoric acid or in conjunction with selenium dioxide can create a high contrast visual substrate onto which other compositional elements can be added. | 0 | Metallurgy |
Fitness in this model is the probability that an individual survives to reproduce. In the simplest implementation of the model, developmentally stable genotypes survive (i.e. their fitness is ) and developmentally unstable ones do not (i.e. their fitness is ). | 1 | Gene expression + Signal Transduction |
One of the most important features of chemical synapses is that they are the site of action for the majority of psychoactive drugs. Synapses are affected by drugs, such as curare, strychnine, cocaine, morphine, alcohol, LSD, and countless others. These drugs have different effects on synaptic function, and often are restricted to synapses that use a specific neurotransmitter. For example, curare is a poison that stops acetylcholine from depolarizing the postsynaptic membrane, causing paralysis. Strychnine blocks the inhibitory effects of the neurotransmitter glycine, which causes the body to pick up and react to weaker and previously ignored stimuli, resulting in uncontrollable muscle spasms. Morphine acts on synapses that use endorphin neurotransmitters, and alcohol increases the inhibitory effects of the neurotransmitter GABA. LSD interferes with synapses that use the neurotransmitter serotonin. Cocaine blocks reuptake of dopamine and therefore increases its effects. | 1 | Gene expression + Signal Transduction |
Five basic modes of alternative splicing are generally recognized.
* Exon skipping or cassette exon: in this case, an exon may be spliced out of the primary transcript or retained. This is the most common mode in mammalian pre-mRNAs.
* Mutually exclusive exons: One of two exons is retained in mRNAs after splicing, but not both.
* Alternative donor site: An alternative 5 splice junction (donor site) is used, changing the 3 boundary of the upstream exon.
* Alternative acceptor site: An alternative 3 splice junction (acceptor site) is used, changing the 5 boundary of the downstream exon.
* Intron retention: A sequence may be spliced out as an intron or simply retained. This is distinguished from exon skipping because the retained sequence is not flanked by introns. If the retained intron is in the coding region, the intron must encode amino acids in frame with the neighboring exons, or a stop codon or a shift in the reading frame will cause the protein to be non-functional. This is the rarest mode in mammals but the most common in plants.
In addition to these primary modes of alternative splicing, there are two other main mechanisms by which different mRNAs may be generated from the same gene; multiple promoters and multiple polyadenylation sites. Use of multiple promoters is properly described as a transcriptional regulation mechanism rather than alternative splicing; by starting transcription at different points, transcripts with different 5-most exons can be generated. At the other end, multiple polyadenylation sites provide different 3 end points for the transcript. Both of these mechanisms are found in combination with alternative splicing and provide additional variety in mRNAs derived from a gene.
<br>These modes describe basic splicing mechanisms, but may be inadequate to describe complex splicing events. For instance, the figure to the right shows 3 spliceforms from the mouse hyaluronidase 3 gene. Comparing the exonic structure shown in the first line (green) with the one in the second line (yellow) shows intron retention, whereas the comparison between the second and the third spliceform (yellow vs. blue) exhibits exon skipping. A model nomenclature to uniquely designate all possible splicing patterns has recently been proposed. | 1 | Gene expression + Signal Transduction |
Smelting involves thermal reactions in which at least one product is a molten phase.
Metal oxides can then be smelted by heating with coke or charcoal (forms of carbon), a reducing agent that liberates the oxygen as carbon dioxide leaving a refined mineral. Concern about the production of carbon dioxide is only a recent worry, following the identification of the enhanced greenhouse effect.
Carbonate ores are also smelted with charcoal, but sometimes need to be calcined first.
Other materials may need to be added as flux, aiding the melting of the oxide ores and assisting in the formation of a slag, as the flux reacts with impurities, such as silicon compounds.
Smelting usually takes place at a temperature above the melting point of the metal, but processes vary considerably according to the ore involved and other matters. | 0 | Metallurgy |
Subgrain rotation recrystallization is a type of continuous dynamic recrystallization. Continuous dynamic recrystallization involves the evolution of low-angle grains into high-angle grains, increasing their degree of misorientation. One mechanism could be the migration and agglomeration of like-sign dislocations in the LAGB, followed by grain boundary shearing. The transformation occurs when the subgrain boundaries contain small precipitates, which pin them in place. As the subgrain boundaries absorb dislocations, the subgrains transform into grains by rotation, instead of growth. This process generally occurs at elevated temperatures, which allows dislocations to both glide and climb; at low temperatures, dislocation movement is more difficult and the grains are less mobile.
By contrast, discontinuous dynamic recrystallization involves nucleation and growth of new grains, where due to increased temperature and/or pressure, new grains grow at high angles compared to the surrounding grains. | 0 | Metallurgy |
Non-metallic inclusions, the presence of which defines purity of steel, are classified by chemical and mineralogical content, by stability and by origin. By chemical content non-metallic inclusions are divided into the following groups:
#sulfides (simple — FeS, MnS, AlS, CaS, MgS, ZrS and others; compound — FeS·FeO, MnS·MnO and others);
#nitrides (simple — ZrN, TiN, AlN, CeN and others; compound — Nb(C, N), V(c, N) and others), which can be found in alloyed steel and has strong nitride-generative elements in its content: titanium, aluminium, vanadium, cerium and others;
#silicates
#oxides (simple — FeO, MnO, CrO, SiO, AlO, TiO and others; compound — FeO·FeO, FeO·AlO, FeO·CrO, MgO·AlO, 2FeO·SiO and others;
The majority of inclusions in metals are oxides and sulfides since the content of phosphorus is very small.
Silicates are very detrimental to steels, especially if it has to undergo heat treatment at a later stage.
Usually nitrides are present in special steels that contain an element with a high affinity to nitrogen.
By mineralogical content, oxygen inclusions divide into the following main groups:
* Free oxides — FeO, MnO, CrO, SiO (quartz), AlO (corundum) and others
* Spinels — compound oxides formed by bi and trivalent elements
Ferrites, chromites and aluminates are in this group.
*silicates, which are present in steel like a glass or SiO with admixture of iron, manganese, chromium, aluminium and tungsten oxides and also crystalline silicates. Silicates are the biggest group among non-metallic inclusions. In liquid steel non-metallic inclusions are in solid or liquid condition. It depends on the melting temperature.
By stability, non-metallic inclusions are either stable or unstable. Unstable inclusions are those that dissolve in dilute acids (less than 10%concentration). Unstable inclusions are iron and manganese sulfides and also some free oxides.
Present-day levels of steel production allow to move off from the metal different inclusions. However, in general the content of inclusions in different steels varies within wide limits and has a big influence on the metal properties. | 0 | Metallurgy |
Electrometallurgy involves metallurgical processes that take place in some form of electrolytic cell. The most common types of electrometallurgical processes are electrowinning and electro-refining. Electrowinning is an electrolysis process used to recover metals in aqueous solution, usually as the result of an ore having undergone one or more hydrometallurgical processes. The metal of interest is plated onto the cathode, while the anode is an inert electrical conductor. Electro-refining is used to dissolve an impure metallic anode (typically from a smelting process) and produce a high purity cathode. Fused salt electrolysis is another electrometallurgical process whereby the valuable metal has been dissolved into a molten salt which acts as the electrolyte, and the valuable metal collects on the cathode of the cell. The fused salt electrolysis process is conducted at temperatures sufficient to keep both the electrolyte and the metal being produced in the molten state. The scope of electrometallurgy has significant overlap with the areas of hydrometallurgy and (in the case of fused salt electrolysis) pyrometallurgy. Additionally, electrochemical phenomena play a considerable role in many mineral processing and hydrometallurgical processes. | 0 | Metallurgy |
Artificial introduction of long dsRNAs or siRNAs has been adopted as a tool to inactivate gene expression, both in cultured cells and in living organisms. Structural and functional resolution of small RNAs as the effectors of RNA silencing has had a direct impact on experimental biology. For example, dsRNA may be synthesized to have a specific sequence complementary to a gene of interest. Once introduced into a cell or biological system, it is recognized as exogenous genetic material and activates the corresponding RNA silencing pathway. This mechanism can be used to effect decreases in gene expression with respect to the target, useful for investigating loss of function for genes relative to a phenotype. That is, studying the phenotypic and/or physiologic effects of expression decreases can reveal the role of a gene product. The observable effects can be nuanced, such that some methods can distinguish between “knockdown” (decrease expression) and “knockout” (eliminate expression) of a gene. RNA interference technologies have been noted recently as one of the most widely utilized techniques in functional genomics. Screens developed using small RNAs have been used to identify genes involved in fundamental processes such as cell division, apoptosis and fat regulation. | 1 | Gene expression + Signal Transduction |
A majority of the adhesion GPCRs are orphan receptors and work is underway to de-orphanize many of these receptors. Adhesion GPCRs get their name from their N-terminal domains that have adhesion-like domains, such as EGF, and the belief that they interact cell to cell and cell to extra cellular matrix. While ligands for many receptors are still not known, researchers are utilizing drug libraries to investigate compounds that can activate GPCRs and using these data for future ligand research.
One adhesion GPCR, GPR56, has a known ligand, collagen III, which is involved in neural migration inhibition. GPR56 has been shown to be the cause of polymicrogyria in humans and may play a role in cancer metastasis. The binding of collagen III to GPR56 occurs on the N-terminus and has been narrowed down to a short stretch of amino acids. The N-terminus of GPR56 is naturally glycosylated, but this glycosylation is not necessary for collagen III binding. Collagen III, results in GPR56 to signal through Gα12/13 activating RhoA. | 1 | Gene expression + Signal Transduction |
Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the BIRC5 gene.
Survivin is a member of the inhibitor of apoptosis (IAP) family. The survivin protein functions to inhibit caspase activation, thereby leading to negative regulation of apoptosis or programmed cell death. This has been shown by disruption of survivin induction pathways leading to increase in apoptosis and decrease in tumour growth. The survivin protein is expressed highly in most human tumours and fetal tissue, but is completely absent in terminally differentiated cells. These data suggest survivin might provide a new target for cancer therapy that would discriminate between transformed and normal cells. Survivin expression is also highly regulated by the cell cycle and is only expressed in the G2-M phase. It is known that Survivin localizes to the mitotic spindle by interaction with tubulin during mitosis and may play a contributing role in regulating mitosis. The molecular mechanisms of survivin regulation are still not well understood, but regulation of survivin seems to be linked to the p53 protein. It also is a direct target gene of the Wnt pathway and is upregulated by beta-catenin. | 1 | Gene expression + Signal Transduction |
LPA is the result of phospholipase A2 action on phosphatidic acid. The SN-1 position can contain either an ester bond or an ether bond, with ether LPA being found at elevated levels in certain cancers. LPA binds the high-affinity G-protein coupled receptors LPA1, LPA2, and LPA3 (also known as EDG2, EDG4, and EDG7, respectively). | 1 | Gene expression + Signal Transduction |
: ATP + HO ⟶ ADP + HPO + H
Adenosine triphosphate, or ATP, acts as a free energy "currency" in all living organisms. In a spontaneous dephosphorylation reaction 30.5 kJ/mol is released, which is harnessed to drive cellular reactions. Overall, nonspontaneous reactions coupled to the dephosphorylation of ATP are spontaneous, due to the negative free energy change of the coupled reaction. This is important in driving oxidative phosphorylation. ATP is dephosphorylated to ADP and inorganic phosphate.
On the cellular level, the dephosphorylation of ATPases determines the flow of ions into and out of the cell. Proton pump inhibitors are a class of drug that acts directly on ATPases of the gastrointestinal tract. | 1 | Gene expression + Signal Transduction |
The Schikorr reaction can be viewed as two distinct processes:
* the anaerobic oxidation of two Fe(II) (Fe) into Fe(III) (Fe) by the protons of water. The reduction of two water protons is accompanied by the production of molecular hydrogen (H), and;
* the loss of two water molecules from the iron(II) and iron(III) hydroxides giving rise to its dehydration and to the formation of a thermodynamically more stable phase iron(II,III) oxide.
The global reaction can thus be decomposed in half redox reactions as follows:
:2 (Fe → Fe + e) (oxidation of 2 iron(II) ions)
:2 (HO + e → ½ H + OH) (reduction of 2 water protons)
to give:
:2 Fe + 2 HO → 2 Fe + H + 2 OH
Adding to this reaction one intact iron(II) ion for each two oxidized iron(II) ions leads to:
:3 Fe + 2 HO → Fe + 2 Fe + H + 2 OH
Electroneutrality requires the iron cations on both sides of the equation to be counterbalanced by 6 hydroxyl anions (OH):
:3 Fe + 6 OH + 2 HO → Fe + 2 Fe + H + 8 OH
:3 Fe(OH) + 2 HO → Fe(OH) + 2 Fe(OH) + H
For completing the main reaction, two companion reactions have still to be taken into account:
The autoprotolysis of the hydroxyl anions; a proton exchange between two OH, like in a classical acid–base reaction:
:OH + OH → O + HO
:acid 1 + base 2 → base 1 + acid 2, or also,
:2 OH → O + HO
it is then possible to reorganize the global reaction as:
:3 Fe(OH) + 2 HO → (FeO + HO) + (FeO + 3 HO) + H
:3 Fe(OH) + 2 HO → FeO + FeO + 4 HO + H
:3 Fe(OH) → FeO + FeO + 2 HO + H
Considering then the formation reaction of iron(II,III) oxide:
it is possible to write the balanced global reaction:
:3 Fe(OH) → (FeO·FeO) + 2 HO + H
in its final form, known as the Schikorr reaction:
:3 Fe(OH) → FeO + 2 HO + H | 0 | Metallurgy |
Photolysis is performed resulting in photoactivation of the TIVA tag in the target cell or cells. Specifically, uncaging of the TIVA tag is accomplished using a 405-nm laser while measuring FRET excited by 514 nm. During this process, the mRNA-capturing moiety is released and subsequently anneals to the poly(A) tail of cellular mRNA. To confirm that the cell is not damaged during photolysis, the cell is imaged with the confocal microscope. | 1 | Gene expression + Signal Transduction |
In mineralogy, an inclusion is any material that is trapped inside a mineral during its formation. In gemology, an inclusion is a characteristic enclosed within a gemstone, or reaching its surface from the interior.
According to Hutton's law of inclusions, fragments included in a host rock are older than the host rock itself. | 0 | Metallurgy |
In the 1980s, the company began piping wastewater up to 14 miles to evaporation ponds on or near Ivanpah Dry Lake, east of Interstate 15 near Nevada. This pipeline repeatedly ruptured during cleaning operations to remove mineral deposits called scale. The scale is radioactive because of the presence of thorium and radium, which occur naturally in the rare-earth ore. A federal investigation later found that some 60 spills—some unreported—occurred between 1984 and 1998, when the pipeline and chemical processing at the mine were shut down. In all, about 600,000 gallons of radioactive and other hazardous waste flowed onto the desert floor, according to federal authorities. By the end of the 1990s, Unocal was served with a cleanup order and a San Bernardino County district attorney's lawsuit. The company paid more than $1.4 million in fines and settlements. After preparing a cleanup plan and completing an extensive environmental study, Unocal in 2004 won approval of a county permit that allowed the mine to operate for another 30 years. The mine passed a key county inspection in 2007. | 0 | Metallurgy |
Persistent slip-bands (PSBs) are associated with strain localisation due to fatigue in metals and cracking on the same plane. Transmission electron microscopy (TEM) and three-dimensional discrete dislocation dynamics (DDD) simulation were used to reveal and understand dislocations type and arrangement/patterns to relate it to the sub-surface structure. PSB – ladder structure – is formed mainly from low-density channels of mobile gliding screw dislocation segments and high-density walls of dipolar edge dislocation segments piled up with tangled bowing-out edge segment and different sizes of dipolar loops scattered between the walls and channels.
One type of dislocation loop forms the boundary of a completely enclosed patch of slipped material on the slip plane which terminates at the free surface. Widening of the slip band: Screw dislocation can have high enough resolved shear stress for a glide on more than one slip plane. Cross-slip can occur. But this leaves some segments of dislocation on the original slip plane. Dislocation can cross-slip back on to a parallel primary slip plane. where it forms a new dislocation source, and the process can repeat. These walls in PSBs are a ‘dipole dispersion’ form of stable arrangement of edge dislocations with minimal long-range stress field which has a minimal long-range stress field. This is different to slip-bands that is a planar stack of a stable array that has a strong long-range stress field. Thus, – in the free surface – cut and open (elimination) of dislocation loops at the surface cause the irreversible/persistent surface step associated with slip-bands.
Surface relief through extrusion occurs on the Burger's vector direction and extrusion height and PSB depth increase with PSB thickness. PSB and planar walls are parallel and perpendicularly aligned with the normal direction of the Critical resolved shear stress, respectively. And once dislocation saturate and reach its sessile configuration, cracks were observed to nucleate and propagate along PSB extrusions. To summarise, contrary to 2D line defects, the field at the slip-band tip is due to three-dimensional interactions where the slip band extrusion simulates a sink-like dislocation blooming along the slip band axis. The magnitude of the gradient deformation field ahead of the slip band depends on the slip height and the mechanical conditions for propagation is influenced by the emitted dislocations long range field.A surface marking, or slip band, appears at the intersection of an active slip plane and the free surface of a crystal. Slip occurs in avalanches separated in time. Avalanches from other slip systems crossing a slip plane containing an active source led to the observed stepped surface markings, with successive avalanches from the given source displaced relative to each other.
Dislocations are generated on a single slip plane They point out that a dislocation segment (Frank–Read source), lying in a slip plane and pinned at both ends, is a source of an unlimited number of dislocation loops. In this way the grouping of dislocations into an avalanche of a thousand or so loops on a single slip plane can be understood. Each dislocation loop has a stress field that opposes the applied stress in the neighbourhood of the source. When enough loops have been generated, the stress at the source will fall to a value so low that additional loops cannot form. Only after the original avalanche of loops has moved some distance away can another avalanche occur.
Generation of the first avalanche at a source is easily understood. When the stress at the source reaches r*, loops are generated, and continue to be generated until the back-stress stops the avalanche. A second avalanche will not occur immediately in polycrystals, for the loops in the first avalanche are stopped or partially stopped at grain boundaries. Only if the external stress is increased substantially will a second avalanche be formed. In this way the formation of additional avalanches with rising stress can be understood.
It remains to explain the displacement of successive avalanches by a small amount normal to the slip plane, thereby accounting for the observed fine structure of slip bands. A displacement of this type requires that a Frank–Read source move relative to the surface where slip bands are observed.
In situ nano-compression work in Transmission electron microscopy (TEM) reveals that the deformation of a-Fe at the nanoscale is an inhomogeneous process characterized by a series of short displacement bursts and intermittent large displacement bursts. The series of short bursts correspond to the collective movement of dislocations within the crystal. The large single bursts are from SBs nucleated from the specimen surface. These results suggest that the formation of SBs can be considered as a source-limited plasticity process. The initial plastic deformation is characterized by the multiplication/ movement of a few dislocations over short distances due to the availability of dislocation sources within the nano-blade. Once it has reached a stage at which the mobile dislocations along preferred slips planes have moved through the nano-blade or become entangled in sessile configurations and further dislocation movement is difficult within the crystal, plasticity is carried out by the formation of SBs, which nucleate from the surface and then propagate through the nano-blade.
Fisher et al. proposed that SBs are dynamically generated from a Frank–Read source at the specimen surface and are terminated by their own stress field in single crystals. The displacement burst behaviour reported by Kiener and Minor on compressing Cu single crystal nanopillars. Obviously suppressed the progress of serrated yielding (a series of short strain bursts) relative to that without the spinodal nanostructure. The results revealed that during compression deformation, the spinodal nanostructure confined the movement of dislocations (leading to a significant increase in dislocation density), causing a notable strengthening effect, and also kept the slip band morphology planar.
Dislocation activity assists the growth of austenite precipitates and provide quantitative data for revealing the stress field generated by interface migration. The jerky nature of the tip moving rate is probably due to the accumulation and relaxation of stress field near the tip. After leaving from the tip, the dislocation loop expands rapidly ahead of the tip thus the change in tip velocity is concomitant with dislocation emission. It indicates that the emitted dislocation is strongly repelled by the stress field present at the lath tip. When the loop meets the foil surface, it breaks into two dislocation segments that leave a visible trace, due to the presence of a thin oxide layer on the surface. The emission of a dislocation loop from the tip may also affect tip moving rate via interaction between the local dislocation loop and the possible interfacial dislocations in the semi-coherent interface surrounding the tip. consequently, the tip halted temporarily. The net shear stress acting on each dislocation results from a combination of the stress field at the lath tip (τ), the image stress tending to attract the dislocation loop to the surface (τ), the line tension (τ) and the interaction stress between dislocations (τ). This implies the strain field due to the transformation of austenite is large enough to cause the nucleation and emission of dislocations from an austenite lath tip. | 0 | Metallurgy |
The enzyme N-myristoyltransferase (NMT) or glycylpeptide N-tetradecanoyltransferase is responsible for the irreversible addition of a myristoyl group to N-terminal or internal glycine residues of proteins. This modification can occur co-translationally or post-translationally. In vertebrates, this modification is carried about by two NMTs, NMT1 and NMT2, both of which are members of the GCN5 acetyltransferase superfamily. | 1 | Gene expression + Signal Transduction |
CREB regulated transcription coactivator 2, also known as CRTC2, is a protein which in humans is encoded by the CRTC2 gene. | 1 | Gene expression + Signal Transduction |
Effectene Reagent is used in conjunction with the enhancer and the DNA condensation buffer (Buffer EC) to achieve high transfection efficiency. In the first step of Effectene–DNA complex formation, the DNA is condensed by interaction with the enhancer in a defined-buffer system. Effectene Reagent is then added to the condensed DNA to produce condensed Effectene–DNA complexes. The Effectene–DNA complexes are mixed with the medium and directly added to the cells.
Effectene Reagent spontaneously forms micelle structures exhibiting no size or batch variation (as may be found with pre-formulated liposome reagents). This feature ensures reproducibility of transfection-complex formation. The process of highly condensing DNA molecules and then coating them with Effectene Reagent is an effective way to transfer DNA into eukaryotic cells. | 1 | Gene expression + Signal Transduction |
Bacterial anaerobic corrosion is the bacterially-induced oxidation of metals. Corrosion of metals typically alters the metal to a form that is more stable. Thus, bacterial anaerobic corrosion typically occurs in conditions favorable to the corrosion of the underlying substrate. In humid, anoxic conditions the corrosion of metals occurs as a result of a redox reaction. This redox reaction generates molecular hydrogen from local hydrogen ions. Conversely, anaerobic corrosion occurs spontaneously. Anaerobic corrosion primarily occurs on metallic substrates but may also occur on concrete. | 0 | Metallurgy |
Difficulties have been encountered in the definition of the technological parameters that drive the process.
Two broad categories of generators, also known as power supplies, are in use on EDM machines commercially available: the group based on RC circuits and the group based on transistor-controlled pulses.
In both categories, the primary parameters at setup are the current and frequency delivered. In RC circuits, however, little control is expected over the time duration of the discharge, which is likely to depend on the actual spark-gap conditions (size and pollution) at the moment of the discharge. Also, the open circuit voltage (i.e. the voltage between the electrodes when the dielectric is not yet broken) can be identified as steady state voltage of the RC circuit.
In generators based on transistor control, the user is usually able to deliver a train of pulses of voltage to the electrodes. Each pulse can be controlled in shape, for instance, quasi-rectangular. In particular, the time between two consecutive pulses and the duration of each pulse can be set. The amplitude of each pulse constitutes the open circuit voltage. Thus, the maximum duration of discharge is equal to the duration of a pulse of voltage in the train. Two pulses of current are then expected not to occur for a duration equal or larger than the time interval between two consecutive pulses of voltage.
The maximum current during a discharge that the generator delivers can also be controlled. Because other sorts of generators may also be used by different machine builders, the parameters that may actually be set on a particular machine will depend on the generator manufacturer. The details of the generators and control systems on their machines are not always easily available to their user. This is a barrier to describing unequivocally the technological parameters of the EDM process. Moreover, the parameters affecting the phenomena occurring between tool and electrode are also related to the controller of the motion of the electrodes.
A framework to define and measure the electrical parameters during an EDM operation directly on inter-electrode volume with an oscilloscope external to the machine has been recently proposed by Ferri et al. These authors conducted their research in the field of μ-EDM, but the same approach can be used in any EDM operation. This would enable the user to estimate directly the electrical parameters that affect their operations without relying upon machine manufacturer's claims. When machining different materials in the same setup conditions, the actual electrical parameters of the process are significantly different. | 0 | Metallurgy |
G protein-coupled receptors (GPCRs) are a large family of integral membrane proteins that respond to a variety of extracellular stimuli. Each GPCR binds to and is activated by a specific ligand stimulus that ranges in size from small molecule catecholamines, lipids, or neurotransmitters to large protein hormones. When a GPCR is activated by its extracellular ligand, a conformational change is induced in the receptor that is transmitted to an attached intracellular heterotrimeric G protein complex. The G alpha subunit of the stimulated G protein complex exchanges GDP for GTP and is released from the complex.
In a cAMP-dependent pathway, the activated G alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP).
Increases in concentration of the second messenger cAMP may lead to the activation of
* cyclic nucleotide-gated ion channels
* exchange proteins activated by cAMP (EPAC) such as RAPGEF3
* popeye domain containing proteins (Popdc)
* an enzyme called protein kinase A (PKA).
The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated only if cAMP is present. Once PKA is activated, it phosphorylates a number of other proteins including:
* enzymes that convert glycogen into glucose
* enzymes that promote muscle contraction in the heart leading to an increase in heart rate
* transcription factors, which regulate gene expression
* also phosphorylate AMPA receptors
Specificity of signaling between a GPCR and its ultimate molecular target through a cAMP-dependent pathway may be achieved through formation of a multiprotein complex that includes the GPCR, adenylyl cyclase, and the effector protein. | 1 | Gene expression + Signal Transduction |
Alzheimers disease involves the progressive degeneration of the brain, severely impacting mental faculties. Since the Ca hypothesis of Alzheimers was proposed in 1994, several studies have shown that disruptions in Ca signaling are the primary cause of Alzheimers disease. Familial Alzheimers disease has been strongly linked to mutations in the presenilin 1 (PS1), presenilin 2 (PS2), and amyloid precursor protein (APP) genes. All of the mutated forms of these genes observed to date have been found to cause abnormal Ca signaling in the ER. Mutations in PS1 have been shown to increase IP-mediated Ca release from the ER in several animal models. Calcium channel blockers have been used to treat Alzheimer's disease with some success, and the use of lithium to decrease IP turnover has also been suggested as a possible method of treatment. | 1 | Gene expression + Signal Transduction |
Several hnRNPs interact with telomeres, which protect the ends of chromosomes from deterioration and are often associated with cell longevity. hnRNP D associates with the G-rich repeat region of the telomeres, possibly stabilizing the region from secondary structures which would inhibit telomere replication.
hnRNP has also been shown to interact with telomerase, the protein responsible for elongating telomeres and prevent their degradation. hnRNPs C1 and C2 associate with the RNA component of telomerase, which improves its ability to access the telomere. | 1 | Gene expression + Signal Transduction |
In geology, a deformation mechanism is a process occurring at a microscopic scale that is responsible for changes in a material's internal structure, shape and volume. The process involves planar discontinuity and/or displacement of atoms from their original position within a crystal lattice structure. These small changes are preserved in various microstructures of materials such as rocks, metals and plastics, and can be studied in depth using optical or digital microscopy. | 0 | Metallurgy |
Selective leaching can be used to produce powdered materials with extremely high surface area, such as Raney nickel and other heterogeneous catalysts. Selective leaching can be the pre-final stage of depletion gilding. | 0 | Metallurgy |
The model and its variants have a number of simplifying assumptions. Three of them are listing below.
#The organisms are modeled as gene regulatory networks. The models assume that gene expression is regulated exclusively at the transcriptional level;
#The product of a gene can regulate the expression of (be a regulator of) that source gene or other genes. The models assume that a gene can only produce one active transcriptional regulator;
#The effects of one regulator are independent of effects of other regulators on the same target gene. | 1 | Gene expression + Signal Transduction |
A conditional gene knockout allows gene deletion in a tissue in a tissue specific manner. This is required in place of a gene knockout if the null mutation would lead to embryonic death, or a specific tissue or cell type is of specific interest. This is done by introducing short sequences called loxP sites around the gene. These sequences will be introduced into the germ-line via the same mechanism as a knockout. This germ-line can then be crossed to another germline containing Cre-recombinase which is a viral enzyme that can recognize these sequences, recombines them and deletes the gene flanked by these sites.
Genes not involved in early development have been effectively studied using knockout approaches that use gene deletion. However, it is typically not possible to knock off genes that are active during early development without the organism suffering a fatal outcome. One method around this is conditional knockout. Utilizing a site-specific recombinase called Cre, the original conditional knockout technique recombined short target sequences known as LoxP. Since then, other recombinases have been created and employed in conditional knockout experiments. | 1 | Gene expression + Signal Transduction |
As found by Brooks, et al., while lactate is disposed of mainly through oxidation and only a minor fraction supports gluconeogenesis, lactate is the main gluconeogenic precursor during sustained exercise.
Brooks demonstrated in his earlier studies that little difference in lactate production rates were seen in trained and untrained subjects at equivalent power outputs. What was seen, however, was more efficient clearance rates of lactate in the trained subjects suggesting an upregulation of MCT protein.
Local lactate use depends on exercise exertion. During rest, approximately 50% of lactate disposal take place through lactate oxidation whereas in time of strenuous exercise (50-75% VO2 max) approximately 75-80% of lactate is used by the active cell, indicating lactate’s role as a major contributor to energy conversion during increased exercise exertion. | 1 | Gene expression + Signal Transduction |
Copper metallurgy in Africa encompasses the study of copper production across the continent and an understanding of how it influenced aspects of African archaeology. | 0 | Metallurgy |
Understanding of genetic regulatory circuits are key in the field of synthetic biology, where disparate genetic elements are combined to produce novel biological functions. These biological gene circuits can be used synthetically to act as physical models for studying regulatory function.
By engineering genetic regulatory circuits, cells can be modified to take information from their environment, such as nutrient availability and developmental signals, and react in accordance to changes in their surroundings . In plant synthetic biology, genetic regulatory circuits can be used to program traits to increase crop plant efficiency by increasing their robustness to environmental stressors. Additionally, they are used to produce biopharmaceuticals for medical intervention. | 1 | Gene expression + Signal Transduction |
Hormones have the following effects on the body:
* stimulation or inhibition of growth
* wake-sleep cycle and other circadian rhythms
* mood swings
* induction or suppression of apoptosis (programmed cell death)
* activation or inhibition of the immune system
* regulation of metabolism
* preparation of the body for mating, fighting, fleeing, and other activity
* preparation of the body for a new phase of life, such as puberty, parenting, and menopause
* control of the reproductive cycle
* hunger cravings
A hormone may also regulate the production and release of other hormones. Hormone signals control the internal environment of the body through homeostasis. | 1 | Gene expression + Signal Transduction |
Ethylene binds to it specific transmembrane receptor present on the cell membrane of endoplasmic reticulum. There are different ethylene receptor isoforms. Five isoforms are known in Arabidopsis thaliana which are named ethylene response/receptor 1 (ETR1), ethylene response sensor 1 (ERS1), ETR2, ERS2, and ethylene insensitive 4 (EIN4). The ETR1 is similar (conserved sequence) in different plants but with slight amino acid differences. A. thaliana receptors are classified into two subfamilies based on genetic relationship and common structural features, namely subfamily 1 that includes ETR1 and ERS1, and subfamily 2 that consists of ETR2, ERS2, and EIN4. In tomato there are seven types of ethylene receptors named SlETR1, SlETR2, SlETR3, SlETR4, SlETR5, SlETR6, and SlETR7 (Sl for Solanum lycopersicum, the scientific of tomato).
All ethylene receptors have similar organisation: a short N-terminal domain, three conserved transmembrane domains towards the N-terminus, followed by a GAF domain of unknown function, and then signal output motifs in the C-terminal region. The N-terminus is exposed on the lumen of the endoplasmic reticulum, and the C-terminus that is exposed to the cytoplasm of the cell. The N-terminus contains the sites for binding of ethylene, dimerization and membrane localization. Two similar receptors combine to form a homodimer through a disulfide bridge forming a cysteine-cysteine interaction. However, the main membrane localization is done by the transmembrane domain, which can also bind ethylene with the help of copper as a cofactor. Copper ion is supplied by a transmembrane protein responsive-to-antagonist 1 (RAN1) from antioxidant protein 1 (ATX1) via tiplin, or directly by copper transport protein.
Although the receptors are functionally active as dimers, only one copper ion binds to such dimer, indicating that one receptor dimer binds only one ethylene molecule. Mutations in the binding sites stop ethylene binding and also make plants insensitive to ethylene. Cys-65 in the protein helix 2 is particularly important as the binding site of copper ion as mutation in it stops copper and ethylene binding. The C-terminus is basically a bacterial two-component system with kinase activity and response regulator. ETR1 has histidine kinase activity, whereas ETR2, ERS2, and EIN4 have serine/threonine kinase activity, and ERS1 has both. The histidine kinase in ETR1 is not required for ethylene signaling. | 1 | Gene expression + Signal Transduction |
Silicon carbide was the first commercially important semiconductor material. A crystal radio "carborundum" (synthetic silicon carbide) detector diode was patented by Henry Harrison Chase Dunwoody in 1906. It found much early use in shipboard receivers. | 0 | Metallurgy |
The Chalcolithic occupation at Norşuntepe can be divided in 3 phases. The oldest Phase I dates to the Middle Chalcolithic and included Ubaid-type pottery. Phase II represents the Late Chalcolithic and during its final levels, more complex architecture appeared in the excavated area. | 0 | Metallurgy |
Around 1750, colonial raw materials poured into the British Isles, and factories began to appear. The earlier hardware with its chiseled and filed details fast gave way to less expensive, but equally functional hardware of similar but unadorned design. H and HL hinges are a good example of this transition.
After the American Revolution machines were invented to make screws and to produce rolled iron in thin sheets. By about 1800 cheap screws were readily available. Cast iron technology had long been available – now machine-made screws allowed such hardware to be economically mounted. Butt type hinges can be seen during this "Federal" Period (1800–1830) – but they quickly fell from favor, probably because they were subject to breakage.
A more obvious change in the shutter hardware was noted in shutter bolts. The common slide plate and keeper style of bolt started to appear. It was simpler to fabricate and operate than the earlier "strap style lock". This bolt relied on both the new cheap fasteners and the readily available plate iron. This bolt also relied on machines and "dies." This form of shutter bolt has been made continually ever since.
Strap hinges continued to dominate in the marketplace for hanging shutters. Drive pintles started to be replaced by similar pintles cut off and mounted on a piece of thin plate material and again fastened with the new screws. This is the precursor of the "plate pintle".
Changes in construction have been noted in the same period. Structures were built with openings into which pre-fabricated windows were installed. The earliest examples date from around 1810 and used a variation on the strap hinge. Instead of mounting the pintle to the surface of the structure, a new form was designed. This pintle was a flat plate of about two inches high and notched to one half of its height and formed to a female barrel. Holes were punched in the side of the pintle, and it was screwed directly to the side of the window before the window was installed on the structure. The strap hinges were modified to match the new pintles and the hinge was of the same width as the pintle and notched to one half of its height. A pin to mate with the female pintle was welded in the hinge. Examples of this type proved to be very durable and were in regular and widespread use through the 1870s.
Often when the shutters were removed – usually in the 20th century – cast type pintles were hit with a hammer and broken off flush with the edge of the window. The shutters often found their way into the basements of the home to provide coal bins for newly installed central heat or were nailed up in the barn to partition off pig sties or calf pens.
Cast iron tie-backs became much more popular during the Federal period – usually mounted on arms extending from the window sills. The "Federal Shell" was the dominant pattern in this period. | 0 | Metallurgy |
Characterization of the RRNPP family of quorum sensing regulators (which stands for proteins Rap, NprR, PrgX, PlcRd) were used in comparisons with ropB to postulate its structural functions. The Rap protein derived from Bacilli regulates sporulation, the NprR protein in Bacillus thuringiensis regulates necrotrophism, the PrgX protein regulates conjugation in Enterococcus faecalis, and PlcR protein regulates transcription of virulence factors in both Bacullis thuringiensis and Bacillus cereus. Similarities were observed in conserved asparagine residues on the TPR motifs of each of these proteins and in ropB. | 1 | Gene expression + Signal Transduction |
An on-line method of measuring hydrogen in aluminum is then required to characterize and optimize the process, which helps ensure the quality of outgoing products and monitors the performance of these degassing processes. Traditional laboratory methods, such as hot extraction, are too expensive for routine quality assurance, and too slow for effective process control. The Reduced Pressure Test (RPT) is often used on the foundry floor. The RPT is a semi-quantitative method with limited accuracy that provides an indication of the hydrogen level. | 0 | Metallurgy |
Grain boundary sliding is a plastic deformation mechanism where crystals can slide past each other without friction and without creating significant voids as a result of diffusion. The deformation process associated with this mechanism is referred to as granular flow. The absence of voids results from solid-state diffusive mass transfer, locally enhanced crystal plastic deformation, or solution and precipitation of a grain boundary fluid. This mechanism operates at a low strain rate produced by neighbor switching. Grain boundary sliding is grain size- and temperature-dependent. It is favored by high temperatures and the presence of very fine-grained aggregates where diffusion paths are relatively short. Large strains operating in this mechanism do not result in the development of a lattice preferred orientation or any appreciable internal deformation of the grains, except at the grain boundary to accommodate the grain sliding; this process is called superplastic deformation. | 0 | Metallurgy |
A transcription unit is a set of one or more genes transcribed from a single promoter. A TU may also include regulatory protein binding sites affecting this promoter and a terminator. A complex operon with several promoters contains, therefore, several transcription units. A transcription unit must include all the genes in an operon. | 1 | Gene expression + Signal Transduction |
Purely decorative work is rare among Minoan bronzes, and is comparatively poor in quality. There are several statuettes, very completely modelled but roughly cast; they are solid and unchased, with blurred details. Well known are a figure of a praying or dancing woman from the Troad, now at Berlin, and another from Hagia Triada; praying men from Tylissos and Psychro, another in the British Museum, a flute-player at Leyden, and an ambitious group of a man turning a somersault over a charging bull, known as the Minoan Bull-leaper. This last was perhaps a weight; there are smaller Mycenaean weights in the forms of animals, filled with lead, from Rhodes and Cyprus. Among the latest Mycenaean bronzes found in Cyprus are several tripod-stands of simple openwork construction, a type that has also been found with transitional material in Crete and in Early Iron Age (Geometric) contexts on the Greek mainland. Some more elaborate pieces, cast in designs of ships and men and animals, belong to a group of bronzes found in the Idaean cave in Crete, most of which are Asiatic works of the 9th or 8th centuries BC. The openwork tripods may have had the same origin. They are probably not Greek. | 0 | Metallurgy |
Alloys that are not bronze and brass have had a limited representation in the literature for archaeometallurgy. This is mostly due to lack of interest or evidence in the archaeological record. Arsenical copper is one such limited research topic with some experimental work done by Pollard, Thomas, and Williams. Through several experimental smeltings of copper ores including arsenic, Pollard, Thomas, and Williams found that arsenic in copper is retained in higher levels when a lower smelting temperature is used, implying that arsenical copper may have been the result of early smelting technologies where temperatures were unable to pass a certain point.
Lead experimentation has been limited mostly because of its ease in production. Ore containing lead can be easily smelted, re-melted, and worked and as such there is not much difficulty in understanding how past societies may have produced lead. When lead experiments are conducted, they are done much in the same fashion as copper smelting experiments taking notes on quantitative elements such as completion time, airflow rates, fuel usage, and the resulting amount and composition of metal from the smelt. In addition, lead is a toxic element and special care has to take place in order to experiment with it, which makes limitations on the experiments. | 0 | Metallurgy |
The laser peening process using computer control is described in AMS 2546. Like many other surface enhancement technologies, direct measuring of the results of the process on the workpiece during processing is not practical. Therefore, the process parameters of pulse energy and duration, water and opaque overlays are closely monitored during processing. Other quality control systems are also available that rely on pressure measurements such as electromagnetic acoustic transducers (EMAT), Velocity Interferometer System for Any Reflector (VISAR) and PVDF gauges, and plasma radiometers. Almen strips are also used, but they function as a comparison tool and do not provide a definitive measure of laser peening intensity. The resultant residual stresses imparted by the laser peening process are routinely measured by industry using x-ray diffraction techniques for the purposes of process optimization and quality assurance. | 0 | Metallurgy |
Subsets and Splits