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This class of proteins has been implicated in the regulation of cytoskeleton assembly, cytosolic enzymes, and membrane dynamics. P11's involvement with the cytoskeleton may aid the transport of other proteins throughout the cell and to the cell membrane. Unlike other S-100 proteins, the second EF-hand of protein p11 is incapable of binding calcium due to a series of mutations caused by deletions and substitutions. Annexin II, which is attracted to negatively charged phospholipids, binds to p11 at the Ca2+ binding site. In addition, Annexin II has been implicated in membrane-cytoskeleton interactions and in regulations of ion currents and substances across the membrane.
P11 and annexin II form a heterotetrameric protein complex that imitates the structure and function of S-100 proteins activated by the binding of calcium. This tetrameric complex is more stable than the p11 dimer, therefore the overexpression of the annexin II gene results in higher levels of p11 protein. Function P11 is an integral part of cellular structural scaffolding that interacts with plasma membrane proteins through its association with annexin II. Recently, it was discovered to form a complex with annexin I though the mechanism remains unknown. It works together with cytosolic and peripheral membrane-associated proteins such as AHNAK in the development of the intracellular membrane.
P11 has been implicated in the transportation of proteins involved in mood regulation, nociception, and cell polarization. It is found in cell types throughout the body though it is located predominantly in the lungs and kidneys. It is involved in the trafficking of proteins to the plasma membrane and can be expressed on the cell surface as a receptor. Many of the transported proteins are cell surface receptors in signal transduction pathways and ion channels. P11 facilitates nociception, Ca2+ uptake, and cell polarization. Complexed with the annexin II, p11 binds receptor and channel proteins and guides them to the cell surface, resulting in increased membrane localization and consequent magnified functional expression of these proteins.
Ion channels are among the several proteins that are transported through the interaction with p11. Some of these proteins include Nav1.8, TRPV5, TRPV6, TASK-1, and ASIC1a. Nav1.8 is a tetrodotoxin-resistant sodium channel that replaces lost sodium after cell damage. Increased expression of these channels alters the magnitude of the sodium current across the membrane. TRPV5 and TRPV6 are transient receptor potential channels selective for Ca+ and Mg2+ ions. TASK-1 is a two-pore domain K+ channel TWIK-related acid-sensitive K (TASK). P11 can also function as a retention factor, preventing TASK-1 from leaving the endoplasmic reticulum. ASIC1a is an acid-sensing ion channel involved in the pain sensory pathway, which is regulated by p11.
Although the exact mechanism is unclear, p11 protein has shown to be essential in the regulation of serotonin signaling in the brain. Serotonin (5-hydroxytryptamine or 5-HT), is a neurotransmitter found in the central and peripheral nervous systems. It is involved in mechanisms responsible for memory formation and learning, but is most known for its role in the regulation muscle contraction, appetite, sleep, and mood. Varying levels of serotonin found in the brain are associated with the development of mood disorders, such as clinical depression. P11 interacts with the serotonin receptor proteins, 5-HT receptors such as 5-HT1B, modulating the receptor signal transduction pathways activated by the binding of serotonin.
P11 also recruits the cell surface expression of the 5-HT4 receptor, increasing its concentration at the synapse. This results in more rapid serotonin-dependent activities. 5-HT4 is involved in the regulation of kinase activity in the central nervous system, phosphorylating target proteins, and facilitating endosomal activities. P11 is coexpressed with 5-HT4 mRNA and its protein in parts of the brain associated with depression, suggesting that their functions are linked and influence mood. Protein p11 can also be presented on the cell surface as a receptor for tissue-type plasminogen activator (tPA) and plasminogen. Plasmin production by many cells is dependent on p11.
Interactions S100A10 has been shown to interact with TRPV5, TRPV6, TASK-1, ASIC1a, CTSB, BAD, KCNK3, UBC and ANXA2. There is a specificity in the interaction between p11 and 5-HT1B. In a two-hybrid screen using twenty six out of 29 double-positive prey clones containing the gene encoding p11. This study showed that p11 interacted with 5-HT1B receptors but not with 5-HT1A, 5-HT2A, 5-HT5A, 5-HT6, dopamine D1 or D2 receptors, two irrelevant baits (C{Delta}115 and pRP21), or the empty plasmid. The specific interaction has been verified in three other ways: In HeLa cells and brain tissue p11 was found to coimmunoprecipitate with 5-HT1B receptors; Immunofluorescence studies show colocalization between p11 and 5-HT1B receptors at the cell surface; and distribution of p11 mRNA in the brain resembles that of 5-HT1B receptor mRNA.
The table below shows the proteins that interact with p11 and the functional role of p11 in these interactions Table 1 Regulation Regulation of protein activity The p11 and annexin II complex is regulated by the phosphorylation of SerII on the annexin II molecule by protein kinase C (PKC). This phosphorylation hinders the complex's ability to bind to certain target molecules. Protein Kinase A (PKA) reverses the effects of PKC by activating a phosphatase, which reactivates the complex through dephosphorylation. Regulation of transcription Current experiments on animals have shown that various factors and physiological stimuli have been successful in regulating the levels of p11 protein transcription.
Some of these factors are shown in the table below. Table 2 Clinical significance Depression Depression is a widespread, debilitating disease affecting persons of all ages and backgrounds. Depression is characterized by a plethora of emotional and physiological symptoms including feelings of sadness, hopelessness, pessimism, guilt, a general loss of interest in life, and a sense of reduced emotional well-being or low energy. Very little is known about the underlying pathophysiology of clinical depression and other related mood-disorders including anxiety, bipolar disorder, ADD, ADHD, and Schizophrenia. The p11 protein has been intimately linked to mood disorders, to be specific, depression, due to its role in serotonin systems via its interactions with serotonin 5-HT receptors.
Serotonin affects diverse systems including the cardiovascular, renal, immune, and gastrointestinal systems. Current research focuses on the neurotransmitter's relationship with mood-regulation. Under experimentation, mice deficient in the p11 protein display depression-like behaviors. Knockout experiments in which the gene coding for protein p11 was deleted from the mouse genome caused them to show signs of depression. This is also observed in humans. On the other hand, those with sufficient amount of p11 protein behave normally. When mice that showed depressive symptoms were administered anti-depressant drugs, their levels of p11 were found to increase at the same rate, as antidepressants affected their behavioral changes.
In addition, post-mortem comparisons of brain tissues showed much lower levels of p11 in depressed compared to control subjects. Levels of p11 have been found to be substantially lower in depressed humans and helpless mice, which suggests that altered p11 levels may be involved in the development of depression-like symptoms. Treatment Most of the current drugs and treatments for depression and anxiety increase levels of serotonin transmission among neurons. Selective Serotonin Reuptake Inhibitors (SSRIs), a very successful class of drugs, are known to increase the amount of serotonin available to brain cells quite rapidly. Despite this, their therapeutic effects take a period of several weeks to months.
Recent studies show that protein p11 increases the concentration of the serotonin 5-HT receptors at neuronal synapses, thereby rendering serotonin signaling much more efficient. The interaction with the serotonin 1b receptor (5-HT1B) and p11 can be summarized as follows: When p11 levels increases, the number of 5-HT1B receptors on the cell surface increase proportionately. An increase in the number of 5-HT1B receptors on the surface of the neuron increase the effectiveness of serotonin communication across the synapse. On the other hand, when p11 levels decrease, fewer 5-HT1B receptors migrate from inside the neuron to the cell membrane at the synaptic cleft, thus lowering the efficiency with which serotonin signaling can occur across the synapse.
These findings suggest that, although the serotonin levels are immediately introduced via medication, the period of time within which the medicine alleviates the patient's depression most likely relies on other regulatory proteins. Thus, given protein p11's interaction with serotonin 5-HT receptors and the increasing evidence of the protein's correlation to mood disorders, this protein has been identified as a target for research in the development of future antidepressants. Treatment with antidepressants (a tricyclic and monoamine oxidase inhibitor) and electroconvulsive therapy (ECT) caused an increase in the amount of p11 in the brain of these mice - the same biochemical change.
The levels of the p11 protein in humans and mice with symptoms of depression were substantially lower in comparison to the levels of p11 in non-depressed animals. Leading researcher Paul Greengard and his colleagues hypothesized that increasing p11 levels would result in the mice exhibiting antidepressant-like behaviors, and the opposite if p11 protein levels were reduced. They used a test that is used to measure antidepressant-like activity to affirm this hypothesis. In their findings, over-expressed p11 genes, compared to the control mice, had increased mobility and more 5-HT1B receptors at the cell surface, which made possible more serotonin transmission. When researchers "knocked out" the p11 gene in mice, they found that the knockout mice had fewer receptors at the cell surface, reduced serotonin signaling, reduced responsiveness to sweet reward, and decreased mobility, behaviors all characteristic of depression-like behaviors.
Also, the 5-HT1B receptors of p11 knockout mice were less responsive to serotonin and antidepressant drugs compared to those of control mice, which further implicates p11 in the main action of antidepressant medications. Antidepressant manipulations increase the p11 levels, whereas depressant manipulations reduce it. Therefore, in order to achieve an anti-depression effect, antidepressant medications should focus on the main action of the p11 proteins and increase levels of the protein. Future clinical trials At the current time, a study by the National Institutes of Health Clinical Center (CC) is recruiting participants for a study that will compare levels of p11 protein in people with and without major depressive disorder (MDD) and determine whether p11 levels in patients are affected by treatment with citalopram (Celexa), a serotonin reuptake inhibitor.
If successful, a more personalized treatment of MDD will be available in the future. References Further reading External links Associated story on U.S. National Public Radio Category:Mood disorders Category:S100 proteins
Phaclofen, or phosphonobaclofen, is a selective antagonist for the GABAB receptor. References Category:GABAB receptor antagonists Category:Phosphonic acids Category:Chloroarenes
Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of an enlarged prostate. A few months may be required before benefits occur. It is also used for scalp hair loss in men and as a part of hormone therapy in transgender women. It is taken by mouth. Common side effects include sexual problems, breast tenderness, and breast enlargement. Other side effects include an increased risk of certain forms of prostate cancer, depression, and angioedema. Exposure during pregnancy, including use by the partner of a pregnant women may result in harm to the baby.
Dutasteride is a 5α-reductase inhibitor, and hence is a type of antiandrogen. It works by decreasing the production of dihydrotestosterone (DHT), an androgen sex hormone. Dutasteride was patented in 1993 by GlaxoSmithKline and was approved for medical use in 2001. It is available as a generic medication. A month supply in the United Kingdom costs the NHS about £12 as of 2019. In the United States, the wholesale cost of this amount is about $6.66. In 2016, it was the 274th most prescribed medication in the United States with more than a million prescriptions. Medical uses Enlarged prostate Dutasteride is used for treating benign prostatic hyperplasia (BPH); colloquially known as an "enlarged prostate".
It is approved by the Food and Drug Administration (FDA) in the U.S. for this indication. Prostate cancer A 2010 Cochrane review found a 25–26% reduction in the risk of developing prostate cancer with 5α-reductase inhibitor chemoprevention. However, 5α-reductase inhibitors have been found to increase the risk of developing certain rare but aggressive forms of prostate cancer (27% risk increase), although not all studies have observed this. There is insufficient data to determine if they have an effect on the overall risk of death from prostate cancer. Scalp hair loss Dutasteride is approved for the treatment of male androgenetic alopecia in South Korea and Japan at a dosage of 0.5 mg per day.
It has been found in several studies to improve hair growth in men more rapidly and to a greater extent than 2.5 mg/day finasteride. The superior effectiveness of dutasteride relative to finasteride for this indication is considered to be related to the fact that the inhibition of 5α-reductase and consequent prevention of scalp DHT production is more complete with dutasteride. Dutasteride is also used off-label in the treatment of female pattern hair loss. Excessive hair growth Although no reports specific to dutasteride currently exist, 5α-reductase inhibitors like finasteride have been found to be effective in the treatment of hirsutism (excessive facial and/or body hair growth) in women.
In a study of 89 women with hyperandrogenism due to persistent adrenarche syndrome, finasteride produced a 93% reduction in facial hirsutism and a 73% reduction in bodily hirsutism after 2 years of treatment. Other studies using finasteride for hirsutism have also found it to be clearly effective. Dutasteride may be more effective than finasteride for this indication due to the fact that its inhibition of the 5α-reductase enzyme is comparatively more complete. Transgender hormone therapy Dutasteride is sometimes used as a component of hormone therapy for transgender women in combination with an estrogen and/or another antiandrogen like spironolactone. It may be useful for treating scalp hair loss or in those who have issues tolerating spironolactone.
Available forms Dutasteride is provided in the form of soft oil-filled gelatin oral capsules containing 0.5 mg dutasteride each. Contraindications Women who are or who may become pregnant should not handle the drug. Dutasteride can cause birth defects, specifically ambiguous genitalia and undermasculinization, in male fetuses. This is due to its antiandrogenic effects and is seen naturally in 5α-reductase deficiency. As such, women who are pregnant should never take dutasteride. People taking dutasteride should not donate blood to prevent birth defects if a pregnant women receives blood and, due to its long elimination half-life, should also not donate blood for at least 6 months after the cessation of treatment.
Children and people with known significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride should not take dutasteride. Adverse effects Dutasteride has overall been found to be well tolerated in studies of both men and women, producing minimal side effects. Adverse effects include headache and gastrointestinal discomfort. Isolated reports of menstrual changes, acne, and dizziness also exist. There is a small risk of gynecomastia (breast development or enlargement) in men. The risk of gynecomastia with 5α-reductase inhibitors is about 2.8%. The FDA has added a warning to dutasteride about an increased risk of high-grade prostate cancer. While the potential for positive, negative or neutral changes to the potential risk of developing prostate cancer with dutasteride has not been established, evidence has suggested it may temporarily reduce the growth and prevalence of benign prostate tumors, but could also mask the early detection of prostate cancer.
The primary area for concern is for patients who may develop prostate cancer whilst taking dutasteride for benign prostatic hyperplasia, which in turn could delay diagnosis and early treatment of the prostate cancer, thereby potentially increasing the risk of these patients developing high-grade prostate cancer. A 2018 meta-analysis found no higher risk of breast cancer with 5α-reductase inhibitors. Sexual dysfunction, such as erectile dysfunction, loss of libido, or reduced semen volume, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride. This is linked to lower quality of life and can cause stress in relationships. It has been reported that in a subset of men, these adverse sexual side effects may persist even after discontinuation of finasteride or dutasteride.
Some have decreased sperm numbers as low as 10% of pretreatment values. Several small studies have reported an association between 5α-reductase inhibitors and depression. However, most studies have not observed this side effect. There have also been reports in a subset of men of long-lasting depression persisting even after discontinuation of dutasteride. Overdose There is no specific antidote for overdose of dutasteride. Treatment of dutasteride overdose should be based on symptoms and should be supportive. The long elimination half-life of dutasteride should be taken into consideration in the event of an overdose of the medication. Dutasteride has been used in clinical studies at doses of up to 40 mg/day for a week (80 times the therapeutic dosage) and 5 mg/day for 6 months (10 times the therapeutic dosage) with no significant safety concerns or additional side effects, respectively.
Interactions 5α-Reductase inhibitors can also prevent the formation of neurosteroid metabolites like allopregnanolone from progesterone and hence may reduce or block the sedative, anticonvulsant, anxiolytic, and various other effects of progesterone, particularly in the case of oral progesterone (which is disproportionately converted into these metabolites due to first-pass metabolism). Pharmacology Pharmacodynamics Dutasteride belongs to a class of drugs called 5α-reductase inhibitors, which block the action of the 5α-reductase enzymes that convert testosterone into DHT. It inhibits all three forms of 5α-reductase, and can decrease DHT levels in the blood by up to 98%. Specifically it is a competitive, mechanism-based (irreversible) inhibitor of all three isoforms of 5α-reductase, types I, II, and III ( values are 3.9 nM for type I and 1.8 nM for type II).
This is in contrast to finasteride, which is similarly an irreversible inhibitor of 5α-reductase but only inhibits the type II and III isoenzymes. As a result of this difference, dutasteride is able to achieve a reduction in circulating DHT levels of up to 98%, whereas finasteride is able to achieve a reduction of only 65 to 70%. In spite of the differential reduction in circulating DHT levels, the two drugs decrease levels of DHT to a similar extent of approximately 85 to 90% in the prostate gland, where the type II isoform of 5α-reductase predominates. Since 5α-reductases degrade testosterone to DHT, the inhibition of them could cause an increase in testosterone.
However, a 2018 review found that initiation of 5α-reductase inhibitors did not result in a consistent increase in testosterone levels, with some studies showing increases and others showing no change. There was no statistically significant change in testosterone levels from 5α-reductase inhibitors in the overall meta-analysis, though men with lower baseline testosterone levels may a rise in testosterone levels. In addition to inhibition of DHT production, 5α-reductase inhibitors like dutasteride are also neurosteroidogenesis inhibitors, preventing the 5α-reductase-mediated biosynthesis of various neurosteroids including allopregnanolone (from progesterone), (from deoxycorticosterone), and 3α-androstanediol (from testosterone). These neurosteroids are potent positive allosteric modulators of the GABAA receptor and have been found to possess antidepressant, anxiolytic, and pro-sexual effects in animal research.
For this reason, prevention of neurosteroid formation may be involved in the sexual dysfunction and depression that has been associated with 5α-reductase inhibitors like dutasteride. Pharmacokinetics The oral bioavailability of dutasteride is approximately 60%. Food does not adversely affect the absorption of dutasteride. Peak plasma levels occur 2 to 3 hours after administration. Levels of dutasteride in semen have been found to be 3 ng/mL, with no significant effects on DHT levels in sexual partners. The drug is extensively metabolized in the liver by CYP3A4. It has three major metabolites, including 6'-hydroxydutasteride, 4'-hydroxydutasteride, and 1,2-dihydrodutasteride; the former two are formed by CYP3A4, while the latter is not.
All three metabolites are active; 6'-hydroxydutasteride has similar potency as a 5α-reductase inhibitor to dutasteride, while the other two are less potent. Dutasteride has an extremely long terminal or elimination half-life of about 4 or 5 weeks. The elimination half-life of dutasteride is increased in the elderly (170 hours for men age 20–49 years, 300 hours for men age >70 years). No dosage adjustment is necessary in the elderly nor in renal impairment. Because of its long elimination half-life, dutasteride remains in the body for a long time after discontinuation and can be detected for up to 4 to 6 months.
In contrast to dutasteride, finasteride has a short terminal half-life of only 5 to 8 hours. Dutasteride is eliminated mainly in the feces (40%) as metabolites. A small portion (5%) is eliminated unchanged in the urine. Chemistry Dutasteride, also known as N-[2,5-bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, is a synthetic androstane steroid and a 4-azasteroid. It is an analogue of finasteride in which the tert-butyl amide moiety has been replaced with a 2,5-bis(trifluoromethyl)phenyl group. History Dutasteride was patented in 1996 and was first described in the scientific literature in 1997. It was approved by the FDA for the treatment of BPH in November 2001 and was introduced into the United States market the following year under the brand name Avodart.
Dutasteride has subsequently been introduced in many other countries, including throughout Europe and South America. The patent protection of dutasteride expired in November 2015 and the drug has since become available in the United States in a variety of low-cost generic formulations. It was approved for the treatment of scalp hair loss in South Korea since 2009 and in Japan since 2015. It has not been approved for this indication in the United States, though it is often used off-label. Society and culture Generic names Dutasteride is the generic name of the drug and its , , , and .
Brand names Dutasteride is sold primarily under the brand name Avodart and, in combination with tamsulosin (see dutasteride/tamsulosin), under the brand names Combodart and Duodart. It is also sold under a variety of generic brand names. Dutasteride is also available in combination with alfuzosin under the brand names Alfusin-D and Dutalfa, but only in India. Availability Dutasteride is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, many other European countries, Australia, and South Africa, as well as in Latin America, Asia, and elsewhere. It is available as a generic medication in the United States and other countries.
Research Dutasteride has been studied in combination with bicalutamide in the treatment of prostate cancer. A study found that dutasteride, which blocks the formation of the neurosteroid allopregnanolone from progesterone, is effective in reducing symptoms in women with premenstrual dysphoric disorder. References External links Drug information from the NIH Category:5α-Reductase inhibitors Category:Androstanes Category:Carboxamides Category:Diketones Category:Hair loss medications Category:Hair removal Category:Hormonal antineoplastic drugs Category:Lactams Category:Prostate cancer Category:Teratogens Category:Trifluoromethyl compounds Category:RTT
The English mathematician Alan Turing introduced a concept, which came to be known as a Turing pattern, in a 1952 paper entitled "The Chemical Basis of Morphogenesis". This foundational paper describes how patterns in nature, such as stripes and spots, can arise naturally from a homogeneous, uniform state. Overview The original theory, a reaction–diffusion theory of morphogenesis, has served as an important model in theoretical biology. Reaction–diffusion systems have attracted much interest as a prototype model for pattern formation. Patterns such as fronts, hexagons, spirals, stripes and dissipative solitons are found as solutions of Turing-like reaction–diffusion equations. The parameters will depend on the physical system that is under consideration.
In the context of fish skin pigmentation, the associated equation is a three field reaction–diffusion where the linear parameters are associated with pigmentation cell concentration and the diffusion parameters are not the same for all fields. In dye-doped liquid crystals, photoisomerization process in the liquid crystal matrix is described as a reaction–diffusion equation of two fields (liquid crystal order parameter and concentration of cis-isomer of the azo-dye). Both systems have very different physical mechanisms on the chemical reactions and diffusive process, but on a phenomenological level, both have the same ingredients. Turing-like patterns have also been demonstrated to arise in developing organisms without the classical requirement of diffusible morphogens.
Studies in chick and mouse embryonic development suggest that the patterns of feather and hair-follicle precursors can be formed without a morphogen pre-pattern, and instead are generated through self-aggregation of mesenchymal cells underlying the skin. In these cases, a uniform population of cells can form regularly patterned aggregates that depend on the mechanical properties of the cells themselves and the rigidity of the surrounding extra-cellular environment. Regular patterns of cell aggregates of this sort were originally proposed in a theoretical model formulated by George Oster, which postulated that alterations in cellular motility and stiffness could give rise to different self-emergent patterns from a uniform field of cells.
This mode of pattern formation may act in tandem with classical reaction-diffusion systems, or independently to generate patterns in biological development. As well as in biological organisms, Turing patterns occur in other natural systems – for example, the wind patterns formed in sand. Although Turing's ideas on morphogenesis and Turing patterns remained dormant for many years, they are now inspirational for much research in mathematical biology. It is a major theory in developmental biology; for example, a morphogenetic theory of lymphangiogenesis predicts that VEGFC can form Turing patterns to regulate the process in the zebrafish embryo. Turing patterns can also be created in nonlinear optics as demonstrated by the Lugiato–Lefever equation.
See also Evolutionary developmental biology Mathematical and theoretical biology Patterns in nature Reaction–diffusion system References Bibliography (See also extended version, June 2012.) Category:1952 in England Category:1952 introductions Category:Pattern formation Category:Patterns Category:Mathematical modeling Category:Parabolic partial differential equations Category:Biological processes Category:Chaos theory Category:Alan Turing
Foot rot, or infectious pododermatitis, is a hoof infection commonly found in sheep, goats, and cattle. As the name suggests, it rots away the foot of the animal, more specifically the area between the two toes of the affected animal. It is extremely painful and contagious. It can be treated with a series of medications, but if not treated, the whole herd can become infected. The cause of the infection in cattle is two species of anaerobic bacteria, Fusobacterium necrophorum and Bacteroides melaninogenicus. Both bacteria are common to the environment in which cattle live, and Fusobacterium is present in the rumen and fecal matter of the cattle.
In sheep, F. necrophorum first invades the interdigital skin following damage to the skin, and causes interdigital lesions and slight inflammation. The second stage of the disease is marked by the invasion of the foot by the foot rot bacterium Dichelobacter nodosus, a Gram-negative anaerobe. Usually, an injury to the skin between the hooves allows the bacteria to infect the animal. Another cause of foot rot may be high temperatures or humidity, causing the skin between the hooves to crack and let the bacteria infect the foot. This is one of the reasons foot rot is such a major problem in the summer.
Foot rot is easily identifiable by its appearance and foul odor. Treatment is usually with an antibiotic medication, and preventing injury to the feet is the best way to prevent foot rot. The disease is different in cattle and sheep and cross-infection is not thought to occur. Signs of infection The first sign of a foot-rot infection is when the skin between the claws of the hoof begins to swell (cellulitis). Swelling usually appears 24 hours after infection. The skin between the toes may be very red and tender and the toes may separate because of all the swelling. This is very painful to the animal and can cause lameness.
The animal may also have a raised body temperature. A crack can develop along the infected part and is yellow in color. The foot will have a foul odor. Tendons and joints in the area can become infected, which is much harder to treat. A condition known as "super foot rot" is seen in some animals. Super foot rot infection occurs much faster and is usually much more severe. Most normal foot rot treatments will not cure this foot rot and a veterinarian should be contacted immediately. Vaccines have been developed, but their efficacy is questionable and the immunity they provide is of short duration.
See also Trench foot Thrush (horse) References Further reading W.G. Kvasnica, DVM, Ben Bruce, Ph.D., Ron Torell, MS. Foot Rot of Cattle External links Image of a foot with foot rot Foot rot information Information on foot rot in sheep Foot rot in Estonian Category:Bovine diseases Category:Sheep and goat diseases Category:Bacterial diseases
The shch-el-1 (Cyrillic script: Щэл1) was Russia's first diesel locomotive. It was designed by Yakov Modestovich Gakkel and built by the Putilov Plant and the Baltic Shipyard. It was completed in 1924 and named "The Lenin Memorial Diesel Locomotive". Powertrain The prime mover was a Vickers 10 cylinder diesel engine. According to Westwood, this was "presumably salvaged from a British submarine lost in the Baltic in 1919". The electric generators were also of submarine type but were made in Italy. Details of the traction motors are unknown. Service After trials, the locomotive worked on the Moscow-Kursk line but spent a lot of time out of service.
It was withdrawn in 1927, after covering 25,000 miles, and was then put to work as a mobile generator. Preservation The locomotive is preserved at the Russian Railway Museum in Saint Petersburg. References Category:Railway locomotives introduced in 1924 shch-el-1 Category:5 ft gauge locomotives
A water level; [Alfadolasticho] is any device utilizing the surface of liquid water to establish a horizontal plane of reference; used to determine the apparent inclination of an object or surface and for matching elevations of locations that are too far apart for a spirit level to span. The simplest water level is a section of clear tubing, partially filled with water. Water is easily procured for use, and easily discarded after use. The ends are held vertical, and the rest of the tubing lies on the ground or floor. The water level at each end of the tube will be at the same elevation, whether the two ends are adjacent or far apart.
Water levels have been used for many years. The water level is lower-tech than the laser level, but it can be more accurate over long distances, and works without a sightline, such as around corners. To avoid error, all of the water should be at the same temperature. Other sources of error include difficulty reading due to meniscus. If the water level is used often, dye can be added to the water to make it easier to see. If the water level is used outdoors in winter, antifreeze can be added to the water. Automotive window washer fluid can also be used for antifreeze and increased visibility.
Additionally it inhibits the formation of error-causing bubbles. A surfactant (surface active agent), such as hand-dishwashing liquid detergent, can be added to the water to significantly lower the surface tension of the water. This liquid solution will flow more easily and more rapidly in the tube than plain water, so operation of the device will be more precise, repeatable, and responsive – particularly when using a small-diameter tube. Also, this liquid solution can be emptied from a small-diameter tube more easily than plain water. References External links How to Build a Simple but Effective Water Level Category:Construction equipment Category:Inclinometers Category:Surveying
In enzymology, a D-ornithine 4,5-aminomutase () is an enzyme that catalyzes the chemical reaction D-ornithine (2R,4S)-2,4-diaminopentanoate Hence, this enzyme has one substrate, D-ornithine, and one product, (2R,4S)-2,4-diaminopentanoate. This enzyme belongs to the family of isomerases, specifically those intramolecular transferases transferring amino groups. The systematic name of this enzyme class is D-ornithine 4,5-aminomutase. Other names in common use include D-alpha-ornithine 5,4-aminomutase, and D-ornithine aminomutase. This enzyme participates in d-arginine and d-ornithine metabolism. It has 3 cofactors: pyridoxal phosphate, Cobamide coenzyme, and Dithiothreitol. References Category:EC 5.4.3 Category:Pyridoxal phosphate enzymes Category:Enzymes of unknown structure
Agnes of Jesus, O.P., (born Agnès Galand and also known as Agnes of Langeac; November 17, 1602 – October 19, 1634) was a French Catholic nun of the Dominican Order. She was prioress of her monastery at Langeac, and is today venerated in the Roman Catholic Church, having been beatified by Pope John Paul II on November 20, 1994. Life Agnès Galand was born on November 17, 1602, in Le Puy-en-Velay, France, the third of seven children of Pierre Galand, a cutler by trade, and his wife, Guillemette Massiote. When she was five years old, Agnes was entrusted to a religious institute for her education.
Even from that early age, she showed a strong sense of spiritual maturity. She consecrated herself to the Virgin Mary at the age of seven. Agnes joined the Dominican Monastery of St. Catherine of Siena at Langeac in 1623. At her receiving of the religious habit she took the name Agnes of Jesus. Soon after her own profession, she was assigned to serve as the Mistress of novices for the community. Agnes was elected to lead her community as prioress in 1627. She was later deposed from this office, but she accepted her demotion with indifference and grace. She died on October 19, 1634, in Langeac.
Spiritual legacy Notable visions Agnes was noted even during her lifetime as a mystic. Saint Louis Marie de Montfort records the following anecdote: I shall simply relate an incident which I read in the life of Mother Agnes of Jesus, a Dominican nun of the convent of Langeac in Auvergne. ... One day the Blessed Virgin appeared to Mother Agnes and put a gold chain around her neck to show her how happy she was that Mother Agnes had become the slave of both her and her Son. And St. Cecilia, who accompanied our Lady, said to her, "Happy are the faithful slaves of the Queen of Heaven, for they will enjoy true freedom."
In 1631, Agnes experienced the most famous of her visions, in which the Blessed Virgin Mary urged her to pray for an unknown priest with the command, "Pray to my Son for the Abbé of Prébrac (near Cugnaux)." Monsignor Jean-Jacques Olier was the current holder of that office, and while at a retreat led by Saint Vincent de Paul, he experienced a vision in which Mother Agnes appeared to him, though he was unacquainted with her. He sought out the nun who had appeared to him in the dream. When he met Agnes, she told him: "I have received orders from the Holy Virgin to pray for you.
God has destined you to open the first seminaries in France." Olier would go on to found the Society of Saint-Sulpice. Before her death, she related to her community her great desire that they pray for priests. She also had visions of both her guardian angel and Satan. Veneration and beatification A cause for her beatification was introduced on April 19, 1713. She was declared venerable on March 19, 1808, by Pope Pius VII. Pope John Paul II beatified her on November 20, 1994. At her beatification ceremony, John Paul II called Agnes "truly blessed", noting her willingness to submit to God's plan for her, "offering her intellect, will, and freedom to the Son of Man, that he might transform them and harmonize them totally with his own!"
Her feast day is October 19. Blessed Hyacinthe-Marie Cormier, beatified on the same day as Agnes, cited the example of Agnes's life as his inspiration for joining the Dominican Order. He would go on to be elected the seventy-sixth Master General of the Dominicans in 1904. References External links A document about Bl. Agnes's visions of her guardian angel Monastère de Langeac (Monastère Sainte-Catherine-de-Sienne) A spiritual biography of Bl. Agnes Category:1602 births Category:1634 deaths Category:17th-century Christian mystics Category:People from Le Puy-en-Velay Category:Dominican nuns Category:Dominican beatified people Category:French Roman Catholic religious sisters and nuns Category:Dominican mystics Category:French beatified people Category:Marian visionaries Category:Angelic visionaries
Yuliya Arturovna Aug (; born June 8, 1970) is a Russian actress. Her film credits include The Student, Ekaterina and Leto. Aug was born in Leningrad. References External links Category:1970 births Category:Soviet actresses Category:Russian actresses Category:Living people Category:Recipients of the Nika Award Category:Actresses from Saint Petersburg Category:Russian theatre directors Category:Russian Academy of Theatre Arts alumni Category:Russian State Institute of Performing Arts alumni
The abolition of slavery occurred at different times in different countries. It frequently occurred sequentially in more than one stage – for example, as abolition of the trade in slaves in a specific country, and then as abolition of slavery throughout empires. Each step was usually the result of a separate law or action. This timeline shows abolition laws or actions listed chronologically. It also covers the abolition of serfdom. Although slavery is still abolished de jure in all countries, some practices akin to it continue today in many places throughout the world. Ancient times Medieval times N.B. : Many of the listed reforms were reversed over succeeding centuries.
1500–1700 (Early Modern) 1701–1799 (Late Modern) 1800–1829 1830–1849 1850–1899 1900–1949 1950–present See also Abolitionism History of slavery List of abolitionist forerunners (by Thomas Clarkson) Reparations for slavery Slave Trade Acts Sexual slavery Slavery at common law Slavery in modern Africa Timeline of the civil rights movement References Further reading Bales, Kevin. "Disposable People" (University of California Press, 2012) Campbell, Gwyn. The Structure of Slavery in Indian Ocean Africa and Asia (Frank Cass, 2004) Drescher, Seymour. Abolition: A History of Slavery and Antislavery (Cambridge University Press, 2009) Finkelman, Paul, and Joseph Miller, eds. Macmillan Encyclopedia of World Slavery (2 vol 1998) Gordon, M. Slavery in the Arab World (1989) Hinks, Peter, and John McKivigan, eds.
Encyclopedia of Antislavery and Abolition (2 vol. 2007) 795pp; Lovejoy, Paul. Transformations in Slavery: A History of Slavery in Africa (Cambridge UP, 1983) Morgan, Kenneth. Slavery and the British Empire: From Africa to America (2008) Rodriguez, Junius P., ed. The Historical Encyclopedia of World Slavery (1997) Rodriguez, Junius P., ed. Encyclopedia of Emancipation and Abolition in the Transatlantic World (2007) Psychiatric Slavery by psychiatrist Thomas Szasz External links Timeline – What happened before 1807? The Royal Naval Museum Timeline – What happened after 1807? The Royal Naval Museum Slavery and Abolition American Abolitionists and Antislavery Activists, comprehensive list of abolitionist and anti-slavery activists and organizations in the United States, including US and international anti-slavery timelines.
Category:Abolitionism Category:History of slavery Abolition of slavery and serfdom
In mathematics, computer science and especially graph theory, a distance matrix is a square matrix (two-dimensional array) containing the distances, taken pairwise, between the elements of a set. Depending upon the application involved, the distance being used to define this matrix may or may not be a metric. If there are elements, this matrix will have size . In graph-theoretic applications the elements are more often referred to as points, nodes or vertices. Non-metric distance matrices In general, a distance matrix is a weighted adjacency matrix of some graph. In a network, a directed graph with weights assigned to the arcs, the distance between two nodes of the network can be defined as the minimum of the sums of the weights on the shortest paths joining the two nodes.
This distance function, while well defined, is not a metric. There need be no restrictions on the weights other than the need to be able to combine and compare them, so negative weights are used in some applications. Since paths are directed, symmetry can not be guaranteed, and if cycles exist the distance matrix may not be hollow. An algebraic formulation of the above can be obtained by using the min-plus algebra. Matrix multiplication in this system is defined as follows: Given two matrices and , their distance product is defined as an matrix such that . Note that the off-diagonal elements that are not connected directly will need to be set to infinity or a suitable large value for the min-plus operations to work correctly.
A zero in these locations will be incorrectly interpreted as an edge with no distance, cost, etc. If is an matrix containing the edge weights of a graph, then (using this distance product) gives the distances between vertices using paths of length at most edges, and is the distance matrix of the graph. An arbitrary graph on vertices can be modeled as a weighted complete graph on vertices by assigning a weight of one to each edge of the complete graph that corresponds to an edge of and zero to all other edges. for this complete graph is the adjacency matrix of .
The distance matrix of can be computed from as above, however, calculated by the usual matrix multiplication only encodes the number of paths between any two vertices of length at most . Metric distance matrices The value of a distance matrix formalism in many applications is in how the distance matrix can manifestly encode the metric axioms and in how it lends itself to the use of linear algebra techniques. That is, if with is a distance matrix for a metric distance, then the entries on the main diagonal are all zero (that is, the matrix is a hollow matrix), i.e.
for all , all the off-diagonal entries are positive ( if ), (that is, a non-negative matrix), the matrix is a symmetric matrix (), and for any and , for all (the triangle inequality). This can be stated in terms of tropical matrix multiplication When a distance matrix satisfies the first three axioms (making it a semi-metric) it is sometimes referred to as a pre-distance matrix. A pre-distance matrix that can be embedded in a euclidean space is called a Euclidean distance matrix. Another common example of a metric distance matrix arises in coding theory when in a block code the elements are strings of fixed length over an alphabet and the distance between them is given by the Hamming distance metric.
The smallest non-zero entry in the distance matrix measures the error correcting and error detecting capability of the code. Applications Hierarchical clustering A distance matrix is necessary for hierarchical clustering. Phylogenetic analysis Distance matrices are used in phylogenetic analysis. Other uses In bioinformatics, distance matrices are used to represent protein structures in a coordinate-independent manner, as well as the pairwise distances between two sequences in sequence space. They are used in structural and sequential alignment, and for the determination of protein structures from NMR or X-ray crystallography. Sometimes it is more convenient to express data as a similarity matrix. It is used to define the distance correlation.
Examples For example, suppose these data are to be analyzed, where pixel Euclidean distance is the distance metric. The distance matrix would be: These data can then be viewed in graphic form as a heat map. In this image, black denotes a distance of 0 and white is maximal distance. See also Data clustering Computer Vision Min-plus matrix multiplication References Category:Metric geometry Category:Bioinformatics Category:Matrices
Wigton is a civil parish and town in the Borough of Allerdale in Cumbria, England. It contains 51 listed buildings that are recorded in the National Heritage List for England. Of these, one is listed at Grade II*, the middle of the three grades, and the others are at Grade II, the lowest grade. Most of the listed buildings are in or near the town centre, and mainly comprise shops and houses. There are also churches, public houses, hotels, schools, a bank, and a memorial drinking fountain. Further from the town centre, the listed buildings include a farmhouse and barn, a former mill, a war memorial, and a milestone.
__NOTOC__ Key Buildings References Citations Sources Category:Lists of listed buildings in Cumbria Listed buildings in
International Virtual Aviation Organisation VZW (IVAO) is a non-profit association which operates a free-of-charge online flight-simulation network. Following free registration users can connect to the IVAO Network (IVAN) either as a virtual air traffic controller or as a virtual pilot and engage and interact with each other in a massively multiplayer environment utilising real-world aviation procedures, phraseology and techniques. Overview IVAO, with more than 210,000 registered members, is one of the largest online flight simulation networks that allow users to act as either a virtual pilot or air traffic controller. IVAO relies solely on software developed by its own staff of volunteers.
Air Traffic Controllers can connect to the IVAO network using IVAO's radar client, IvAc, that emulates the interface of a modern, real-world air traffic control radar scope. Pilots can connect using their flight simulator and the built-in pilot client, IvAp. All pilots and ATC thereby interact on a dedicated, one-world server environment that tries to simulate world-wide air traffic on an "as real as it gets" basis. While the largest part of IVAO's active membership is based in Europe, new divisions are continually being created to spread the network coverage world-wide. IVAO logs all flight and controlling hours and offers its members to obtain virtual pilot and ATC ranks by undergoing training and passing theoretical and practical exams based around real-world aviation regulations and procedures.
A fully integrated VA system offers virtual airlines the ability to operate on the IVAO Network even with fictional airline callsigns and liveries. Events and regular gatherings are organised on a daily basis by divisions or members. With approximately 8,000 connections per day and an average weekday peak between 600 and 900 simultaneous connections, IVAO reached its current simultaneous connection record during the annual "Crowded Skies" event on December 10, 2016, with 3,004 members flying or controlling at the same time. History The first steps for setting up flight simulation in a massively-multiplayer online environment were taken with the creation of SquawkBox and ProController in the mid-1990s.
These two programs were connected to FSD, a simple flight simulator multiplayer server, which allowed the evolution from a one-to-one (one ATC and one plane) environment to a many-to-many environment. Using these programs, SATCO (now VATSIM) was the first large network to create an online air traffic simulation environment. On December 16, 1998 IVAO was founded when a group of people left SATCO to form a new network after management conflicts developed within the organisation. In late 2005, another management conflict, this time within the IVAO organisation, led to a further split. The incumbent president of IVAO continued with IVAO.org, while other members of management continued the organisation under IVAO.aero.
In 2007, IVAO was officially registered as a non-profit organisation under Belgian law. IVAO also has took part in FlightSimCon 2013, 2014, 2015 and 2016, held in Hartford, Connecticut. The formal status of IVAO has been changed into advertising bureau on September 1st 2015 and therefore IVAO has to pay VAT since October 1st 2015. In December 2019, IVAO Launched its Official BETA of 3 new pieces of software; Altitude - The IVAO Pilot Client, Aurora - The IVAO ATC Client, and Artifice - The Connector (Formerly IvAI). IVAO utilized its Virtual Sky media platform for the initial news release.
Virtual Sky IVAO has an official online media outlet dedicated to the Flight Simulation Community as a whole. "Virtual Sky" . It is a source of high-quality and authenticated news the aims to facilitate and enrich the discussions within the flight simulation community. Production is the responsibility of the Public Relations department, specifically the Virtual Sky Manager. Previously, in 2008, it was published in the form of an online magazine with quarterly updates. Countries with active divisions IVAO has active divisions in 73 countries spanning six continents. The active status means IVAO Headquarters has elected a staff team who represent it in the respective country and operates the division on its behalf.
This ensures members of each active country are offered up-to-date charts and personal one-to-one trainings adapted to local procedures. Some of the divisions are "multi-country" which means more than one country fall under one specific division. References External links Category:Aviation websites Category:Microsoft Flight Simulator add-ons Category:Massively multiplayer online games Category:Flight simulation video games
The ATR 72 is a twin-engine turboprop, short-haul regional airliner developed and produced in France and Italy by aircraft manufacturer ATR (Aerei da Trasporto Regionale or Avions de transport régional), a joint venture formed by French aerospace company Aérospatiale (now Airbus) and Italian aviation conglomerate Aeritalia (now Leonardo S.p.A.). The number "72" in its name is derived from the aircraft's standard seating configuration in a passenger-carrying configuration, which could seat 72–78 passengers in a single-class arrangement. During the 1980s, French aerospace company Aérospatiale and Italian aviation conglomerate Aeritalia merged their work on a new generation of regional aircraft. For this purpose, a new jointly owned company was established, ATR, for the purpose of developing, manufacturing, and marketing their first airliner, which was later designated as the ATR 42.
On 16 August 1984, the first model of the series, designated as the ATR 42-300, performed the type's maiden flight. During the mid-1980s, the ATR 72 was developed as a stretched variant of the ATR 42. On 27 October 1989, Finnish airline Finnair became the first airline to operate the type in revenue service. The ATR 72 has also been used as a corporate transport, cargo aircraft, and maritime patrol aircraft. To date, all of the ATR series have been completed at the company's final assembly line in Toulouse, France; ATR benefits from sharing resources and technology with Airbus SE, which has continued to hold a 50% interest in the company.
Successive models of the ATR 72 have been developed. Typical updates have included new avionics, such as a glass cockpit, and the adoption of newer engine versions to deliver enhanced performance, such as increased efficiency and reliability and reductions in operating costs. The aircraft share a high degree of commonality with the smaller ATR 42, which is also still in production. Development Origins During the mid-1980s, ATR sought to introduce a larger airliner with capacity. This new regional airliner, designated as the ATR 72, was directly developed from the earlier ATR 42 and continued to share many commonalities with it; the principal difference between the two airliners was an increase in the maximum seating capacity from 48 to 78 passengers.
This was principally achieved by stretching the fuselage by , along with an increase of the wingspan, the use of more powerful engines, and increased fuel capacity by about 10%. On 15 January 1986, the launch of the stretched ATR 72 programme was announced. On 27 October 1988, the first prototype performed its maiden flight; one year later, on September 25, 1989, the ATR 72 received airworthiness certification from the French Directorate General for Civil Aviation. During the following month, on 27 October 1989, Finnish airline Finnair became the first airline to introduce the aircraft into service. Since the ATR 72 is assembled on the same production line as the smaller ATR 42, along with sharing the majority of subsystems, components, and manufacturing techniques, the two types support each other to remain in production.
This factor may have been crucial as, by 2015, the ATR 42 was the only 50-seat regional aircraft that was still being manufactured. During 2000, the combined global ATR fleet reached its 10,000,000th flight, during which a distance around 4 billion km (2.5 billion statute miles) had been flown and around 450 million passengers had flown on board ATR-built aircraft. The 2007 production set a new record for the programme's sales; a total of 113 new ATR aircraft had been ordered during a single year. By the end of 2014, ATR had received 1,000 orders for the type and delivered a total of 754, leaving a backlog of 246 aircraft.
Within the ATR company, various organisational changes were implemented. On 10 July 1998, ATR launched its new Asset Management Department. In June 2001, EADS and Alenia Aeronautica, ATR's parent companies, decided to reinforce their partnership, regrouping all industrial activities related to regional airliners into the ATR consortium. On 3 October 2003, ATR became one of the first aircraft manufacturers to be certified under ISO 9001-2000 and EN/AS/JISQ 9100, the worldwide quality standard for the aeronautics industry. During July 2004, ATR and Brazilian aircraft manufacturer Embraer announced a co-operation agreement on the AEROChain Portal for the purpose of delivering improved customer service.
During April 2009, ATR announced the launch of its 'Door-2-Door' service as a new option in its comprehensive customer services range. Further development Since 2008, ATR has been a participant in the European Clean Sky Joint Technology Initiative. On 8 July 2015, an ATR 72-600 'green' technology demonstrator performed its first flight; the demonstrator was used for testing new composite materials for insulation, air conditioning systems, electrical distribution systems, and energy dispersal modifications to evaluate their effect on the aircraft's overall efficiency as a contribution to the Clean Sky initiative. ATR's senior vice-president for engineering Alessandro Amendola indicated that the elimination of all uses of bleed air was a key aim in the designing of an all-electric architecture as well as improving engine efficiency; the minimising of peak electrical loads was also a stated priority.
During March 2016, a second round of flight trials dedicated the testing of all-electric systems architecture using the demonstrator was completed; analysis is set to continue. The current production version is the ATR 72-600 series. On 2 October 2007, ATR CEO Stéphane Mayer announced the launch of the −600 series aircraft; the ATR 42–600 and ATR 72–600 featured various improvements to increase efficiency, dispatch reliability, lower fuel burn and operating costs. While broadly similar to the earlier -500 model; differences include the adoption of improved PW127M engines, a new glass cockpit, and a variety of other minor improvements.
As a consequence of strong demand for the -600 series, ATR decided to invest in the establishment of a second, more modern final assembly line and acquisition of more hangar space at its Toulouse site, along with a new large completion and delivery area; overall, the manufacturing operation expanded to four times the footprint that it had in 2005. Speaking in October 2015, ATR CEO Patrick de Castelbajac stated that the firm was set to produce in excess of 90 aircraft that year, and that the new manufacturing facilities could support a production rate of up to 120 per year.
At the time, the company had a backlog of orders for 300 aircraft, sufficient for three years of production. During 2017, a new in-house financing and leasing division was established by ATR in order to offer customers a greater degree of support and expand the company's range of services. Considerable emphasis has been placed upon the continuous development of ATR's aircraft models. Speaking at the Farnborough Airshow in July 2016, the CEO of ATR Patrick de Castelbajac stated that the company was currently examining the possibility of replacing the current Pratt & Whitney Canada PW127 engine with either a new offer from P&WC, or a GE38 derivative from GE Aviation.
Although expressing satisfaction with the PW127 engine and its supplier, Castelbajac noted the design's age and the need to remain competitive with the latest regional jets. To be a worthwhile exercise, any re-engine exercise would require a 15 per cent improvement in fuel-burn and 20-25 per cent reduction of direct maintenance costs. Additionally, Castelbajac sees the potential re-engine as a "bridge" to the eventual development of a larger 100-seat aircraft. During the mid-2010s, reports emerged that the development of a further stretched 90-seat ATR model was under consideration as well; allegedly, shareholder Airbus was relatively unenthusiastic on proceeding with such a development, while Airbus CEO Fabrice Brégier favoured a focus on resolving manufacturing issues.
However, in January 2018, ATR's parent company Leonardo announced that the 100-seat program has been formally brought to a close. Design The ATR 72 is a turboprop-powered regional airliner, capable of accommodating a maximum of 78 passengers. It is powered by a pair of Pratt & Whitney Canada PW100 turboprop engines, which drive an arrangement of four or six-bladed propellers supplied by Hamilton Standard. Earlier models of the ATR 72 are equipped with the older PW124B engine, rated at 2,400 shp, whilst later-built aircraft are powered by the newer PW127 engine, rated at a maximum of 2,750 shp to achieve improved "hot and high" takeoff performance.
It can land and takeoff in high airports with short runways like the Andorra Airport. It employs carbonfibres for 30% of the wing by weight, for a 20% weight reduction. In a standard configuration, the aircraft does not have an auxiliary power unit; when present it is installed within the C4 cargo section. Most operators of the ATR 72 equip their aircraft with a propeller brake (referred to as "Hotel Mode") that stops the propeller on the No. 2 (right) engine, allowing the turbine to continue running and provide both airflow and electrical power to the aircraft while on the ground.
In the majority of configurations, passengers board the ATR 72 using the rear door, a relatively unusual configuration for a passenger aircraft, while the front door is typically used for the loading and unloading of cargo; early customer Finnair intentionally ordered its ATR 72s with a front passenger door so that it could utilize the jet bridges at Helsinki Airport, while operator Air New Zealand's standard rear door aircraft can use jet bridges at airports with this equipment. While passengers are boarding or disembarking the aircraft, a tail stand is set into place as standard procedure to guard against the aircraft nose lifting off the ground.
Operational history 2011 was a record-breaking year for sales at ATR. According to ATR's CEO Filippo Bagnato, sales had continued to grow during the Great Recession despite the downturn experienced by most aviation companies as "fuel consumption that can be half that of the alternatives and [with] lower maintenance costs". Bagnato noted the strength of Africa as a market for the type, as well at the firm's aircraft being capable of serving destinations that would otherwise be inaccessible with other aircraft due to the austere conditions of many airstrips and runways in the region, as well as the ability to operate autonomously without any reliance upon ground support equipment.
For 2013, ATR claimed a 48 percent global market share for regional aircraft deliveries between 50 and 90 seats (comprising both turboprops and jets), making it the dominant manufacturer in this market segment. That same year, during which firm orders for 10 ATR 42-600s and 79 ATR 72-600s were recorded, leasing companies were responsible for 70 per cent of these; according to ATR's CEO Filippo Bagnato: "Years ago, we were not even considered by the lessors; now they see ATRs as a good investment". Several major leasing companies operate their own ATR fleets, such as Dubai Aerospace Enterprise (DAE), who placed an order for 20 ATR 72s along with options for another 20 in February 2014, and Nordic Aviation Capital (NAC), who ordered a fleet of 30 ATR 72s during June 2013, along with options for up to 55 further airliners.
Placing their first order during 2011, by December 2012, Singaporean leasor Avation had a combined total of 20 ATR 72s on order; by February 2016, the number on order for had risen to 35 aircraft. During May 1997, ATR achieved their first breakthrough sale in China, placed by operator China Xinjiang Airlines and the Civil Aviation Administration of China (CAAC). By 2013, while the Asia Pacific region had comprised the majority of ATR's sales when geographically ranked; however, orders from Chinese airlines remained elusive; Bagnato ascribed this anomaly to local market conditions dictating the typical use of larger aircraft, as well as a Chinese government policy of imposing high tariffs on the import of foreign-built fixed-wing aircraft.
During late 2014, ATR set up a new office in Beijing and hired several former Airbus sales personnel with the aim of launching the type in the Chinese market. ATR believed that many of the already-flown routes did not suit larger 150-seat aircraft; however, of the roughly 2,600 commercial aircraft flying in China at that time, only 68 had a capacity of less than 90 seats and of these, fewer than 20 were powered by turboprop engines. In response to airlines often wanting to replace their early production ATR models with the latest generation ATR series, as well as to answer demand from cargo operators for the type, ATR has operated two separate dedicated freighter conversion programmes, known as the Bulk Freighter (tube version) and the ULD Freighter.
Both conversions involve complete stripping of furnishings along with the addition of floor strengthening, new window plugs and 9g restraining nets, six additional longitudinal tracks for added flexibility, and an E-Class cabin; the ULD model can accommodate standard ULD-packaged cargo, such as LD3 containers or pallets, which were loaded via a large cargo door located on the port forward side. Undertaken by a range of companies, such as Alenia subsidiary Aeronavali, Texas-based M7 Aerospace; French firms Indraéro Siren and Aeroconseil, Canadian Infinion Certification Engineering, and Spanish company Arrodisa, by October 2012, in excess of one-fifth of all first-generation ATR 42 and ATR 72 aircraft had already been converted to freighters.
Iran Air During February 2016, ATR signed a deal with flag carrier Iran Air for a batch of 20 ATR 72-600s, along with options for 20 more aircraft and post-purchase services, such as engine maintenance. Made possible by a negotiated relaxation of international sanctions against Iran, during June 2017, a €1 billion Iranian contract was finalised for the 20 airliners; the delivery of the first four aircraft occurred within weeks of the deal being completed. US sanctions against Iran were reimposed in August 2018, by which time 13 of the order of 20 aircraft had been delivered. In April 2019 the US Office of Foreign Assets Control (OFAC) issued a two-year licence to ATR to allow it to supply spare parts and other essentials to keep the fleet of 13 ATR 72-600s in operation.
However, the remaining 7 ATR 72-600s from the 2016 order remain sanctioned and in storage. Turkish Navy While primarily used as a civil aircraft, some ATR 72s have been adapted to perform in various military functions, such as utility aircraft and maritime patrol aircraft (MPA). The Turkish Navy, which initially decided to purchase ten ATR 72–500 MPA, later expanded its order to eight aircraft: Two ATR 72–600 TMUA (utility) versions, and six ATR 72–600 TMPA (ASW/ASuW) versions. The armed ATR 72 TMPA variant was developed in cooperation with Turkish Aerospace Industries (TAI), and incorporated additional sensors and mission systems to perform its intended combat role.
During 2013, the two ATR 72–600 TMUA aircraft were delivered to the Turkish Navy. Italian Air Force The Italian Air Force also selected the ATR 72–500 MP, designated as the P-72A, to serve as a multirole maritime patrol, electronic surveillance and C4 platform. The original Italian requirement for a Breguet Atlantic replacement had also called for ASW and anti-surface warfare (ASuW) capabilities, however, during 2014, the contract was renegotiated to a configuration that excluded these capabilities. An anticipated P-72B variant for ASW and ASuW operations may later be pursued; accordingly, provisions were made to allow for the four P-72As on order to be adapted to the P-72B configuration.