A practical reference on elevated plus maze: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2025-11-30 and is reviewed periodically as new material appears.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, written TKPRPGP in one-letter notation. Its structure consists of the immunomodulatory tetrapeptide tuftsin, Thr-Lys-Pro-Arg, extended at the carboxyl terminus by a Pro-Gly-Pro segment. The molecular formula is commonly given as C33H57N11O9, corresponding to a monoisotopic mass near 751.4 Da and an average molecular mass near 751.9 Da. All seven residues are proteinogenic amino acids, and the molecule carries no modified side chains or non-natural linkages.
The compound was designed at the Institute of Molecular Genetics of the Russian Academy of Sciences during the 1980s and 1990s. The stated design goal was to retain the immunomodulatory and central nervous system activity attributed to tuftsin while improving resistance to enzymatic breakdown. Adding a proline-rich tail to the short parent peptide was a deliberate strategy, because proline residues restrict the conformations available to many peptidases. The same laboratory produced Semax, an ACTH fragment analog, and both compounds were developed in parallel as short, enzymatically stabilized peptides intended for intranasal use.
Selank is not a naturally occurring peptide and has no known endogenous counterpart in human physiology. Russian-language sources frequently call it TP-7, while English-language sources use the name Selank almost exclusively. Database indexing is uneven, partly because early reports appeared in regional journals that are not widely cataloged. Some summaries describe the material as a tuftsin analog and others as a synthetic heptapeptide; the labels overlap rather than conflict. Citing the primary sequence resolves ambiguity more reliably than the research or trade name alone.
Laboratory work relies on standard behavioral paradigms. Rodents are tested in the elevated plus maze, open field, and passive avoidance tasks, with outcomes compared against diazepam or vehicle controls. Intranasal dosing is used most often because it bypasses first-pass metabolism, though intraperitoneal and intravenous routes also appear in published protocols. Biochemical endpoints include tissue BDNF concentrations, cytokine levels, and monoamine metabolites. Human data are limited to small Russian trials reporting reduced anxiety scores; most were not prospectively registered, and few employed independent outcome assessment.
Measuring peptide exposure inside the brain is technically difficult. Selank is degraded rapidly in plasma, and assays must separate intact peptide from fragments, which favors targeted mass spectrometry over immunoassays alone. Reported half-lives are short, on the order of minutes, so effects observed hours later are attributed to downstream signaling rather than to the parent compound. Blood-brain barrier permeability is debated and rarely quantified directly. Gaps include absent dose-response characterization, inconsistent reporting of purity, and almost no pharmacokinetic data from human participants.
Selank is studied chiefly as an animal-model anxiolytic with proposed secondary effects on memory and immune signaling. Reported mechanisms include modulation of the GABA-A receptor complex, inhibition of enkephalin-degrading enzymes, and shifts in monoamine turnover within limbic structures. Some experiments describe increased expression of brain-derived neurotrophic factor in the hippocampus after repeated dosing. No single molecular target has been confirmed, and the peptide does not bind any receptor with the selectivity typical of a conventional small-molecule drug. Mechanism therefore remains a set of hypotheses rather than an established pathway.
| Property | Value | Notes |
|---|---|---|
| Peptide sequence | Thr-Lys-Pro-Arg-Pro-Gly-Pro | Seven residues; tuftsin plus a Pro-Gly-Pro tail |
| Molecular formula | C33H57N11O9 | Commonly reported value for the free peptide |
| Monoisotopic mass | Roughly 751.4 Da | Average molecular mass near 751.9 Da |
| Appearance | White to off-white powder | Typically supplied as a lyophilized solid |
| Solubility class | Freely soluble in water | Also dissolves in saline and other polar solvents |
Quality assessment of Selank samples typically combines purity determination with identity confirmation and counter-ion analysis. Purity is usually reported as a percentage by chromatographic area, with values above 95 percent often quoted for research-grade material. Water content and residual solvents are checked in lyophilized batches because they affect both stability and accurate mass determination. A reported purity figure does not by itself establish that a sample is the intended sequence, so orthogonal methods are needed to rule out sequence isomers or truncation products.
Characterization of Selank in laboratory settings relies on standard peptide analytical techniques. Reverse-phase high-performance liquid chromatography separates the peptide from related impurities and degradation products, while mass spectrometry confirms molecular identity through accurate mass measurement. Amino acid analysis and peptide sequencing verify the primary structure when reference material is unavailable. Because Selank is a short chain, fragmentation-based analysis produces a diagnostic ion pattern that supports confident identification.
Peptide stability depends strongly on temperature, moisture, and pH. Lyophilized Selank is generally most stable when stored cold and dry, with freezer temperatures commonly used for long-term storage. In solution, the compound is susceptible to hydrolysis and to microbial growth if it is not handled aseptically. The C-terminal proline-rich extension appears to slow enzymatic cleavage relative to tuftsin, though quantitative degradation rates vary with the matrix and the conditions tested. Published stability data specific to Selank remain sparse.
Once dissolved, the peptide is markedly less stable than the dry powder. Aqueous solutions are subject to backbone hydrolysis and to microbial growth when they are handled without sterile technique. Buffered solutions near neutral pH are common for short-term laboratory work, while acidic conditions are sometimes used to improve solubility. Analytical laboratories generally prepare working solutions fresh rather than storing them, and a residual water film left in a reopened vial can seed degradation even when the container appears dry.
Reversed-phase high-performance liquid chromatography is the standard technique for estimating peptide purity. The result is a peak-area percentage, which describes how much of the detected material elutes as the main peak in one run. Mass spectrometry confirms the molecular mass and can reveal truncated, adducted, or otherwise modified species. Amino acid analysis or tandem mass spectrometry can address sequence fidelity when identity is in doubt. None of these measurements, taken alone, establishes that a sample is fit for any specific purpose.
=== Strategies === A long-acting insulin is used to approximate the basal secretion of insulin by the pancreas, which varies in the course of the day. NPH/isophane, lente, ultralente, glargine, and detemir may be used for this purpose. The advantage of NPH is its low cost, the fact that you can mix it with short-acting forms of insulin, thereby minimizing the number of injections that must be administered, and that the activity of NPH will peak 4–6 hours after administration, allowing a bedtime dose to balance the tendency of glucose to rise with the dawn, along with a smaller morning dose to balance the lower afternoon basal need and possibly an afternoon dose to cover evening need. A disadvantage of bedtime NPH is that if not taken late enough (near midnight) to place its peak shortly before dawn, it has the potential of causing hypoglycemia. One theoretical advantage of glargine and detemir is that they only need to be administered once a day, although in practice many people find that neither lasts a full 24 hours. They can be administered at any time during the day as well, provided that they are given at the same time every day. Another advantage of long-acting insulins is that the basal component of an insulin regimen (providing a minimum level of insulin throughout the day) can be decoupled from the prandial or bolus component (providing mealtime coverage via ultra-short-acting insulins), while regimens using NPH and regular insulin have the disadvantage that any dose adjustment affects both basal and prandial coverage.
The chemical energy stored in ATP (the bond of its third phosphate group to the rest of the molecule can be broken, allowing more stable products to form, thereby releasing energy for use by the cell) can then be used to drive processes requiring energy, including biosynthesis, locomotion, or transportation of molecules across cell membranes.
This shows that when the reaction is exothermic (ΔHo, the standard enthalpy change, is negative), then K decreases with increasing temperature, in accordance with Le Châtelier's principle. The approximation involved is that the standard enthalpy change, ΔHo, is independent of temperature, which is a good approximation only over a small temperature range. Thermodynamic arguments can be used to show that
Majority (about 70% to 80%) is converted to bicarbonate ions (HCO3–) by the enzyme carbonic anhydrase in the red blood cells, by the reaction: CO2 + H2O → H2CO3 → H+ + HCO3– 5–10% is dissolved in blood plasma 5–10% is bound to hemoglobin as carbamino compounds Hemoglobin, the main oxygen-carrying molecule in red blood cells, carries both oxygen and carbon dioxide. However, the CO2 bound to hemoglobin does not bind to the same site as oxygen. Instead, it combines with the N-terminal groups on the four globin chains. However, because of allosteric effects on the hemoglobin molecule, the binding of CO2 decreases the amount of oxygen that is bound for a given partial pressure of oxygen. This is known as the Haldane Effect, and is important in the transport of carbon dioxide from the tissues to the lungs. Conversely, a rise in the partial pressure of CO2 or a lower pH will cause offloading of oxygen from hemoglobin, which is known as the Bohr effect.
Sources: en.wikipedia.org
=== Acute exposures === In case reports of humans intentionally or accidentally ingesting high concentrations of copper salts (doses usually not known but reported to be 20–70 grams of copper), a progression of symptoms was observed including abdominal pain, headache, nausea, dizziness, vomiting and diarrhea, tachycardia, respiratory difficulty, hemolytic anemia, hematuria, massive gastrointestinal bleeding, liver and kidney failure, and death. Episodes of acute gastrointestinal upset following single or repeated ingestion of drinking water containing elevated levels of copper (generally above 3–6 mg/L) are characterized by nausea, vomiting, and stomach irritation. These symptoms resolve when copper in the drinking water source is reduced. Three experimental studies were conducted that demonstrate a threshold for acute gastrointestinal upset of approximately 4–5 mg/L in healthy adults, although it is not clear from these findings whether symptoms are due to acutely irritant effects of copper and/or to metallic, bitter, salty taste. In an experimental study with healthy adults, the average taste threshold for copper sulfate and chloride in tap water, deionized water, or mineral water was 2.5–3.5 mg/L. This is just below the experimental threshold for acute gastrointestinal upset.
== Overview == One of the distinguishing features of ColdFusion is its associated scripting language, ColdFusion Markup Language (CFML). CFML compares to the scripting components of ASP, JSP, and PHP in purpose and features, but its tag syntax more closely resembles HTML, while its script syntax resembles JavaScript. ColdFusion is often used synonymously with CFML, but there are additional CFML application servers besides ColdFusion, and ColdFusion supports programming languages other than CFML, such as server-side Actionscript and embedded scripts that can be written in a JavaScript-like language known as CFScript. Originally a product of Allaire and released on July 2, 1995, ColdFusion was developed by brothers Joseph J. Allaire and Jeremy Allaire. In 2001 Allaire was acquired by Macromedia, which in turn was acquired by Adobe Systems Inc in 2005. ColdFusion is most often used for data-driven websites or intranets, but can also be used to generate remote services such as REST services, WebSockets, SOAP web services or Flash remoting. It is especially well-suited as the server-side technology to the client-side ajax. ColdFusion can also handle asynchronous events such as SMS and instant messaging via its gateway interface, available in ColdFusion MX 7 Enterprise Edition.
=== Monk === On February 14, 2025, Jonathan Monk became the third offender of the case to stand trial for the 2017 Pasquotank County prison murders. Jury selection lasted from February to March 2025. On March 18, 2025, the jury found Monk guilty of all 13 criminal charges, including four counts of first degree murder. During the sentencing phase, the defence sought to seek mercy for Monk and implored the jury to sentence Monk to life without parole, on account of Monk's troubled childhood, caused by his mother's neglect and that his early exposure to abuse caused long-lasting psychological issues to him while growing up. On March 27, 2025, 38-year-old Jonathan Monk was sentenced to death by Judge Jeffery B. Foster upon the jury's unanimous recommendation for capital punishment. Apart from the four death sentences, Monk also received 60 to 81 years in prison for attempted first degree murder, felony burning a public building, felony attempted escape, and felony riot. Monk was transferred into the Federal Bureau of Prisons system and was held at USP Lee briefly before joining Brady and Buckman at ADX Florence on December 23, 2025.
=== Places of worship === There are three Church of England churches in Wilmslow: St Bartholomew's, St Anne's and St John's. St Bartholomew's is a 16th-century building, which was modified in the 19th century; it has a turreted bell tower. The first rector of the church was a Thomas Dale, who is buried beneath a headstone presumably engraved by him outside the entrance to the church. Wilmslow Methodist Church occupies a modern building close to the town centre, replacing an 1886 building which itself replaced the original 1798 church, built seven years after John Wesley's death. The Sacred Heart & St Teresa's Church is the Roman Catholic church and dates from the late 19th century. Dean Row Chapel, 2 miles (3.2 km) east of the town centre, is a Grade II* listed building built around the end of the 17th century. Initially Presbyterian, it is now a Unitarian chapel. There is also a United Reformed Church in Wilmslow, close to the town centre.
Valve announced Episode Three in May 2006, planning to release it by Christmas 2007. Concept art appeared in 2007. Valve released little information in the following years, with no clarity on whether further Half-Life games were coming. In 2011, Wired described Episode Three as vaporware. In 2017, Business Insider described it as "the world's most anticipated game", but said that it had become a "farce". Valve eventually canceled Episode Three and abandoned episodic development, as they wanted to create more ambitious games. According to the level designer Dario Casali, "We found ourselves creeping ever forward towards, 'Well, let's just keep putting more and more, and more, and more stuff in this game because we want to make it as good as we can,' and then we realized these episodes are turning more into sequels." The team became fatigued with Half-Life and struggled to discover new gameplay mechanics. The designer Robin Walker said Valve used Half-Life games to "solve some interesting collision of technology and art that had reared itself". Working on Episode Three, they failed to find a unifying idea that provided a sense of "wonderment, or opening, or expansion". Additionally, Valve had started developing a new game engine, Source 2. As developing Half-Life 2 and the original Source engine simultaneously had created problems, Valve delayed development of a new Half-Life until Source 2 was complete. After completing other projects, such as the multiplayer game Left 4 Dead (2008), the team felt the opportunity to create Episode Three had passed.
Sources: en.wikipedia.org
Reconstructions of rainfall amount in the tropics in the geological past are mostly based on δ18O of speleothems or δD of biogenic lipids, both of which are thought of as proxies for the isotopic composition of precipitation.
Early research in the 19th and 20th centuries on osmosis and diffusion provided the foundation for understanding the passive movement of molecules across cell membranes. In 1855, the physiologist Adolf Fick was the first to define osmosis and simple diffusion as the tendency for solutes to move from a region of higher concentration to a lower concentration, also very well-known as Fick's Laws of Diffusion. Through the work of Charles Overton in the 1890s, the concept that the biological membrane is semipermeable became important to understanding the regulation of substances in and out of the cells. The discovery of facilitated diffusion by Wittenberg and Scholander suggested that proteins in the cell membrane aid in the transport of molecules. In the 1960s - 1970s, studies on the transport of glucose and other nutrients highlighted the specificity and selectivity of membrane transport proteins. Technological advancements in biochemistry helped isolate and characterize these proteins from cell membranes. Genetic studies on bacteria and yeast identified genes responsible for encoding transporters. This led to the discovery of glucose transporters (GLUT proteins), with GLUT1 being the first to be characterized. Identification of gene families encoding various transporters, such as solute carrier (SLC) families, also advanced knowledge on uniporters and its functions. Newer research is focusing on techniques using recombinant DNA technology, electrophysiology and advanced imaging to understand uniporter functions.
On 31 October 1899, General Sir Redvers Henry Buller, a much-respected commander, arrived in South Africa with the Army Corps, made up of the 1st, 2nd and 3rd divisions. Buller originally intended an offensive straight up the railway leading from Cape Town through Bloemfontein to Pretoria. Finding on arrival that British troops were under siege, he split his army corps into detachments to relieve the besieged garrisons. One division, led by Lieutenant General Lord Methuen, was to follow the Western Railway to the north and relieve Kimberley and Mafeking. A smaller force of 3,000, led by Major General William Gatacre, was to push north towards the railway junction at Stormberg and secure the Cape Midlands District from Boer raids and rebellions by Boer inhabitants. Buller led the major part of the army corps to relieve Ladysmith to the east. The initial results of this offensive were mixed, with Methuen winning bloody skirmishes in the Battle of Belmont on 23 November, the Battle of Graspan on 25 November, and at a larger engagement, the Battle of Modder River, on 28 November resulting in British losses of 71 dead and over 400 wounded. British commanders had been trained on the lessons of the Crimean War and were adept at battalion and regimental set pieces, with columns manoeuvring in jungles, deserts and mountainous regions. What British generals failed to comprehend was the impact of destructive fire from trench positions and the mobility of cavalry raids.
Middle ear and inner ear (barotitis or aerotitis) Paranasal sinuses (causing aerosinusitis) Lungs may be affected by both under-pressure or, more commonly, overpressure relative to the external pressure Eyes (the under-pressure air space is inside the diving mask or swimming goggles) Skin (when wearing a diving suit which creates an air space) Brain and cranium (temporal lobe injury secondary to temporal bone rupture) Teeth (causing barodontalgia, i.e., barometric pressure related dental pain, or dental fractures) Genital squeeze and associated urinary complications of P-valve use Intestinal barotrauma is caused by over-expansion of gas trapped in the intestines during ascent.
Sources: en.wikipedia.org
The sequence is Thr-Lys-Pro-Arg-Pro-Gly-Pro, written TKPRPGP in one-letter code. It combines the tetrapeptide tuftsin with a carboxyl-terminal Pro-Gly-Pro extension. This full sequence identifies the molecule more precisely than the research name.
No peptide with this exact sequence has been identified as an endogenous substance. It is a laboratory-designed analog of tuftsin, a naturally occurring immunomodulatory tetrapeptide. The Pro-Gly-Pro extension has no known natural source.
Proline introduces conformational constraints that make a peptide less accessible to common peptidases. This is a standard stabilization strategy in peptide design. The added residues also increase the distance between the active tuftsin portion and typical cleavage sites.
Intranasal administration predominates in both animal and human research because it avoids hepatic first-pass metabolism. Injectable and intraperitoneal routes appear in animal work mainly for comparison.