A practical reference on freeze-thaw cycle: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-07-21. Anything still debated is marked as such rather than presented as settled.
Selank is a hydrophilic peptide and dissolves readily in water and in aqueous buffers. The lyophilised powder is typically a white to off-white solid. Because short peptides are prone to hydrolysis and oxidation, handling benefits from limiting exposure to heat, moisture and strong light. Working solutions are commonly prepared in sterile water or saline, and repeated freeze-thaw cycles are avoided to reduce aggregation and loss of activity. These practices reflect general laboratory convention rather than published stability specifications.
Dry powder is normally held at -20 degrees Celsius or lower, in a sealed container with desiccant and protection from light. Reconstituted solutions are usually kept at 2 to 8 degrees Celsius for short periods and frozen for longer ones. Proline residues at several positions are generally associated with some resistance to peptidase attack, but chemical stability still declines at neutral to alkaline pH and at elevated temperature. Exact shelf-life figures are product-specific and are not standardised across suppliers.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Appearance | White to off-white powder | Lyophilised solid form |
| Solubility class | Freely soluble in water | Hydrophilic heptapeptide |
| Dry storage temperature | -20 degrees Celsius or lower | Sealed, desiccated, protected from light |
| Solution storage | 2 to 8 degrees Celsius short term | Avoid repeated freeze-thaw cycles |
| Common identification method | Reversed-phase HPLC with mass spectrometry | Confirms purity and molecular mass |
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. Its four N-terminal residues reproduce tuftsin, a tetrapeptide fragment of the immunoglobulin heavy chain, while the C-terminal Pro-Gly-Pro extension is a synthetic addition. The peptide has a molecular mass near 752 daltons and carries a net positive charge at physiological pH because of the arginine and lysine side chains. Published indexes list it under the name Selank and the sequence abbreviation TKPRPGP. Solid-phase peptide synthesis is the standard production route for research quantities.
Development took place at the Institute of Molecular Genetics of the Russian Academy of Sciences, where a series of short peptides were designed in the 1980s and 1990s. Selank was selected from variants of tuftsin that showed resistance to plasma peptidases. Russian regulatory approval covers it as an anxiolytic agent given intranasally. Outside that market the compound is normally handled as a research chemical rather than a medicine, and no widely recognised international pharmacopoeial monograph exists. The name Selank is a coined trade designation rather than a systematic chemical name.
Enzymatic stability motivates the extra three residues at the carboxyl end. Native tuftsin is cleaved quickly by circulating aminopeptidases and carboxypeptidases, which limits its duration of action and its usefulness as a tool compound. Extending the chain with proline-rich segments is a common design tactic because proline constrains the backbone and slows proteolysis. The same Pro-Gly-Pro motif appears in other Russian-developed peptides of the era. Whether the full seven-residue chain is required for activity, or whether it acts mainly as a prodrug releasing tuftsin, remains unresolved.
Pharmacokinetic data are limited. Like most short peptides, Selank is vulnerable to plasma and tissue peptidases, and its measured half-life in circulation is short, on a minutes scale. The Pro-Gly-Pro tail slows this degradation but does not eliminate it. Intranasal administration is the route described in most reports, with absorption through the nasal mucosa and a hypothesized path into the central nervous system that avoids the blood-brain barrier. Direct measurements of human brain exposure are unavailable, so distribution claims rest on inference from animal work.
Clinical evidence comes mainly from small studies conducted in Russia, several of which were open-label or lacked robust blinding. Reported outcomes include lower anxiety scores, changes in attention measures, and effects on asthenic states following illness. Sample sizes are typically in the tens of participants, and independent replication outside the region is scarce. Reviews published in English generally note the limited methodological quality of the underlying trials. Whether the compound produces clinically meaningful effects under rigorous conditions remains unresolved.
Proposed mechanisms center on modulation of the GABA system, but no single molecular target has been confirmed. Rodent studies report changes in GABA-A receptor expression and in the turnover of serotonin, dopamine, and norepinephrine in several brain regions. Increases in brain-derived neurotrophic factor and its receptor have also been described after repeated administration. These findings come largely from animal models, and the degree to which they describe human neurochemistry remains an open question. The mechanism is best characterized as multi-system and not fully resolved.
Proposed mechanisms centre on the GABAergic system. Animal and tissue studies report changes in GABA-A receptor expression and reduced activity of GABA transaminase, the enzyme that degrades GABA. Effects on monoamine turnover, including serotonin and dopamine pathways, are also described, and a separate line of work links the peptide to increased expression of brain-derived neurotrophic factor in hippocampal tissue. Most of these findings come from rodent models and cell preparations. How the individual observations combine into a single coherent mode of action is not settled.
Pharmacokinetic data are sparse and largely derived from animal work. After intranasal administration the peptide appears in plasma within minutes, and reported half-lives are short, on the order of minutes to tens of minutes. Degradation proceeds through ordinary proteolytic cleavage into constituent amino acids and smaller fragments. Direct evidence that intact Selank reaches brain tissue in meaningful amounts is limited, and the extent of blood-brain barrier penetration is debated. Some authors argue that fragments, not the parent peptide, carry much of the observed activity.
Published clinical work is concentrated in Russian-language journals and generally involves small samples without independent replication. Systematic reviews in English note the shortage of randomised, placebo-controlled trials and the difficulty of verifying methods from translated reports. Outcome measures vary between studies, which complicates pooling of results. Interest in the compound as a cognitive or anxiolytic agent therefore rests on a thinner evidence base than the volume of citations suggests. Replication in well-powered trials with preregistered endpoints would be needed before firm conclusions about efficacy can be drawn.
Identity and purity of selank are established with reversed-phase high-performance liquid chromatography coupled to mass spectrometry. The peptide elutes from C18 columns with acetonitrile gradients in water containing trifluoroacetic acid or formic acid, and detection is usually performed by ultraviolet absorbance near 214 nm. Electrospray ionization in positive mode gives a doubly protonated ion near m/z 377, consistent with a mass of about 752 Da. Amino acid analysis or tandem mass spectrometry of fragment ions confirms the sequence. Because the molecule has no aromatic residues, it lacks a usable 280 nm chromophore, so low-wavelength detection or mass spectrometry is required.
Peptide bonds in selank are susceptible to hydrolysis under strongly acidic or basic conditions, and the terminal proline residues are vulnerable to exopeptidase activity in biological samples. Lyophilized powder stored dry at -20 °C typically remains stable for extended periods, whereas aqueous solutions degrade faster and may lose measurable purity within days to weeks depending on pH, temperature, and microbial load. Repeated freeze-thaw cycles promote aggregation and adsorption to container surfaces. For analytical work, solutions are usually prepared fresh, kept cold, and used within a single working day.
Handling follows standard practice for research peptides. Material is weighed in a low-humidity environment because the powder absorbs atmospheric moisture. Purity is reported as the percentage area of the main peak in a chromatogram, with specifications commonly set at 95 percent or higher; values below that threshold indicate the presence of truncated or modified species. Residual trifluoroacetate from purification is often present and may affect mass balance. Certificates of analysis should state the analytical method, the column and gradient used, and the lot-specific retention time so that results can be compared across suppliers.
=== Wettability and absorption === Some atmospheric effects on the functionality of adhesive devices can be characterized by following the theory of surface energy and interfacial tension. It is known that γ12 = (1/2)W121 = (1/2)W212. If γ12 is high, then each species finds it favorable to cohere while in contact with a foreign species, rather than dissociate and mix with the other. If this is true, then it follows that when the interfacial tension is high, the force of adhesion is weak, since each species does not find it favorable to bond to the other. The interfacial tension of a liquid and a solid is directly related to the liquid's wettability (relative to the solid), and thus one can extrapolate that cohesion increases in non-wetting liquids and decreases in wetting liquids. One example that verifies this is polydimethyl siloxane rubber, which has a work of self-adhesion of 43.6 mJ/m2 in air, 74 mJ/m2 in water (a nonwetting liquid) and 6 mJ/m2 in methanol (a wetting liquid). This argument can be extended to the idea that when a surface is in a medium with which binding is favorable, it will be less likely to adhere to another surface, since the medium is taking up the potential sites on the surface that would otherwise be available to adhere to another surface. Naturally this applies very strongly to wetting liquids, but also to gas molecules that could adsorb onto the surface in question, thereby occupying potential adhesion sites.
== Early life == Carlisle was selected by Essendon with pick 24 in the 2009 National Draft. Like fellow draftee Jake Melksham, he is a local to the Essendon area. He played with the Calder Cannons in the TAC Cup and Craigieburn in the EDFL. He represented Vic Metro in the 2009 AFL National Under 18 Championships and was part of the 2009 Premiership team.
==== Suicide ==== LSD has led to suicide weeks or months after ingestion. LSD was originally categorized as a schedule I controlled substance because of the suicide of Diane Linkletter 6 months after she took LSD. There are several case reports of suicidal reactions to LSD.
In wound-healing in urodeles it is the quick response of anti-inflammatory macrophages which have been shown to be key to their regeneration capabilities. In one study, it was found that limbs would not regenerate in those urodeles with depleted macrophages and instead would scar with permanent loss of functionality. Knowing how regeneration occurs in animals such as these may have great implications for how wound-healing is tackled in medicine and research has been aimed at this area, as a result.
Sources: en.wikipedia.org
=== Booster preparations === The Atlas booster used for MA-9 sported several technical improvements, most notably an enhanced propulsion system with a hypergolic igniter that would eliminate the need for hold-down time at launch to prevent rough combustion. With seven successful Mercury launches in a row, the failures of the early days seemed like a distant memory by early 1963 and NASA officials had a high degree of confidence in the Atlas that overshadowed its still spotty launch record. At the first meeting of senior MSFC officials for the year (January 11), Walter Williams noted that the Air Force had yet to provide an explanation for two Atlas F failures during the second half of 1962. Until the investigation committees released their findings and cleared the Atlas D of guilt by association, Cooper's flight could be delayed. During the seven months between Schirra's and Cooper's flights, there were five failures of Atlas D vehicles (one of them an Atlas-Agena, the rest operational ICBM tests). NASA did not let its guard down on the Atlas, despite the recent high degree of success enjoyed by Project Mercury. When Atlas 130D received its factory rollout on January 30, it was found to have damaged wiring and had to be sent back for repairs. At his first press conference on February 8, Gordon Cooper admitted to not knowing much about the booster problems and focused instead on the enhancements made to his Mercury capsule.
==== Dosage and regulation ==== Cats may have their mealtimes strictly scheduled and planned to match with injection times, especially when on insulin with a pronounced peak action like Caninsulin/Vetsulin or Humulin N. If the cat free-feeds and normally eats little bits all day or night, it may be best to use a very slow-acting insulin to keep a constant level of blood glucose. Some veterinarians still use the outdated recommendation of using Humulin "N" or NPH insulin for cats, which is very fast-acting for most cats. The slower-acting Lente and Ultralente (Humulin L and Humulin U) insulins were discontinued in 2005, so most cats are treated with either the veterinary PZI insulins or the new full-day analogs glargine (Lantus) and detemir (Levemir). The first goal is to regulate the cat's blood glucose by keeping the blood glucose values in a comfortable range for the cat during most of the day. This may take a few weeks to achieve. The most successful documented method is tight regulation with Lantus or Levemir. Typical obstacles to regulation include:
=== Hyperaldosteronism === Primary aldosteronism, also known as primary hyperaldosteronism, is characterized by the overproduction of aldosterone by the adrenal glands, when not a result of excessive renin secretion. It leads to arterial hypertension (high blood pressure) associated with hypokalemia, usually a diagnostic clue. Secondary hyperaldosteronism, on the other hand, is due to overactivity of the renin–angiotensin system. Conn's syndrome is primary hyperaldosteronism caused by an aldosterone-producing adenoma. Depending on cause and other factors, hyperaldosteronism can be treated by surgery and/or medically, such as by aldosterone antagonists. The ratio of renin to aldosterone is an effective screening test to screen for primary hyperaldosteronism related to adrenal adenomas. It is the most sensitive serum blood test to differentiate primary from secondary causes of hyperaldosteronism. Blood obtained when the patient has been standing for more than 2 hours are more sensitive than those from when the patient is lying down. Before the test, individuals should not restrict salt and low potassium should be corrected before the test because it can suppress aldosterone secretion.
Sources: en.wikipedia.org
== Causes == Migraines are believed to result from a mix of genetic, environmental, and neurological factors. Migraine runs in families, with heritability estimates of 34–64%, but this rarely reflects a single gene defect. Rather, a variety of genetic factors that mostly relate to the nervous system and blood vessels may raise migraine risk. Migraine often occurs along with conditions such as depression, anxiety, and bipolar disorder, which may have a bidirectional relationship (either one can worsen the other). Shared genetic and neurobiological mechanisms likely contribute to risk factors underlying multiple conditions.
== History == A 13th century manuscript by Ibn Nafis contains the earliest known description of capillaries. The manuscript records Ibn Nafis' prediction of the existence of the capillaries which he described as perceptible passages (manafidh) between pulmonary artery and pulmonary vein. These passages would later be identified by Marcello Malpighi as capillaries. He further states that the heart's two main chambers (right and left ventricles) are separate and that blood cannot pass through the (interventricular) septum. William Harvey did not explicitly predict the existence of capillaries, but he saw the need for some sort of connection between the arterial and venous systems. In 1653, he wrote, "...the blood doth enter into every member through the arteries, and does return by the veins, and that the veins are the vessels and ways by which the blood is returned to the heart itself; and that the blood in the members and extremities does pass from the arteries into the veins (either mediately by an anastomosis, or immediately through the porosities of the flesh, or both ways) as before it did in the heart and thorax out of the veins, into the arteries..." Marcello Malpighi was the first to observe directly and correctly describe capillaries, discovering them in a frog's lung 8 years later, in 1661. August Krogh discovered how capillaries provide nutrients to animal tissue. For his work he was awarded the 1920 Nobel Prize in Physiology or Medicine.
The main step of the process is the negative selection of newly generated trypsin peptides using a specialized polymer. The polymer ignores the unreactive primary amines blocked by their tags, allowing them to be separated from trypsin generated peptides by ultrafiltration for Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) analysis. These mature and neo-N-termini will differ in ratios between the protease treated versus untreated samples and make up the proteolytic fingerprint of a protease. TAILS is also compatible with Stable isotope labeling by amino acids in cell culture (SILAC). COFRADIC was the earliest technique to capitalize on negative selection to enrich for protein N-termini. Sample proteins are first blocked by reduction and alkylation at their primary amines before endopeptidase treatment. Its negative selection method relies on strong cation exchange chromatography (SCX) to enrich for peptides representing N- and C-termini of proteins based on differences in peptide charge and pH. Additional orthogonal chromatography treatments change the biochemical character of the peptides for further enrichment before final LC-MS/MS analysis. Groups have continued to adapt and improve this technology for protease-substrate discovery. C-terminomics has always been complicated due to the chemical nature of its targets. Carboxyl groups are less reactive than primary amines, making C-terminomic techniques more complex than established N-terminomic approaches.
In general USPTO rejections on the sole grounds of the invention's being "inoperative" are rare, since such rejections need to demonstrate "proof of total incapacity", and cases where those rejections are upheld in a Federal Court are even rarer: nevertheless, in 2000, a rejection of a cold fusion patent was appealed in a Federal Court and it was upheld, in part on the grounds that the inventor was unable to establish the utility of the invention. A U.S. patent might still be granted when given a different name to disassociate it from cold fusion, though this strategy has had little success in the US: the same claims that need to be patented can identify it with cold fusion, and most of these patents cannot avoid mentioning Fleischmann and Pons' research due to legal constraints, thus alerting the patent reviewer that it is a cold-fusion-related patent. David Voss said in 1999 that some patents that closely resemble cold fusion processes, and that use materials used in cold fusion, have been granted by the USPTO. The inventor of three such patents had his applications initially rejected when they were reviewed by experts in nuclear science; but then he rewrote the patents to focus more on the electrochemical parts so they would be reviewed instead by experts in electrochemistry, who approved them. When asked about the resemblance to cold fusion, the patent holder said that it used nuclear processes involving "new nuclear physics" unrelated to cold fusion.
Sources: en.wikipedia.org
Dry powder is normally held at -20 degrees Celsius or below in a sealed, light-protected container with desiccant. Brief room-temperature handling during weighing is generally tolerated. Storage instructions vary between suppliers, so the accompanying certificate of analysis should be followed.
Reversed-phase HPLC establishes purity, while mass spectrometry confirms the expected molecular mass. Sequence confirmation may use tandem mass spectrometry or peptide mapping. A certificate of analysis typically reports these results alongside the analytical method applied.
In Russia it is a registered medicine available by prescription. In many other countries it is not approved for human use and is supplied only as a research chemical. Import and possession rules differ by jurisdiction, and buyers are responsible for checking local requirements.
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.