A practical reference on freeze-thaw: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2025-09-14. Anything still debated is marked as such rather than presented as settled.
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.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Primary route studied | Intranasal | Also examined parenterally in animal work |
| Reported plasma half-life | Minutes to tens of minutes | Values vary widely between reports |
| Main model systems | Rodent behavioural and cell assays | Human trials are few and small |
| Principal proposed targets | GABA-A receptor, GABA transaminase | Monoamine and neurotrophic pathways also reported |
| Evidence grade | Preliminary | Limited independent replication |
Reported pharmacological effects center on reduced anxiety-like behavior in animal models and on measures of memory and learning. Proposed contributing mechanisms include modulation of GABAergic signaling, shifts in monoamine turnover, and changes in the activity of enzymes that degrade neuropeptides. Effects on the expression of genes linked to neuroplasticity have also been described. No single molecular target is widely accepted, and whether the behavioral findings arise from one pathway or several remains an open question.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was designed as a stabilized analogue of tuftsin, a naturally occurring tetrapeptide fragment derived from the immunoglobulin heavy chain. The additional Pro-Gly-Pro segment at the carboxyl terminus is intended to slow enzymatic cleavage. The compound is usually described in the literature as a synthetic peptide with anxiolytic and cognitive-related activity, a label that reflects a research context rather than an approved therapeutic category.
Most published work on selank originates from a small number of research groups in the Russian Federation. A large share of that record appears in Russian-language journals, which limits access for readers who rely on English-indexed databases. Independent replication by laboratories outside the original research network is sparse in publicly available sources. This concentration of origin and language is a frequently noted feature when the compound is summarized in broader reviews of synthetic peptides.
Development work on the compound began in the 1980s and 1990s at the Institute of Molecular Genetics in Moscow, within the same research programme that produced the peptide Semax. Early investigators sought a tuftsin derivative with improved resistance to enzymatic breakdown and with activity in the central nervous system after peripheral administration. Most of the primary literature from this period was published in Russian, a factor that still shapes how easily the findings can be checked by outside groups.
Naming for this compound is not fully standardised in English sources. The spelling Selanc appears in some transliterations, and catalogue entries may instead list the peptide sequence itself as the identifier. Reference material sometimes groups it with other short synthetic peptides studied for behavioural effects, which can create confusion when citations are compared. Distinguishing the exact sequence from related tuftsin analogues is therefore a practical first step when reviewing any dataset or specification sheet.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, frequently abbreviated as TKPRPGP. It was designed as a structural analogue of tuftsin, a naturally occurring tetrapeptide released by enzymatic cleavage of the immunoglobulin heavy chain. The two additional proline residues at the C-terminal end extend the parent chain and change how the molecule behaves in solution. The free peptide has a calculated molecular mass of approximately 751.9 g/mol and is generally supplied as a lyophilised white to off-white powder.
Lyophilized selank is normally supplied as a dry powder and is considered stable for extended periods when kept cold and dry. Moisture uptake is the main practical threat, because absorbed water promotes both hydrolysis and aggregation in the solid state. Vials are usually warmed to room temperature before opening so that condensation does not form on the powder. Supplier documentation commonly specifies -20 °C for routine storage, with -80 °C used for material intended to be archived for years.
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.
Published work on this peptide almost always uses intranasal delivery, with drops or a spray applied to the nasal mucosa. Some animal experiments have used subcutaneous or intraperitoneal injection, and a smaller number have compared routes directly. Oral administration is not a focus of the literature, because short peptides of this size are broken down by digestive enzymes and cross intestinal barriers poorly. How much of an intranasal dose reaches the bloodstream intact in humans remains an open question.
Animal studies have examined behaviour in tests of anxiety, memory retention and stress response, and several report changes in neurotrophic or neurotransmitter-related markers. The human evidence base is much smaller, consisting mainly of short trials conducted in Russia with limited reporting in English-language journals. Sample sizes are modest and outcome measures vary between studies, so the findings are best described as preliminary. Independent replication under modern trial standards has not been widely reported.
Outside its country of origin the compound is generally handled as a research chemical rather than an approved medicine. No regulatory approval from the United States Food and Drug Administration or the European Medicines Agency has been granted for human use. Identity and purity are normally checked by reverse-phase high-performance liquid chromatography, with mass spectrometry used to confirm the molecular mass. Lyophilised material is stored cold and desiccated, and repeated freeze-thaw cycles are avoided.
=== Levinthal's paradox === In 1969, Cyrus Levinthal noted that, because of the very large number of degrees of freedom in an unfolded polypeptide chain, the molecule has an astronomical number of possible conformations. An estimate of 3300 or 10143 was made in one of his papers. Levinthal's paradox is a thought experiment based on the observation that if a protein were folded by sequential sampling of all possible conformations, it would take an astronomical amount of time to do so, even if the conformations were sampled at a rapid rate (on the nanosecond or picosecond scale). Based upon the observation that proteins fold much faster than this, Levinthal then proposed that a random conformational search does not occur, and the protein must, therefore, fold through a series of meta-stable intermediate states.
==== Indonesia ==== In 2008, 7-Eleven announced plans to expand its business in Indonesia through a master franchise agreement with Modern Sevel Indonesia. Modern Sevel Indonesia's initial plans were to focus on opening stores in Jakarta, targeting densely populated commercial and business areas. There were 190 7-Eleven stores in Indonesia as of 2014 which then reduced to only 166 stores in September 2016. 7-Eleven then closed its doors in Indonesia in 2017, citing low sales.
Coghill made Andrew J. Moyer available to work on penicillin with Heatley, while Florey left to see if he could arrange for a pharmaceutical company to manufacture penicillin. As a first step to increasing yield, Moyer replaced sucrose in the growth media with lactose. An even larger increase occurred when Moyer added corn steep liquor, a byproduct of the corn industry that the NRRL routinely tried in the hope of finding more uses for it. The effect on penicillin was dramatic; Heatley and Moyer found that it increased the yield tenfold. At the Yale New Haven Hospital in March 1942, Anne Sheafe Miller, the wife of Yale University's athletics director, Ogden D. Miller, was succumbing to a streptococcal septicaemia contracted after a miscarriage. Her doctor, John Bumstead, was also treating John Fulton for an infection at the time. He knew that Fulton knew Florey, and that Florey's children were staying with him. He went to Fulton to plead for some penicillin. Florey had returned to the UK, but Heatley was still in the United States, working with Merck. A phone call to Richards released 5.5 grams of penicillin earmarked for a clinical trial, which was despatched from Washington, D. C., by air. The effect was dramatic; within 48 hours her 41 °C (106 °F) fever had abated and she was eating again. Her blood culture count had dropped from 100 to 150 bacteria colonies per millilitre to just one. Bumstead suggested reducing the penicillin dose from 200 milligrams; Heatley warned him not to.
Matthias Hans Tschöp (born 7 April 1967) is a German physician and scientist. He is the President of LMU Munich. He previously was Chief Executive Officer and Scientific Director of Helmholtz Zentrum München, and Vice President for the Research Area Health of the Helmholtz Association of German Research Centers. He was an Alexander von Humboldt Professor and Chair of Metabolic Diseases at the Technical University of Munich, and an Adjunct Professor at Yale University.
Endless Chain Ridge is a 16-kilometre-long (9.9-mile), 2,867-metre-high (9,406-foot), mountainous ridge located in Jasper National Park, in the Canadian Rockies of Alberta, Canada. The ridge is situated at the southern end of the Maligne Range, and east of the confluence of the Sunwapta River with the Athabasca River. Seen from the Icefields Parkway, the ridge is relatively unimpressive, but from the east side it appears as a rugged chain of peaks, all quite difficult to climb.
Sources: en.wikipedia.org
Colin Ayton Greenhalgh, Principal, Hills Road Sixth Form College, Cambridge. For services to Education. Ian Gregg, Chairman, River Tweed Commissioners and Tweed Foundation. For services to Salmon and Trout Fishing. Vernon Charles Grove, Administrator, Wales and Chester Circuit, Lord Chancellor's Department. Rex Farrow Gyngell, . For political and public service. Arthur Barry Haines, Chair, Aerodynamics Group, Royal Aeronautical Society. For services to Aerodynamics. Eunice Hanna. For political service. Lieutenant Colonel Grattan Herbert Hart, . For services to the Royal British Legion in Sussex. Robert James Hasson, Assistant Controller (Collection and Personnel), Board of Inland Revenue. Anthony Roger Heath. For services to the Administration of Justice. Jennifer Mary Toresen, Lady Hemingford. For services to the community in Hemingford Abbots, Cambridgeshire and to the British Red Cross Society. Desmond Charles Henley, Embalmer. For services in the Aftermath of Disasters. Damon Graham Hill. For services to Motor Racing. John William Hoaen, Grade 7, Department of Trade and Industry. Margaret Edith Hobrough, Principal and Chief Executive, Godalming Sixth Form College, Surrey. For services to Education. Brigadier David Hendry Hodge, . For services to the Territorial Auxiliary and Volunteer Reserve Association in the North of England. The Reverend Roger Graham Holloway. For services to Export. John Hood. For services to Industry. John Trevor Hopkins, Headmaster, Bishop Stopford School, Kettering, Northamptonshire. For services to Education.
In 1953, scientists at the Sloan Kettering Institute in New York City demonstrated that cigarette tar painted on the skin of mice caused fatal cancers. This work attracted much media attention; the New York Times and Life both covered the issue. The Reader's Digest published an article entitled "Cancer by the Carton". On January 11, 1964, the United States Surgeon General's Report on Smoking and Health was published; this led millions of American smokers to quit, the banning of certain types of advertising, and required warning labels on tobacco products. These results were first widely accepted in the medical community and publicized among the general public in the mid-1960s. The medical community's resistance to the idea that smoking tobacco caused disease has been attributed to bias from nicotine-dependent doctors, the novelty of the adaptations needed to apply epidemiological techniques and heuristics to non-infectious diseases, and cigarette industry pressure. The harmful health effects of smoking have been significant for the development of the science of epidemiology. As the mechanism of carcinogenicity is radiomimetic or radiological, the effects are stochastic. Definite statements can be made only on the relatively increased or decreased probabilities of contracting a given disease. For a particular individual, it is impossible to definitively prove a direct causal link between exposure to a radiomimetic poison such as tobacco smoke and the cancer that follows; such statements can only be made at the aggregate population level.
The compounds of sulfur and iodine are recovered and reused, hence the process is called the sulfur–iodine cycle. This process is endothermic and must occur at high temperatures, so energy in the form of heat has to be supplied. The sulfur–iodine cycle has been proposed as a way to supply hydrogen for a hydrogen-based economy. It is an alternative to electrolysis, and does not require hydrocarbons like current methods of steam reforming. But note that all of the available energy in the hydrogen so produced is supplied by the heat used to make it.
In 1998, the Angiosperm Phylogeny Group published a phylogeny for flowering plants based on an analysis of DNA sequences from most families of flowering plants. As a result of this work, many questions, such as which families represent the earliest branches of angiosperms, have now been answered. Investigating how plant species are related to each other allows botanists to better understand the process of evolution in plants. Despite the study of model plants and increasing use of DNA evidence, there is ongoing work and discussion among taxonomists about how best to classify plants into various taxa. Technological developments such as computers and electron microscopes have greatly increased the level of detail studied and the speed at which data can be analysed.
=== In amphibians === In some animals (such as the claw-toed frog Xenopus laevis) production of MSH is increased when the animal is in a dark location. This causes pigment to be dispersed in pigment cells in the toad's skin, making it become darker, and harder for predators to spot. The pigment cells are called melanophores and therefore, in amphibians, the hormone is often called melanophore-stimulating hormone.
Sources: en.wikipedia.org
==== Binding site identification ==== Binding site identification is the first step in structure based design. If the structure of the target or a sufficiently similar homolog is determined in the presence of a bound ligand, then the ligand should be observable in the structure in which case location of the binding site is trivial. However, there may be unoccupied allosteric binding sites that may be of interest. Furthermore, it may be that only apoprotein (protein without ligand) structures are available and the reliable identification of unoccupied sites that have the potential to bind ligands with high affinity is non-trivial. In brief, binding site identification usually relies on identification of concave surfaces on the protein that can accommodate drug sized molecules that also possess appropriate "hot spots" (hydrophobic surfaces, hydrogen bonding sites, etc.) that drive ligand binding.
Prior to its inclusion in newborn screening, short-chain acyl-CoA dehydrogenase deficiency (SCADD) was thought to be life-threatening. Most patients identified via newborn screening as having this enzyme deficiency were asymptomatic, to the extent that SCADD was removed from screening panels in a number of regions. Without the cohort of patients identified by newborn screening, this clinical phenotype would likely not have been identified.
In one interpretation of the film's plot, a scientific process supposedly extracts hydrogen from water, then burns the hydrogen to generate power, and leaves only water as a residue, essentially a chemical perpetual motion. The movie never clarifies how the hydrogen is extracted from the water, nor how water is still left over. The character Dr. Shannon makes contradictory statements in the combination of ideas mashed together: one time he says this is accomplished with a laser with millions of degrees, another time he says frequencies of sound and sonoluminescence. In one scene, the movie shows a bubbling container reminiscent of cold fusion electrolytic cells and another reference sustained fusion. A character in the film claims that a glass of water could power Chicago for weeks, but no clear explanation is ever given as to whether this is by simply burning hydrogen released by highly efficient means or through nuclear processes. The film's title is also misleading, since "chain reaction" is related to nuclear fission, not fusion. The film is based on the premise that free energy suppression is real. The main character is told that his discovery is too disruptive: energy would suddenly be cheap, oil would no longer be necessary, oil companies would go bankrupt, and such sudden economic changes would throw society into chaos.
Mercury-Atlas 9 was the final crewed space mission of the U.S. Mercury program, launched on May 15, 1963, from Launch Complex 14 at Cape Canaveral, Florida. The spacecraft, named Faith 7, completed 22 Earth orbits before splashing down in the Pacific Ocean, piloted by astronaut Gordon Cooper, then a United States Air Force major. The Atlas rocket was No. 130-D, and the Mercury spacecraft was No. 20. As of October 2026, this mission marks the last time an American was launched alone to conduct an entirely solo orbital mission.
Sources: en.wikipedia.org
Reports describe modulation of GABA signalling, changes in monoamine turnover and effects on neurotrophic factor expression. These observations come mainly from animal and cell studies. A single unifying mechanism has not been demonstrated.
The peptide enters plasma rapidly and is broken down by ordinary proteases into amino acids and shorter fragments. Reported half-lives are short. Whether meaningful amounts of the intact molecule reach the brain is an open question.
Most clinical reports are small, published in Russian and not independently replicated. English-language reviews highlight the absence of large randomised trials. Conclusions about efficacy should be treated as provisional.
Identity is confirmed by matching the retention time in reversed-phase chromatography against a reference standard and by measuring the molecular mass with mass spectrometry. Tandem mass spectrometry or amino acid analysis can verify the sequence of the seven residues. Because the peptide contains no aromatic amino acids, detection at 280 nm is not useful.