glass transition comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2026-07-08. Where a claim depends on a specific study, the study is described rather than over-claimed.
Handling practices aim to prevent moisture ingress and mechanical damage. Vials should remain stoppered and crimped until use, and reconstitution should follow the labeled diluent and volume. Shipping may involve temperature-controlled containers and desiccants, but direct contact between desiccant and product is avoided. Regulatory guidance expects documented storage conditions, excursion assessments, and stability commitments. Open questions remain about how best to predict long-term stability from short accelerated studies for every formulation class.
After lyophilization, the product is usually a porous cake or powder with a large internal surface area. This structure can absorb moisture quickly if exposed to humid air, so vials are sealed under vacuum or an inert gas. Moisture uptake may lower the glass transition temperature of the dried matrix and accelerate chemical or physical degradation. Storage conditions therefore depend on the formulation, container, and intended shelf life. Some products remain stable at room temperature, while others require refrigeration or freezing.
Quality control for lyophilized products includes appearance, cake structure, reconstitution time, pH, residual moisture, and potency. Residual moisture is a key attribute because excess water can reduce stability, while excessively low moisture may cause structural changes or aggregation in some systems. Stability studies compare real-time and accelerated conditions to estimate shelf life. Analytical methods must be validated for the specific matrix, container, and moisture range. Sterility and container integrity are also monitored for sterile products.
Freezing determines ice crystal structure and pore size, which affect drying speed and product uniformity. Rapid freezing creates small crystals, while slow freezing creates larger crystals and often faster sublimation. During primary drying, chamber pressure is held below the vapor pressure of ice, and shelf temperature supplies heat for sublimation. The ice front recedes, leaving a porous matrix. Thermal limits such as collapse and eutectic temperatures set safe boundaries for formulation. These limits vary with solute composition and concentration.
Secondary drying removes bound water that remains after ice sublimation. Shelf temperature is raised gradually while pressure remains low, reducing water content to a target range. Over-drying can cause brittleness or electrostatic issues, while under-drying affects stability. The endpoint is often judged by pressure rise tests, temperature measurements, or water content analysis. Scale-up depends on matching heat and mass transfer across equipment sizes. Small changes in shelf temperature or pressure can alter cycle length substantially.
Lyophilization, or freeze-drying, removes water from a material by freezing it and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intervening liquid state. It is used for heat-sensitive materials that would degrade in conventional drying. The three stages are freezing, primary drying, and secondary drying, each with distinct temperature and pressure requirements. In practice, cycle design balances these variables.
| Property | Value | Notes |
|---|---|---|
| Typical appearance | White to off-white porous cake or powder | Color and structure vary with formulation. |
| Typical reconstitution time | Seconds to several minutes | Diluent, agitation, and temperature affect rate. |
| Typical storage temperature | 2–8 °C, 15–25 °C, or ≤−20 °C | Product-specific; protect from moisture and light. |
| Typical container closure | Glass vial with rubber stopper and crimp seal | Closure must limit moisture ingress. |
| Typical stability indicator | Residual moisture, potency, and reconstitution time | Monitored throughout shelf life. |
Residual moisture is a key quality attribute for lyophilized products. Water that remains after secondary drying can affect chemical stability, cake structure, and shelf life. Karl Fischer titration is a common method for measuring water content in the dried solid. The target range varies by product, but many biologics are dried to between 0.5% and 3% water by weight. Acceptable limits are set during development and confirmed by stability studies.
Stability studies examine how temperature, humidity, and time influence a lyophilized product. Accelerated conditions provide early information about degradation pathways, while long-term studies support shelf-life claims. The glass transition temperature of the dried formulation can indicate its physical stability, and storage above this temperature may increase molecular mobility and lead to collapse or aggregation. Container closure integrity also matters because moisture or oxygen ingress can degrade the product, so vial stoppers and seals are part of the quality system.
Lyophilization is a dehydration technique in which a product is frozen and the solvent is removed under reduced pressure. The low pressure allows ice to sublimate directly into vapor without passing through a bulk liquid phase. This differs from conventional drying, where heat drives evaporation and can damage heat-sensitive structures. The process is used for biological materials, pharmaceutical formulations, and some foods. Its main advantage is preservation of porous structure and rapid reconstitution.
Freezing is the first stage and sets the ice structure that later becomes the pore network. The formulation is cooled below its freezing point, often with a controlled ramp, and solutes concentrate as ice forms. Primary drying then lowers chamber pressure and supplies heat to sublime the ice. The product temperature must stay below its collapse or eutectic temperature to prevent structural loss. Secondary drying raises the temperature modestly to remove bound water and achieve a low residual moisture.
A freeze-dryer consists of a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. Vials, ampoules, or bulk trays hold the product during the cycle. The condenser traps water vapor as ice at a temperature lower than the product. Cycle development balances shelf temperature, chamber pressure, and time. Scale-up can be difficult because heat and mass transfer change with equipment size, so process analytical tools and conservative validation are often used.
Lyophilized products are typically hygroscopic and require protection from moisture during storage. Manufacturers seal them in glass vials, often under vacuum or an inert gas such as nitrogen. The container closure system, including the stopper and crimp seal, must prevent water vapor ingress. Storage temperature varies from controlled room temperature to refrigerated or frozen conditions, depending on the formulation. Humidity-controlled environments are essential because even brief exposure to ambient air can degrade the product.
Stability of a lyophilized product depends on its glass transition temperature, the temperature at which the amorphous cake transitions from a glassy to a rubbery state. Storage below this temperature minimizes molecular mobility and slows chemical degradation. If the storage temperature exceeds the glass transition temperature, the cake may collapse, shrink, or become sticky. Accelerated stability studies at elevated temperatures and humidity help predict shelf life, but they do not always reflect real-time behavior. Residual moisture content also plays a critical role in long-term stability.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen to convert liquid water into ice. Next, the pressure is reduced below the triple point of water so that ice changes directly into vapor without passing through a liquid phase. This step is called primary drying. The result is a porous solid or cake that retains the original shape of the frozen solution.
After primary drying, secondary drying removes water that remains bound to the material. This stage raises the shelf temperature while maintaining low pressure, which encourages desorption of unfrozen water. Residual moisture can be reduced to a low percentage, improving stability for many products. The process parameters, including freezing rate, shelf temperature, and chamber pressure, influence the final pore structure and reconstitution behavior. Control of these variables helps prevent collapse or meltback during drying.
A substrate (quartz, silicon, stainless steel, carbon fibers, etc.) is coated with a catalytic metal (Fe, Co, Ni) layer. Typically that layer is iron and is deposited via sputtering to a thickness of 1–5 nm. A 10–50 nm underlayer of alumina is often also put down on the substrate first. This imparts controllable wetting and good interfacial properties. When the substrate is heated to the growth temperature (~600 to 850 °C), the continuous iron film breaks up into small islands with each island then nucleating a carbon nanotube. The sputtered thickness controls the island size and this in turn determines the nanotube diameter. Thinner iron layers drive down the diameter of the islands and drive down the diameter of the nanotubes grown. The amount of time the metal island can sit at the growth temperature is limited as they are mobile and can merge into larger (but fewer) islands. Annealing at the growth temperature reduces the site density (number of CNT/mm2) while increasing the catalyst diameter. The as-prepared carbon nanotubes always have impurities such as other forms of carbon (amorphous carbon, fullerene, etc.) and non-carbonaceous impurities (metal used for catalyst). These impurities need to be removed to make use of the carbon nanotubes in applications.
A common criticism of both the PDCAAS and the DIAAS is that calculating the PDCAAS/DIAAS of a diet solely based on the PDCAAS/DIAAS of the individual constituents is misleading, because one food may provide an abundance of an amino acid that the other is missing, in which case the PDCAAS/DIAAS of the diet is higher than that of any one of the constituents. To arrive at the final result, all individual amino acids would have to be taken into account, so the protein quality of each constituent would be superfluous. For example, various cereals have protein qualities between 0.4 and 0.8 and are generally limited by lysine, but contain more than enough methionine. Legumes, with the exception of soy, generally have protein qualities between 0.5 and 0.8 and are limited by methionine rather than lysine. When eaten together in the optimal ratio, the quality of the combined constituent may be as high as 1.0, because each constituent's protein is complemented by the other. A more extreme example would be the combination of gelatine (which contains virtually no tryptophan and thus has a PDCAAS close to 0) with isolated tryptophan (which, lacking all other essential amino acids, also has a PDCAAS of 0). Despite individual scores of 0, the combination of both in adequate amounts has a positive PDCAAS, with the limiting amino acids isoleucine, threonine, and methionine.
Two days later, the same crew and machine set FAI records for flying payloads of 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 and 80-tonne payloads over a 1,000 km closed circuit at an average of 962 km/h. Of these 18 records, one was broken by a Tu-144 in 1983, five were superseded or discontinued and 12 still stood in 2010. In September 1982 the type made a sales call on Bulgaria, followed by calls in July 1983 on Hungary and Czechoslovakia. Potential buyers received no hard information on the type in advance. Little solid information was given during the sales calls: "constructor Novosilov sidestepped all questions [on fuel consumption] ... [the] chief pilot ... provided a measure of veiled explanation: 'The consumption of the Il-86 is not higher than that of the Il-18,' he said." While welcomed as “proof of friendship with the USSR,” these sales calls failed to attract orders. Observers tacitly noted that the aircraft marked a 10/15-year lag by Soviet civil aviation compared with the West.
The positive side of freedom of association is that the law protects everyone against adverse action for joining a union, and also taking part in collective action including strikes that count as "protected industrial action". If an employee alleges that the employer has taken adverse action for a prohibited reason, "it is presumed that the action was, or is being, taken for that reason or with that intent, unless the [employer] proves otherwise." The claimant may apply to the Fair Work Commission which holds a conference, compulsory in cases of dismissal, and the FWC may arbitrate with the parties' consent. Despite the intent of Parliament, in Board of Bendigo Regional Institute of Technical and Further Education v Barclay the High Court held that the reverse burden of proof made it legitimate to focus on the subjective reasons of the decision-maker, so that direct "testimony from the decision-maker which is accepted as reliable is capable of discharging the burden", and that this achieved a "balance". The High Court repeated this stance in CFMEU v BHP Coal Pty Ltd, where a striking worker held a sign saying "No principles SCABS No Guts", and was dismissed for violating BHP's "workplace conduct policy". The High Court sided with the employer's assertion that dismissal was for uncivil language, not union activity, and said that a claimant would only be protected from an employer's deliberate and conscious victimisation, not employers who make out they (supposedly) inadvertently took adverse action.
Sources: en.wikipedia.org
=== Effects and precautions === Normal functioning of the kidney, brain, liver, heart, and other systems can be affected by uranium exposure, because, besides being weakly radioactive, uranium is a toxic metal. Uranium is also a reproductive toxicant. Radiological effects are generally local because alpha radiation, the primary form of 238U decay, has a very short range, and will not penetrate skin. Alpha radiation from inhaled uranium has been demonstrated to cause lung cancer in exposed nuclear workers. The Centers for Disease Control have published one study stating that neither natural nor depleted uranium have been classified with respect to carcinogenicity. Exposure to its decay products, especially radon, is a significant health threat, and uranium processing produces wastes contaminated with radium which in turn produces radon gas. Because of its long half-life, purified uranium will not produce significant amounts of daughter nuclides for millions of years. Exposure to strontium-90, iodine-131, and other fission products is unrelated to uranium exposure, but may result from medical procedures or exposure to spent reactor fuel or fallout from nuclear weapons. Although accidental inhalation exposure to a high concentration of uranium hexafluoride has resulted in human fatalities, those deaths were associated with the generation of highly toxic hydrofluoric acid and uranyl fluoride rather than with uranium itself. Finely divided uranium metal presents a fire hazard because uranium is pyrophoric; small grains will ignite spontaneously in air at room temperature.
=== Designed nucleic acid systems === Scientists can encode digital information onto a single strand of synthetic DNA. In 2012, George M. Church encoded one of his books about synthetic biology in DNA. The 5.3 Mb of data was more than 1000 times greater than the previous largest amount of information to be stored in synthesized DNA. A similar project encoded the complete sonnets of William Shakespeare in DNA. More generally, algorithms such as NUPACK, ViennaRNA, Ribosome Binding Site Calculator, Cello, and Non-Repetitive Parts Calculator enables the design of new genetic systems. Many technologies have been developed for incorporating unnatural nucleotides and amino acids into nucleic acids and proteins, both in vitro and in vivo. For example, in May 2014, researchers announced that they had successfully introduced two new artificial nucleotides into bacterial DNA. By including individual artificial nucleotides in the culture media, they were able to exchange the bacteria 24 times; they did not generate mRNA or proteins able to use the artificial nucleotides.
Martin Bernal author and leading pioneer in the creation of Pan-African studies, of Sephardi ancestry, most famous for his work Black Athena. Drusilla Beyfus (1927–2026) was a British etiquette writer. She was married to the journalist and critic Milton Shulman. Julie Bindel (born 20 July 1962) English radical feminist writer of Roman Catholic and Jewish ancestry. Lajos Bíró, 22 August 1880 – 9 September 1948, was a Hungarian Jewish author, novelist, playwright, and screenwriter who wrote many films from the early 1920s through the late 1940s. Jeremy Black (historian) (born 1955) historian, writer; author of "The Holocaust: History and Memory"; senior fellow at the Center for the Study of America and the West at the Foreign Policy Research Institute in Philadelphia, Pennsylvania; author of over 180 books, principally on British politics and international relations; has been described as "the most prolific historical scholar of our age"; He has published on military and political history, including Warfare in the Western World, 1882–1975 (2001) and The World in the Twentieth Century (2002); editor of Archives, journal of the British Records Association, from 1989 to 2005.
Sources: en.wikipedia.org
==== Cytoplasmic transcription and replication ==== Once in the cytoplasm, the SeV genomic RNA is getting involved, as a template, in two different RNA synthetic processes performed by RNA-dependent RNA polymerase, which consists of L and P proteins: (1) transcription to generate mRNAs and (2) replication to produce a positive-sense antigenome RNA that in turn acts as a template for production of progeny negative-strand genomes. RNA-dependent RNA polymerase promotes the generation of mRNAs methylated cap structures. The NP protein is thought to have both structural and functional roles This protein concentration is believed to regulate the switch from RNA transcription to RNA replication. The genomic RNA functions as the template for the viral RNA transcription until the NP protein concentration increases. As the NP protein accumulates, the transition from the transcription to the replication occurs. The NP protein encapsidates the genomic RNA, forming a helical nucleocapsid which is the template for RNA synthesis by the viral RNA polymerase. The protein is a crucial component of the following complexes NP-P (P, phosphoprotein), NP-NP, nucleocapsid-polymerase, and RNA-NP. All these complexes are needed for the viral RNA replication. Research has demonstrated that de novo synthesis of the NP and P proteins is essential for efficient viral transcription. Studies using SeV mutants deficient in NP or P proteins, with genome replication disabled, revealed that the P protein is necessary for viral gene expression.
Laboratory mice Dogs Big cats Horses Cattle Chickens Bananaquit Gyrfalcon Kermode bears Rock pocket mice Domestic rabbits Antarctic fur seals Mammoth A study on unrelated British and Irish individuals demonstrated that over 80% of people with red hair and/or fair skin that tan poorly have a dysfunctional variant of the MC1R gene. This is compared to less than 20% in people with brown or black hair, and less than 4% in people showing a good tanning response. Asp294His (rs1805009) is a single nucleotide polymorphism (SNP) in the MC1R gene and it is associated with red hair and light skin type. Other SNPs in the gene, Arg151Cys and Arg160Trp, are also associated with red hair. The Out-of-Africa model proposes that modern humans originated in Africa and migrated north to populate Europe and Asia. These migrants most likely had a functional MC1R variant and, accordingly, dark hair and skin as displayed by indigenous Africans today. As humans migrated north, the absence of high levels of solar radiation in northern Europe and Asia relaxed the selective pressure on active MC1R, allowing the gene to mutate into dysfunctional variants without reproductive penalty, then propagate by genetic drift. Studies show the MC1R Arg163Gln allele has a high frequency in East Asia and may be part of the evolution of light skin in East Asian populations. No evidence is known for positive selection of MC1R alleles in Europe and there is no evidence of an association between the emergence of dysfunctional variants of MC1R and the evolution of light skin in European populations.
=== Bipolar disorder === Endoxifen is used to treat manic or mixed episodes associated with bipolar I disorder in India. It has been found that the endoxifen improves manic symptoms as well as mixed episode symptoms of patients with bipolar I disorder and has been considered an effective and well-tolerated treatment for this condition. Bipolar disorder is associated with overactive protein kinase C (PKC) intracellular signaling. To date, there have been three phases of clinical trials. And, in the phase III trials, endoxifen reduced the total Young Mania Rating Scale (YMRS) score from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery–Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). The endoxifen is well-tolerated by the subjects as depicted in the changes in Clinical Global Impression-Severity of Illness scores.
Sources: en.wikipedia.org
Collapse occurs when the product temperature rises above its collapse or eutectic temperature during drying. The frozen matrix loses structure, producing a shrunken or melted appearance. This can slow reconstitution and may affect stability.
Karl Fischer titration is a common method, along with loss on drying and thermogravimetric analysis. Each method has different sensitivity and sample requirements. Results should be interpreted with the product's formulation and container in mind.
No. Lyophilization removes water but is not a sterilization step. Sterile products are typically filtered and filled aseptically before freezing, and container closure integrity is maintained afterward.
Conventional drying uses heat to evaporate liquid water, often at temperatures that can degrade sensitive materials. Lyophilization freezes the material first and then removes water by sublimation under vacuum. This avoids prolonged exposure to liquid water and high heat.