Everything below concerns glass transition. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-05-10. Where a claim depends on a specific study, the study is described rather than over-claimed.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen so that water becomes ice; then the surrounding pressure is lowered below the vapor pressure of ice. Heat is applied gently so ice changes directly to vapor without passing through a bulk liquid phase. The vapor is collected on a cold condenser, leaving a dry porous matrix. This process differs from simple evaporation because the material remains frozen during the main drying stage.
The process usually has three stages: freezing, primary drying, and secondary drying. Freezing sets the ice crystal structure and can determine pore size in the final cake. Primary drying removes free ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, although some water may remain as part of the solid. Cycle parameters depend on formulation, fill volume, vial type, and equipment performance.
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.
Handling and storage practices aim to keep the cake intact and dry. Vials are typically stored upright at controlled temperatures, often between 2 °C and 8 °C or at -20 °C for longer-term use. Reconstitution involves adding a suitable diluent and gently mixing until the solid dissolves. Shaking or rapid injection of diluent can create foam or damage sensitive molecules. Once reconstituted, the product may require refrigeration and use within a defined period.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilisation is the British spelling; the process is not simple evaporation. |
| Primary drying pressure | 0.05–0.3 mbar | Pressure must remain below the vapor pressure of ice at the product temperature. |
| Sublimation temperature | Below 0 °C | Ice changes directly to vapor while the product remains frozen. |
| Typical shelf temperature | −40 to −10 °C | Exact setting depends on formulation critical temperature and equipment. |
| Cycle duration | 12–72 hours | Time varies with fill volume, formulation, and dryer performance. |
Equipment for lyophilization includes a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. A refrigeration system cools the shelves and condenser below the product's freezing point. Process monitoring often uses Pirani and capacitance manometers, thermocouples, and resistance sensors. Cycle development balances product quality with time and energy use. Some products are annealed during freezing to improve crystallization of bulking agents. Open questions remain about scaling cycles between laboratory, pilot, and production freeze-dryers.
Lyophilization, also called freeze-drying, removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts free water into ice and may also produce a glassy phase. Primary drying then lowers chamber pressure so ice sublimes directly to vapor without passing through a liquid stage. Secondary drying raises the temperature modestly to remove bound water. The result is a porous, dry solid that usually reconstitutes quickly. Each stage influences pore structure, residual moisture, and stability.
The physics of lyophilization depends on phase boundaries and heat and mass transfer. During primary drying, heat supplied to the product must equal the latent heat of sublimation, while water vapor moves through the drying cake to the condenser. If shelf temperature or pressure is set too high, the ice front can exceed the collapse temperature, causing meltback or pore collapse. If conditions are too cold, drying slows and costs rise. Formulation excipients, vial geometry, and freezing rate alter these limits.
Analytical methods for lyophilized solids must account for the low moisture content and the fragile cake. Karl Fischer titration is widely used for water content, while near-infrared spectroscopy can measure moisture non-destructively in sealed containers. X-ray diffraction and modulated differential scanning calorimetry help identify crystalline or amorphous phases. Residual solvent analysis may be needed if organic solvents were used during formulation. The combination of these methods supports batch release and long-term stability assessment.
Lyophilized products are typically stored as sealed solids in vials or syringes. Moisture ingress is a major concern because many dried cakes are hygroscopic and can lose stability when exposed to humid air. Storage temperature depends on the formulation; some products are kept refrigerated, while others are stable at room temperature. Container closure integrity and headspace moisture are often monitored. Light protection may also be required for some photosensitive materials.
Many of these forms are initially water-soluble, which is a disadvantage where the material must retain its shape within the body. Stability is achieved by increasing the beta-sheet content, through treatment with methanol or ethanol, exposure to water vapour, mechanical stretching, or controlled heating. Because the same ordered structure governs both strength and the rate of degradation, this step also serves as the principal means of tuning a material's properties.
As of 2016, Mister Donut Japan had over "1,300 stores, making it the largest donut chain in the country." and as of June 2016, Duskin Co., Ltd. was also operating Mister Donut stores in China, Taiwan, South Korea, Thailand, the Philippines, Indonesia, Japan, and Malaysia. In 2020, Dunkin' Brands was purchased by Sandy Springs-based Inspire Brands, and Mister Donut's trademark management became part of Inspire.
The scientific study of the nervous system increased significantly during the second half of the twentieth century, principally due to advances in molecular biology, electrophysiology, and computational neuroscience. This has allowed neuroscientists to study the nervous system in all its aspects: how it is structured, how it works, how it develops, how it malfunctions, and how it can be changed. Compared to psychiatry and psychology, which also study the functioning of the brain, Neuroscience emerged from the earlier fields of Neuro-Immuno-Modulation and Neuroimmunology, which made remarkable breakthroughs beginning with 1945. For example, it became possible to understand, in much detail, the complex processes occurring within a single neuron. Neurons are cells specialized for communication. They are able to communicate with neurons and other cell types through specialized junctions called synapses, at which electrical or electrochemical signals can be transmitted from one cell to another. Many neurons extrude a long thin filament of axoplasm called an axon, which may extend to distant parts of the body and are capable of rapidly carrying electrical signals, influencing the activity of other neurons, muscles, or glands at their termination points. A nervous system emerges from the assemblage of neurons that are connected to each other in neural circuits, and networks. The vertebrate nervous system can be split into two parts: the central nervous system (defined as the brain and spinal cord), and the peripheral nervous system.
Colloquially, radioactive materials can be described as "hot," and non-radioactive materials can be described as "cold." There are instances in which cold iodide is administered to people in order to prevent the uptake of hot iodide by the thyroid gland. For example, blockage of thyroid iodine uptake with potassium iodide is used in nuclear medicine scintigraphy and therapy with some radioiodinated compounds that are not targeted to the thyroid, such as iobenguane (MIBG), which is used to image or treat neural tissue tumors, or iodinated fibrinogen, which is used in fibrinogen scans to investigate clotting. These compounds contain iodine, but not in the iodide form. However, since they may be ultimately metabolized or break down to radioactive iodide, it is common to administer non-radioactive potassium iodide to insure that metabolites of these radiopharmaceuticals is not sequestered by the thyroid gland and result in a concentrated radiation dose to that tissue. Potassium iodide has been distributed to populations exposed to nuclear fission accidents such as the Chernobyl disaster. The iodide solution SSKI, a saturated solution of potassium (K) iodide in water, has been used to block absorption of the radioiodine. Tablets containing potassium iodide are now also manufactured and stocked in central disaster sites by some governments for this purpose.
Sources: en.wikipedia.org
== In literature == The literary lich developed from monsters found in earlier classic sword and sorcery fiction, which is filled with powerful sorcerers who use their magic to triumph over death. Many of Clark Ashton Smith's short stories feature powerful wizards whose magic enables them to return from the dead. Several stories by Robert E. Howard, such as the novella Skull-Face (1929) and the short story "Scarlet Tears", feature undying sorcerers who retain a semblance of life through mystical means, their bodies reduced to shriveled husks with which they manage to maintain inhuman mobility and active thought. The term lich, used as an archaic word for corpse (or body), is commonly used in these stories. Ambrose Bierce's tale of possession "The Death of Halpin Frayser" features the word in its introduction, referring to a corpse. H. P. Lovecraft also used the word in "The Thing on the Doorstep" (published 1937) where the narrator refers to the corpse of his friend possessed by a sorcerer. Liches are sometimes depicted using a magical device called a phylactery to anchor their souls to the physical world so that if their body is destroyed they can rise again over and over, as long as the phylactery remains intact. Other imagery surrounding demiliches, in particular that of a jeweled skull, is drawn from the early Fritz Leiber story "Thieves' House". Gary Gygax, one of the co-creators of Dungeons & Dragons, said that he based the description of a lich included in the game on the short story "The Sword of the Sorcerer" (1969) by Gardner Fox.
== Accumulation of toxic substances == In some areas of the United States where aquatic environments have tested positive for elevated levels of toxins, such as mercury, arsenic, chromium, and copper, signs are posted with warnings about the consumption of fish caught in those areas. Concentration of mercury biomagnifies as it passes up the food chain from organisms on lower trophic levels to apex predators. It bioaccumulates in the tissues of larger, long-lived, predatory fish. When compared to smaller, short-lived fish, bowfin tend to concentrate mercury at higher levels, thereby making them less safe for human consumption.
== History == Leveraging advanced computational bioinformatics, brilacidin and other defensin mimetics were first developed by University of Pennsylvania-based researchers. Their efforts were consolidated, and officially incorporated, in 2002, under the company name PolyMedix. PolyMedix conducted pre-clinical and clinical research with brilacidin through a completed Phase 2a human clinical trial with positive results. After discontinuing a clinical trial for an unrelated compound PolyMedix filed for Chapter 7 bankruptcy protection on 1 April 2013. Cellceutix acquired the PolyMedix assets and intellectual property, including the licenses and patents for brilacidin and the rest of the HDP-mimetic pipeline, from bankruptcy court which on 4 September 2013, approved Cellceutix's stalking horse bid. On 7 June 2017, Cellceutix Announced a Company Name Change to Innovation Pharmaceuticals Inc. On 9 June 2017, the stock ticker name was effectively changed to "IPIX".
By 1999, the economy had rebounded with a growth of 5.4 per cent, followed by an 8.5 per cent growth in 2000. Mahathir later recalled that his decision to peg the ringgit to the US dollar in 1998 felt like "putting his head on the chopping block". In the 1990s, Mahathir found himself at odds with Malaysian royalty over conflicting economic interests. In response to conflicts between Malaysian royals and prospective business leaders, Mahathir's government passed a resolution on royal activities. In the 1992 Gomez Incident, Sultan Iskandar's son, a representative field hockey player, was suspended from competition for five years for assaulting an opponent. Iskandar retaliated by pulling all Johor hockey teams out of national competitions. When a local coach criticised his decision, Iskandar ordered him to his palace and beat him. The federal parliament unanimously censured Iskandar, and Mahathir took the opportunity to remove the constitutional immunity of the sultans from civil and criminal suits. The press backed Mahathir and, in an unprecedented development, started airing allegations of misconduct by members of Malaysia's royal families. As the press revealed examples of the rulers' extravagant wealth, Mahathir resolved to cut financial support to royal households. With the press and the government pitted against them, the sultans capitulated to the government's proposals. Their powers to deny assent to bills were limited by further constitutional amendments passed in 1994.
==== Delivery methods ==== Honokiol is most commonly taken orally. There are a number of supplements available containing honokiol. Magnolia tea made from the bark of the tree is also a common delivery method of honokiol. Both Native American and Japanese medicine use tea gargles to treat toothaches and sore throats. Because honokiol is highly hydrophobic it must be dissolved in a lipid for many delivery methods. In many current animal studies the compound is dissolved in a lipid emollient and delivered through intraperitoneal injection. There is ongoing work developing liposomal emulsions for IV delivery.
Sources: en.wikipedia.org
In 2009, Valve hired IceFrog, the developer of Defense of the Ancients, a Warcraft III mod. IceFrog led the development of a sequel not associated with the Warcraft elements, Dota 2, released in 2013. Alongside Dota 2 in 2011, Valve started the International, an annual esports tournament for Dota 2 with a prize pool supported by Valve and funds from microtransactions from battle passes purchased by players. Valve released Portal 2 in April 2011. As with the original Portal, Valve employed a Digipen student team to help develop it; the team behind Tag: The Power of Paint implemented the new gel gameplay. In April 2010, Valve launched Steam for Mac OS X along with ports of several of its games including the Half-Life series. The Screen Digest analyst Ed Barton estimated Valve's 2010 revenue to be in the "high hundreds of millions of dollars". As of 2011, Valve had an estimated worth of $2 to 4 billion and employed 250 people; according to Newell, this made it more profitable per employee than Google or Apple. Most of Valve's revenue came from Steam, which controlled 50 to 70% of the market for downloaded PC games in 2011. By 2011, Valve had replaced episodic development with a platform-oriented approach, whereby games such as Left 4 Dead 2 and Team Fortress 2 were continually updated through Steam updates. In June 2012, Valve hired the economist Yanis Varoufakis to study the online economies of their games. That December, Valve acquired Star Filled Studios, a two-person studio, to open a San Francisco office.
=== Multi-locus sequence typing === Multilocus sequence typing (MLST) is the sequencing of numerous loci to diagnose an organism by comparing DNA sequences to a database of known organisms. This method is often used to compare isolates or strains of the same species to see if they are indistinguishable or different from each other. This is common for tracking food-borne illnesses and public health outbreaks. Most MLST assays are published in scientific journals so consistent methods are used worldwide. There are also public databases available for tracking and comparisons.
What distinguishes the androgen backdoor from the classical pathway is whether 5α-reduction initiates or terminates the pathway. In the backdoor pathway, 5α-reduction of progesterone (P4) or 17α-hydroxyprogesterone (17OHP) occurs at or near the beginning of the pathway respectively. Conversely, in the classical pathway, 5α-reduction is the final step, where testosterone is converted into dihydrotestosterone (DHT). The backdoor pathway splits into two subpathways at P4, proceeding through either 17OHP or 5α-DHP before merging again at 5α-Pdiol. The biosynthetic intermediate 5α-Pdiol in turn is converted into DHT in two chemical steps.
Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. Elevated ALP often suggests biliary disease and warrants workup with ultrasound. It can also be found on the mucosal epithelium of the small intestine, proximal convoluted tubule of the kidneys, bone, liver, and placenta. It plays an important role in lipid transposition in small intestines and calcification of bones. 50% of all the serum ALP activities in blood are contributed by bone. Acute viral hepatitis usually has normal or increased ALP. For example, hepatitis A has increased ALP due to cholestasis (impaired bile formation or bile flow obstruction) and would have the feature of prolonged itching. Other causes include: infiltrative liver diseases, granulomatous liver disease, abscess, amyloidosis of the liver and peripheral arterial disease. Mild elevation of ALP can be seen in liver cirrhosis, hepatitis, and congestive cardiac failure. Transient hyperphosphataemia is a benign condition in infants, and can reach normal level in 4 months. In contrast, low levels of ALP is found in hypothyroidism, pernicious anemia, zinc deficiency, and hypophosphatasia. ALP activity is significantly increased in the third trimester of pregnancy. This is due to increased synthesis from the placenta as well as increased synthesis in the liver induced by large amounts of estrogens. Levels in the third trimester can be as much as 2-fold greater than in non-pregnant women. As a result, ALP is not a reliable marker of hepatic function in pregnant women.
The theory of classical irreversible thermodynamics treats self-assembly under a generalized chemical potential within the framework of dissipative systems. The second law of thermodynamics requires that overall entropy increases, yet life is distinguished by its great degree of organization. Therefore, a boundary is needed to separate ordered life processes from chaotic non-living matter. A functional protocell, which must exhibit Darwinian evolution, has not yet been achieved in a laboratory setting. Irene Chen and Jack W. Szostak suggest that elementary protocells can give rise to primitive forms of differential reproduction, competition, and energy storage. Competition for membrane molecules would favor stabilized membranes, suggesting a selective advantage for cross-linked fatty acids and even modern phospholipids. Such micro-encapsulation would allow for metabolism within the membrane and the exchange of small molecules, while retaining large biomolecules inside. Such a membrane is needed for a cell to create its own electrochemical gradient. Fatty acid vesicles in alkaline hydrothermal vent conditions can be stabilized by isoprenoids, synthesized by the formose reaction; the advantages and disadvantages of isoprenoids within the lipid bilayer in different microenvironments might have led to the divergence of the membranes of archaea and bacteria. Vesicles can undergo an evolutionary process under pressure cycling conditions.
Sources: en.wikipedia.org
The main change is sublimation, in which ice becomes water vapor without melting into liquid water. This occurs when the chamber pressure is held below the vapor pressure of ice while mild heat is supplied. The result is a dry, porous solid that retains much of its original shape.
Freezing determines ice crystal size, solute distribution, and the pore network left after drying. A slow or fast freezing rate can produce different cake structures and affect reconstitution. It also sets whether the formulation follows an amorphous or crystalline drying path.
It removes most free water during primary drying and part of the bound water during secondary drying. A small residual moisture content often remains and is specified for each product. Complete removal is generally neither practical nor desirable for stability.
Residual moisture can influence chemical degradation, cake collapse, and long-term stability. Low moisture levels usually improve stability, but each product has an optimal range.