A practical reference on Residual moisture: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2025-12-24 and is reviewed periodically as new material appears.
Quality assessment of a lyophilized product includes cake appearance, residual moisture, reconstitution time, and container closure integrity. A uniform, porous cake suggests that freezing and drying stayed within the formulation's design space. Cracks, shrinkage, meltback, or a glassy film can indicate thermal abuse or a formulation problem. Analysts also test for subvisible particles and sterility when the product requires those specifications. Visual inspection alone cannot confirm biological activity or chemical stability, so it is combined with analytical methods.
Stability programs monitor lyophilized products under defined temperature and humidity conditions over time. Real-time studies at recommended storage conditions are the reference, while accelerated studies provide early signals of degradation pathways. Because a dry cake can still undergo oxidation, hydrolysis, or aggregation, stability depends on residual moisture, excipients, and container headspace. Open questions include how best to predict long-term stability from short accelerated runs and how vial-to-vial variability affects shelf life. Current guidance treats these predictions as product-specific rather than universally generalizable.
Freeze-dried materials are hygroscopic to varying degrees and can take up moisture after drying. Storage therefore often uses sealed glass vials, rubber stoppers, and crimp seals to limit contact with ambient humidity. A desiccant may be included for moisture-sensitive products, although it is not universal. Controlled room temperature is sufficient for many lyophilizates, while others require refrigeration or freezing. Moisture ingress remains a primary cause of cake collapse, chemical degradation, and loss of reconstitution performance.
The physics of lyophilization couples heat transfer, mass transfer, and phase behavior. Sublimation requires a vapor pressure difference between the ice front and the chamber, and the dried layer adds resistance to vapor flow. Amorphous formulations are characterized by a glass transition temperature of the maximally freeze-concentrated solute, often denoted Tg'. Crystalline bulking agents can provide structure, while amorphous excipients stabilize labile components. Open questions remain about spatial heterogeneity, edge effects, and how laboratory cycles scale to production.
Lyophilization is a drying process in which a solvent, usually water, is removed from a frozen material by sublimation under reduced pressure. The material is first solidified, then placed under vacuum so that ice transitions directly to vapor without a bulk liquid phase. This approach suits heat-sensitive substances that would degrade during conventional evaporation. Primary drying removes unbound ice, while secondary drying reduces water that remains adsorbed to the solid matrix. The result is a porous, lightweight solid that can be reconstituted later.
| Property | Value | Notes |
|---|---|---|
| Cake appearance | Uniform porous plug | Cracks, shrinkage, or meltback suggest process deviation. |
| Reconstitution time | 10 seconds to 5 minutes | Depends on cake structure, diluent, and agitation. |
| Typical storage humidity | Below 60% relative humidity | Lower humidity limits moisture uptake by hygroscopic cakes. |
| Container closure | Glass vial, elastomer stopper, crimp seal | Seal integrity limits moisture and oxygen ingress. |
| Common moisture test | Karl Fischer titration | Measures residual water content in the dried solid. |
Reconstitution involves adding a suitable diluent, often sterile water or a buffer, to the dried cake. Gentle swirling or inversion helps dissolve the material without creating excessive foam. The time required for complete dissolution can range from seconds to several minutes and depends on the cake structure and the diluent. Improper reconstitution, such as vigorous shaking or using the wrong diluent, can cause protein aggregation or loss of activity. After reconstitution, the product may have a limited shelf life and should be used according to its labeling.
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.
In practice, lyophilization is slower and more energy intensive than simple drying. Cycle times can range from hours to several days depending on load, container, and formulation. Amorphous materials may require excipients that help preserve structure during freezing and drying. The method is widely used for biological materials, pharmaceuticals, and foods where heat drying would cause unacceptable change. Open questions remain about scaling cycles between laboratory and production equipment, and this gap affects technology transfer.
Lyophilization removes water by freezing a material and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intermediate liquid state. Because the material remains frozen during primary drying, the structure often stays porous. This porous matrix can rehydrate quickly when water is added back. The low pressure also allows vapor to leave the solid matrix without boiling.
A typical cycle begins with freezing, which fixes the material into a solid and determines ice crystal size. Primary drying then raises heat under vacuum so ice sublimes, often near or below the collapse temperature of the formulation. Secondary drying removes bound water that remains after ice is gone, usually by gently warming the product. Each stage balances heat input against pressure to avoid melting or structural damage. Temperature probes and pressure sensors guide the transition between stages.
Storage conditions depend on the formulation and the intended shelf life. Many pharmaceutical and biological freeze-dried products are kept at 2–8 °C, while some stable foods and reagents tolerate room temperature. Others require −20 °C or colder to slow chemical degradation or aggregation. Protection from light and oxygen is common because oxidation can continue in the dry state. Stability studies usually monitor potency, appearance, moisture, and reconstitution time over months or years. Predictions from accelerated studies are useful but may not fully capture real-time changes.
Quality control for freeze-dried lots combines visual inspection with instrumental tests. Cake appearance, color, and shrinkage are recorded against a reference, while residual moisture is measured by Karl Fischer titration or loss on drying. Thermal analysis can reveal phase transitions and crystallization events, and X-ray diffraction distinguishes amorphous from crystalline solids. Microbiological tests and container closure integrity checks are also routine for sterile products. Analytical methods must be validated for the matrix, because excipients and low moisture can affect accuracy. Open questions include how best to predict long-term stability from short-term data.
Lyophilized solids are often hygroscopic, so handling occurs in controlled low-humidity areas or glove boxes when the material is exposed. Vials remain sealed with elastomeric stoppers and aluminum crimps until use, because airborne moisture can raise residual water and shorten shelf life. The porous cake is fragile and may crack, shrink, or powder during transport. Personnel typically avoid repeated warming and cooling of sealed units, which can draw moisture through closures. These practices aim to preserve the low water content achieved during drying.
The physical chemistry of freezing influences whether a formulation forms an amorphous glass or a crystalline solid. Amorphous systems can collapse if product temperature rises above the glass transition temperature of the freeze concentrate. Crystalline systems may show eutectic melting, where ice and solute melt together at a fixed temperature. Formulators add bulking agents, lyoprotectants, and buffers to preserve structure and biological activity. The optimum cycle keeps product temperature below critical thresholds during primary drying while allowing efficient sublimation.
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.
Alpha cells (α-cells) are endocrine cells that are found in the Islets of Langerhans in the pancreas. Alpha cells secrete the peptide hormone glucagon in order to increase glucose levels in the blood stream.
In 1910, Hahn was appointed professor by the Prussian Minister of Culture and Education, August von Trott zu Solz. Two years later, Hahn became head of the Radioactivity Department of the newly founded Kaiser Wilhelm Institute for Chemistry (KWIC) in Berlin-Dahlem (in what is today the Hahn-Meitner-Building of the Free University of Berlin). This came with an annual salary of 5,000 marks (equivalent to €29,000 in 2021). In addition, he received 66,000 marks in 1914 (equivalent to €369,000 in 2021) from Knöfler for the mesothorium process, of which he gave 10 per cent to Meitner. The new institute was inaugurated on 23 October 1912 in a ceremony presided over by Kaiser Wilhelm II. The Kaiser was shown glowing radioactive substances in a dark room. The move to new accommodation was fortuitous, as the wood shop had become heavily contaminated by radioactive liquids that had been spilt, and radioactive gases that had vented and then decayed and settled as radioactive dust, making sensitive measurements impossible. To ensure that their clean new laboratories stayed that way, Hahn and Meitner instituted strict procedures. Chemical and physical measurements were conducted in different rooms, people handling radioactive substances had to follow protocols that included not shaking hands, and rolls of toilet paper were hung next to every telephone and door handle. Strongly radioactive substances were stored in the old wood shop, and later in a purpose-built radium house on the institute grounds.
Tendons are not elastic and are even less stretchy. Tendons are categorized as a connective tissue. Connective tissue supports, surrounds, and binds the muscle fibres. They contain both elastic and non-elastic tissue.
=== Direct analysis of biotransformations === An adaptation of DESI is used to analyze enzyme-triggered chemical reactions, known as biotransformations, in enzymes and their products. Coupled with high-resolution mass spectrometry, this procedure, known as DiBT-MS, can analyze a substrate 10-10,000 times quicker than LC-MS. DESI specifically can analyze the products in situ, removing the need for high solvent usage and creating these quicker analysis times.
== Lewis acid strength in non-aqueous solutions == Lewis acids have been classified in the ECW model and it has been shown that there is no one order of acid strengths. The relative acceptor strength of Lewis acids toward a series of bases, versus other Lewis acids, can be illustrated by C-B plots. It has been shown that to define the order of Lewis acid strength at least two properties must be considered. For Pearson's qualitative HSAB theory the two properties are hardness and strength while for Drago's quantitative ECW model the two properties are electrostatic and covalent.
Sources: en.wikipedia.org
This was an enormous social change, doing much to increase Conservative support amongst new homeowners and which Heseltine often cites as one of his major achievements. Heseltine noted that, "no single piece of legislation has enabled the transfer of so much capital wealth from the state to the people." He said that the 'right to buy' policy had two main objectives: to give people what they had wanted, and to reverse the trend of ever-increasing dominance of the State over the life of the individual. He said: "There is in this country a deeply ingrained desire for home ownership. The Government believe that this spirit should be fostered. It reflects the wishes of the people, ensures the wide spread of wealth through society, encourages a personal desire to improve and modernize one's own home, enables parents to accrue wealth for their children and stimulates the attitudes of independence and self-reliance that are the bedrock of a free society." Many of the homes sold were "street properties" rather than flats, which arguably helped to ghettoise the remaining council tenants on run-down inner city estates. In fact, in Crick's view, he deserves only limited credit; it had been a Conservative commitment since 1974, and much of the detailed work was done by his juniors Hugh Rossi (in opposition) and John Stanley (in government).
== Histidine-specific protein kinases == Histidine kinases (EC 2.7.13.-) are structurally distinct from most other protein kinases and are found mostly in prokaryotes as part of two-component signal transduction mechanisms. A phosphate group from ATP is first added to a histidine residue within the kinase, and later transferred to an aspartate residue on a 'receiver domain' on a different protein, or sometimes on the kinase itself. The aspartyl phosphate residue is then active in signaling. Histidine kinases are found widely in prokaryotes, as well as in plants, fungi and eukaryotes. The pyruvate dehydrogenase family of kinases in animals is structurally related to histidine kinases, but instead phosphorylate serine residues, and probably do not use a phospho-histidine intermediate.
However, major drawbacks of SMB are the inability of separating a mixture into three fractions and the lack of solvent gradient applicability. In the case of antibodies, the state-of-the-art technique is based on batch affinity chromatography (with Protein A or Protein G as ligands) which is able to selectively bind antibody molecules. In general, affinity techniques have the advantage of purifying biomolecules with high yields and purities but the disadvantages are in general the high stationary phase cost, ligand leaching and reduced cleanability. The MCSGP process can result in purities and yields comparable to those of purification using Protein A. The second application example for the MCSGP prototype is the separation of three MAb variants using a preparative weak cation-exchange resin. Although the intermediately eluting MAb variant can only be obtained with 80% purity at recoveries close to zero in a batch chromatographic process, the MCSGP process can provide 90% purity at 93% yield. A numerical comparison of the MCSGP process with the batch chromatographic process, and a batch chromatographic process including ideal recycling, has been performed using an industrial polypeptide purification as the model system. It shows that the MCSGP process can increase the productivity by a factor of 10 and reduce the solvent requirement by 90%.
Narrated by Jonathan Cullen, produced by Andy Paterson, directed by Patrick Forbes 22 September Fighting the G-Force, it looked at the Brooks Air Force Base in Texas; F-16 aircraft of the United States Air Force Thunderbirds; a G-force simulator on 30 May 1997, where a pilot experiences G-LOC; Major Mark Arlinghaus of the Thunderbirds; Captain Rick Forster, an F-16 instructor; Luke Air Force Base in Arizona, where F-16 pilots were trained; Major Rob Kesterson, an instructor with the 62nd Fighter Squadron; Lt Toby Brallier of the 62nd Fighter Squadron, who blacked out, but he was in a two-seat F-16 trainer; Holloman Air Force Base in New Mexico, where all USAF pilots learn about G-LOC, and are medically tested; Captain John Condojani and G-suits; a G-force centrifuge, rotating once every two seconds; pilots referred to G-LOC as 'doing the funky chicken'; to fly in an A-10, a pilot had to cope with 7.5G, and there were no exceptions; F-16 pilots had to cope with 9G; Captain Rick Fofi, a physical training officer with the USAF; women had been allowed to fly USAF fighter aircraft since 1993; Dr William Albery, chief of USAF aerospace medical research; Colonel James Dooley of flight motion effects at Brooks AFB in Texas, in the Armstrong Laboratory, named after Harry George Armstrong, known for the Armstrong limit; taller pilots were more susceptible to G-LOC; when the German Air Force inherited East German pilots, it discovered that the East German air force believed that G-LOC could be prevented by ruthless selection of pilots and better fitness preparation; Wing Commander Andreas Valentiner of the Luftwaffe Institute of Aviation Medicine; the German Air Force decided to ruthlessly select pilots by G-LOC in a centrifuge as well, before any training commenced - it was the only NATO air force to do this; Dr Brendan Godfrey, director of the Armstrong Laboratory; Captain Kelly Greene of Wright-Patterson Air Force Base in Ohio; Colonel Ron Hill, head of the Crew Systems Directorate; Finley Barfield, chief engineer of the F-16, and what became the Automatic Ground Collision Avoidance System, to avoid controlled flight into terrain (CFIT); Dr Paul Werchan of Brooks AFB; Dr Gene McCall of the United States Air Force Scientific Advisory Board; the Northrop Grumman RQ-4 Global Hawk, planned to first fly in late 1997. Narrated by Piers Gibbon, produced by Simon Berthon, directed by Mark Rubens, made by 3BM Television with The Learning Channel (TLC) 29 September The Iceberg Cometh, about the dangers of icebergs in the Atlantic Ocean; for every metre above surface, four metres are below; the icebergs are made of snow that fell half a million years ago; Greenland is as large as western Europe; icebergs can travel thirty miles a day; the International Ice Patrol was formed in 1914, and now checks half a million square miles; patrols take place three times a week from March to July in the Atlantic Marine Ecozone; glaciologist Peter Wadhams of the University of Cambridge; the North Greenland Ice Core Project (NGRIP) began in 1995. Produced by David Frank, directed by Cathy Rogers, made by RDF Television with the Discovery Channel 13 October Coma, on 4 June 1996 a 32-year-old woman was beaten unconscious in New York Central Park; she was one of four women beaten by 22-year-old John Royster, with the last, 62-year-old Evelyn Alvarez on Park Avenue, not surviving, and Royster was caught from a fingerprint, and was sentenced to life without parole in 1998; neurosurgeon Jamshid Ghajar; the Jamaica Hospital Medical Center, where a nine year old boy, Alex, had been hit by a car, and had severe head trauma, and had a head CT scan; the 'second accident' in the first week in hospital, where the brain swelled, and blocked the flow of blood; a tube was inserted into the brain, to release fluid from swelling, known as a ventriculostomy; the New York Hospital Pediatric ICU, now the Weill Cornell Medical Center; on day two, the eye pupils began to dilate, which can indicate brain swelling, and the intracranial pressure increased, until day three: by day twenty, Alex began to show greater responses, and by day 39, he was walking, and will make a good recovery; neurosurgeon Randall Chesnut, of Oregon, now at the University of Washington School of Medicine; Nicole Ward had a car accident, with a brain injury, but makes a good recovery, thanks to the ventriculostomy procedure; the International Conference on Recent Advances in Neurotraumatology (ICRAN) in early September 1996 at the University of Bologna in Rimini in north-east Italy, where new guidelines of the American Academy of Neurology would be disseminated, from work by the Colorado Medical Society in 1991. A US production, narrated by Piers Gibbon, produced by Paula Apsell, directed by Linda Garmon, made by Nova and WGBH. Shown on Nova on 7 October 1997 20 October Superhighway Robbery, an updated repeat 27 October Sun Storm, about geomagnetic storms, with Nicola Fox of the Heliophysics Science Division; Mike Lockwood (physicist); the March 1989 geomagnetic storm and Hydro-Québec's electricity transmission system; Telesat of Ottawa, and the High Altitude Observatory; a warning system for geomagnetic storms, the Cluster satellite network, was to be launched on 4 June 1996 on board Ariane flight V88, but the launch was a disaster; historical solar records at the Armagh Observatory showed how weather fluctuated with solar activity over the years, John Butler found a connection with Earth temperature; Brian Tinsley looked at electrical charge in clouds causing rain, found by aircraft of the National Center for Atmospheric Research (NCAR); Ernest Hildner of the Space Weather Prediction Center; North American Aerospace Defense Command (NORAD); Daniel N. Baker of the Laboratory for Atmospheric and Space Physics; the Advanced Composition Explorer, launched in August 1997, would detect the magnetic polarity of any solar winds. Narrated by Robin Ellis, directed by Dan Chambers, produced by Robert Eagle, made by Eagle & Eagle 3 November Natural Born Genius?, about inherited intelligence; the population geneticist Robert Plomin, who came to London in 1994; bioethicist Jonathan Glover; psychologist Camilla Benbow of Iowa State University, and the Study of Mathematically Precocious Youth; statistician Charles Spearman was the first to conduct research into general intelligence in 1904, and found that schoolchildren who were good at one academic subject were also good at other subjects and vice versa, and invented the term g factor (psychometrics), although Francis Galton had briefly looked at the subject; psychologist Ian Deary of the University of Edinburgh, where much research on intelligence has been conducted; Alfred Binet of France invented the intelligence test, so that low-scoring children could be given extra help; cognitive psychologist Michael Howe of the University of Exeter believed that the 11-plus exams in England, for grammar school entrance, could possibly label children; much educational testing took place in the US, as the government believed in it, by the Educational Testing Service (ETS); psychologist Stephen J. Ceci disputed reading cast-iron outcomes of individual intelligence tests, but nonetheless believed that general intelligence could be predicted across a population as a whole; Chris Allander of the Army School of Recruiting; Michael Howe conducted environmental education research of parental support, and if that was as much a factor as genetic or innate ability - environmental educational research largely ignored any genetic component, which Robert Plomin dismissed; psychologist Sandra Scarr had conducted much research on adopted children, which largely and conclusively proved the case for genetically inherited intelligence and abilities - and she believed that you could only teach subjects to children of whom had enough capability; Robert Plomin's wife, psychologist Judith Dunn, and varying intelligence of children within individual families; identical twins raised apart had identical IQ scores; psychologist Thalia C. Eley of the Institute of Psychiatry, Psychology and Neuroscience; from Robert Plomin's exhaustive adoption genetic studies, he finds a genetic link. Narrated by Barbara Flynn, produced by Rosalind Arden, directed by David Cresswell, made by John Gau Productions. John Gau had made Triumph of the Nerds the year before 10 November Losing It, about the persistence of sportspeople in the face of adversity; Steve Backley, javelin thrower gained three world records and was European champion in 1990 at the age of 21, but at the 1991 World Championships in Athletics in Tokyo, he didn't get past the qualifying round, where he had to throw 82m but he could only manage 78m; a fortnight later he threw 91m, gaining the British and Commonwealth records; mental strength is often the difference between success and failure; Doug Sanders, the American golfer, missed a straightforward put at the 1970 British Open; Sally Gunnell at the 1992 Olympics; sports psychologist Dave Collins (a former Royal Marine); footballer Lee Chapman who suffered a loss of confidence in 1982; Sally Gunnell, despite feeling intensely nervous before the final on 19 August of the 1993 World Championships in Athletics in Stuttgart, came first and broke the world record; Scottish golfer Sam Torrance and mental preparation for the zone; cricketer Michael Atherton; tennis player Mark Cox; neuroscientist Susan Greenfield, Baroness Greenfield, and alpha waves or alpha rhythm; banishing negative thoughts; Paul Holmes, sports psychologist of the Great Britain Pistol Squad (run by British Shooting since 2007); total mental absorption, denoted by alpha wave brain activity on an ECG, appeared to strongly help success; psychologist David Milner. Narrated by sports commentator Brian Moore, produced by Geoff Deehan, made by Union Pictures 17 November The Day the Earth Was Hit, the Tunguska event on 30 June 1908; David Morrison (astrophysicist) of NASA Ames; Duncan Steel of The Spaceguard Foundation; physicist Edward Teller; Russian mineralogist Leonid Kulik lead the investigation in 1927; the Tunguska explosion had the strength of a 15 megatonne nuclear explosion; astrophysicist Victor Clube and Bill Napier of Armagh Observatory; scientists from Tomsk State University visit Vanavara (rural locality) in the Siberian summer; the 1945 nuclear explosions had similarities in explosive effect to the Tunguska event; Benny Peiser; the Beta Taurids meteor shower; geochemist Evgeny Kolesnikov of Moscow University; tests at Sandia National Laboratories by Mark Boslough; astronomer Eleanor F. Helin of JPL, who worked on the Near-Earth Asteroid Tracking programme. Narrated by Anthony Hyde, produced by Simon Welfare, directed by Stephen White, made by Granite Productions 24 November When Pigs Ruled the World, about the species that survived the extinction event 250 million years ago, to give rise to mammals; Roger Smith of the South African Museum in the Karroo desert; Scottish paleontologist Mike Benton of the University of Bristol; Peter Ward (paleontologist) of the University of Washington; around 1977 a farmer found a strange footprint, made by a therapsid, the ancestor of mammals, in the Guadalupian part of the middle Permian; biologist Colin Tudge, and how large genetic variety was needed for rapid natural selection to occur, to go from sauropsids to synapsids; animatronics technician Neill Gorton would develop a working moving model; the Moschops plant eater, the more dangerous carnivore Anteosaurus, and the slower Lystrosaurus; paleontologists did not know whether therapsids laid eggs, or have birth to live animals; nasal concha bones; the Permian–Triassic extinction event, 252 million years ago, which scientists did not know the direct cause, and had taken place over 100,000 years; Pangaea was formed 350 million years ago; Tony Hallam of the University of Birmingham, and the events in the Triassic; due the extinction event, Lystrosaurus became much greater in number, as its predators had become extinct; small reptiles evolved into the dinosaurs, and Lystrosaurus evolved into rodents; loss of species was being counted on Madagascar; conservationist Joanna Durbin (now of the Climate, Community & Biodiversity Alliance) and the population of Lemur monkeys on Madagascar; Colin Tudge believed that mass extinctions were integral to evolution; Lystrosaurus lasted for ten million years. Narrated by Roger Allam, produced by Joanne Reay, directed by Howard Reay, made by The Mission, with the Discovery Channel 1 December Mindreaders, about autistic traits; Simon Baron Cohen at Cambridge; Temple Grandin in east Colorado; experimental psychologist Alison Gopnik of the University of California, Berkeley; the Sally–Anne test; Helen Tager-Flusberg, and Williams syndrome; Nancy Etcoff of Harvard Medical School; Phineas Gage; neurologist Robert T. Knight of UC Berkeley; Turner syndrome, where females miss the other X chromosome, and have autistic characteristics; David Skuse of the UCL Great Ormond Street Institute of Child Health found that if this X chromosome originated from the mother, the chances of autistic characteristics were much higher; female brains were typically more attuned to faces than male brains; the book An Anthropologist on Mars. Narrated by British actor Bernard Hill, produced by John Wyver, directed by Jeremy Taylor, made by Illuminations Productions. The female actress was Zoe Margolis, later known for Girl with a One-Track Mind 15 December The Conspiracy of Science, about biotechnology companies in Boston (US); David Kent of Genzyme; the Economic Espionage Act of 1996; the murder of Tsunao Saitoh, and his daughter, in May 1996; Steven Rosenberg of the National Cancer Institute; David Blumenthal of Massachusetts General Hospital; a study by Sandoz (now Novartis) into calcium channel blockers, such as felodipine, by Curt Furberg; full disclosure, or lack of any, of known adverse effects remains a greatly controversial subject. Narrated by Neil Pearson, produced by Geoff Deehan, directed by Tim Shawcross, made by Union Pictures with The Learning Channel (TLC) 22 December Moscow, We Have a Problem, about the Mir EO-23 collision in 1997; Mir had a fire on 24 February 1997; Michael Foale travelled to Mir in May 1997 on Atlantis; the father of Michael Foale was an RAF Meteor pilot; Mir had been in orbit since February 1987, 248 miles above the Earth; the shuttle was docked with Mir for five days; cosmonaut Konstantin Feoktistov, designer of Mir; Mir was only meant to last three years; the oxygen that the cosmonauts breathe originates from the crew's urine; on 24 June 1997, due to saving money on a radar system, a manual docking of the Progress resupply vehicle took place, where the Progress vehicle hit a module, side on; NASA never conducted docking without radar, in such a possibly dangerous way; Vladimir Solovyov (cosmonaut), director of the RKA Mission Control Center; cosmonaut Vasily Tsibliyev accidentally disconnected an important power cable; two more cosmonauts arrived to mend the module on 14 August 1997; the two previous cosmonauts returned to Earth; on 15 September 1997, Mir came close to a NASA satellite; the International Space Station would be launched in June 1998, to cost £20bn; Frank L. Culbertson Jr, director from 1995 of the Shuttle–Mir program; Michael Foale returned to Earth on 27 September 1997 after 142 days, on the Atlantis shuttle; cosmonaut Sergei Krikalev. Narrated by Haydn Gwynne, produced by Julian Ware, directed by Patrick Fleming, made by ITN Factual
=== Cancer treatment === Pardaxin inhibits proliferation and induces apoptosis of human cancer cell lines. Its 33-amino acid structure contains many cationic and amphipathic amino acids. This makes it easier for it to interact with anionic membranes, such as those in tumor cells, which are inherently more acidic because of the acidic environment created by more glycolysis. Pardaxin initiates caspase-dependent and caspase-independent apoptosis in human cervical carcinoma cells. Pardaxin triggers reactive oxygen species (ROS). ROS production disrupts protein folding and induces the unfolded protein response (UPR). This causes stress on the endoplasmic reticulum, which releases calcium. This leads to an increase in mitochondrial calcium, dropping its membrane potential. The pore permeability changes, and Cytochrome c (Cyt c) is released. Cyt c activates the caspase chain that leads to apoptosis. ROS also activates the JNK pathway. JNK is phosphorylated, which leads to the phosphorylation of AP-1 (transcription factor consisting of cFOS and Cjun). This results in the activation of caspases as well. ROS also causes a caspase independent pathway that results in apoptosis. When the mitochondrial membrane potential changes, apoptosis-inducing factors (AIFs) are also released. These trigger apoptosis when they enter the nucleus, not needing to involve caspases.
Sources: en.wikipedia.org
== Medical uses == The most common indication for butorphanol is management of migraine using the intranasal spray formulation. It may also be used parenterally for management of moderate-to-severe pain, as a supplement for balanced general anesthesia, and management of pain during labor. Butorphanol is also quite effective at reducing post-operative shivering (owing to its kappa agonist activity). Butorphanol is more effective in reducing pain in women than in men.
=== Legal status === Eptinezumab was approved for medical use in the United States in February 2020. In November 2021, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended the granting of a marketing authorization for the medicinal product Vyepti, intended for the prophylaxis of migraine. The applicant for this medicinal product is H. Lundbeck A/S. Eptinezumab was approved for medical use in the European Union in January 2022.
== Biological function == Inositol, phosphatidylinositol, and some of their mono- and polyphosphates function as secondary messengers in a number of intracellular signal transduction pathways. They are involved in a number of biological processes, including:
There is significant controversy about the level of risk of stroke from neck manipulation. It may be that manipulation can cause dissection, or it may be that the dissection is already present in some people who seek manipulative treatment. At this time, conclusive evidence does not exist to support either a strong association between neck manipulation and stroke, or no association. However, the two most authoritative articles on the subject, recent literature reviews and analyses, conclude that although there exists an association between stroke from vertebral artery dissection and chiropractic adjustment, there is insufficient evidence to indicate that the adjustment caused the dissection. A recent meta-analysis of the published data on the topic also looked to apply Hill's criteria for assigning causation in biological systems to the relationship between chiropractic adjustment and cervical artery dissection, finding that the relationship did not fulfill the required criteria for causality.
US575002A patent on 01.Dec.1897 to Alexander Lodyguine (Lodygin, Russia) describes filaments made of rare metals, amongst them was tungsten. Lodygin invented a process where rare metals such as tungsten can be chemically treated and heat-vaporized onto an electrically heated thread-like wire (platinum, carbon, gold) acting as a temporary base or skeletal form. (US patent 575,002). Lodygin later sold the patent rights to General Electric. In 1902, Siemens developed a tantalum lamp filament that was more efficient than even graphitized carbon filaments since they could operate at higher temperature. Since tantalum metal has a lower resistivity than carbon, the tantalum lamp filament was quite long and required multiple internal supports. The metal filament gradually shortened in use; the filaments were installed with large slack loops. Lamps used for several hundred hours became quite fragile. Metal filaments had the property of breaking and re-welding, though this would usually decrease resistance and shorten the life of the filament. General Electric bought the rights to use tantalum filaments and produced them in the US until 1913. From 1898 to around 1905, osmium was also used as a filament in lamps made by Carl Auer von Welsbach. The metal was so expensive that used lamps could be returned for partial credit. It could not be made for 110 V or 220 V so several lamps were wired in series for use on standard voltage circuits. These were primarily sold in Europe.
Sources: en.wikipedia.org
Many dried cakes are hygroscopic and can adsorb water during storage or handling. Absorbed moisture may lower the glass transition temperature and promote chemical reactions. Sealed packaging and controlled humidity reduce this risk.
Cake collapse usually means the product became too warm during the drying cycle. The dried matrix loses porosity and may appear shrunken or glassy. Collapse can slow reconstitution and may signal altered stability, though not every collapsed cake fails specifications.
Karl Fischer titration is a common method for measuring residual water in lyophilized solids. Loss on drying and thermogravimetric analysis are also used in some settings. The chosen method should be validated for the specific formulation and moisture range.
Freezing only converts liquid to solid. Lyophilization adds vacuum and controlled warming so frozen solvent sublimes, leaving a dry porous solid. The two steps are related but not interchangeable.