The short version of secondary drying fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2026-08-01 and is reviewed periodically as new material appears.
Lyophilization removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts liquid water into ice and concentrates dissolved solids. Primary drying then lowers chamber pressure so ice changes directly into vapor without passing through a liquid phase. Secondary drying raises the shelf temperature to remove bound water that remains after ice sublimation. The result is a dry, porous structure that can be reconstituted later.
Formulation composition influences whether freeze-drying produces an intact cake or a collapsed mass. Excipients such as sugars and polymers can raise the collapse temperature and provide bulk during drying. The critical temperature for primary drying is often the collapse temperature or the glass transition temperature of the maximally concentrated phase. If the product temperature exceeds this threshold, the frozen matrix may soften and lose structure. Established practice therefore links shelf temperature and chamber pressure to the formulation's thermal properties.
The physics of freeze-drying couples heat transfer, mass transfer, and phase change. Heat supplied through the shelf must reach the sublimation front without melting the ice or degrading the product. Water vapor then travels through the already dried layer and leaves the chamber, where low pressure and cold traps keep it from returning. The dried layer acts as a resistance to vapor flow, so drying rate changes as the front recedes. Open questions remain about how pore structure and formulation heterogeneity affect drying uniformity at larger scales.
The low pressure used during drying allows water vapor to move from the ice surface to a cold condenser. Energy supplied as heat drives sublimation but must stay below the collapse temperature of the frozen matrix. If the product becomes too warm, the frozen structure may soften or melt, reducing pore formation and slowing drying. Formulations often include bulking agents, stabilizers, or buffers to support a rigid cake. The final moisture content depends on formulation, freezing rate, and the length of secondary drying.
Freeze-drying is distinct from simple evaporation and from spray drying. Evaporation removes water at temperatures above freezing, while spray drying rapidly dries droplets in a heated gas stream. Lyophilization avoids high temperatures, which can be useful for heat-sensitive materials such as proteins, vaccines, and some foods. The porous cake produced by sublimation dissolves or rehydrates more quickly than a dense dried mass. Not all materials tolerate freezing or the pH shifts that can occur as solutes concentrate during ice formation.
| Property | Value | Notes |
|---|---|---|
| Common name | Freeze-drying | Process removes water by sublimation under vacuum. |
| Typical primary drying shelf temperature | -40 C to -10 C | Set below the formulation's collapse temperature. |
| Typical chamber pressure | 0.05-0.3 mbar | Low pressure allows ice to sublime below its triple point. |
| Water content after drying | 0.5-3% by weight | Higher values may reduce storage stability for some materials. |
| Key thermal parameter | Collapse temperature | Measured by freeze-drying microscopy or differential scanning calorimetry. |
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.
A typical cycle begins with freezing, sometimes including an annealing step to control ice crystal size. Freezing conditions influence the pore network that later allows vapor escape. During primary drying, shelf temperature and chamber pressure are set so heat enters the product while its temperature stays below the collapse or eutectic point. Secondary drying then raises the shelf temperature to desorb bound water and lower residual moisture. Cycle design depends on formulation, fill volume, container type, and equipment capability.
A formulation often contains excipients that protect the active ingredient during freezing and drying. Bulking agents provide structure, while lyoprotectants stabilize sensitive molecules. The freezing step can produce ice crystals whose size and distribution affect the drying rate, and cycle design includes freezing, annealing, and drying phases. If the product temperature rises above a critical value, the cake may collapse or lose its porous structure. Successful lyophilization therefore depends on the interaction between formulation, equipment, and cycle design.
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.
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.
=== Magnesium sulfate overdose === It is also used to counteract an overdose of Epsom salts magnesium sulfate, which is often administered to pregnant women in order to prophylactically prevent seizures (as in a patient experiencing preeclampsia). Magnesium sulfate is no longer given to pregnant women who are experiencing premature labor in order to slow or stop their contractions (other tocolytics are now used instead due to better efficacy and side effect profiles). Excess magnesium sulfate results in magnesium sulfate toxicity, which results in both respiratory depression and a loss of deep tendon reflexes (hyporeflexia).
== Death == Shortly after midnight on January 19, 2005, Bentley was driving alone when he was killed in a single-car accident in southern California's Ventura County. He was driving on Highway 118 near Simi Valley (30 miles northwest of Los Angeles). Witnesses to the accident stated that Bentley's vehicle was travelling at a high speed towards the Rocky Peak Fire Road off ramp. After running through a stop sign, the vehicle went through a chain-link fence situated across the street and rolled down an embankment. Bentley was ejected from the vehicle into traffic where five cars struck him. He sustained multiple blunt force injuries and was pronounced dead at 12:23 a.m. Bentley was survived by his two daughters and his mother Loyce Bentley. A memorial service for Bentley was held at Forest Lawn Memorial Home in Hollywood Hills, on January 24, 2005. He was buried at Forest Lawn Memorial Park, Hollywood Hills.
=== Warfare and weapons === At RAF Bomber Command, Dyson and colleagues proposed removing two gun turrets from Avro Lancaster bombers, to cut the catastrophic losses due to German fighters in the Battle of Berlin. A Lancaster without turrets could fly 50 mph (80 km/h) faster and be much more manoeuvrable.
== History == The first full description of diabetic ketoacidosis is attributed to Julius Dreschfeld, a German-British pathologist working in Manchester, United Kingdom. In his description, which he gave in an 1886 lecture at the Royal College of Physicians in London, he drew on reports by Adolf Kussmaul as well as describing the main ketones, acetoacetate and β-hydroxybutyrate, and their chemical determination. The condition remained almost universally fatal until the discovery of insulin in the 1920s; by the 1930s, mortality had fallen to 29 percent, and by the 1950s it had become less than 10 percent. The entity of cerebral edema due to DKA was described in 1936 by a team of doctors from Philadelphia. Numerous research studies since the 1950s have focused on the ideal treatment for diabetic ketoacidosis. A significant proportion of these studies have been conducted at the University of Tennessee Health Science Center and Emory University School of Medicine. Treatment options studied have included high- or low-dose intravenous, subcutaneous or intramuscular (e.g. the "Alberti regime") insulin, potassium supplementation, need for a loading dose of insulin, and the appropriateness of using bicarbonate therapy in moderate DKA. Various questions remain unanswered, such as whether bicarbonate administration in severe DKA makes any real difference to the clinical course, and whether an insulin loading dose is needed in adults.
Sources: en.wikipedia.org
The lethal yellow (Ay) mutation is due to an upstream deletion at the start site of agouti transcription. This deletion causes the genomic sequence of agouti to be lost, except the promoter and the first non-encoding exon of Raly, a ubiquitously expressed gene in mammals. The coding exons of agouti are placed under the control of the Raly promoter, initiating ubiquitous expression of agouti, increasing production of pheomelanin over eumelanin and resulting in the development of a yellow phenotype. The viable yellow (Avy) mutation is due to a change in the mRNA length of agouti, as the expressed gene becomes longer than the normal gene length of agouti. This is caused by the insertion of a single intracisternal A particle (IAP) retrotransposon upstream to the start site of agouti transcription. In the proximal end of the gene, an unknown promoter then causes agouti to be constitutionally activated, and individuals to present with phenotypes consistent with the lethal yellow mutation. Although the mechanism for the activation of the promoter controlling the viable yellow mutation is unknown, the strength of coat color has been correlated with the degree of gene methylation, which is determined by maternal diet and environmental exposure. As agouti itself inhibits melanocortin receptors responsible for eumelanin production, the yellow phenotype is exacerbated in both lethal yellow and viable yellow mutations as agouti gene expression is increased.
=== Blood pressure control === Modulating and ameliorating diabetic complications may improve the overall quality of life for diabetic patients. For example, a 2008 study concluded that when elevated blood pressure was tightly controlled, diabetic related deaths were reduced by 32% compared to those with less controlled blood pressure.
=== Convenience, automation === In vitro methods can be miniaturized and automated, yielding high-throughput screening methods for testing molecules in pharmacology or toxicology. In toxicology, U.S. agencies such as the EPA use high-throughput in vitro screening to test large numbers of chemicals and reduce the need for animal-based toxicity tests.
In addition, the serotonin 5-HT1B receptor has been found to be required for psilocybin's persisting antidepressant- and anxiolytic-like effects as well as acute hypolocomotion in animals. In humans, ketanserin blocked psilocybin's hallucinogenic effects but not all of its cognitive and behavioral effects. Serotonin 5-HT2C receptor activation and downstream inhibition of the mesolimbic dopamine pathway may be involved in the limited addictive potential of serotonergic psychedelics like psilocybin. The drug shows pronounced biased agonism at the serotonin 5-HT2C receptor. In addition to its psychedelic effects, psilocin has been found to produce psychoplastogenic effects in animals, including dendritogenesis, spinogenesis, and synaptogenesis. It has been found to promote neuroplasticity in the brain in a rapid, robust, and sustained manner with a single dose. These effects appear to be mediated by intracellular serotonin 5-HT2A receptor activation. The psychoplastogenic effects of psilocybin and other serotonergic psychedelics may be involved in their potential therapeutic benefits in the treatment of psychiatric disorders such as depression. They may also be involved in the effects of microdosing. Psilocin was also reported to act as a highly potent positive allosteric modulator of the tropomyosin receptor kinase B (TrkB), one of the receptors of brain-derived neurotrophic factor (BDNF), but subsequent studies failed to reproduce these findings and instead found no interaction of psilocin with TrkB.
The experiment showed that C-1 of glycine was found almost exclusively in the glycyl portion of hadacidin while formate, the 3-carbon of serine, and the 2-carbon of glycine were incorporated into both the glycyl and formyl portions of the hydroxamate. N-Hydroxyglycine was incorporated into hadacidin at a rate equal to that for glycine in 3-hr periods and to a much greater extent in longer time periods. N-Hydroxyglycine, but not glycine, brought about a net stimulation of hydroxamate production. Nitroacetic acid, glyoxylic acid oxime, and formylglycine were not rapidly incorporated into hadacidin. Experiments showed that the hydroxylamino oxygen atom of hadacidin is derived from oxygen gas rather than water. The experimental results are consistent with the hypothesis that the biosynthesis of hadacidin occurs by N-oxygenation of glycine to yield N-hydroxyglycine followed by N-formylation to yield the hydroxamate.
Sources: en.wikipedia.org
George Walker Bush was born on July 6, 1946, at Grace-New Haven Hospital in New Haven, Connecticut. He is the first child of George Herbert Walker Bush and Barbara Pierce, and was raised in Midland and Houston, Texas. His five siblings are Robin, Jeb, Neil, Marvin and Dorothy. Robin died from leukemia at the age of three in 1953. His paternal grandfather, Prescott Bush, was a U.S. senator from Connecticut. His father was Ronald Reagan's vice president from 1981 to 1989 and the 41st president of the United States from 1989 to 1993. Bush has distant English and German ancestry, along with more distant (over seven generations removed) Dutch, Welsh, Irish, French, and Scottish roots. Bush attended public schools in Midland, Texas, until the family moved to Houston after he had completed seventh grade. He then spent two years at The Kinkaid School, a college-preparatory school in Piney Point Village, Texas. Bush later attended Phillips Academy, a boarding school in Andover, Massachusetts, where he played baseball and was the head cheerleader during his senior year. He attended Yale University from 1964 to 1968, graduating with a Bachelor of Arts degree in history. During this time, he was a cheerleader and a member of the Delta Kappa Epsilon, serving as the president of the fraternity during his senior year. Bush became a member of the Skull and Bones society as a senior. Bush was a rugby union player and was on Yale's 1st XV. He characterized himself as an average student.
=== Helix structure === In 1948, Pauling discovered that many proteins included helical (see alpha helix) shapes. Pauling had deduced this structure from X-ray patterns and from attempts to physically model the structures. (Pauling was also later to suggest an incorrect three chain helical DNA structure based on Astbury's data.) Even in the initial diffraction data from DNA by Maurice Wilkins, it was evident that the structure involved helices. But this insight was only a beginning. There remained the questions of how many strands came together, whether this number was the same for every helix, whether the bases pointed toward the helical axis or away, and ultimately what were the explicit angles and coordinates of all the bonds and atoms. Such questions motivated the modeling efforts of Watson and Crick.
=== Nearest neighbor recognition === Nearest neighbor recognition (NNR) is a technique used to describe molecular interactions and patterns between lipid formations. Under thermal conditions it is used to recognize the preferences of lipids to closely interact with another lipid that has similar or different properties. It provides a molecular depiction of lipid bilayer formations by detecting and quantifying the tendency of exchangeable monomers to become what is termed as "nearest-neighbors" of one another in similar environments.
=== 1988 === 11 February Running to Time, about the new InterCity 225; the National Express Coaches Rapide service; the project team of the Intercity 225, with project director Mike Rollin, and Mike Newman of GEC; the 225 train had to be delivered on 14 February 1988, with an operational life of thirty years; the InterCity 125 was not intended to have been primarily developed - in a board meeting, the commercial directors were not technologically knowledgeable of trains, and asked about alternatives, to be told by an engineering director that a 125 mph diesel train could be developed in two years, so the HST began at that meeting; the British Rail APT-E prototype, powered by the Leyland 2S/350 gas turbine; in 1974 BR commissioned the APT-P, which had ten years of development, due to the active tilting suspension; the 225 train was possibly to enter service on the UK's only large electrified line, the West Coast Main Line, but the much-straighter and faster East Coast Main Line was being electrified, so BR decided to implement the 225 train on the ECML instead; Crewe railway station, which opened in 1837, and where trains were first built nearby in 1843; Steve Corfield, of Crewe Works; the unsprung mass of a train, and Cardan shafts; Roger Ford of Modern Railways; John Prideaux, director of InterCity; David Carter of DCA in Warwick, who designed the livery; the Modernisation Plan was published in December 1954, which had advocated the electrification of the ECML, and the phasing-out of steam travel; the late-1980s ECML electrification had cost BR £350m - it was not government-funded, with 2,800 miles of copper wire, and 33,000 support masts, overseen by Don Heath; all of the improvements in the UK were on old lines of track, but France and Germany had built entire new electrified lines - the TGV was planned from the mid-1960s; G. Freeman Allen of Jane's World Railways; the 225 train underframe being built at Crewe Works; GEC Traction at Preston, Lancashire, Al Reed, the separately excited (Armature Controlled DC Motor) brushed DC electric motor, and Gerald West; the right-angle gearboxes were built by David Brown Ltd and Voith of Heidenheim an der Brenz in southern Germany; Eric Black of Metro-Cammell in Washwood Heath; the ST41 bogies were made by SIG Combibloc Group of Neuhausen am Rheinfall in Switzerland. Narrated by Robin Ellis, produced by Patrick Uden, directed by Paul Fabricius, made by Uden Associates. 12 February Playing with Fire 17 July The Air Fix!, about aviation safety; a television adaptation of a black comedy theatre production by 35-year-old James Castle, dressed as an airline pilot, largely featuring Turkish Airlines Flight 981, the Ermenonville air disaster, in France on 3 March 1974, to this day the worst airliner crash, without any survivors, with 177 British people killed, when a cargo door ruptured, and the subsequent enquiry led to a cover up by the airline and aviation authority; the DC10 had known design failings in its fuselage, and its cargo door design was known to be faulty by the aircraft manufacturer; the American Airlines Flight 96 crash had happened on 12 June 1972, involving a design failure of the cargo door, but the FAA nonetheless gave the DC-10 a certificate of airworthiness; the DC10 had been rushed into service; James Castle accused the aircraft industry of callous negligence; James Castle had been a British Airways aircraft maintenance technician from 1969 to 1977 at Heathrow Airport; he listed the numbers of children that lost one or both parents in the crash, and the numbers of women who were widowed; the theatre production had been going since December 1986, directed by Caroline Noh Narrated by James Castle, produced by Ben Gooder, made by Uden Associates 24 July Nic's Boat, about Nic Bailey, a 37-year-old architect with Foster and Partners; he designed a 40-ft trimaran, called MTC, for the Carlsberg Single-Handed Trans-Atlantic Race on 5 June 1988; he had helped to design the 1978 Sainsbury Centre for Visual Arts in Norwich and the Renault Centre in Swindon; boat builder Spud Rowsell in Exmouth, with Phil Morrison; the hull cost £46,000, and the rigging cost £46,000; the mast and rigging were fitted at Topsham, Devon; Robin Knox-Johnston; French yacht designer Bruno Fehrenbach; he sailed the Atlantic between the Rhumb Line Route and the Great Circle Route; some yachts made the journey to Newport, Rhode Island in ten days; the yacht mast was constructed by Proctor South West. Produced by Michael Wills, directed by Bob Bee, made by Juniper Productions 31 July The Living Dead 7 August Zen and the Art of TV Manufacture, a Panasonic TV factory in South Wales; in 1933 the company founder Kōnosuke Matsushita established seven guiding commercial principles; the Fidelity TV factory in west London was given one year - 1988 - to turn its fortunes around or be closed; the factory's closure was announced to the workforce on 25 January 1988, with the site closing at the end of July 1988; Amstrad bought the Fidelity name in May 1988. Narrated by Alan Howard, directed by Patrick Uden, produced by Michael Proudfoot, made by Uden Associates 14 August How Good Is Soviet Science?, about the political inhibition of Soviet technology in the 1980s; in many ways the Soviet Union in 1987 was a backward and underdeveloped nation, with food queues; the Soviet system didn't respond to changes in demand - everything was planned years in advance; physicist Alexander Prokhorov, who won the Nobel Prize for Physics in 1964; Russians were proud of mathematicians Pafnuty Chebyshev and Nikolai Lobachevsky; large government centrally planned projects were compatible with the communist system, notably its space programme; by the 1970s, the Russians realised that they were some distance behind other countries, such as in disciplines of computing and genetics; science teaching was emphasised at Soviet schools, and English was well taught as well; after secondary schools, half went into science; theoretical science was where Soviet teaching excelled, such as at the Steklov Institute of Mathematics; Yuri Ovchinnikov wanted to improve Soviet science; in the early 1950s, the Soviet Union tried to ignore the findings of genetics, through the work of Trofim Lysenko, who claimed that genetics was anti-communist, known as Lysenkoism leading to many scientists being imprisoned and executed; in the 1960s, a set of large biological research centres were built at Pushchino; one of the most well-built research institutes was the Shemyakin Institute of Bioorganic Chemistry, for biotechnology; Stalin did not like computer science, and it was largely banned until 1958; the Soviets were always years behind in computer science; the first recognisable transistor Soviet computer was the BESM-6 in the 1960s; later computers were the ES EVM series, copied from the IBM System/360; the Akademgorodok (Academic City) in Novosibirsk; the Institute of Automation and Electrometry researched optical memory on holographic slides to and much work on lasers; collaboration between Soviet research and Soviet industry was long-winded, maybe almost impossible - the centrally planned Soviet industry could not sufficiently adapt for short-term changes, as it had to be monotonously planned years in advance, for mass production; Soviet government research was perhaps excellent nonetheless; not many Soviet scientists could travel to international conferences; dissemination of current worldwide science was limited throughout the Soviet Union, due to widespread government restrictions; Suite No. 2 in B minor, BWV 1067. Narrated by US technology historian Loren Graham, produced by Chris Durlacher, directed by Martin Smith, made by Uden Associates, NDR and WGBH. Shown on Nova on 17 November 1987 and 22 March 1988 21 August Toys for the Boys, about the Williams racing team; Graham Hill and Jim Clark in 1967; Tomorrow's World in 1967, narrated by Derek Cooper; journalist Peter Windsor of Williams; aerodynamicist Frank Dernie, head of research at Williams; Keith Botsford, motor racing editor of the Sunday Times; the German racing manager Alfred Neubauer, in the late 1930s; there were 18 F1 teams, with 7 being British; Mobil Oil paid Williams £2.5m for advertising on the cars of Nigel Mansell and Riccardo Patrese; the Williams FW11; racing driver Howden Ganley; part of a BBC Horizon documentary broadcast on 9 March 1981, featuring the Williams FW07, and likewise narrated by Martin Jarvis and produced by Patrick Uden; engineering director Sir Patrick Head; Bach Mass in B minor; Mike Hawthorn, was killed on a public road, the A3 Guildford bypass, in his Jaguar Mark 1 on 22 January 1959; Canadian Gilles Villeneuve was thrown from his Ferrari, when qualifying for the 1982 Belgian Grand Prix; Swedish Ronnie Peterson, died after an accident on the start line at the 1978 Italian Grand Prix; Italian Elio de Angelis was killed in May 1986 at the Circuit Paul Ricard in south-east France; British Piers Courage burned to death at the 1970 Dutch Grand Prix; Jim Clark hit a tree on 7 April 1968 at the 1968 Deutschland Trophäe in the north-west of Baden-Württemberg; German Jochen Rindt was killed at the 1970 Italian Grand Prix after winning the championship in the same year, which was awarded posthumously; Bach Mass in B minor; Frank Williams had a crash on 8 March 1986 in the south of France, with Peter Windsor, in a Ford Sierra, making him quadraplegic; the Williams wind tunnel; Alan Jones waving the British flag at the 1980 Grand Prix; the 1988 season Williams car had a Judd V8 engine; the closing fanfare of Les préludes by Liszt; the documentary ends with German military march Prussia's Glory. Narrated by Martin Jarvis, produced by Patrick Uden, made by Uden Associates 28 August Cold Spring, Morning Sun, about atomic physicist Joan Hinton and her husband Erwin Engst. Joan's mother was teacher Carmelita Hinton. Joan worked on the top secret Manhattan Project at Los Alamos in 1944 which produced the atomic bombs that were dropped on Hiroshima and Hagasaki in the summer of 1945. After the war, Joan, her brother Bill, and her husband Erwin (Sid) Engst travelled to China to join Mao Ze Dong and the cultural revolution. Over the next five decades, Joan and Sid became pioneers in Chinese agricultural science and technology. Narrated by Liza Goddard, written, produced and directed by Chris Haws, Made by InCA. 18 September Taking the Tunnel, who would be travelling through the Channel Tunnel; the tunnel would open in May 1993; Colin Kirkland, technical director of Eurotunnel; Roger Vickerman of the University of Kent; historian Corelli Barnett, and how France and Germany spent money after the war improving rail infrastructure; journalist Kathy Watson; a working model was built of the two Channel rail terminals; 90% of the tunnel went through chalk; the French end was built much more water-tight than the English end, due to the worse geology; the tunnel was around one mile long at the English end, to meet the French side in 1990; the Single Market would stop duty free sales on the Channel ferries; the former Night Ferry across the Channel, which operated until 30 October 1980; TGV Est would connect Bordeaux, and TGV Nord would connect to Germany, the Netherlands, with a spur to the new tunnel; Richard D. North; tolls on the autoroutes discouraged local traffic, which slowed down British motorways; Daniel Ghouzi of Transmanche; Martin Simmons of Kent County Council; A292 junction of M20; Corelli Barnett believed that the British civil service was best at fudging, whereas the French civil service had been trained differently at the French grandes ecoles; a VTG ship from Dover to Dieppe carried trains; freight journeys over 250 miles were most cost effective by rail, but did lack logistical flexibility at either end; Michael Barclay of Tiphook Rail; a distribution centre in Paddock Wood in Kent, built by the Spanish Transfesa; UIC gauge was the main European gauge for freight; Artura Boix of Transfesa; Richard Hope of Railway Gazette; British trains had a 25 tonne axle weight, more than the European 22 tonnes; early plans for the new Eurostar trains, which would be dual voltage for travelling in England and France; rail writer Geoffrey Freeman Allen; the French trains would leave from the Gard du Nord; customs checks would be at the British end in London, but not in France; British Rail planned a high speed line across Kent to open in 1998 from King's Cross, but it would not open until September 2003, and to London in November 2007; Roger Ford of Modern Railways. Narrated by Geoffrey Palmer, produced by Patrick Uden, directed by Paul Fabricius, made by Uden Associates 25 September Road Test about road transport in the UK; there were two million vehicles in the UK in 1930; a test drive would be conducted from The Point, Milton Keynes at 8.30am to Maidstone, by different routes - Mike McDonald of the University of Southampton and Margaret Bell of the University of Nottingham in a Volvo 850 would go across London, and Peter Bonsall and Howard Kirby of the University of Leeds in a Volkswagen Passat B3, would follow the M25 to the north of London, George Hazel of Napier College and John Wootten in a Ford Granada would follow the M25 south of London, and Martin J. H. Mogridge would take the train on the new Thameslink from Bedford railway station via Blackfriars Railway Bridge; the test would be directed from the Road Traffic Research Centre at Middlesex Polytechnic, with Chris Wright, Peter Hills from Newcastle University, and psychologist Ivan Brown from the Applied Psychology Unit (MRC Cognition and Brain Sciences Unit) in Cambridge; variable-message signs (VMS) on the M6; before joining the M25, the vehicles had an average speed of 50 mph; the early plans in the 1940s for the M25, which the M25 to the south and west of London, now largely follows; when the M25 needed to be built, in the 1960s, many environmental objections had arisen for it to be built; Russ Kane in Capital Radio's Flying Eye; David Marsh at the AA Roadwatch studio in north London; the ramp meter, installed on the M6 by John Wootten; all of London's traffic lights were controlled from a computer centre in Westminster, with software (Split Cycle Offset Optimisation Technique) developed by Dennis Robertson; the Volvo 850 enters London along the Edgware Road and Park Lane to Hyde Park Corner; the prototype Autoguide system invented by Ian Catling; automatic vehicle identification (AVI) and piezoelectric strips developed at the University of Nottingham Department of Civil Engineering, and tested by Peter Davies on the Nottingham ring road, next to the QMC; the Volkswagen Passat arrives first at the Great Danes Hotel, making the 107 miles in two hours seventeen minutes, an average speed of 47 mph; the route south of London - 119 miles, also has a 47 mph average speed; the 96-mile rail journey had an average speed of 35 mph; the programme content would be copied by Top Gear fifteen years later. Narrated by Martin Jarvis, produced by David Sharp, directed by Mike Tomlinson, made by Orlando Productions 9 October Look, No Hands! about technology outpacing human knowledge; Hubert Dreyfus of University of California, Berkeley; Martin Corbett, industrial psychologist at the University of Warwick; work by Mike Cooley, and systems design; mechanical engineer Frederick Winslow Taylor and his meticulous improvements to industrial methods, in his book The Principles of Scientific Management; John Harris, manager of the Rolls-Royce helicopter engine plant at Leavesden, Hertfordshire; perhaps automation in engineering manufacturing processes could perhaps add or enhance, rather than totally replace, which required and produced less directly competent workers. Produced by Debra Hauer, directed by Christopher Rawlence, made by Hauer Rawlence Productions 16 October Spytech, John Pike of the Federation of American Scientists and how the Space Shuttle was built mostly for low Earth orbit reconnaissance satellites; but the Titan 34D was also available for many spy satellite launches; Christopher Andrew of the University of Cambridge; Harry Rositzke of the CIA, and the disastrous Operation Red Sox, from 1949 to 1953; William Colby, Director from 1973 to 1976 of the CIA, and how spying methods that worked in Germany during World War II were simply hopeless in a possibly more bizarre culture of communist eastern Europe in the early 1950s, so Ferret missions by B-29 aircraft over the border were attempted instead, but many were shot down; the Americans decided to go for high-altitude reconnaissance; on 1 May 1960, an aircraft photographing a missile construction factory, pilot was sentenced to 10 years, but released after two years in exchange for Rudolf Abel; H. Keith Melton and notorious improvised technology of the KGB; the Russian defector Stanislav Levchenko; the burst transmission method; camera lenses for spy satellites made by Itek; the Space Shuttle was built to maintain and repair the Key Hole set of spy satellites, such as KH-11 KENNEN, launched by the National Reconnaissance Office (NRO) in 1976, and introduced digital photography, and EOSAT and its Landsat program; Jeffrey T. Richelson, a writer on national security; Major-General George Keegan of the Twenty-Fifth Air Force described how the Soviet Union got to know when spy satellites would be overhead, and would hide anything sensitive; listening satellites sent their data to the NSA at Fort Meade in Maryland, such as data from Magnum, launched by the secret STS-51-C mission in January 1985; Paul Bracken and all-source intelligence fusion; Soviet intelligence in the US was quite widespread, with up to 800 spies operating out of Soviet trade missions, and operated much more widespread than the US had attempted; the new KH-12 satellite, that launched in November 1992, could see through clouds. Narrated by Mike Short, produced by Claudia Milne, made by Twenty Twenty 23 October Bamboo, the importance of bamboo to the Chinese economy; Prof Hsiung Wenyue of the Bamboo Research Centre of Nanjing Forestry University; bamboo structures do not collapse in high winds; over a thousand species of bamboo; bamboo dies out for ten years, then grows again; only 15% of China can be cultivated; bamboo can grow four feet in 24 hours, it is the fastest growing plant; bamboo has a tensile strength twice as much as timber; hospitals in China worked with herbal remedies; bamboo traders had quotas set by the Chinese government; bamboo shoots were mostly exported to Japan; growing bamboo helped soil structure; the Chinese government encouraged the growing of bamboo, as an alternative to timber. Narrated by Jenny Agutter, produced by Michael Blakstad, directed by Patrick Fleming, made by Workhouse Productions, made in cooperation with China Central Television 30 October Heavy Metal, chemist Neil Ward of the University of Surrey, who found abnormal pregnancies; medical doctor Robin Russell-Jones of the Campaign for Lead Free Air; environmental chemist Brian Davies of the University of Bradford; footage from the 1971 BBC A Public Poison, with chemist Derek Bryce-Smith, and Patrick Lawther of St Bartholomew's Hospital; Gloria all'Egitto from Aida by Giuseppe Verdi, with the assembly line of the Rover 800; Robin Brundle; Eric Fountain of Vauxhall Motors; Ojos Criollos by Louis Moreau Gottschalk. Narrated by Catherine Robins, produced by Michael Blakstad, made by Workhouse Productions 13 November Free Flight, about gliding, with Derek Piggott in a Rolladen-Schneider LS4 at Booker Gliding Centre in Buckinghamshire; in the UK there were about 350,000 flights and 2 deaths each year; a Schleicher ASW 24 in a wind tunnel with Loek Boermans at TU Delft Faculty of Aerospace Engineering in the Netherlands; the Schleicher ASH 25 with glider pilot John Jeffries at London Gliding Club west of Dunstable; at Wasserkuppe, a 3,000 ft mountain in the east of Hesse in the centre of Germany is where gliding mostly developed in the 1920s by the Deutsche Forschungsanstalt für Segelflug, due to German powered-aircraft manufacturing being legally restricted; nearby at Poppenhausen, Hesse is Alexander Schleicher GmbH & Co, with designer Gerhard Waibel, where gliders had wings made from carbon fibre, and covered in kevlar for torsional stiffness; the first glider of a contemporary design was the Akaflieg Stuttgart fs24 in 1951. Narrated by Robert Gary 20 November Chaos, Tim Palmer of the ECMWF; mathematician Robert L. Devaney; German mathematician Heinz-Otto Peitgen and fractal geometry; strange attractors in dynamical systems, such as weather systems; David Rand of the University of Warwick, and period-doubling bifurcation, discovered in 1975 by mathematician Mitchell Feigenbaum discovered; fractal landscapes; British mathematician Michael Barnsley, and affine transformations, which are applied to digital image processing; the chaos game; Soviet physicist Lev Landau; physicist Harry Swinney of the University of Texas; economist James B. Ramsey; Ian Stewart of the University of Warwick, and the unpredictable rotation of Hyperion. Written, produced and directed by Chris Haws, the programme was made by Independent Communications Associates (InCA). In 1989, it won the SciTech Award for best scientific documentary. 27 November The Art of Deception, about camouflage, deception, decoys and stealth. The Northrop Grumman B-2 Spirit was first displayed on Tuesday 22 November 1988, just five days before the programme was aired. Featured interviewees include: Richard P. Hallion of Wright-Patterson Air Force Base; Peter Varnish of the Admiralty Research Establishment at Funtington in West Sussex; defence writer Antony Preston; Roy Behrens of the Art Academy of Cincinnati; Lt Col Chris Nash of Surveillance, Target Acquisition, Night Observation and Counter-surveillance (STANOC); Major William Marshak of the AAMRL - now the 711th Human Performance Wing; Captain Brian Perowne, commanding officer of HMS Brazen (F91); aviation writer Bill Sweetman, and Commander Patrick Walker, commanding officer of HMS Trafalgar (S107) a Royal Navy hunter-killer submarine; John Hall of the Admiralty Research Establishment (former Admiralty Experiment Works) at Haslar. Narrated by Nick Chilvers, Written, produced and directed by Chris Haws, made by InCA and WGBH Boston
== Class C peptidomimetics == These structural mimetics include molecules that are highly modified when compared to their parent peptide sequence. Usually, a small-molecular scaffold is applied to project groups in analogy to the bioactive conformation of a peptide.
Sources: en.wikipedia.org
Primary drying removes ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, often under the same vacuum. The two stages differ in the water state being removed.
Freezing determines ice crystal size, pore structure, and the concentration of solutes in remaining liquid. Faster freezing generally creates smaller ice crystals and a denser dried matrix. These features affect drying rate and reconstitution behavior.
Lyophilization reduces water content but usually leaves a small amount of water in the dried material. Some water remains bound to solids or trapped in the dried matrix. Very low water targets can require extended secondary drying, which may alter product stability.
Lyophilization relies on sublimation, so water moves from solid ice to vapor without becoming liquid. The material is frozen, pressure is reduced, and controlled heat is supplied. Vapor is captured on a cold condenser, leaving a dry porous solid.