title: Tatra (company)

text: In February 2008, Tatra announced the world's first and only air-cooled engine meeting the then forthcoming Euro 5 emissions standards. The press release claims 7.5 times lower emissions of particulates and 3.5 times lower emission of nitrogen oxides compared to the previous engine. Further, production of air-cooled engines should significantly reduce the production of greenhouse gases due to the absence of liquid cooling systems. All Tatra vehicles from February 2008 onwards should use the new engine.A month later, Tatra CEO Ronald Adams told "The Prague Post" Tatra could return to producing passenger cars, saying: "We would not come back to compete with the large automobile mass producers such as Volkswagen, Škoda, Toyota etc. But we might come back with a replica of the old Tatra cars using a current undercarriage and driveline from one of the major automotive producers." The company has launched a feasibility study, hoping to produce one thousand replicas of their legendary Tatraplan and 603 cars in 2010.


title: Tatra (company)

text: In July 2008 pictures of a fuel cell concept car designed by Mike Jelinek, the Tatra 903, were shown.


title: Tatra (company)

text: Unlike most Eastern Bloc manufacturers, Tatra enjoyed modest sales success in Western Europe, where its truck line had a reputation for simplicity and durability. No effort was made to distribute Tatra's unusual automobiles in the West, though a small number did find their way to collectors in Western Europe, and even to the United States. The end of the Cold War did not help Tatra's fortunes, as the company made no inroads in Western Europe's already crowded automobile market. The introduction of competitors, such as Mercedes-Benz and Peugeot into the Czech Republic, further eroded Tatra's sales. Production of the passenger cars ended in 1999.


title: Tatra (company)

text: Among Western collectors, Tatra automobiles remain largely unknown. The largest display of Tatra vehicles in the United States is at the Lane Motor Museum in Nashville, Tennessee. The museum's eclectic automobile collection contains 12 Tatra models, including a T-613 ambulance. When talk show host and car collector Jay Leno visited the museum, the founder picked him up in a 1947 Tatra 87, prompting Leno to purchase one himself. Leno soon became an advocate for the brand. In the United States, the few Tatra clubs are closely associated with Citroën clubs, as many Tatra collectors also collect Citroën DS series cars.


title: Tatra (company)

text: The first truck manufactured at Kopřivnice in 1898 was a flatbed with two liquid-cooled side-by-side-mounted two-cylinder Benz engines each at 2.7 L capacity with total power output of 8.8 kW (12 hp) placed after the rear axle and cargo capacity of 2.5 ton. The unique feature of the engines setup was that the engines could be operated sequentially depending on the load requirements. No 1 engine was started via a cranking handle and had a flywheel attached and No 2 engine without the flywheel was connected via a gear clutch and started by the first engine already running.


title: Tatra (company)

text: The second truck manufactured was once again a flatbed R type of 2.5 ton cargo capacity built in 1909. Powered by liquid-cooled petrol four-cylinder engine of 4.1 L capacity and power output of 18.4 kW (25 hp) with the engine placed above front axle which is the conventional design to this day. The vehicle featured solid rubber tyres and semi-elliptic leaf spring suspension. In 1910 Tatra manufactured its first bus the Omnibus type SO with total production of five units.


title: Tatra (company)

text: The first true serial truck production at Tatra was instigated by the beginning of World War I. In the year 1914 there were only two trucks made, type T 14/40 HP; however by 1915's end the production jumped to a total of 105 TL-2 units, and the following year, 1916, the numbers rose to a total of 196 TL-2 and 30 TL-4. Production peaked in 1917 with 19 TL-2 and 303 TL-4 models, but then production declined, and a similar number of vehicles of one type manufactured in a year was not achieved or surpassed until 1936 with the T 27 model.


title: Tatra (company)

text: Technically models TL-2 and TL-4 were almost identically designed; in fact TL-4 evolved from TL-2 where both had liquid-cooled OHC engines of max power output of . The TL-2 had a GVM and GCM, TL-4 had GVM and GCM respectively. Both types remained in production in small series until 1927. The TL-4 is considered the first truck to come out of NW (Nesselsdorfer Wagen-bau) to carry the name Tatra in 1919.


title: Tatra (company)

text: After the introduction of Tatra 11 and Tatra 12 cars with their distinctive backbone tube design and swing axles, Tatra introduced its first truck on the same basis, the light utility Tatra 13 powered by 2-cylinder air-cooled petrol engine with power output 8.8 kW (12 hp) and cargo capacity. Further models followed, and in 1926, T23 and T24 were introduced, nicknamed "bulldogs", which could be considered Tatra's precursors to COE designed trucks. Improved version T13 was introduced as T26 with a more powerful 4-cylinder flat air-cooled engine and in six-wheeler chassis created capable offroad light utility truck which later evolved into T72 model which was heavily used by Czechoslovakian army at the time and was also manufactured under license by the French company Lorraine-Dietrich. In 1933 Tatra built a limited series of T25 heavy artillery hauler with 4 and 6-cylinder petrol engines. The most popular Tatra truck before World War II was type T27 powered by 4-cylinder petrol or diesel engines, which remained in production for nearly 17 years (1930–1947) with total production of 7,620 units. By adding an extra axle to the rear the type T28 was created; however, it was not successful and only limited production resulted in a mainly bus chassis. In the period from 1931 to 1938 Tatra also built a small utility truck based on the chassis from T30 named Tatra T43 which remain popular with small business owners. T72 model successfully continued the line to T82 built mainly for military in cargo and personnel transport between 1935 and 1938 and further to T92 and T93 built for the Romanian army from 1938 to 1941 which were identical except T93 had also a driven front axle.


title: Tatra (company)

text: Following the Nazi occupation of Czechoslovakia the production at Kopřivnice was annexed by the Germans for the supply of trucks needed by the Wehrmacht. Apart from the existing line up of T27, T92/92 a new heavy truck, the T81, commenced production featuring liquid-cooled 12.5 L V8 diesel engine with a power output of , in 6×4 axle configuration. This vehicle evolved in 1942 into the T111 which continued in production until 1962, with the total of 33,690 units made. The T111 also featured Tatra's first air-cooled diesel engine, a massive V12 originally designed for the armoured Sd.Kfz. 234 Puma. In the latter stages of World War II Tatra was instrumental in the development of air-cooled diesel engines for German tanks. In late 1944 General Heinz Guderian ordered that production of the Type 38(t) Hetzer tank be modified to incorporate a Tatra Type 928 V-8 air-cooled diesel engine, though this order was delayed so production could continue uninterrupted. After the war the T111 contributed heavily to the rebuilding effort in Central and Eastern Europe and a memorial was built at Magadan, Siberia, for its exploits in the Far East of the USSR.


title: Tatra (company)

text: The decision to replace the reliable but ageing T111 was taken in 1952 based on central planning economy of socialist government where directive was made to Tatra N.P. that it should concentrate on the manufacture of 7 to 10 ton capacity commercial vehicles and in 1956 first T137 and T138 trucks were exhibited at the Czechoslovak machinery expo in Brno. Production of the T111 continued alongside the T138 series until 1962. The T138 itself continued in production until 1969 when it was replaced by the T148, which provided an increase in power output, reliability and product improvements.


title: Tatra (company)

text: In 1967 Tatra began production of the T813 off-road truck using its modular construction technology; the model incorporated the latest trends in commercial vehicle design such as cab-over-engine (COE) and wide profile tyres. It featured a new V12 engine and all military versions had a central tyre inflation/deflation system as standard equipment. The T813 was designed to tow loads up to 100 ton GCM and it was a familiar sight on the roads in Czechoslovakia hauling large, often over-sized loads.


title: Tatra (company)

text: The Tatra 815 was designed for extreme off-road conditions, and its road versions are derived from the off-road original. After the 53rd session of the Council for Mutual Economic Assistance, a directive was issued that Tatra N.P. would be the sole supplier of off-road commercial vehicles of <12 ton capacity for Eastern Bloc countries, leading to a modernization of the company and its production models. Following extensive testing at different sites, including Siberia, the type T815 was introduced in 1982 with production starting in 1983. The T815 was made of 142 main assembly components as opposed to the 219 main assembly components of its predecessor. The engine's power output was increased by up to 45% and a new COE tiltable cabin was introduced. Modular engine designs resulted in offerings of V8, V10 or V12 engines with or without turbocharger.


title: Tatra (company)

text: T815 was upgraded to T815-2 with minor cosmetic changes and improved ergonomics and safety – the biggest change was the engine emissions accordance with the "Euro0" limits and to Euro I limits in 1993 (turbocharged V8 engine only since this time for the full legislation; the Deutz 513 air-cooled V8 engine was offered as an alternative). The TerrNo1, introduced in 1997, featured a redesigned cabin as well as better sound and heat insulation than the previous models. The TerrNo1 was based on the same frame as the previous models, so its cabin could be retrofitted to all type T815s built since 1993. In 2000, the TerrNo1 cabin was again redesigned, and for the first time there was an option to fit liquid-cooled engines.


title: Tatra (company)

text: The TerrNo1 model introduced the 'KingFrame rear axle suspension setup. Another step in evolution for the T3B engine came with the Euro II emission limits. Following further improvements in 2003, the T815 had the new Euro III T3C V8 engine mated to all new 14-speed range+split gearbox as well as an option for engines from other suppliers such as Caterpillar, Cummins, Detroit Diesel, Deutz and MTU to be fitted. In September 2006, Tatra introduced its Euro IV compliant turbocharged T3D engine with the SCR exhaust technology and in February 2008 the company introduced the world's first Euro V-compliant air-cooled diesel engine based on the T3D engine.


title: Tatra (company)

text: The T816 (T815-6) Armax and Force series, derivatives of Tatra 815, were introduced in 1993 after Tatra participated in the tender process to supply heavy duty off-road trucks to the UAE armed forces. After two years of bidding, the company secured a contract worth $180 million.


title: Tatra (company)

text: The resulting model became known as T816 "LIWA" (Arabic for "desert"). The latest model intended for military customers is the T817 (T815-7), marketed primarily toward the armed services of NATO member countries as a high-mobility heavy-duty tactical truck with a low profile cabin for C-130 Hercules transportability.


title: Tatra (company)

text: During the 1990s, Tatra decided to produce a bonneted CBE heavy duty off-road truck to continue the successful line started with the T111. This resulted in the T163 Jamal, which was put into full production in 1999 after the first prototypes were built in 1997 and following extensive testing. The T163 was purpose-built to be a heavy duty dump truck due to demand, and was based on Tatra's signature backbone tube chassis construction with its cabin being designed by Jiří Španihel. The truck is used mainly on construction sites and in quarries.


title: Tatra (company)

text: Tatra was also a successful bidder for the Czech Army replacement of aging Praga V3S (with the Tatra I6 air-cooled engine – one half of the T111 V12 one) medium off-road truck with T810 which technically is not a "genuine" Tatra as its origin goes back to when former Czech company ROSS, in partnership with Renault Trucks, obtained a contract to supply the army with medium size off-road trucks, the "ROSS R210 6×6". The company however went bankrupt in 1998 and Tatra bought full rights to the design, then modernized and reintroduced it as T810 while continuing cooperation with Renault. Under the deal Renault supplies the cabins and the engines and Praga supplied axles and transmissions for the prototypes; however, the whole project has been dogged by controversy due to the way Tatra had obtained the contract, its relationship with supplier Praga and the subsequent court case brought against it by Praga.


title: Tatra (company)

text: The serial T810 vehicles are equipped with the new design Tatra rigid axles with the WABCO disc brakes, with the ZF Ecolite transmission and Steyr drop box.


title: Tatra (company)

text: Tatra and Navistar Defence introduced at Eurosatory Exposition in Paris, France (Jun 14–18 2010), the results of their strategic alliance since October 2009, the models ATX6 (universal container carrier) and ATX8 (troop carrier). The vehicles appear to be based on Tatra 815-7 (T817) 6×6, 8×8 chassis, suspension and cabins while using Navistar engines and other components. Under the deal Navistar Defence and Tatra A.S. will market the vehicles in North America, which includes sales to the United States military and foreign military sales financed by the United States government. Tatra will source parts and components through Navistar's global parts and support network for Tatra trucks delivered in markets outside of North America as well as market Navistar-Tatra vehicles around the world in their primary markets.


title: Tatra (company)

text: The Terex Corporation, an American company, acquired the majority ownership (71%) of Tatra in late 2003. As of late 2006, however, majority ownership (80.51%) was in the hands of Tatra Holdings s.r.o., an international consortium comprising Vectra Limited of UK, Sam Eyde of the U.S., KBC Private Equity of Belgium, Meadowhill s.r.o. of Czech Republic and Ronald Adams of the U.S. On 15 December 2006, a contract was signed between Tatra and the Czech Republic for 556 trucks at roughly $130 million, or 2.6 billion Czech crowns. This contract was signed in lieu of replacement of older military vehicles.


title: Tatra (company)

text: In April 2007, Tatra announced that it had already matched its production in 2006 and produced 1,600 vehicles. In 2007, Tatra planned to produce between 2,300 and 2,500 vehicles. In contrast to previous years, Tatra has increased employment by the hundreds within the past two quarters, has reversed previous errors, and was growing again.


title: Tatra (company)

text: In August 2011, DAF Trucks announced it had built up a 19% stake in Tatra, which was to use DAF cabs and Paccar engines. DAF dealers were to sell Tatra off-road trucks.


title: Tatra (company)

text: In March 2013, Tatra was sold in auction for 176 mil CZK (c. 7 mil euro) due to its debts to Truck Development company (renamed to Tatra Trucks) based in Ostrava, Czech Republic. Production continues. In 2013 Tatra sold 722 trucks, the most since 2008. Approximately two-thirds of units were exported. In 2016, Tatra increased production by 56% and sold 1326 vehicles, all produced vehicles were sold.


title: Tatra (company)

text: Tatra does not rely just on serial production, but also supplies individual, highly specialized custom-made vehicles. The company also sells its own chassis. The current serial production models are:


title: Tatra (company)

text: Several fire brigardes and civil protection (THW) mostly in eastern Germany are traditionally using Tatra trucks. Tatra own Fire brigade conversion company THT are building vehicles for fire brigares and civil protection. Popular in germany is a large Water tender and pumper based on the Tatra 815. The vehicle's water tank has a volume of 4,000 liters or more and a seperat tank for foam agent. The 4×4-transmission and a gear wading depth of 1.20m make it usuabel for rough terrain. In German use the vehicle is called "TLF4000" (Tanklöschfahrzeug 4000) and primarily used at airports and to fight forest fires.


title: Tatra (company)

text: In 2021 the Bundeswehr fire brigade ordered 76 Tatra firefighting vehicles to fight forest fires (ordered by BwFuhrparkService GmbH). The basis is the Tatra T 815-7 4×4 chassis, equipment by Austrian Rosenbauer Group.


title: Tatra (company)

text: Tatra had a truck-building joint venture in India called Tatra Vectra Motors Ltd, formerly called Tatra Trucks India Ltd. It is a joint venture between Tatra and the Vectra Group from England. In 2002, the company received a 1,070 trucks order from the Government of India. Tatra's growing involvement in India's defense industry has been cited as an example of growing relations between Czech Republic and India.


title: Tatra (company)

text: In 2009, Vectra announced a new joint venture with Russia's Kamaz to form Kamaz Vectra Motors Limited to manufacture Kamaz trucks in India. This joint venture replaced the former Tatra Vectra venture. The manufacturing plant is located in Hosur, Tamil Nadu. The fully integrated manufacturing facility includes an engine assembly and testing plant, a cabin welding shop, a frame fabrication shop and a test track. Most Tatra trucks for sale in India are manufactured in collaboration with Bharat Earth Movers Limited (BEML).


title: Tatra (company)

text: Tatra was part of a 2012 investigation in what has been described a "procurement scam" involving former BEML chief VRS Natarajan.


title: Tatra (company)

text: Reportedly following one of the Israeli-Arab conflicts, Israel tested some Tatras captured from the Egyptian armed forces. The Israel Defense Forces' command was apparently quite impressed with their performance, independent air cooling, and their capabilities as military trucks in long-range raiding operations in desert terrain, and became interested in including these trucks in their arsenal. As direct purchase from Czechoslovakia was impossible due to its alignment with Israeli foes, the lore has it that Israelis used the well-paid services of Nicolae Ceauşescu-led Romania, in cooperation with an American Company called ATC (American Truck Company) to purchase military trucks, including desert-equipped Tatras, leading to jokes that "Romania has a new desert". Current photos of various Israeli weapon systems, including SPYDER slated for India, show new Tatras as the carrier vehicles.


title: Tatra (company)

text: A number of Tatra trucks entered service in the Israeli Army's various sectors, with the brand mark of "American Truck Company", under which Tatras were sold from the U.S. market and exported to Israel.


title: Tatra (company)

text: "American Truck Company" was a quasi-independent company set up by Terex, when they controlled Tatra, to import Tatra vehicles in both knock down kits or fully built and carry out assembly operations, repair and service, body building on chassis in the United States. These trucks were offered to the military and other government organizations and were badged and sold in the United States under the ATC brand. ATC badged Tatras were fitted with American Cummins turbodiesel engines in place of the Tatra's air-cooled diesel.


title: Tatra (company)

text: The Ringhoffer-Tatra Works Ltd. produced several aircraft and aero-engines in the 1930s and 1940s before annexation by Germany, and after under the orders of the RLM. Among the aircraft produced were the following:-


title: Hemodialysis

text: Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinine and urea and free water from the blood when the kidneys are in a state of kidney failure. Hemodialysis is one of three renal replacement therapies (the other two being kidney transplant and peritoneal dialysis). An alternative method for extracorporeal separation of blood components such as plasma or cells is apheresis.


title: Hemodialysis

text: Hemodialysis can be an outpatient or inpatient therapy. Routine hemodialysis is conducted in a dialysis outpatient facility, either a purpose-built room in a hospital or a dedicated, stand-alone clinic. Less frequently hemodialysis is done at home. Dialysis treatments in a clinic are initiated and managed by specialized staff made up of nurses and technicians; dialysis treatments at home can be self-initiated and managed or done jointly with the assistance of a trained helper who is usually a family member.


title: Hemodialysis

text: Hemodialysis is the choice of renal replacement therapy for patients who need dialysis acutely, and for many patients as maintenance therapy. It provides excellent, rapid clearance of solutes.


title: Hemodialysis

text: A nephrologist (a medical kidney specialist) decides when hemodialysis is needed and the various parameters for a dialysis treatment. These include frequency (how many treatments per week), length of each treatment, and the blood and dialysis solution flow rates, as well as the size of the dialyzer. The composition of the dialysis solution is also sometimes adjusted in terms of its sodium, potassium, and bicarbonate levels. In general, the larger the body size of an individual, the more dialysis he/she will need. In North America and the UK, 3–4 hour treatments (sometimes up to 5 hours for larger patients) given 3 times a week are typical. Twice-a-week sessions are limited to patients who have a substantial residual kidney function. Four sessions per week are often prescribed for larger patients, as well as patients who have trouble with fluid overload. Finally, there is growing interest in short daily home hemodialysis, which is 1.5 – 4 hr sessions given 5–7 times per week, usually at home. There is also interest in nocturnal dialysis, which involves dialyzing a patient, usually at home, for 8–10 hours per night, 3–6 nights per week. Nocturnal in-center dialysis, 3–4 times per week, is also offered at a handful of dialysis units in the United States.


title: Hemodialysis

text: Hemodialysis often involves fluid removal (through ultrafiltration), because most patients with renal failure pass little or no urine. Side effects caused by removing too much fluid and/or removing fluid too rapidly include low blood pressure, fatigue, chest pains, leg-cramps, nausea and headaches. These symptoms can occur during the treatment and can persist post treatment; they are sometimes collectively referred to as the dialysis hangover or dialysis washout. The severity of these symptoms is usually proportionate to the amount and speed of fluid removal. However, the impact of a given amount or rate of fluid removal can vary greatly from person to person and day to day. These side effects can be avoided and/or their severity lessened by limiting fluid intake between treatments or increasing the dose of dialysis e.g. dialyzing more often or longer per treatment than the standard three times a week, 3–4 hours per treatment schedule.


title: Hemodialysis

text: Since hemodialysis requires access to the circulatory system, patients undergoing hemodialysis may expose their circulatory system to microbes, which can lead to bacteremia, an infection affecting the heart valves (endocarditis) or an infection affecting the bones (osteomyelitis). The risk of infection varies depending on the type of access used (see below). Bleeding may also occur, again the risk varies depending on the type of access used. Infections can be minimized by strictly adhering to infection control best practices.


title: Hemodialysis

text: Venous needle dislodgement (VND) is a fatal complication of hemodialysis where the patient experiences rapid blood loss due to a faltering attachment of the needle to the venous access point.


title: Hemodialysis

text: Unfractioned heparin (UHF) is the most commonly used anticoagulant in hemodialysis, as it is generally well tolerated and can be quickly reversed with protamine sulfate. Low-molecular weight heparin (LMWH) is however, becoming increasingly popular and is now the norm in western Europe. Compared to UHF, LMWH has the advantage of an easier mode of administration and reduced bleeding but the effect cannot be easily reversed. Heparin can infrequently cause a low platelet count due to a reaction called heparin-induced thrombocytopenia (HIT). In such patients, alternative anticoagulants may be used. The risk of HIT is lower with LMWH compared to UHF. Even though HIT causes a low platelet count it can paradoxically predispose thrombosis. In patients at high risk of bleeding, dialysis can be done without anticoagulation.


title: Hemodialysis

text: First-use syndrome is a rare but severe anaphylactic reaction to the artificial kidney. Its symptoms include sneezing, wheezing, shortness of breath, back pain, chest pain, or sudden death. It can be caused by residual sterilant in the artificial kidney or the material of the membrane itself. In recent years, the incidence of first-use syndrome has decreased, due to an increased use of gamma irradiation, steam sterilization, or electron-beam radiation instead of chemical sterilants, and the development of new semipermeable membranes of higher biocompatibility. New methods of processing previously acceptable components of dialysis must always be considered. For example, in 2008, a series of first-use type of reactions, including deaths, occurred due to heparin contaminated during the manufacturing process with oversulfated chondroitin sulfate.


title: Hemodialysis

text: Longterm complications of hemodialysis include hemodialysis-associated amyloidosis, neuropathy and various forms of heart disease. Increasing the frequency and length of treatments has been shown to improve fluid overload and enlargement of the heart that is commonly seen in such patients.


title: Hemodialysis

text: Although a dyalisate fluid, which is a solution containing diluted electrolytes, is employed for the filtration of blood, haemodialysis can cause an electrolyte imbalance. These imbalances can derive from abnormal concentrations of potassium (hypokalemia, hyperkalemia), and sodium (hyponatremia, hypernatremia). These electrolyte imbalances are associated with increased cardiovascular mortality.


title: Hemodialysis

text: The principle of hemodialysis is the same as other methods of dialysis; it involves diffusion of solutes across a semipermeable membrane. Hemodialysis utilizes counter current flow, where the dialysate is flowing in the opposite direction to blood flow in the extracorporeal circuit. Counter-current flow maintains the concentration gradient across the membrane at a maximum and increases the efficiency of the dialysis.


title: Hemodialysis

text: Fluid removal (ultrafiltration) is achieved by altering the hydrostatic pressure of the dialysate compartment, causing free water and some dissolved solutes to move across the membrane along a created pressure gradient.


title: Hemodialysis

text: The dialysis solution that is used may be a sterilized solution of mineral ions and is called dialysate. Urea and other waste products including potassium, and phosphate diffuse into the dialysis solution. However, concentrations of sodium and chloride are similar to those of normal plasma to prevent loss. Sodium bicarbonate is added in a higher concentration than plasma to correct blood acidity. A small amount of glucose is also commonly used. The concentration of electrolytes in the dialysate is adjusted depending on the patient's status before the dialysis. If a high concentration of sodium is added to the dialysate, the patient can become thirsty and end up accumulating body fluids, which can lead to heart damage. On the contrary, low concentrations of sodium in the dialysate solution have been associated with a low blood pressure and intradialytic weight gain, which are markers of improved outcomes. However, the benefits of using a low concentration of sodium have not been demonstrated yet, since these patients can also develop cramps, intradialytic hypotension and low sodium in serum, which are symptoms associated with a high mortality risk.


title: Hemodialysis

text: Three primary methods are used to gain access to the blood for hemodialysis: an intravenous catheter, an arteriovenous fistula (AV) and a synthetic graft. The type of access is influenced by factors such as the expected time course of a patient's renal failure and the condition of their vasculature. Patients may have multiple access procedures, usually because an AV fistula or graft is maturing and a catheter is still being used. The placement of a catheter is usually done under light sedation, while fistulas and grafts require an operation.


title: Hemodialysis

text: There are three types of hemodialysis: conventional hemodialysis, daily hemodialysis, and nocturnal hemodialysis. Below is an adaptation and summary from a brochure of The Ottawa Hospital.


title: Hemodialysis

text: Conventional hemodialysis is usually done three times per week, for about three to four hours for each treatment (Sometimes five hours for larger patients), during which the patient's blood is drawn out through a tube at a rate of 200–400 mL/min. The tube is connected to a 15, 16, or 17 gauge needle inserted in the dialysis fistula or graft, or connected to one port of a dialysis catheter. The blood is then pumped through the dialyzer, and then the processed blood is pumped back into the patient's bloodstream through another tube (connected to a second needle or port). During the procedure, the patient's blood pressure is closely monitored, and if it becomes low, or the patient develops any other signs of low blood volume such as nausea, the dialysis attendant can administer extra fluid through the machine. During the treatment, the patient's entire blood volume (about 5000 cc) circulates through the machine every 15 minutes. During this process, the dialysis patient is exposed to a week's worth of water for the average person.


title: Hemodialysis

text: Daily hemodialysis is typically used by those patients who do their own dialysis at home. It is less stressful (more gentle) but does require more frequent access. This is simple with catheters, but more problematic with fistulas or grafts. The "buttonhole technique" can be used for fistulas requiring frequent access. Daily hemodialysis is usually done for 2 hours six days a week.


title: Hemodialysis

text: The procedure of nocturnal hemodialysis is similar to conventional hemodialysis except it is performed three to six nights a week and between six and ten hours per session while the patient sleeps.


title: Hemodialysis

text: The hemodialysis machine pumps the patient's blood and the dialysate through the dialyzer. The newest dialysis machines on the market are highly computerized and continuously monitor an array of safety-critical parameters, including blood (QB) and dialysate QD) flow rates; dialysis solution conductivity, temperature, and pH; and analysis of the dialysate for evidence of blood leakage or presence of air. Any reading that is out of normal range triggers an audible alarm to alert the patient-care technician who is monitoring the patient. Manufacturers of dialysis machines include companies such as Nipro, Fresenius, Gambro, Baxter, B. Braun, NxStage and Bellco. QB to QD flow rates have to reach 1:2 ratio where QB is set around 250 ml/min and QD is set around 500 ml/min to ensure good dialysis efficiency.


title: Hemodialysis

text: An extensive water purification system is critical for hemodialysis. Since dialysis patients are exposed to vast quantities of water, which is mixed with dialysate concentrate to form the dialysate, even trace mineral contaminants or bacterial endotoxins can filter into the patient's blood. Because the damaged kidneys cannot perform their intended function of removing impurities, molecules introduced into the bloodstream from water improperly purified water can build up to hazardous levels, causing numerous symptoms or death. Aluminum, chlorine and or chloramines, fluoride, copper, and zinc, as well as bacterial fragments and endotoxins, have all caused problems in this regard.


title: Hemodialysis

text: For this reason, water used in hemodialysis is carefully purified before use. A common water purification system includes a multi stage system.


title: Hemodialysis

text: The water is first softened. Next the water is run through a tank containing activated charcoal to adsorb organic contaminants, and chlorine and chloramines. The water may then be temperature-adjusted if needed. Primary purification is then done by forcing water through a membrane with very tiny pores, a so-called reverse osmosis membrane. This lets the water pass, but holds back even very small solutes such as electrolytes. Final removal of leftover electrolytes is done in some water systems by passing the water through an electrodeionization (EDI) device, which removes any leftover anions or cations and replace them with hydroxyl and hydrogen ions, respectively, leaving ultrapure water.


title: Hemodialysis

text: Even this degree of water purification may be insufficient. The trend lately is to pass this final purified water (after mixing with dialysate concentrate) through an ultrafiltration membrane or absolute filter. This provides another layer of protection by removing impurities, especially those of bacterial origin, that may have accumulated in the water after its passage through the original water purification system.


title: Hemodialysis

text: Once purified water is mixed with dialysate (also called dialysis fluid) concentrate consisting of: sodium, potassium, calcium, magnesium and dextrose mixed in an acid solution; this solution is mixed with the purified water and a chemical buffer. This forms the dialysate solution, which contains the basic electrolytes found in human blood. This dialysate solution contains charged ions that conducts electricity. During dialysis, the conductivity of dialysis solution is continuously monitored to ensure that the water and dialysate concentrate are being mixed in the proper proportions. Both excessively concentrated dialysis solution and excessively dilute solution can cause severe clinical problems.


title: Hemodialysis

text: Chemical buffers such as bicarbonate or lactate can alternatively be added to regulate the pH of the dialysate. Both buffers can stabilize the pH of the solution at a physiological level with no negative impacts on the patient. There is some evidence of a reduction in the incidence of heart and blood problems and high blood pressure events when using bicarbonate as the pH buffer compared to lactate. However, the mortality rates after using both buffers do not show a significative difference.


title: Hemodialysis

text: The dialyzer is the piece of equipment that actually filters the blood. Almost all dialyzers in use today are of the hollow-fiber variety. A cylindrical bundle of hollow fibers, whose walls are composed of semi-permeable membrane, is anchored at each end into potting compound (a sort of glue). This assembly is then put into a clear plastic cylindrical shell with four openings. One opening or blood port at each end of the cylinder communicates with each end of the bundle of hollow fibers. This forms the "blood compartment" of the dialyzer. Two other ports are cut into the side of the cylinder. These communicate with the space around the hollow fibers, the "dialysate compartment." Blood is pumped via the blood ports through this bundle of very thin capillary-like tubes, and the dialysate is pumped through the space surrounding the fibers. Pressure gradients are applied when necessary to move fluid from the blood to the dialysate compartment.


title: Hemodialysis

text: Dialyzer membranes come with different pore sizes. Those with smaller pore size are called "low-flux" and those with larger pore sizes are called "high-flux." Some larger molecules, such as beta-2-microglobulin, are not removed at all with low-flux dialyzers; lately, the trend has been to use high-flux dialyzers. However, such dialyzers require newer dialysis machines and high-quality dialysis solution to control the rate of fluid removal properly and to prevent backflow of dialysis solution impurities into the patient through the membrane.


title: Hemodialysis

text: Dialyzer membranes used to be made primarily of cellulose (derived from cotton linter). The surface of such membranes was not very biocompatible, because exposed hydroxyl groups would activate complement in the blood passing by the membrane. Therefore, the basic, "unsubstituted" cellulose membrane was modified. One change was to cover these hydroxyl groups with acetate groups (cellulose acetate); another was to mix in some compounds that would inhibit complement activation at the membrane surface (modified cellulose). The original "unsubstituted cellulose" membranes are no longer in wide use, whereas cellulose acetate and modified cellulose dialyzers are still used. Cellulosic membranes can be made in either low-flux or high-flux configuration, depending on their pore size.


title: Hemodialysis

text: Another group of membranes is made from synthetic materials, using polymers such as polyarylethersulfone, polyamide, polyvinylpyrrolidone, polycarbonate, and polyacrylonitrile. These synthetic membranes activate complement to a lesser degree than unsubstituted cellulose membranes. However, they are in general more hydrophobic which leads to increased adsorption of proteins to the membrane surface which in turn can lead to complement system activation. Synthetic membranes can be made in either low- or high-flux configuration, but most are high-flux.


title: Hemodialysis

text: Nanotechnology is being used in some of the most recent high-flux membranes to create a uniform pore size. The goal of high-flux membranes is to pass relatively large molecules such as beta-2-microglobulin (MW 11,600 daltons), but not to pass albumin (MW ~66,400 daltons). Every membrane has pores in a range of sizes. As pore size increases, some high-flux dialyzers begin to let albumin pass out of the blood into the dialysate. This is thought to be undesirable, although one school of thought holds that removing some albumin may be beneficial in terms of removing protein-bound uremic toxins.


title: Hemodialysis

text: Whether using a high-flux dialyzer improves patient outcomes is somewhat controversial, but several important studies have suggested that it has clinical benefits. The NIH-funded HEMO trial compared survival and hospitalizations in patients randomized to dialysis with either low-flux or high-flux membranes. Although the primary outcome (all-cause mortality) did not reach statistical significance in the group randomized to use high-flux membranes, several secondary outcomes were better in the high-flux group. A recent Cochrane analysis concluded that benefit of membrane choice on outcomes has not yet been demonstrated. A collaborative randomized trial from Europe, the MPO (Membrane Permeabilities Outcomes) study, comparing mortality in patients just starting dialysis using either high-flux or low-flux membranes, found a nonsignificant trend to improved survival in those using high-flux membranes, and a survival benefit in patients with lower serum albumin levels or in diabetics.


title: Hemodialysis

text: High-flux dialysis membranes and/or intermittent internal on-line hemodiafiltration (iHDF) may also be beneficial in reducing complications of beta-2-microglobulin accumulation. Because beta-2-microglobulin is a large molecule, with a molecular weight of about 11,600 daltons, it does not pass at all through low-flux dialysis membranes. Beta-2-M is removed with high-flux dialysis, but is removed even more efficiently with IHDF. After several years (usually at least 5–7), patients on hemodialysis begin to develop complications from beta-2-M accumulation, including carpal tunnel syndrome, bone cysts, and deposits of this amyloid in joints and other tissues. Beta-2-M amyloidosis can cause very serious complications, including spondyloarthropathy, and often is associated with shoulder joint problems. Observational studies from Europe and Japan have suggested that using high-flux membranes in dialysis mode, or IHDF, reduces beta-2-M complications in comparison to regular dialysis using a low-flux membrane.


title: Hemodialysis

text: Dialyzers come in many different sizes. A larger dialyzer with a larger membrane area (A) will usually remove more solutes than a smaller dialyzer, especially at high blood flow rates. This also depends on the membrane permeability coefficient "K" for the solute in question. So dialyzer efficiency is usually expressed as the "KA" – the product of permeability coefficient and area. Most dialyzers have membrane surface areas of 0.8 to 2.2 square meters, and values of "KA" ranging from about 500 to 1500 mL/min. "KA", expressed in mL/min, can be thought of as the maximum clearance of a dialyzer at very high blood and dialysate flow rates.


title: Hemodialysis

text: The dialyzer may either be discarded after each treatment or be reused. Reuse requires an extensive procedure of high-level disinfection. Reused dialyzers are not shared between patients. There was an initial controversy about whether reusing dialyzers worsened patient outcomes. The consensus today is that reuse of dialyzers, if done carefully and properly, produces similar outcomes to single use of dialyzers.


title: Hemodialysis

text: Dialyzer Reuse is a practice that has been around since the invention of the product. This practice includes the cleaning of a used dialyzer to be reused multiple times for the same patient. Dialysis clinics reuse dialyzers to become more economical and reduce the high costs of "single-use" dialysis which can be extremely expensive and wasteful. Single used dialyzers are initiated just once and then thrown out creating a large amount of bio-medical waste with no mercy for cost savings. If done right, dialyzer reuse can be very safe for dialysis patients.


title: Hemodialysis

text: There are two ways of reusing dialyzers, manual and automated. Manual reuse involves the cleaning of a dialyzer by hand. The dialyzer is semi-disassembled then flushed repeatedly before being rinsed with water. It is then stored with a liquid disinfectant(PAA) for 18+ hours until its next use. Although many clinics outside the USA use this method, some clinics are switching toward a more automated/streamlined process as the dialysis practice advances. The newer method of automated reuse is achieved by means of a medical device that began in the early 1980s. These devices are beneficial to dialysis clinics that practice reuse – especially for large dialysis clinical entities – because they allow for several back to back cycles per day. The dialyzer is first pre-cleaned by a technician, then automatically cleaned by machine through a step-cycles process until it is eventually filled with liquid disinfectant for storage. Although automated reuse is more effective than manual reuse, newer technology has sparked even more advancement in the process of reuse. When reused over 15 times with current methodology, the dialyzer can lose B2m, middle molecule clearance and fiber pore structure integrity, which has the potential to reduce the effectiveness of the patient's dialysis session. Currently, as of 2010, newer, more advanced reprocessing technology has proven the ability to eliminate the manual pre-cleaning process altogether and has also proven the potential to regenerate (fully restore) all functions of a dialyzer to levels that are approximately equivalent to single-use for more than 40 cycles. As medical reimbursement rates begin to fall even more, many dialysis clinics are continuing to operate effectively with reuse programs especially since the process is easier and more streamlined than before.


title: Hemodialysis

text: Hemodialysis was one of the most common procedures performed in U.S. hospitals in 2011, occurring in 909,000 stays (a rate of 29 stays per 10,000 population). This was an increase of 68 percent from 1997, when there were 473,000 stays. It was the fifth most common procedure for patients aged 45–64 years.


title: Hemodialysis

text: Many have played a role in developing dialysis as a practical treatment for renal failure, starting with Thomas Graham of Glasgow, who first presented the principles of solute transport across a semipermeable membrane in 1854. The artificial kidney was first developed by Abel, Rountree, and Turner in 1913, the first hemodialysis in a human being was by Haas (February 28, 1924) and the artificial kidney was developed into a clinically useful apparatus by Kolff in 1943 – 1945. This research showed that life could be prolonged in patients dying of kidney failure.


title: Hemodialysis

text: Willem Kolff was the first to construct a working dialyzer in 1943. The first successfully treated patient was a 67-year-old woman in uremic coma who regained consciousness after 11 hours of hemodialysis with Kolff's dialyzer in 1945. At the time of its creation, Kolff's goal was to provide life support during recovery from acute renal failure. After World War II ended, Kolff donated the five dialyzers he had made to hospitals around the world, including Mount Sinai Hospital, New York. Kolff gave a set of blueprints for his hemodialysis machine to George Thorn at the Peter Bent Brigham Hospital in Boston. This led to the manufacture of the next generation of Kolff's dialyzer, a stainless steel Kolff-Brigham dialysis machine.


title: Hemodialysis

text: According to McKellar (1999), a significant contribution to renal therapies was made by Canadian surgeon Gordon Murray with the assistance of two doctors, an undergraduate chemistry student, and research staff. Murray's work was conducted simultaneously and independently from that of Kolff. Murray's work led to the first successful artificial kidney built in North America in 1945–46, which was successfully used to treat a 26-year-old woman out of a uraemic coma in Toronto. The less-crude, more compact, second-generation "Murray-Roschlau" dialyser was invented in 1952–53, whose designs were stolen by German immigrant Erwin Halstrup, and passed off as his own (the "Halstrup–Baumann artificial kidney").


title: Hemodialysis

text: By the 1950s, Willem Kolff's invention of the dialyzer was used for acute renal failure, but it was not seen as a viable treatment for patients with stage 5 chronic kidney disease (CKD). At the time, doctors believed it was impossible for patients to have dialysis indefinitely for two reasons. First, they thought no man-made device could replace the function of kidneys over the long term. In addition, a patient undergoing dialysis developed damaged veins and arteries, so that after several treatments, it became difficult to find a vessel to access the patient's blood.


title: Hemodialysis

text: The original Kolff kidney was not very useful clinically, because it did not allow for removal of excess fluid. Swedish professor Nils Alwall encased a modified version of this kidney inside a stainless steel canister, to which a negative pressure could be applied, in this way effecting the first truly practical application of hemodialysis, which was done in 1946 at the University of Lund. Alwall also was arguably the inventor of the arteriovenous shunt for dialysis. He reported this first in 1948 where he used such an arteriovenous shunt in rabbits. Subsequently, he used such shunts, made of glass, as well as his canister-enclosed dialyzer, to treat 1500 patients in renal failure between 1946 and 1960, as reported to the First International Congress of Nephrology held in Evian in September 1960. Alwall was appointed to a newly created Chair of Nephrology at the University of Lund in 1957. Subsequently, he collaborated with Swedish businessman Holger Crafoord to found one of the key companies that would manufacture dialysis equipment in the past 50 years, Gambro. The early history of dialysis has been reviewed by Stanley Shaldon.


title: Hemodialysis

text: Belding H. Scribner, working with the biomechanical engineer Wayne Quinton, modified the glass shunts used by Alwall by making them from Teflon. Another key improvement was to connect them to a short piece of silicone elastomer tubing. This formed the basis of the so-called Scribner shunt, perhaps more properly called the Quinton-Scribner shunt. After treatment, the circulatory access would be kept open by connecting the two tubes outside the body using a small U-shaped Teflon tube, which would shunt the blood from the tube in the artery back to the tube in the vein.


title: Hemodialysis

text: In 1962, Scribner started the world's first outpatient dialysis facility, the Seattle Artificial Kidney Center, later renamed the Northwest Kidney Centers. Immediately the problem arose of who should be given dialysis, since demand far exceeded the capacity of the six dialysis machines at the center. Scribner decided that he would not make the decision about who would receive dialysis and who would not. Instead, the choices would be made by an anonymous committee, which could be viewed as one of the first bioethics committees.


title: Hemodialysis

text: For a detailed history of successful and unsuccessful attempts at dialysis, including pioneers such as Abel and Roundtree, Haas, and Necheles, see this review by Kjellstrand.


title: Guardians of the Galaxy (soundtrack)

text: Guardians of the Galaxy: Awesome Mix Vol. 1 (Original Motion Picture Soundtrack) is the soundtrack album for the Marvel Studios film "Guardians of the Galaxy". Featuring the songs present on Peter Quill's mixtape in the film, the album was released by Hollywood Records on July 29, 2014. A separate film score album, Guardians of the Galaxy (Original Score), composed by Tyler Bates, was also released by Hollywood Records on the same date, along with a deluxe version featuring both albums. The soundtrack album reached number one on the US "Billboard" 200 chart, becoming the first soundtrack album in history consisting entirely of previously released songs to top the chart.


title: Guardians of the Galaxy (soundtrack)

text: The album topped the "Billboard" Top Soundtracks chart for 11 consecutive weeks and 16 weeks in total. As of April 2017, it has sold over 1.75 million copies in the United States alone, and has been certified Platinum by the RIAA. The album was the US's second best-selling soundtrack album of 2014, behind Disney's "Frozen".


title: Guardians of the Galaxy (soundtrack)

text: In August 2013 the film's director, James Gunn, posted on his Facebook page that Tyler Bates would be composing the film's score. Gunn stated that Bates will write some of the score first so that he can film to the music, as opposed to scoring to the film. In February 2014, Gunn revealed that the film would incorporate songs from the 1960s and 1970s, such as "Hooked on a Feeling", on a mixtape in Quill's Walkman, which acts as a way for him to stay connected to the Earth, home, and family he lost. In May 2014, Gunn added that using the songs from the 60s and 70s were "cultural reference points", saying, "It's striking the balance throughout the whole movie, through something that is very unique, but also something that is easily accessible to people at the same time. The music and the Earth stuff is one of those touchstones that we have to remind us that, yeah, [Quill] is a real person from planet Earth who's just like you and me. Except that he's in this big outer space adventure."


title: Guardians of the Galaxy (soundtrack)

text: All songs—with the exception of "Spirit in the Sky", which is played in the trailer—are featured in the film. "Never Been to Spain" by Three Dog Night, "Magic" by Pilot, and "Livin' Thing" by Electric Light Orchestra were also used during filming; however, the scenes in which they were featured were cut from the final version of the film. "Wichita Lineman" by Glen Campbell and "Mama Told Me (Not to Come)" by Three Dog Night were originally considered for the film instead of "Moonage Daydream". "Fox on the Run" by Sweet and "Surrender" by Cheap Trick were also considered for the film. Both would be used for "Guardians of the Galaxy Vol. 2"s "Awesome Mix Vol. 2".


title: Guardians of the Galaxy (soundtrack)

text: By August 2014, "Guardians of the Galaxy: Awesome Mix Vol. 1" had reached the top of the "Billboard" 200 chart, becoming the first soundtrack album consisting entirely of previously released songs to top the chart. By September 2014, "Guardians of the Galaxy: Awesome Mix Vol. 1" was the second best-selling soundtrack album in the US with 426,000 copies sold at that time. The album was also the second soundtrack album released by Disney Music Group that year to reach No. 1 on the aforementioned chart. The album was certified Gold by the Recording Industry Association of America, eight weeks after its release. An exclusive vinyl LP edition of the soundtrack was also released on September 16, 2014. The vinyl LP has been sold 367,000 units till December, 2019; making the LP 3rd best-selling vinyl album of the decade. On November 28, 2014, the soundtrack got a limited edition cassette tape release exclusive to retailers associated with Record Store Day's Black Friday event, and is the first cassette release by Disney Music Group since 2003's "".


title: Guardians of the Galaxy (soundtrack)

text: The soundtrack became the fifth best-selling album of 2014, selling a total of 898,000 copies that year.


title: Guardians of the Galaxy (soundtrack)

text: In January 2015, the album was certified platinum by the RIAA. It has sold 1.75 million total copies in the United States, with 11,000 coming from cassette sales. Worldwide, "Guardians of the Galaxy: Awesome Mix Vol. 1" sold over 2.5 million copies in 2014.


title: Telomere

text: A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.


title: Telomere

text: In the early 1970s, Soviet theorist Alexei Olovnikov first recognized that chromosomes could not completely replicate their ends; this is known as the "end replication problem". Building on this, and accommodating Leonard Hayflick's idea of limited somatic cell division, Olovnikov suggested that DNA sequences are lost every time a cell replicates until the loss reaches a critical level, at which point cell division ends.


title: Telomere

text: In 1975–1977, Elizabeth Blackburn, working as a postdoctoral fellow at Yale University with Joseph G. Gall, discovered the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends. Blackburn, Carol Greider, and Jack Szostak were awarded the 2009 Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.


title: Telomere

text: In 1983, Barbara McClintock, an American cytogeneticist and the first woman to receive an unshared Nobel Prize in Physiology or Medicine, received the Nobel Prize for observing that the chromosomes lacking end parts became "sticky" and hypothesized the existence of a special structure at the chromosome tip that would maintain chromosome stability.


title: Telomere

text: During DNA replication, DNA polymerase cannot replicate the sequences present at the 3' ends of the parent strands. This is a consequence of its unidirectional mode of DNA synthesis: it can only attach new nucleotides to an existing 3'-end (that is, synthesis progresses 5'-3') and thus it requires a primer to initiate replication. On the leading strand (oriented 5'-3' within the replication fork), DNA-polymerase continuously replicates from the point of initiation all the way to the strand's end with the primer (made of RNA) then being excised and substituted by DNA. The lagging strand, however, is oriented 3'-5' with respect to the replication fork so continuous replication by DNA-polymerase is impossible, which necessitates discontinuous replication involving the repeated synthesis of primers further 5' of the site of initiation (see lagging strand replication). The last primer to be involved in lagging-strand replication sits near the 3'-end of the template (corresponding to the potential 5'-end of the lagging-strand). Originally it was believed that the last primer would sit at the very end of the template, thus, once removed, the DNA-polymerase that substitutes primers with DNA (DNA-Pol δ in eukaryotes) would be unable to synthesize the "replacement DNA" from the 5'-end of the lagging strand so that the template nucleotides previously paired to the last primer would not be replicated. It has since been questioned whether the last lagging strand primer is placed exactly at the 3'-end of the template and it was demonstrated that it is rather synthesized at a distance of about 70-100 nucleotides which is consistent with the finding that DNA in cultured human cell is shortened by 50-100 base pairs per cell division.


title: Telomere

text: If coding sequences are degraded in this process, potentially vital genetic code would be lost. Telomeres are non-coding, repetitive sequences located at the termini of linear chromosomes to act as buffers for those coding sequences further behind. They "cap" the end-sequences and are progressively degraded in the process of DNA replication.


title: Telomere

text: The "end replication problem" is exclusive to linear chromosomes as circular chromosomes do not have ends lying without reach of DNA-polymerases. Most prokaryotes, relying on circular chromosomes, accordingly do not possess telomeres. A small fraction of bacterial chromosomes (such as those in "Streptomyces", "Agrobacterium", and "Borrelia"), however, are linear and possess telomeres, which are very different from those of the eukaryotic chromosomes in structure and function. The known structures of bacterial telomeres take the form of proteins bound to the ends of linear chromosomes, or hairpin loops of single-stranded DNA at the ends of the linear chromosomes.


title: Telomere

text: At the very 3'-end of the telomere there is a 300 base pair overhang which can invade the double-stranded portion of the telomere forming a structure known as a T-loop. This loop is analogous to a knot, which stabilizes the telomere, and prevents the telomere ends from being recognized as breakpoints by the DNA repair machinery. Should non-homologous end joining occur at the telomeric ends, chromosomal fusion would result. The T-loop is maintained by several proteins, collectively referred to as the shelterin complex. In humans, the shelterin complex consists of six proteins identified as TRF1, TRF2, TIN2, POT1, TPP1, and RAP1. In many species, the sequence repeats are enriched in guanine, e.g. TTAGGG in vertebrates, which allows the formation of G-quadruplexes, a special conformation of DNA involving non-Watson-Crick base pairing. There are different subtypes depending on the involvement of single- or double-stranded DNA, among other things. There is evidence for the 3'-overhang in ciliates (that possess telomere repeats similar to those found in vertebrates) to form such G-quadruplexes that accommodate it, rather than a T-loop. G-quadruplexes present an obstacle for enzymes such as DNA-polymerases and are thus thought to be involved in the regulation of replication and transcription.


title: Telomere

text: Many organisms have an ribonucleoprotein enzyme called telomerase, which carries out the task of adding repetitive nucleotide sequences to the ends of the DNA. Telomerase "replenishes" the telomere "cap" and requires no ATP In most multicellular eukaryotic organisms, telomerase is active only in germ cells, some types of stem cells such as embryonic stem cells, and certain white blood cells. Telomerase can be reactivated and telomeres reset back to an embryonic state by somatic cell nuclear transfer. The steady shortening of telomeres with each replication in somatic (body) cells may have a role in senescence and in the prevention of cancer. This is because the telomeres act as a sort of time-delay "fuse", eventually running out after a certain number of cell divisions and resulting in the eventual loss of vital genetic information from the cell's chromosome with future divisions.


title: Telomere

text: Telomere length varies greatly between species, from approximately 300 base pairs in yeast to many kilobases in humans, and usually is composed of arrays of guanine-rich, six- to eight-base-pair-long repeats. Eukaryotic telomeres normally terminate with 3′ single-stranded-DNA overhang, which is essential for telomere maintenance and capping. Multiple proteins binding single- and double-stranded telomere DNA have been identified. These function in both telomere maintenance and capping. Telomeres form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle, stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA, and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.


title: Telomere

text: Apart from the end replication problem, in vitro studies have shown that telomeres accumulate damage due to oxidative stress and that oxidative stress-mediated DNA damage has a major influence on telomere shortening in vivo. There is a multitude of ways in which oxidative stress, mediated by reactive oxygen species (ROS), can lead to DNA damage; however, it is yet unclear whether the elevated rate in telomeres is brought about by their inherent susceptibility or a diminished activity of DNA repair systems in these regions. Despite widespread agreement of the findings, widespread flaws regarding measurement and sampling have been pointed out; for example, a suspected species and tissue dependency of oxidative damage to telomeres is said to be insufficiently accounted for. Population-based studies have indicated an interaction between anti-oxidant intake and telomere length. In the Long Island Breast Cancer Study Project (LIBCSP), authors found a moderate increase in breast cancer risk among women with the shortest telomeres and lower dietary intake of beta carotene, vitamin C or E. These results suggest that cancer risk due to telomere shortening may interact with other mechanisms of DNA damage, specifically oxidative stress.


title: Telomere

text: Telomere shortening is associated with aging, mortality, and aging-related diseases. Based upon comparison between individuals of different ages, telomere length is negatively associated with the number of cell divisions in germ and tumor cells. This leads to the link between age and telomere length, as one might expect, the older an individual is the more times their cells have replicated their genome and divided. In contrast to humans, mice have been demonstrated to have significantly longer telomeres. This could demonstrate how the effects of telomere shortening might have a different or no effect on other eukaryotes, as the older mice had no significant difference in telomere length than younger mice. Furthermore, the role and importance of telomeres appears to have varying degrees of importance among model organisms. Common model organisms such as mice, S. cerevisiae, and C. elegans, were able to withstand the knockdown of telomerase with little effect for multiple generations. Despite the resiliency of these eukaryotes, a decrease in telomerase function in humans resulted in multiple threatening complications after only a few generations. This carries implications on the importance of preserving telomeres in human health.


title: Telomere

text: The age of a father plays a role in the length of a child's telomeres, which has evolutionary implications. Although leukocyte telomeres shorten with age, sperm telomeres lengthen with age. Shorter telomeres are theorized to impose lower energy costs (due to less replication) but also have immune system-related and other aging- and disease-related costs, so the effect of paternal age on telomere length might be an adaptation to increase the chances that the child will be fit for the environment they're born into. Telomerase is normally triggered by cancer cells, however in some cases, cancer cells use a mechanism called alternative telomere lengthening to retain telomeres.


title: Telomere

text: Meta-analyses found that increased perceived psychological stress was associated with a small decrease in telomere length—but that these associations attenuate to no significant association when accounting for publication bias. The literature concerning telomeres as integrative biomarkers of exposure to stress and adversity is dominated by cross-sectional and correlational studies, which makes causal interpretation problematic. A 2020 review argued that the relationship between psychosocial stress and telomere length appears strongest for stress experienced in utero or early life.


title: Telomere

text: The phenomenon of limited cellular division was first observed by Leonard Hayflick, and is now referred to as the Hayflick limit. Significant discoveries were subsequently made by a group of scientists organized at Geron Corporation by Geron's founder Michael D. West, that tied telomere shortening with the Hayflick limit. The cloning of the catalytic component of telomerase enabled experiments to test whether the expression of telomerase at levels sufficient to prevent telomere shortening was capable of immortalizing human cells. Telomerase was demonstrated in a 1998 publication in "Science" to be capable of extending cell lifespan, and now is well-recognized as capable of immortalizing human somatic cells.


title: Telomere

text: Two studies on long-lived seabirds demonstrate that the role of telomeres is far from being understood. In 2003, scientists observed that the telomeres of Leach's storm-petrel ("Oceanodroma leucorhoa") seem to lengthen with chronological age, the first observed instance of such behaviour of telomeres.


title: Telomere

text: A study reported that telomere length of different mammalian species correlates inversely rather than directly with lifespan, and concluded that the contribution of telomere length to lifespan remains controversial. There is little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities.


title: Telomere

text: Telomeres are critical for maintaining genomic integrity and may be factors for age-related diseases. Laboratory studies show that telomere dysfunction or shortening is commonly acquired due the process of cellular aging and tumor development. The function of telomeres is widely accepted as a buffer against tumor growth, to protect chromosome structure, and prevent the loss of vital genetic information during replication. While telomeres keep the growth and division of somatic cells in check, this can inadvertently select for rapidly dividing cells that have suffered telomere damage. As other cells divide as they are supposed to, the abnormal cells divide much quicker, outcompeting the undamaged cells, while acquiring more DNA damage that could further increase their ability to grow. This results in tumor formation.


title: Telomere

text: Certain lifestyle factors have been shown to prematurely shorten telomere length. Smoking is negatively correlated to telomere length. The average human loses roughly 25-27 base pairs per year due to telomere shortening. A study of telomere length in white blood cells of chronic smokers revealed an additional 5 base pairs lost per year. Obesity is another factor that contributes to accelerated telomere shortening. It is well established that obesity causes increased oxidative stress. Ultimately, this increased oxidative damage can impair DNA and, consequently, reduce telomere length. Furthermore, dietary intake and physical activity decrease the rate of telomere shortening. An increase in consumption of antioxidants such as omega-3 fatty acids, vitamins E, C, and beta-carotene can reduce oxidative stress on DNA. Women with diets consisting of a high intake of these antioxidants revealed longer telomere length and a decreased risk in breast cancer. In relation to obesity, exercise promotes metabolization of fat and detrimental waste products, as well as increases the activity of telomerase. . Moreover, physical activity decreases the expression of proteins associated with apoptosis (p53 and p16) in mice populations, which indicates reduced levels of oxidative stress and thereby telomere shortening.


title: Telomere

text: Observational studies have found shortened telomeres in many types of experimental cancers. In addition, people with cancer have been found to possess shorter leukocyte telomeres than healthy controls. In 2011, meta-analyses suggested 1.4 to 3.0 fold increased risk of cancer for those with the shortest vs. longest telomeres.


title: Telomere

text: Telomeres also exist as a possible drug target. While telomeres serve a vital function in humans, telomerase activity is generally low in most somatic cells and tissues. This provides a unique avenue for targeting eukaryotic pathogens. There are many parasitic strains of eukaryotes such as protozoans and infectious yeast that heavily rely upon telomerase activity to monitor their genome. Since normal telomerase activity in most human cells is low, targeting parasitic telomerase function might be a successful short-term treatment against pathogenic eukaryotes, without causing harm to the host.


title: Telomere

text: Several techniques are currently employed to assess average telomere length in eukaryotic cells. One method is the Terminal Restriction Fragment (TRF) southern blot. A Real-Time PCR assay for telomere length involves determining the Telomere-to-Single Copy Gene (T/S) ratio, which is demonstrated to be proportional to the average telomere length in a cell.


title: Telomere

text: Tools have also been developed to estimate the length of telomere from whole genome sequencing (WGS) experiments. Amongst these are TelSeq, Telomerecat and telomereHunter. Length estimation from WGS typically works by differentiating telomere sequencing reads and then inferring the length of telomere that produced that number of reads. These methods have been shown to correlate with preexisting methods of estimation such as PCR and TRF. Flow-FISH is used to quantify the length of telomeres in human white blood cells. A semi-automated method for measuring the average length of telomeres with Flow FISH was published in Nature Protocols in 2006.


title: Telomere

text: While multiple companies offer telomere length measurement services, the utility of these measurements for widespread clinical or personal use has been questioned. Nobel Prize winner Elizabeth Blackburn, who was co-founder of one company, promoted the clinical utility of telomere length measures.


title: Telomere

text: During the last two decades, eco-evolutionary studies have investigated the relevance of life-history traits and environmental conditions on telomeres of wildlife. Most of these studies have been conducted in endotherms, i.e. birds and mammals. They have provided evidence for the inheritance of telomere length; however, heritability estimates vary greatly within and among species. Age and telomere length often negatively correlate in vertebrates, but this decline is variable among taxa and linked to the method used for estimating telomere length. In contrast, the available information shows no sex differences in telomere length across vertebrates. Phylogeny and life history traits such as body size or the pace of life can also affect telomere dynamics. For example, it has been described across species of birds and mammals. In 2019, a meta-analysis confirmed that the exposure to stressors (e.g. pathogen infection, competition, reproductive effort and high activity level) was associated with shorter telomeres across different animal taxa. Telomeres are also a candidate health biomarker for ecotoxicology studies, however, their use still needs further validation as the current literature is taxonomically biased and limited by a reduced number of experimental and longitudinal approaches.


title: Telomere

text: Although ca. 80% of living animals are ectotherms, the knowledge about telomere dynamics in these species is still limited to a few studies in reptiles, fish, and amphibians, whereas invertebrates telomeres have been virtually not explored. Ectotherms are significantly more likely than endotherms to have variation in somatic telomerase expression. For instance, in many fish, telomerase occurs throughout the body (and associated with this, telomere length is roughly the same across all its tissue). Studies on ectotherms, and other non-mammalian organisms, show that there is no single universal model of telomere erosion; rather, there is wide variation in relevant dynamics across Metazoa, and even within smaller taxonomic groups these patterns appear diverse. Due to the different reproductive timelines of some ectotherms, selection on disease is relevant for a much larger fraction of these creatures’ lives than it is for mammals, so early- and late-life telomere length, and their possible links to cancer, seem especially important in these species from a life history theory point of view. Indeed, ectotherms are more sensitive to environmental variation than endotherms and factors such as temperature are known to their growth and maturation rates, thus, ectothermic telomeres are predicted to be greatly affected by climate change.


title: Redis

text: Redis (; Remote Dictionary Server) is an in-memory data structure store, used as a distributed, in-memory key–value database, cache and message broker, with optional durability. Redis supports different kinds of abstract data structures, such as strings, lists, maps, sets, sorted sets, HyperLogLogs, bitmaps, streams, and spatial indices. The project was developed and maintained by Salvatore Sanfilippo, starting in 2009. From 2015 until 2020, he led a project core team sponsored by Redis Labs. Salvatore Sanfilippo left Redis as the maintainer in 2020. It is open-source software released under a BSD 3-clause license. In 2021, not long after the original author and main maintainer left, Redis Labs dropped the Labs from its name and now is known simply as "Redis".


title: Redis

text: The name Redis means Remote Dictionary Server. The Redis project began when Salvatore Sanfilippo, nicknamed "antirez", the original developer of Redis, was trying to improve the scalability of his Italian startup, developing a real-time web log analyzer. After encountering significant problems in scaling some types of workloads using traditional database systems, Sanfilippo began in 2009 to prototype a first proof of concept version of Redis in Tcl. Later Sanfilippo translated that prototype to the C language and implemented the first data type, the list. After a few weeks of using the project internally with success, Sanfilippo decided to open source it, announcing the project on Hacker News. The project began to get traction, particularly among the Ruby community, with GitHub and Instagram being among the first companies adopting it.


title: Redis

text: In October 2018, Redis 5.0 was released, introducing Redis Stream – a new data structure that allows storage of multiple fields and string values with an automatic, time-based sequence at a single key.


title: Redis

text: Redis popularized the idea of a system that can be considered a store and a cache at the same time. It was designed so that data is always modified and read from the main computer memory, but also stored on disk in a format that is unsuitable for random data access. The formatted data is only reconstructed into memory once the system restarts.


title: Redis

text: Redis also provides a data model that is very unusual compared to a relational database management system (RDBMS). User commands do not describe a query to be executed by the database engine but rather specific operations that are performed on given abstract data types. Therefore data must be stored in a way which is suitable later for fast retrieval. The retrieval is done without help from the database system in form of secondary indexes, aggregations or other common features of traditional RDBMS. The Redis implementation makes heavy use of the fork system call, to duplicate the process holding the data, so that the parent process continues to serve clients while the child process creates an in-memory copy of the data on disk.


title: Redis

text: According to monthly DB-Engines rankings, Redis is often the most popular key–value database. Redis has also been ranked the #4 NoSQL database in user satisfaction and market presence based on user reviews, the most popular NoSQL database in containers, and the #4 Data store of 2019 by ranking website stackshare.io. It was voted most loved database in the Stack Overflow Developer Survey in 2017, 2018, 2019, 2020 and 2021.


title: Redis

text: Many programming languages have Redis language bindings on the client side, including: ActionScript, C, C++, C#, Chicken, Clojure, Common Lisp, Crystal, D, Dart, Delphi, Elixir, Erlang, Go, Haskell, Haxe, Io, Java, Nim, JavaScript (Node.js), Julia, Lua, Objective-C, OCaml, Perl, PHP, Pure Data, Python, R, Racket, Ruby, Rust, Scala, Smalltalk, Swift, and Tcl. Several client software programs exist in these languages.


title: Redis

text: Redis maps keys to types of values. An important difference between Redis and other structured storage systems is that Redis supports not only strings, but also abstract data types:


title: Redis

text: The type of a value determines what operations (called commands) are available for the value. Redis supports high-level, atomic, server-side operations like intersection, union, and difference between sets and sorting of lists, sets and sorted sets.


title: Redis

text: Redis typically holds the whole dataset in memory. Versions up to 2.4 could be configured to use what they refer to as virtual memory in which some of the dataset is stored on disk, but this feature is deprecated. Persistence in Redis can be achieved through two different methods. First by snapshotting, where the dataset is asynchronously transferred from memory to disk at regular intervals as a binary dump, using the Redis RDB Dump File Format. Alternatively by journaling, where a record of each operation that modifies the dataset is added to an append-only file (AOF) in a background process. Redis can rewrite the append-only file in the background to avoid an indefinite growth of the journal. Journaling was introduced in version 1.1 and is generally considered the safer approach.


title: Redis

text: By default, Redis writes data to a file system at least every 2 seconds, with more or less robust options available if needed. In the case of a complete system failure on default settings, only a few seconds of data would be lost.


title: Redis

text: Redis supports master–replica replication. Data from any Redis server can replicate to any number of replicas. A replica may be a master to another replica. This allows Redis to implement a single-rooted replication tree. Redis replicas can be configured to accept writes, permitting intentional and unintentional inconsistency between instances. The publish–subscribe feature is fully implemented, so a client of a replica may subscribe to a channel and receive a full feed of messages published to the master, anywhere up the replication tree. Replication is useful for read (but not write) scalability or data redundancy.


title: Redis

text: When the durability of data is not needed, the in-memory nature of Redis allows it to perform well compared to database systems that write every change to disk before considering a transaction committed. Redis operates as a single process and is single-threaded or double-threaded when it rewrites the AOF (append-only file). Thus, a single Redis instance cannot use parallel execution of tasks such as stored procedures.


title: Redis

text: Redis introduced clustering in April 2015 with the release of version 3.0. The cluster specification implements a subset of Redis commands: all single-key commands are available, multi-key operations (commands related to unions and intersections) are restricted to keys belonging to the same node, and commands related to database selection operations are unavailable. A Redis cluster can scale up to 1,000 nodes, achieve "acceptable" write safety and to continue operations when some nodes fail.


title: Redis

text: Due to the nature of the database design, typical use cases are session caching, full page cache, message queue applications, leaderboards and counting among others. The publish–subscribe messaging paradigm allows real-time communication between servers.


title: Redis

text: Large companies such as Twitter are using Redis, Amazon Web Services offers a managed Redis service called ElastiCache for Redis, Microsoft offers Azure Cache for Redis in Azure, and Alibaba offers ApsaraDB for Redis in Alibaba Cloud.


title: Kingdom of Georgia

text: The Kingdom of Georgia (), also known as the Georgian Empire, was a medieval Eurasian monarchy that was founded in circa 1008 AD. It reached its Golden Age of political and economic strength during the reign of King David IV and Queen Tamar the Great from 11th to 13th centuries. Georgia became one of the pre-eminent nations of the Christian East and its pan-Caucasian empire and network of tributaries stretching from Eastern Europe to Anatolia and northern frontiers of Iran, while also maintaining religious possessions abroad, such as the Monastery of the Cross in Jerusalem and the Monastery of Iviron in Greece. It was the principal historical precursor of present-day Georgia.


title: Kingdom of Georgia

text: Lasting for several centuries, the kingdom fell to the Mongol invasions in the 13th century, but managed to re-assert sovereignty by the 1340s. The following decades were marked by the Black Death, as well as numerous invasions under the leadership of Timur, who devastated the country's economy, population, and urban centers. The Kingdom's geopolitical situation further worsened after the fall of the Byzantine and then Empire of Trebizond by the Ottoman Turks. As a result of these processes, by the end of the 15th century Georgia turned into a fractured entity. This whole series of events also led to the final collapse of the kingdom into anarchy by 1466 and the mutual recognition of its constituent kingdoms of Kartli, Kakheti and Imereti as independent states between 1490 and 1493 – each led by a rival branch of the Bagrationi dynasty, and into five semi-independent principalities – Odishi, Guria, Abkhazia, Svaneti, and Samtskhe.


title: Kingdom of Georgia

text: Early Georgian kingdoms were reduced to feudal regions over the course of the Roman–Persian wars. The area then fell under the control of the early Muslim conquests of the 7th century.


title: Kingdom of Georgia

text: Iberian princes from the Bagrationi dynasty fought against the Arab occupation and came to rule the Tao-Klarjeti region. They established the Kouropalatate of Iberia as a nominal vassal of the Byzantine Empire. By 888, they had gained control of the central Georgian land, Kartli, and restored the Iberian kingship. The Bagrationi dynasty was unable to maintain their kingdom, and it was divided between the three branches of the family. The main branch controlled Tao, while another controlled Klarjeti.


title: Kingdom of Georgia

text: In 736, Marwan ibn Muhammad's invasion of Georgia was repelled by Abkhazians, Lazic and Iberian allies. This successful defense along with increasing struggles against Byzantium helped lead to a process of unification of the Georgian states into a single feudal monarchy. The Georgian Church broke away from Constantinople in the 9th century, instead recognizing the authority of the Catholicate of Mtskheta. The church language was changed from Greek to Georgian.


title: Kingdom of Georgia

text: During the 10th century, David III of Tao invaded the Duchy of Kartli, giving it to his adopted son, who would later be known as Bagrat III of Georgia, with his biological father, Gurgen of Iberia, as regent. In 994, Gurgen was crowned "King of the Iberians". In 975, supported by the Duke of Kartli Ivane Marushidze and David, Bagrat claimed the throne of Kartli, becoming "King of the Kartlians". During this time, the Kingdom of Abkhazia in what is today northeastern Georgia was under the rule of Theodosius the Blind, who did away with Abkhazian traditions. In 978, the Abkhazian aristocracy, dissatisfied with the rule of Theodosius, performed a coup d'état and invited Bagrat to claim the throne of Abkhazia.


title: Kingdom of Georgia

text: Gurgen died in 1008, leaving his throne for Bagrat, allowing Bagrat to become the first king of a unified Abkhazia and Iberia. In his early reign, Bagrat pressed a claim to the kingdom of Khakheti-Hereti to the east, and annexed it in 1010. Bagrat also reduced the autonomy of dynastic princes to stabilize his realm, with his fears focusing on the Klarjeti line of the Bagrationi. In order to secure the throne for his son, George I of Georgia, Bagrat tricked his cousins into a meeting and imprisoned them, and his cousins' children fled to Constantinople, where they requested the aid of the Byzantine Empire to take back their patrimonial land.


title: Kingdom of Georgia

text: Bagrat's reign secured a victory for the Bagratids of Georgia, ending the power-struggles that had plagued the region for centuries. Bagrat had a peaceful foreign policy, successfully avoiding conflicts with the Byzantines and nearby Muslim realms, even though some of David's territory, such as Tao and Tbilisi, remained in Byzantine and Arab control, respectively.


title: Kingdom of Georgia

text: George I's reign was known primarily for its war against the Byzantines. This war had its roots in the 990s, when David III, after losing a rebellion against the Byzantine Emperor Basil II, agreed to cede his lands in Tao to the emperor upon his death. George I, in an attempt to take back the Kuropalates' land, occupied Tao starting from 1015 or 1016, during a Byzantine war with the Bulgarian Empire. When Bulgaria was dealt with in 1021, Basil II turned his attention to Georgia, leading to a two-year-long war and an eventual Byzantine victory. George, as a result, had to abandon his claims in Tao and surrender some of his southwestern lands, which were eventually made into the theme of Iberia. George's son, who would eventually become Bagrat IV, was also given to Basil as a hostage.


title: Kingdom of Georgia

text: Bagrat IV spent the next three years in Constantinople, being released in 1025. George I's death in 1027 saw him succeeded by the 8-year-old Bagrat. By the time Bagrat ascended to the throne, the Bagratids' unification drive had gained much momentum. Many of the Georgian lands, such as Tao, Tbilisi, Kakheti and Hereti, were either under the rule of foreign empires or of independent kings. The loyalty of Georgian nobles was also questionable. Bagrat IV's childhood saw the regency increase the influence of the nobility, something which he tried to stop when he assumed his full powers.


title: Kingdom of Georgia

text: In the later half of the 11th century, the Seljuq Turks invaded nearby regions, prompting greater cooperation between the Georgian and Byzantine governments. In a political arrangement, Bagrat's daughter Maria married the Byzantine co-emperor Michael VII Ducas at some point between 1066 and 1071.


title: Kingdom of Georgia

text: In 1065 the Seljuk sultan Alp Arslan attacked Kartli, taking Tbilisi and building a mosque. During the internecine conflict between Seljuk heirs, George II of Georgia defeated a Seljuk governor, Sarang of Ganja, at the Battle of Partskhisi in 1074. In 1076, the Seljuk sultan Malik Shah I attacked again. Georgia eventually submitted to Malik Shah, paying an annual tribute in order to have peace.


title: Kingdom of Georgia

text: George II ceded the crown to his 16-year-old son David IV in 1089. Under the tutelage of his court minister, George of Chqondidi, David IV suppressed the feudal lords and centralized the power. In 1089–1100, he organized military action to destroy Seljuk troops, beginning the resettlement of occupied regions. In 1099, David IV refused to pay tribute to the Seljuqs.


title: Kingdom of Georgia

text: By 1104, the local king of the eastern Georgia provide of Kakheti, Aghsartan II, was captured by David IV's supporters, reuniting the area. The following year, David IV defeated a Seljuk force in the Battle of Ertsukhi. Over the course of 1110 to 1118, David IV captured the fortresses of Samshvilde, Rustavi, Gishi, and Lori.


title: Kingdom of Georgia

text: Starting in 1118 through 1120, David IV began major military reforms, including the resettlement of several thousand Kipchaks. In exchange, each Kipchak family provided David IV with a soldier, allowing him to establish a standing army. This alliance was aided by David IV's earlier marriage to the Khan's daughter.


title: Kingdom of Georgia

text: Entering 1120, David IV became more expansionist. He invaded the neighbouring Shirvan area and the town of Qabala. From there, he began to successfully attack the Seljuk in the eastern and southwestern areas of Transcaucasia. In 1121, Sultan Mahmud b. Muhammad declared a holy war on Georgia. but David IV defeated his army at the Didgori. Soon after, David IV secured Tbilisi, one of the last Muslim enclave remaining in Georgia, and the capital was moved there, beginning Georgia's Golden Age.


title: Kingdom of Georgia

text: In 1123, David IV liberated Dmanisi, the last Seljuk stronghold in southern Georgia. By 1124, Shirvan was captured along with the Armenian city of Ani. This expanded the kingdom's borders to the Araxes basin.


title: Kingdom of Georgia

text: David IV founded the Gelati Academy, known at the time as "a new Hellas" and "a second Athos". David also composed the "Hymns of Repentance", eight free-verse psalms.


title: Kingdom of Georgia

text: The kingdom continued to flourish under Demetrius I, the son of David. Although his reign saw a disruptive family conflict related to royal succession, Georgia remained a centralized power with a strong military. A talented poet, Demetrius also continued his father's contributions to Georgia's religious polyphony. The most famous of his hymns is Thou Art a Vineyard.


title: Kingdom of Georgia

text: Demetrius was succeeded by his son George III in 1156, beginning a stage of more offensive foreign policy. The same year he ascended to the throne, George launched a successful campaign against the Seljuq sultanate of Ahlat. He freed the important Armenian town of Dvin from Eldiguzid vassalage and was thus welcomed as a liberator in the area.


title: Kingdom of Georgia

text: The unified monarchy maintained its precarious independence from the Byzantine and Seljuk empires throughout the 11th century, and flourished under David IV the Builder ( 1089–1125), who repelled the Seljuk attacks and essentially completed the unification of Georgia with the re-conquest of Tbilisi in 1122. In spite of repeated incidents of dynastic strife, the kingdom continued to prosper during the reigns of Demetrios I (1125–1156), George III (1156–1184), and especially, his daughter Tamar (1184–1213).


title: Kingdom of Georgia

text: With the decline of Byzantine power and the dissolution of the Great Seljuk Empire, Georgia became one of the pre-eminent nations of the region, stretching, at its largest extent, from present-day Southern Russia to Northern Iran, and westwards into Anatolia. The Kingdom of Georgia brought about the Georgian Golden Age, which describes a historical period in the High Middle Ages, spanning from roughly the late 11th to 13th centuries, when the kingdom reached the zenith of its power and development. The period saw the flourishing of medieval Georgian architecture, painting and poetry, which was frequently expressed in the development of ecclesiastic art, as well as the creation of first major works of secular literature. It was a period of military, political, economical and cultural progress. It also included the so-called Georgian Renaissance (also called Eastern Renaissance), during which various human activities, forms of craftsmanship and art, such as literature, philosophy and architecture thrived in the kingdom.


title: Kingdom of Georgia

text: She not only shielded much of her Empire from further Turkish invasions but successfully pacified internal tensions, including a coup organized by her Russian husband Yury Bogolyubsky, prince of Novgorod.


title: Kingdom of Georgia

text: Among the remarkable events of Tamar's reign was the foundation of the Empire of Trebizond on the Black Sea in 1204. This state was established in the northeast of the crumbling Byzantine Empire with the help of the Georgian armies, which supported Alexios I of Trebizond and his brother, David Komnenos, both of whom were Tamar's relatives. Alexios and David were fugitive Byzantine princes raised at the Georgian court. Tamar's Pontic endeavor can also be explained by her desire to take advantage of the Western European Fourth Crusade against Constantinople to set up a friendly state in Georgia's immediate southwestern neighborhood, as well as by the dynastic solidarity to the dispossessed Comnenoi. As a retribution for the attack on Georgian-controlled city of Ani, where 12,000 Christians were massacred in 1208, Georgia's Tamar the Great invaded and conquered the cities of Tabriz, Ardabil, Khoy, Qazvin and others along the way to Gorgan in northeast Persia.


title: Kingdom of Georgia

text: The country's power had grown to such extent that in the later years of Tamar's rule, the Kingdom was primarily concerned with the protection of the Georgian monastic centers in the Holy Land, eight of which were listed in Jerusalem. Saladin's biographer Bahā' ad-Dīn ibn Šaddād reports that, after the Ayyubid conquest of Jerusalem in 1187, Tamar sent envoys to the sultan to request that the confiscated possessions of the Georgian monasteries in Jerusalem be returned. Saladin's response is not recorded, but the queen's efforts seem to have been successful. Ibn Šaddād furthermore claims that Tamar outbid the Byzantine emperor in her efforts to obtain the relics of the True Cross, offering 200,000 gold pieces to Saladin who had taken the relics as booty at the battle of Hattin – to no avail, however.


title: Kingdom of Georgia

text: One of the primary reasons of Georgian political and military decline was the bubonic plague. It was first introduced in 1346 by the soldiers of George the Brilliant returning from a military expedition in south-western Georgia against invading Osmanli tribesmen. It is said that the plague wiped out a large part, if not half of the Georgian populace. This further weakened the integrity of the kingdom, as well as its military and logistic capabilities.


title: Kingdom of Georgia

text: After the devastating invasions by Timur and subsequent enfeeblement of the Kingdom of Georgia, it soon faced a new threat. Timur's death in 1405 marked the beginning of the end of his Empire, unified only by fear and blood of the subjected peoples. Turkomans, particularly the Kara Koyunlu clan, were among the first to rebel against Shah Rukh who ruled most of the Persia and Mawerannahr. Qara Yusuf, ruler of the Kara Koyunlu, defeated Shah Rukh, captured Baghdad, and repulsed Timurids from western Persia. After they established themselves as the new leading power in the middle east. They took advantage of the temporary weakness of Georgians and launched attacks against them, apparently in which, George VII of Georgia was killed. Constantine I of Georgia, fearing further encroachment, allied himself with the Shirvanshah Ibrahim I to counter Turkoman advance and engaged them in the Battle of Chalagan, in which he was defeated and taken captive. In captivity Constantine behaved very proudly, which infuriated Qara Yusuf to such an extent, that he ordered his, his half-brother David's and 300 Georgian nobles' execution. Kara Yusuf put Constantine to death by his own hand.


title: Kingdom of Georgia

text: Alexander I of Georgia who sought to strengthen and restore his declining Kingdom, faced constant invasions by the tribal Turkomans. Alexander re-conquered Lori from the Turkomans in 1431, which was of great importance in securing of the Georgian borders. Around 1434/5, Alexander encouraged the Armenian prince Beshken II Orbelian to attack the Kara Koyunlu clansmen in Siunia and, for his victory, granted him Lori under terms of vassalage. In 1440, Alexander refused to pay tribute to Jahan Shah of the Kara Koyunlu. In March, Jahan Shah surged into Georgia with 20,000 troops, destroyed the city of Samshvilde and sacked the capital city Tbilisi. He massacred thousands of Christians, put heavy indemnity on Georgia, and returned to Tabriz. He also mounted a second military expedition against Georgia in 1444. His forces met those of Alexander's successor, King Vakhtang IV at Akhaltsikhe, but the fighting was inconclusive and Jahan Shah returned to Tabriz once more.