title: Vitamin A

text: Vitamin A status involves eye health via two separate functions. Retinal is an essential factor in rod cells and cone cells in the retina responding to light exposure by sending nerve signals to the brain. An early sign of vitamin A deficiency is night blindness. Vitamin A in the form of retinoic acid is essential to normal epithelial cell functions. Severe vitamin A deficiency, common in infants and young children in southeast Asia causes xerophthalmia characterized by dryness of the conjunctival epithelium and cornea. Untreated, xerophthalmia progresses to corneal ulceration and blindness.


title: Vitamin A

text: The role of vitamin A in the visual cycle is specifically related to the retinal compound. Retinol is converted by the enzyme RPE65 within the retinal pigment epithelium into 11-"cis"-retinal. Within the eye, 11-"cis"-retinal is bound to the protein opsin to form rhodopsin in rod cells and iodopsin in cone cells. As light enters the eye, the 11-"cis"-retinal is isomerized to the "all-trans" form. The "all-trans"-retinal dissociates from the opsin in a series of steps called photo-bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. After separating from opsin, the "all-trans"-retinal is recycled and converted back to the 11-"cis"-retinal form by a series of enzymatic reactions, which then completes the cycle by binding to opsin to reform rhodopsin in the retina. In addition, some of the "all-trans"-retinal may be converted to "all-trans"-retinol form and then transported with an interphotoreceptor retinol-binding protein to the retinal pigmented epithelial cells. Further esterification into "all-trans"-retinyl esters allow for storage of "all-trans"-retinol within the pigment epithelial cells to be reused when needed. It is for this reason that a deficiency in vitamin A will inhibit the reformation of rhodopsin, and will lead to one of the first symptoms, night blindness.


title: Vitamin A

text: Vitamin A deficiency (VAD) caused night blindness is a reversible difficulty for the eyes to adjust to dim light. It is common in young children who have a diet inadequate in retinol and beta-carotene. A process called dark adaptation typically causes an increase in photopigment amounts in response to low levels of illumination. This increases light sensitivity by up to 100,000 times compared to normal daylight conditions. Significant improvement in night vision takes place within ten minutes, but the process can take up to two hours to reach maximal effect. People expecting to work in a dark environment wore red-tinted goggles or were in a red light environment to not reverse the adaptation because red light does not deplete rhodopsin versus what occurs with yellow or green light.


title: Vitamin A

text: Xerophthalmia, caused by a severe vitamin A deficiency, is described by pathologic dryness of the conjunctival epithelium and cornea. The conjunctiva becomes dry, thick, and wrinkled. Indicative is the appearance of Bitot's spots, which are clumps of keratin debris that build up inside the conjunctiva. If untreated, xerophthalmia can lead to dry eye syndrome, corneal ulceration and ultimately to blindness as a result of cornea and retina damage. Although xerophthalmia is an eye-related issue, prevention (and reversal) are functions of retinoic acid having been synthesized from retinal rather than the 11-"cis"-retinal to rhodopsin cycle.


title: Vitamin A

text: Throughout southeast Asia, estimates are that more than half of children under the age of six years have subclinical vitamin A deficiency and night blindness, with progression to xerophthalmia being the leading cause of preventable childhood blindness. Estimates are that each year there are 350,000 cases of childhood blindness due to vitamin A deficiency. The causes are vitamin A deficiency during pregnancy, followed by low transfer of vitamin A during lactation and infant/child diets low in vitamin A or beta-carotene. The prevalence of pre-school age children who are blind due to vitamin A deficiency is lower than expected from incidence of new cases only because childhood vitamin A deficiency significantly increases all-cause mortality.


title: Vitamin A

text: According to a 2017 Cochrane review, vitamin A deficiency, using serum retinol less than 0.70 µmol/L as a criteria, is a major public health problem affecting an estimated 190 million children under five years of age in low- and middle-income countries, primarily in Sub-Saharan Africa and Southeast Asia. In lieu of or in combination with food fortification programs, many countries have implemented public health programs in which children are periodically given very large oral doses of synthetic vitamin A, usually retinyl palmitate, as a means of preventing and treating VAD. Doses were 50,000 to 100,000 IU (International units) for children aged 6 to 11 months and 100,000 to 200,000 IU for children aged 12 months to five years, the latter typically every four to six months. In addition to a 24% reduction in all-cause mortality, eye-related results were reported. Prevalence of Bitot's spots at follow-up were reduced by 58%, night blindness by 68%, xerophthalmia by 69%.


title: Vitamin A

text: RA regulates gene transcription by binding to nuclear receptors known as retinoic acid receptors (RARs; RARα, RARβ, RARγ) which are bound to DNA as heterodimers with retinoid "X" receptors (RXRs; RXRα, RXRβ, RXRγ). RARs and RXRs must dimerize before they can bind to the DNA. Expression of more than 500 genes is responsive to retinoic acid. The process is that RAR-RXR heterodimers recognize retinoic acid response elements on DNA. The receptors undergo a conformational change that causes co-repressors to dissociate from the receptors. Coactivators can then bind to the receptor complex, which may help to loosen the chromatin structure from the histones or may interact with the transcriptional machinery. This response upregulates or downregulates the expression of target genes, including the genes that encode for the receptors themselves. To prevent excess accumulation of RA it must be metabolized and eliminated. Three cytochromes (Cyp26A1, Cyp26B1 Cyp26C1) catalyze the oxidation of RA. The genes for these proteins are induced by high concentrations of RA, thus providing a regulatory feedback mechanism.


title: Vitamin A

text: In vertebrates and invertebrate chordates, RA has a pivotal role during development. Altering levels of endogenous RA signaling during early embryology, both too low and too high, leads to birth defects, including congenital vascular and cardiovascular defects. Of note, fetal alcohol spectrum disorder encompasses congenital anomalies, including craniofacial, auditory, and ocular defects, neurobehavioral anomalies and mental disabilities caused by maternal consumption of alcohol during pregnancy. It is proposed that in the embryo there is competition between acetaldehyde, an ethanol metabolite, and retinaldehyde (retinal) for aldehyde dehydrogenase activity, resulting in a retenoic acid deficiency, and attributing the congenital birth defects to the loss of RA activated gene activation. In support of this theory, ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol or retinal. As for the risks of too much RA, the prescription drugs tretinoin ("all-trans"-retinoic acid) and isotretinoin (13-cis-retinoic acid), used orally or topically for acne treatment, come with warnings to not be used by pregnant women or women who are anticipating becoming pregnant, as they are known human teratogens.


title: Vitamin A

text: Vitamin A deficiency (VAD) has been linked to compromised resistance to infectious diseases. In countries where early childhood VAD is common, vitamin A supplementation public health programs initiated in the 1980s were shown to reduce the incidence of diarrhea and measles, and all-cause mortality. VAD also increases the risk of immune system over-reaction, leading to chronic inflammation in the intestinal system, stronger allergic reactions and autoimmune diseases.


title: Vitamin A

text: Lymphocytes and monocytes are types of white blood cells of the immune system. Lymphocytes include natural killer cells, which function in innate immunity, T cells for adaptive cellular immunity and B cells for antibody-driven adaptive humoral immunity. Monocytes differentiate into macrophages and dendritic cells. Some lymphocytes migrate to the thymus where they differentiate into several types of T cells, in some instances referred to as "killer" or "helper" T cells and further differentiate after leaving the thymus. Each subtype has functions driven by the types of cytokines secreted and organs to which the cells preferentially migrate, also described as trafficking or homing.


title: Vitamin A

text: Reviews based on "in vitro" and animal research describe the role that retinoic acid (RA) has in the immune system. RA triggers receptors in bone marrow, resulting in generation of new white blood cells. RA regulates proliferation and differentiation of white blood cells, the directed movement of T cells to the intestinal system, and to the up- and down-regulation of lymphocyte function. If RA is adequate, T helper cell subtype Th1 is suppressed and subtypes Th2, Th17 and iTreg (for regulatory) are induced. Dendritic cells located in intestinal tissue have enzymes that convert retinal to "all-trans"-retinoic acid, to be taken up by retinoic acid receptors on lymphocytes. The process triggers gene expression that leads to T cell types Th2, Th17 and iTreg moving to and taking up residence in mesenteric lymph nodes and Peyer's patches, respectively outside and on the inner wall of the small intestine. The net effect is a down-regulation of immune activity, seen as tolerance of food allergens, and tolerance of resident bacteria and other organisms in the microbiome of the large intestine. In a vitamin A deficient state, innate immunity is compromised and pro-inflammatory Th1 cells predominate.


title: Vitamin A

text: Deficiencies in vitamin A have been linked to an increased susceptibility to skin infection and inflammation. Vitamin A appears to modulate the innate immune response and maintains homeostasis of epithelial tissues and mucosa through its metabolite, retinoic acid (RA). As part of the innate immune system, toll-like receptors in skin cells respond to pathogens and cell damage by inducing a pro-inflammatory immune response which includes increased RA production. The epithelium of the skin encounters bacteria, fungi and viruses. Keratinocytes of the epidermal layer of the skin produce and secrete antimicrobial peptides (AMPs). Production of AMPs resistin and cathelicidin, are promoted by RA.


title: Vitamin A

text: As some carotenoids can be converted into vitamin A, attempts have been made to determine how much of them in the diet is equivalent to a particular amount of retinol, so that comparisons can be made of the benefit of different foods. The situation can be confusing because the accepted equivalences have changed over time


title: Vitamin A

text: For many years, a system of equivalencies in which an international unit (IU) was equal to 0.3 μg of retinol (~1 nmol), 0.6 μg of β-carotene, or 1.2 μg of other provitamin-A carotenoids was used. This relationship was alternatively expressed by the retinol equivalent (RE): one RE corresponded to 1 μg retinol, to 2 μg β-carotene dissolved in oil, to 6 μg β-carotene in foods, and to 12 μg of either α-carotene, γ-carotene, or β-cryptoxanthin in food.


title: Vitamin A

text: Newer research has shown that the absorption of provitamin-A carotenoids is only half as much as previously thought. As a result, in 2001 the US Institute of Medicine recommended a new unit, the retinol activity equivalent (RAE). Each μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of "dietary" beta-carotene, or 24 μg of the three other dietary provitamin-A carotenoids.


title: Vitamin A

text: Animal models have shown that at the enterocyte cell wall, β-carotene is taken up by the membrane transporter protein scavenger receptor class B, type 1 (SCARB1). Absorbed β-carotene is converted to retinal and then retinol. The first step of the conversion process consists of one molecule of β-carotene cleaved by the enzyme


title: Vitamin A

text: β-carotene-15, 15'-monooxygenase, which in humans and other mammalian species is encoded by the BCM01 gene, into two molecules of retinal. When plasma retinol is in the normal range, gene expression for SCARB1 and BC01 are suppressed, creating a feedback loop that suppresses β-carotene absorption and conversion. Absorption suppression is not complete, as receptor 36 is not downregulated.


title: Vitamin A

text: The US National Academy of Medicine updated Dietary Reference Intakes (DRIs) in 2001 for vitamin A, which included Recommended Dietary Allowances (RDAs). For infants up to 12 months there was not sufficient information to establish a RDA, so Adequate Intake (AI) is shown instead. As for safety, tolerable upper intake levels (ULs) were also established. For ULs, carotenoids are not added when calculating total vitamin A intake for safety assessments.


title: Vitamin A

text: The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. For women and men of ages 15 and older, the PRIs are set respectively at 650 and 750 μg RE/day. PRI for pregnancy is 700 μg RE/day, for lactation 1300/day. For children of ages 1–14 years, the PRIs increase with age from 250 to 600 μg RE/day. These PRIs are similar to the US RDAs. The EFSA reviewed the same safety question as the United States, and set ULs at 800 for ages 1–3, 1100 for ages 4–6, 1500 for ages 7–10, 2000 for ages 11–14, 2600 for ages 15–17 and 3000 μg/day for ages 18 and older for preformed vitamin A, i.e., not including dietary contributions from carotenoids.


title: Vitamin A

text: Vitamin A toxicity hypervitaminosis A occurs when too much vitamin A accumulates in the body. It comes from consumption of preformed vitamin A but not of carotenoids, as conversion of the latter to retinol is suppressed by the presence of adequate retinol.


title: Vitamin A

text: There are historical reports of acute hypervitaminosis from Arctic explorers consuming bearded seal or polar bear liver, both very rich sources of stored retinol, and there are also case reports of acute hypervitaminosis from consuming fish liver, but otherwise there is no risk from consuming too much via commonly consumed foods. Only consumption of retinol-containing dietary supplements can result in acute or chronic toxicity. Acute toxicity occurs after a single or short-term doses of greater than 150,000 μg. Symptoms include blurred vision, nausea, vomiting, dizziness and headache within 8 to 24 hours. For infants ages 0–6 months given an oral dose to prevent development of vitamin A deficiency, bulging skull fontanel was evident after 24 hours, usually resolved by 72 hours. Chronic toxicity may occur with long-term consumption of vitamin A at doses of 25,000–33,000 IU/day for several months. Excessive consumption of alcohol can lead to chronic toxicity at lower intakes. Symptoms may include nervous system effects, liver abnormalities, fatigue, muscle weakness, bone and skin changes and others. The adverse effects of both acute and chronic toxicity are reversed after consumption is stopped.


title: Vitamin A

text: In 2001, for the purpose of determining ULs for adults, the US Institute of Medicine considered three primary adverse effects and settled on two: teratogenicity, i.e., causing birth defects, and liver abnormalities. Reduced bone mineral density was considered, but dismissed because the human evidence was contradictory. During pregnancy, especially during the first trimester, consumption of retinol in amounts exceeding 4,500 μg/day increased the risk of birth defects, but not below that amount, thus setting a "No-Observed Adverse-Effect Level" (NOAEL). Given the quality of the clinical trial evidence, the NOAEL was divided by an uncertainty factor of 1.5 to set the UL for women of reproductive age at 3,000 μg/day of preformed vitamin A. For all other adults, liver abnormalities were detected at intakes above 14,000 μg/day. Given the weak quality of the clinical evidence, an uncertainty factor of 5 was used, and with rounding, the UL was set at 3,000 μg/day. Despite a US UL set at 3,000 μg, it is possible to buy over-the-counter dietary supplement products which are 7,500 μg (25,000 IU), with a label caution statement "Not intended for long term use unless under medical supervision."


title: Vitamin A

text: For children ULs were extrapolated from the adult value, adjusted for relative body weight. For infants, several case studies reported adverse effects that include bulging fontanels, increased intracranial pressure, loss of appetite, hyperirritability and skin peeling after chronic ingestion of the order of 6,000 or more μg/day. Given the small database, an uncertainty factor of 10 divided into the "Lowest-Observed-Adverse-Effect Level" (LOAEL) led to a UL of 600 μg/day.


title: Vitamin A

text: No adverse effects other than carotenemia have been reported for consumption of β-carotene rich foods. Supplementation with β-carotene does not cause hypervitaminosis A. Two large clinical trials (ATBC and CARET) were conducted in tobacco smokers to see if years of β-carotene supplementation at 20 or 30 mg/day in oil-filled capsules would reduce the risk of lung cancer. These trials were implemented because observational studies had reported a lower incidence of lung cancer in tobacco smokers who had diets higher in β-carotene. Unexpectedly, this high-dose β-carotene supplementation resulted in a higher incidence of lung cancer and of total mortality. Taking this and other evidence into consideration, the U.S. Institute of Medicine decided to not set a Tolerable Upper Intake Level (UL) for β-carotene. The European Food Safety Authority, acting for the European Union, also decided to not set a UL for β-carotene.


title: Vitamin A

text: Carotenoderma, also referred to as carotenemia, is a benign and reversible medical condition where an excess of dietary carotenoids results in orange discoloration of the outermost skin layer. It is associated with a high blood β-carotene value. This can occur after a month or two of consumption of beta-carotene rich foods, such as carrots, carrot juice, tangerine juice, mangos, or in Africa, red palm oil. β-carotene dietary supplements can have the same effect. The discoloration extends to palms and soles of feet, but not to the white of the eye, which helps distinguish the condition from jaundice. Consumption of greater than 30 mg/day for a prolonged period has been confirmed as leading to carotenemia.


title: Vitamin A

text: For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin A labeling purposes 100% of the Daily Value was set at 5,000 IU, but it was revised to 900 μg RAE on 27 May 2016. A table of the old and new adult daily values is provided at Reference Daily Intake.


title: Vitamin A

text: Vitamin A is found in many foods. Vitamin A in food exists either as preformed retinol an active form of vitamin A found in animal liver, dairy and egg products, and some fortified foods, or as provitamin A carotenoids, which are plant pigments digested into vitamin A after consuming carotenoid-rich plant foods, typically in red, orange, or yellow colors. Carotenoid pigments may be masked by chlorophylls in dark green leaf vegetables, such as spinach. The relatively low bioavailability of plant-food carotenoids results partly from binding to proteins chopping, homogenizing or cooking disrupts the plant proteins, increasing provitamin A carotenoid bioavailability.


title: Vitamin A

text: Vegetarian and vegan diets can provide sufficient vitamin A in the form of provitamin A carotenoids if the diet contains green leafy vegetables such as spinach and kale, carrots, carrot juice, sweet potatoes and other carotenoid-rich foods. In the U.S., the average daily intake of β-carotene is in the range 2–7 mg.


title: Vitamin A

text: Despite the US setting an adult upper limit of 3,000 μg/day, some companies sell vitamin A as a dietary supplement with amounts of 7,500 μg/day. Two examples are WonderLabs and Pure Prescriptions.


title: Vitamin A

text: Some countries require or recommend fortification of foods. As of January 2022, 37 countries, mostly in Sub-Saharan Africa, require food fortification of cooking oil, rice, wheat flour or maize (corn) flour with vitamin A, usually as retinyl palmitate or retinyl acetate. Examples include Pakistan, oil, 11.7 mg/kg and Nigeria, oil, 6 mg/kg; wheat and maize flour, 2 mg/kg. An additional 12 countries, mostly in southeast Asia have a voluntary fortification program. For example, the government of India recommends 7.95 mg/kg in oil and 0.626 mg/kg for wheat flour and rice. However, compliance in countries with voluntary fortification is lower than countries with mandatory fortification. No countries in Europe or North America fortify foods with vitamin A.


title: Vitamin A

text: Separated from fortification via addition of synthetic vitamin A to foods, means of fortifying foods via genetic engineering have been explored. Research on rice began in 1982. The first field trials of golden rice cultivars were conducted in 2004. The result was "Golden Rice", a variety of "Oryza sativa" rice produced through genetic engineering to biosynthesize beta-carotene, a precursor of retinol, in the edible parts of rice. In May 2018, regulatory agencies in the United States, Canada, Australia and New Zealand had concluded that Golden Rice met food safety standards. On 21 July 2021, the Philippines became the first country to officially issue the biosafety permit for commercially propagating Golden Rice.


title: Vitamin A

text: Delivery of oral high-dose supplements remains the principal strategy for minimizing deficiency. As of 2017, more than 80 countries worldwide are implementing universal VAS programs targeted to children 6–59 months of age through semi-annual national campaigns. Doses in these programs are one dose of 50,000 or 100,000 IU for children aged 6 to 11 months and 100,000 to 200,000 IU for children aged 12 months to five years, every four to six months.


title: Vitamin A

text: Vitamin A deficiency is common in developing countries, especially in Sub-Saharan Africa and Southeast Asia. Deficiency can occur at any age, but is most common in pre-school-age children and pregnant women, the latter due to a need to transfer retinol to the fetus. The causes are low intake of retinol-containing, animal-sourced foods and low intake of carotene-containing, plant-sourced foods. Vitamin A deficiency is estimated to affect approximately one third of children under the age of five around the world, possibly leading to the deaths of 670,000 children under five annually.


title: Vitamin A

text: Between 250,000 and 500,000 children in developing countries become blind each year owing to vitamin A deficiency. Vitamin A deficiency is "the leading cause of preventable childhood blindness", according to UNICEF. It also increases the risk of death from common childhood conditions, such as diarrhea. UNICEF regards addressing vitamin A deficiency as critical to reducing child mortality, the fourth of the United Nations' Millennium Development Goals.


title: Vitamin A

text: During diagnosis, night blindness and dry eyes are signs of vitamin A deficiency that can be recognized without requiring biochemical tests. Plasma retinol is used to confirm vitamin A status. A plasma concentration of about 2.0 μmol/L is normal; less than 0.70 μmol/L (equivalent to 20 μg/dL) indicates moderate vitamin A deficiency, and less than 0.35 μmol/L (10 μg/dL) indicates severe vitamin A deficiency. Breast milk retinol of less than 8 μg/gram milk fat is considered insufficient. One weakness of these measures is that they are not good indicators of liver vitamin A stores as retinyl esters in hepatic stellate cells. The amount of vitamin A leaving the liver, bound to retinol binding protein (RBP), is under tight control as long as there are sufficient liver reserves. Only when liver content of vitamin A drops below approximately 20 μg/gram will concentration in the blood decline.


title: Vitamin A

text: There are causes for deficiency other than low dietary intake of vitamin A as retinol or carotenes. Adequate dietary protein and caloric energy are needed for a normal rate of synthesis of RBP, without which, retinol cannot be mobilized to leave the liver. Systemic infections can cause transient decreases in RBP synthesis even if protein-calorie malnutrition is absent. Chronic alcohol consumption reduces liver vitamin A storage. Non-alcoholic fatty liver disease (NAFLD), characterized by the accumulation of fat in the liver, is the hepatic manifestation of metabolic syndrome. Liver damage from NAFLD reduces liver storage capacity for retinol and reduces the ability to mobilize liver stores to maintain normal circulating concentration.


title: Vitamin A

text: All vertebrate and chordate species require vitamin A, either as dietary carotenoids or preformed retinol from consuming other animals. Deficiencies have been reported in laboratory-raised and pet dogs, cats, birds, reptiles and amphibians, also commercially raised chickens and turkeys. Herbivore species such as horses, cattle and sheep can get sufficient β-carotene from green pasture to be healthy, but the content in pasture grass dry due to drought and long-stored hay can be too low, leading to vitamin A deficiency. Omnivore and carnivore species, especially those toward the top of the food chain, can accrue large amounts of retinyl esters in their livers, or else excrete retinyl esters in urine as a means of dealing with surplus. Before the era of synthetic retinol, cod liver oil, high in vitamins A and D, was a commonly consumed dietary supplement. Invertebrates cannot synthesize carotenoids or retinol, and thus must accrue these essential nutrients from consumption of algae, plants or animals.


title: Vitamin A

text: Recognition of its prevalence and consequences has led to governments and non-government organizations promoting vitamin A fortification of foods and creating programs that administer large bolus-size oral doses of vitamin A to young children every four to six months. In 2008, the World Health Organization estimated that vitamin A supplementation over a decade in 40 countries averted 1.25 million deaths due to vitamin A deficiency. A Cochrane review reported that vitamin A supplementation is associated with a clinically meaningful reduction in morbidity and mortality in children ages six month to five years of age. All-cause mortality was reduced by 14%, and incidences of diarrhea by 12%. However, a Cochrane review by the same group concluded there was insufficient evidence to recommend blanket vitamin A supplementation for infants one to six months of age, as it did not reduce infant mortality or morbidity.


title: Vitamin A

text: Orally consumed retinoic acid (RA), as "all-trans"-tretinoin or 13-"cis"-isotretinoin has been shown to improve facial skin health by switching on genes and differentiating keratinocytes (immature skin cells) into mature epidermal cells. RA reduces the size and secretion of the sebaceous glands, and by doing so reduces bacterial numbers in both the ducts and skin surface. It reduces inflammation via inhibition of chemotactic responses of monocytes and neutrophils. In the US, isotretinoin was released to the market in 1982 as a revolutionary treatment for severe and refractory acne vulgaris. It was shown that a dose of 0.5‑1.0 mg/kg body weight/day is enough to produce a reduction in sebum excretion by 90% within a month or two, but the recommended treatment duration is 4 to 6 months. Isotretinoin is a known teratogen, with an estimated 20‑35% risk of physical birth defects to infants that are exposed to isotretinoin "in utero", including numerous congenital defects such as craniofacial defects, cardiovascular and neurological malformations or thymic disorders. Neurocognitive impairments in the absence of any physical defects has been established to be 30‑60%. For these reasons, physician- and patient-education programs were initiated, recommending that for women of child-bearing age, contraception be initiated a month before starting oral (or topical) isotretinoin, and continue for a month after treatment ended.


title: Vitamin A

text: In addition to the approved use for treating acne vulgaris, researchers have investigated off-label applications for dermatological conditions, such as rosacea, psoriasis, and other conditions. Rosacea was reported as responding favorably to doses lower than used for acne. Isotretinoin in combination with ultraviolet light was shown affective for treating psoriasis. Isotretinoin in combination with injected interferon-alpha showed some potential for treating genital warts. Isotretinoin in combination with topical fluorouracil or injected interferon-alpha showed some potential for treating precancerous skin lesions and skin cancer.


title: Vitamin A

text: Retinoic acids tretinoin ("all-trans"-retinoic acid) and isotretinoin (13-"cis"-retinoic acid) are prescription topical medications used to treat moderate to severe cystic acne and acne not responsive to other treatments. These are usually applied as a skin cream to the face after cleansing to remove make-up and skin oils. Tretinoin and isotretinoin act by binding to two nuclear receptor families within keratinocytes: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). These events contribute to the normalization of follicular keratinization and decreased cohesiveness of keratinocytes, resulting in reduced follicular occlusion and microcomedone formation. The retinoid-receptor complex competes for coactivator proteins of AP-1, a key transcription factor involved in inflammation. Retinoic acid products also reduce sebum secretion, a nutrient source for bacteria, from facial pores.


title: Vitamin A

text: These drugs are US-designated Pregnancy Category C (animal reproduction studies have shown an adverse effect on the fetus), and should not be used by pregnant women or women who are anticipating becoming pregnant. Many countries established a physician- and patient- education pregnancy prevention policy.


title: Vitamin A

text: Trifarotene is a prescription retinoid for the topical treatment acne vulgaris. It functions as a retinoic acid receptor (RAR)-γ agonist.


title: Vitamin A

text: Non-prescription topical products that have health claims for reducing facial acne, combating skin dark spots and reducing wrinkles and lines associated with aging often contain retinyl palmitate. The hypothesis is that this is absorbed and desterified to free retinol, then converted to retinaldehyde and further metabolized to "all-trans"-retinoic acid, whence it will have the same effects as prescription products with fewer side effects. There is some "ex vivo" evidence with human skin that esterified retinol is absorbed and then converted to retinol. In addition to esterified retinol, some of these products contain hydroxypinacolone retinoate, identified as esterified 9-"cis"-retinoic acid.


title: Vitamin A

text: Carotenoid synthesis takes place in plants, certain fungi, and bacteria. Structurally carotenes are tetraterpenes, meaning that they are synthesized biochemically from four 10-carbon terpene units, which in turn were formed from eight 5-carbon isoprene units. Intermediate steps are the creation of a 40-carbon phytoene molecule, conversion to lycopene via desaturation, and then creation of ionone rings at both ends of the molecule. β-carotene has a β-ionone ring at both ends, meaning that the molecule can be divided symmetrically to yield two retinol molecules. α-Carotene has a β-ionone ring at one end and an Ɛ-ionone ring at the other, so it has half the retinol conversion capacity.


title: Vitamin A

text: In most animal species, retinol is synthesized from the breakdown of the plant-formed provitamin, β-carotene. First, the enzyme beta-carotene 15,15'-dioxygenase (BCO-1) cleaves β-carotene at the central double bond, creating an epoxide. This epoxide is then attacked by water creating two hydroxyl groups in the center of the structure. The cleavage occurs when these alcohols are reduced to the aldehydes using NADH. The resultant retinal is then quickly reduced to retinol by the enzyme retinol dehydrogenase. Omnivore species such as dogs, wolves, coyotes and foxes in general are low producers of BCO-1. The enzyme is lacking in felids (cats), meaning that vitamin A requirements are met from the retinyl ester content of prey animals.


title: Vitamin A

text: β-carotene can be extracted from fungus "Blakeslea trispora", marine algae "Dunaliella salina" or genetically modified yeast "Saccharomyces cerevisiae", starting with xylose as a substrate. Chemical synthesis uses either a method developed by BASF or a Grignard reaction utilized by Hoffman-La Roche.


title: Vitamin A

text: The world market for synthetic retinol is primarily for animal feed, leaving approximately 13% for a combination of food, prescription medication and dietary supplement use. Industrial methods for the production of retinol rely on chemical synthesis. The first industrialized synthesis of retinol was achieved by the company Hoffmann-La Roche in 1947. In the following decades, eight other companies developed their own processes. β-ionone, synthesized from acetone, is the essential starting point for all industrial syntheses. Each process involves elongating the unsaturated carbon chain. Pure retinol is extremely sensitive to oxidization and is prepared and transported at low temperatures and oxygen-free atmospheres. When prepared as a dietary supplement or food additive, retinol is stabilized as the ester derivatives retinyl acetate or retinyl palmitate. Prior to 1999, three companies, Roche, BASF and Rhone-Poulenc controlled 96% of global vitamin A sales. In 2001, the European Commission imposed total fines of 855.22 million euros on these and five other companies for their participation in eight distinct market-sharing and price-fixing cartels that dated back to 1989. Roche sold its vitamin division to DSM in 2003. DSM and BASF have the major share of industrial production. A biosynthesis alternative utilizes genetically engineered yeast species "Saccharomyces cerevisiae" to synthesize retinal and retinol, using xylose as a starting substrate. This was accompished by having the yeast first synthesize β-carotene and then the cleaving enzyme β-carotene 15,15'-dioxygenase to yield retinal.


title: Vitamin A

text: Animal research (on mice), which is pre-clinical, also found Retinoid acid, the bioactive metabolite of vitamin A, to have an effect on brain areas responsible for memory and learning.


title: Vitamin A

text: Meta-analyses of intervention and observational trials for various types of cancer report mixed results. Supplementation with β-carotene did not appear to decrease the risk of cancer overall, nor specific cancers including: pancreatic, colorectal, prostate, breast, melanoma, or skin cancer generally. High-dose β-carotene supplementation unexpectedly resulted in a higher incidence of lung cancer and of total mortality in people who were cigarette smokers.


title: Vitamin A

text: For dietary retinol, no effects were observed for high dietary intake and breast cancer survival, risk of liver cancer, risk of bladder cancer or risk of colorectal cancer, although the last review did report lower risk for higher beta-carotene consumption. In contrast, an inverse association was reported between retinol intake and relative risk of esophageal cancer, gastric cancer, ovarian cancer, pancreatic cancer, lung cancer, melanoma, and cervical cancer. For lung cancer, an inverse association was also seen for beta-carotene intake, separate from the retinol results. When high dietary intake was compared to low dietary intake, the decreases in relative risk were in the range of 15 to 20%. For gastric cancer, a meta-analysis of prevention trials reported a 29% decrease in relative risk from retinol supplementation at 1500 μg/day.


title: Vitamin A

text: Fetal alcohol spectrum disorder (FASD), formerly referred to as fetal alcohol syndrome, presents as craniofacial malformations, neurobehavioral disorders and mental disabilities, all attributed to exposing human embryos to alcohol during fetal development. The risk of FASD depends on the amount consumed, the frequency of consumption, and the points in pregnancy at which the alcohol is consumed. Ethanol is a known teratogen, i.e., causes birth defects. Ethanol is metabolized by alcohol dehydrogenase enzymes into acetaldehyde. The subsequent oxidation of acetaldehyde into acetate is performed by aldehyde dehydrogenase enzymes. Given that retinoic acid (RA) regulates numerous embryonic and differentiation processes, one of the proposed mechanisms for the teratogenic effects of ethanol is a competition for the enzymes required for the biosynthesis of RA from vitamin A. Animal research demonstrates that in the embryo, the competition takes place between acetaldehyde and retinaldehyde for aldehyde dehydrogenase activity. In this model, acetaldehyde inhibits the production of retinoic acid by retinaldehyde dehydrogenase. Ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol, retinaldehyde, or retinaldehyde dehydrogenase. Thus, animal research supports the reduction of retinoic acid activity as an etiological trigger in the induction of FASD.


title: Vitamin A

text: Malaria and vitamin A deficiency are both common among young children in sub-Saharan Africa. Vitamin A supplementation to children in regions where vitamin A deficiency is common has repeatedly been shown to reduce overall mortality rates, especially from measles and diarrhea. For malaria, clinical trial results are mixed, either showing that vitamin A treatment did not reduce the incidence of probable malarial fever, or else did not affect incidence, but did reduce slide-confirmed parasite density and reduced the number of fever episodes. The question was raised as to whether malaria causes vitamin A deficiency, or vitamin A deficiency contributes to the severity of malaria, or both. Researchers proposed several mechanisms by which malaria (and other infections) could contribute to vitamin A deficiency, including a fever-induced reduction in synthesis of retinal-binding protein (RBP) responsible for transporting retinol from liver to plasma and tissues, but reported finding no evidence for a transient depression or restoration of plasma RBP or retinol after a malarial infection was eliminated.


title: Vitamin A

text: In 1912, Frederick Gowland Hopkins demonstrated that unknown accessory factors found in milk, other than carbohydrates, proteins, and fats were necessary for growth in rats. Hopkins received a Nobel Prize for this discovery in 1929. By 1913, one of these substances was independently discovered by Elmer McCollum and Marguerite Davis at the University of Wisconsin–Madison, and Lafayette Mendel and Thomas Burr Osborne at Yale University. McCollum and Davis ultimately received credit because they submitted their paper three weeks before Mendel and Osborne. Both papers appeared in the same issue of the "Journal of Biological Chemistry" in 1913. The "accessory factors" were termed "fat soluble" in 1918, and later "vitamin A" in 1920. In 1919, Harry Steenbock (University of Wisconsin–Madison) proposed a relationship between yellow plant pigments (beta-carotene) and vitamin A. In 1931, Swiss chemist Paul Karrer described the chemical structure of vitamin A. Retinoic acid and retinol were first synthesized in 1946 and 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens.


title: Vitamin A

text: During World War II, German bombers would attack at night to evade British defenses. In order to keep the 1939 invention of a new on-board Airborne Intercept Radar system secret from Germany, the British Ministry of Information told newspapers an unproven claim that the nighttime defensive success of Royal Air Force pilots was due to a high dietary intake of carrots rich in beta-carotene, successfully convincing many people.


title: Vitamin A

text: In 1967, George Wald shared the Nobel Prize in Physiology and Medicine for his work on chemical visual processes in the eye. Wald had demonstrated in 1935 that photoreceptor cells in the eye contain rhodopsin, a chromophore composed of the protein opsin and 11-"cis"-retinal. When struck by light, 11-"cis"-retinal undergoes photoisomerization to "all-trans"-retinal and via signal transduction cascade send a nerve signal to the brain. The "all-trans"-retinal is reduced to "all-trans"-retinol and travels back to the retinal pigment epithelium to be recycled to 11-"cis"-retinal and reconjugated to opsin. Wald's work was the culmination of nearly 60 years of research. In 1877, Franz Christian Boll identified a light-sensitive pigment in the outer segments of rod cells of the retina that faded/bleached when exposed to light, but was restored after light exposure ceased. He suggested that this substance, by a photochemical process, conveyed the impression of light to the brain. The research was taken up by Wilhelm Kühne, who named the pigment rhodopsin, also known as "visual purple." Kühne confirmed that rhodopsin is extremely sensitive to light, and thus enables vision in low-light conditions, and that it was this chemical decomposition that stimulated nerve impulses to the brain. Research stalled until after identification of "fat-soluble vitamin A" as a dietary substance found in milkfat but not lard, would reverse night blindness and xerophthalmia. In 1925, Fridericia and Holm demonstrated that vitamin A deficient rats were unable to regenerate rhodopsin after being moved from a light to a dark room.


title: Vanessa Ferlito

text: Vanessa Ferlito is an American actress. She is known for playing Detective Aiden Burn in the first season of the CBS crime drama "", as well as for her recurring portrayal of Claudia Hernandez in FOX drama "24", and for her starring roles as FBI Agent Charlie DeMarco in the USA Network series "Graceland" and as on the CBS crime drama series "". She has also appeared in a number of films, including "Spider-Man 2" (2004), "Shadowboxer" (2005), "Man of the House" (2005), "Gridiron Gang" (2006), "Death Proof" (2007), "Nothing like the Holidays" (2008), "Madea Goes to Jail" (2009), "Julie & Julia" (2009), "" (2010), and "Stand Up Guys" (2012).


title: Vanessa Ferlito

text: Ferlito was born to an Italian-American family in Brooklyn, New York. Her father died of a heroin overdose when she was two years old. Her mother and stepfather own a hair salon in Brooklyn. Before becoming an actress, Ferlito was a Wilhelmina model, and a New York City "club kid". Ferlito is a single mother who gave birth to a son in September 2007.


title: Vanessa Ferlito

text: Ferlito developed acting aspirations early in her life and broke into the entertainment business through a series of guest spots and recurring roles.


title: Vanessa Ferlito

text: In 2003, Ferlito starred as Lizette Sanchez in John Leguizamo's boxing drama "Undefeated", which earned her an NAACP nomination for Outstanding Actress in a TV movie. This was followed in 2004 by a role in "Spider-Man 2". In 2005 Ferlito appeared in Stephen Herek's "Man of the House", opposite Tommy Lee Jones, for which she received positive notice, with "Variety's" Joe Leydon stating that "Vanessa Ferlito is the standout, mainly because she’s the only one who gets enough to do to make a strong impression as a distinctive personality."


title: Vanessa Ferlito

text: On the small screen, Ferlito was a series regular on the first two seasons (2004–2005) of CBS's "", as Aiden Burn, a member of the forensic investigation team led by Gary Sinise. Ferlito has also appeared in other television series, including HBO’s "The Sopranos", NBC’s "Law & Order" and "Third Watch", and had a recurring role as Claudia in FOX's series "24".


title: Vanessa Ferlito

text: After "CSI: NY", Ferlito starred in several films, among them ""; Nora Ephron's "Julie & Julia" opposite Meryl Streep, Stanley Tucci and Amy Adams; Tyler Perry's "Madea Goes to Jail"; and Alfredo De Villa’s "Nothing like the Holidays" (originally titled "Humboldt Park") with Alfred Molina, John Leguizamo and Jay Hernandez. Prior to these, Ferlito appeared in Quentin Tarantino’s "Death Proof" opposite Kurt Russell, a role Tarantino wrote specifically for Ferlito. She also appeared in Lee Daniel's "Shadowboxer" with Helen Mirren and Cuba Gooding Jr.


title: Vanessa Ferlito

text: In 2012, Ferlito was cast in the feature film, "Stand Up Guys", opposite Al Pacino, Christopher Walken and Alan Arkin. She also played Charlie DeMarco on USA Network's "Graceland", which ran between 2013 and 2015. In 2016, Ferlito was added to the cast of "" for the show's third season, playing an FBI special agent who is sent from DC to investigate the NCIS team.


title: Box plot

text: In descriptive statistics, a box plot or boxplot is a method for graphically demonstrating the locality, spread and skewness groups of numerical data through their quartiles. In addition to the box on a box plot, there can be lines (which are called "whiskers") extending from the box indicating variability outside the upper and lower quartiles, thus, the plot is also termed as the box-and-whisker plot and the box-and-whisker diagram. Outliers that differ significantly from the rest of the dataset may be plotted as individual points beyond the whiskers on the box-plot.


title: Box plot

text: Box plots are non-parametric: they display variation in samples of a statistical population without making any assumptions of the underlying statistical distribution (though Tukey's boxplot assumes symmetry for the whiskers and normality for their length). The spacings in each subsection of the box-plot indicate the degree of dispersion (spread) and skewness of the data, which are usually described using the five-number summary. In addition, the box-plot allows one to visually estimate various L-estimators, notably the interquartile range, midhinge, range, mid-range, and trimean. Box plots can be drawn either horizontally or vertically.


title: Box plot

text: The range-bar method was first introduced by Mary Eleanor Spear in her book "Charting Statistics" in 1952 and again in her book "Practical Charting Techniques" in 1969. The box-and-whisker plot was first introduced in 1970 by John Tukey, who later published on the subject in his book "Exploratory Data Analysis" in 1977.


title: Box plot

text: A boxplot is a standardized way of displaying the dataset based on the five-number summary: the minimum, the maximum, the sample median, and the first and third quartiles.


title: Box plot

text: In addition to the minimum and maximum values used to construct a box-plot, another important element that can also be employed to obtain a box-plot is the interquartile range (IQR), as denoted below:


title: Box plot

text: A box-plot usually includes two parts, a box and a set of whiskers as shown in Figure 2. The box is drawn from "Q" to "Q" with a horizontal line drawn in the middle to denote the median. The whiskers can be defined in various ways.


title: Box plot

text: In the most straight-forward method, the boundary of the lower whisker is the minimum value of the data set, and the boundary of the upper whisker is the maximum value of the data set.


title: Box plot

text: Another popular choice for the boundaries of the whiskers is based on the 1.5 IQR value. From above the upper quartile (Q"), a distance of 1.5 times the IQR is measured out and a whisker is drawn "up to" the largest observed data point from the dataset that falls within this distance. Similarly, a distance of 1.5 times the IQR is measured out below the lower quartile (Q") and a whisker is drawn "down to" the lowest observed data point from the dataset that falls within this distance. Because the whiskers must end at an observed data point, the whisker lengths can look unequal, even though 1.5 IQR is the same for both sides. All other observed data points outside the boundary of the whiskers are plotted as "outliers". The outliers can be plotted on the box-plot as a dot, a small circle, a star, "etc.".


title: Box plot

text: The unusual percentiles 2%, 9%, 91%, 98% are sometimes used for whisker cross-hatches and whisker ends to depict the seven-number summary. If the data are normally distributed, the locations of the seven marks on the box plot will be equally spaced. On some box plots, a cross-hatch is placed before the end of each whisker.


title: Box plot

text: Because of this variability, it is appropriate to describe the convention that is being used for the whiskers and outliers in the caption of the box-plot.


title: Box plot

text: Since the mathematician John W. Tukey first popularized this type of visual data display in 1969, several variations on the classical box plot have been developed, and the two most commonly found variations are the variable width box plots and the notched box plots shown in Figure 4.


title: Box plot

text: Variable width box plots illustrate the size of each group whose data is being plotted by making the width of the box proportional to the size of the group. A popular convention is to make the box width proportional to the square root of the size of the group.


title: Box plot

text: Notched box plots apply a "notch" or narrowing of the box around the median. Notches are useful in offering a rough guide of the significance of the difference of medians; if the notches of two boxes do not overlap, this will provide evidence of a statistically significant difference between the medians. The width of the notches is proportional to the interquartile range (IQR) of the sample and is inversely proportional to the square root of the size of the sample. However, there is a uncertainty about the most appropriate multiplier (as this may vary depending on the similarity of the variances of the samples).


title: Box plot

text: One convention for obtaining the boundaries of these notches is to use a distance of formula_2 around the median.


title: Box plot

text: Adjusted box plots are intended to describe skew distributions, and they rely on the medcouple statistic of skewness. For a medcouple value of MC, the lengths of the upper and lower whiskers on the box-plot are respectively defined to be:


title: Box plot

text: For a symmetrical data distribution, the medcouple will be zero, and this reduces the adjusted box-plot to the Tukey's box-plot with equal whisker lengths of formula_4 for both whiskers.


title: Box plot

text: Other kinds of box plots, such as the violin plots and the bean plots can show the difference between single-modal and multimodal distributions, which cannot be observed from the original classical box-plot.


title: Box plot

text: A series of hourly temperatures were measured throghout the day in degrees Fahrenheit. The recorded values are listed in order as follows (°F): 57, 57, 57, 58, 63, 66, 66, 67, 67, 68, 67.


title: Box plot

text: A box plot of the data set can be generated by first calculating five relevant values of this data set: minimum, maximum, median (Q"), first quartile (Q"), and third quartile ("Q").


title: Box plot

text: The minimum is the smallest number of the data set. In this case, the minimum recorded day temperature is 57 °F.


title: Box plot

text: The maximum is the largest number of the data set. In this case, the maximum recorded day temperature is 81 °F.


title: Box plot

text: The median is the "middle" number of the ordered data set. This means that there are exactly 50% of the elements is less than the median and 50% of the elements is greater than the median. The median of this ordered data set is 70 °F.


title: Box plot

text: The first quartile value ("Q" or 25th percentile) is the number that marks one quarter of the ordered data set. In other words, there are exactly 25% of the elements that are less than the first quartile and exactly 75% of the elements that are greater than it. The first quartile value can be easily determined by finding the "middle" number between the minimum and the median. For the hourly temperatures, the "middle" number found between 57 °F and 70 °F is 66 °F.


title: Box plot

text: The third quartile value ("Q" or 75th percentile) is the number that marks three quarters of the ordered data set. In other words, there are exactly 75% of the elements that are less than the third quartile and 25% of the elements that are greater than it. The third quartile value can be easily obtained by finding the "middle" number between the median and the maximum. For the hourly temperatures, the "middle" number between 70 °F and 81 °F is 75 °F.


title: Box plot

text: The interquartile range, or IQR, can be calculated by subtracting the first quartile value (Q") from the third quartile value (Q"):


title: Box plot

text: The upper whisker boundary of the box-plot is the largest data value that is within 1.5 IQR above the third quartile. Here, 1.5 IQR above the third quartile is 88.5 °F and the maximum is 81 °F. Therefore, the upper whisker is drawn at the value of the maximum, which is 81 °F.


title: Box plot

text: Similarly, the lower whisker boundary of the box plot is the smallest data value that is within 1.5 IQR below the first quartile. Here, 1.5 IQR below the first quartile is 52.5 °F and the minimum is 57 °F. Therefore, the lower whisker is drawn at the value of the minimum, which is 57 °F.


title: Box plot

text: Above is an example without outliers. Here is a followup example for generating box-plot with outliers:


title: Box plot

text: The ordered set for the recorded temperatures is (°F): 52, 57, 57, 58, 63, 66, 66, 67, 67, 68, 69, 70, 70, 70, 70, 72, 73, 75, 75, 76, 76, 78, 79, 89.


title: Box plot

text: In this example, only the first and the last number are changed. The median, third quartile, and first quartile remain the same.


title: Box plot

text: In this case, the maximum value in this data set is 89 °F, and 1.5 IQR above the third quartile is 88.5 °F. The maximum is greater than 1.5 IQR plus the third quartile, so the maximum is an outlier. Therefore, the upper whisker is drawn at the greatest value smaller than 1.5 IQR above the third quartile, which is 79 °F.


title: Box plot

text: Similarly, the minimum value in this data set is 52 °F, and 1.5 IQR below the first quartile is 52.5 °F. The minimum is smaller than 1.5 IQR minus the first quartile, so the minimum is also an outlier. Therefore, the lower whisker is drawn at the smallest value greater than 1.5 IQR below the first quartile, which is 57 °F.


title: Box plot

text: An additional example for obtaining box-plot from a data set containing a large number of data points is:


title: Box plot

text: Using the above example that has 24 data points ("n" = 24), one can calculate the median, first and third quartile either mathematically or visually.


title: Box plot

text: Although box plots may seem more primitive than histograms or kernel density estimates, they do have a number of advantages. First, the box plot enables statisticians to do a quick graphical examination on one or more data sets. Box-plots also take up less space and are therefore particularly useful for comparing distributions between several groups or sets of data in parallel (see Figure 1 for an example). Lastly, the overall structure of histograms and kernel density estimate can be strongly influenced by the choice of number and width of bins techniques and the choice of bandwidth, respectively.


title: Box plot

text: Although looking at a statistical distribution is more common than looking at a box plot, it can be useful to compare the box plot against the probability density function (theoretical histogram) for a normal N(0,"σ") distribution and observe their characteristics directly (as shown in Figure 7).


title: Nissan 350Z

text: The Nissan 350Z (known as Nissan Fairlady Z (Z33) in Japan) is a two-door, two-seater sports car that was manufactured by Nissan Motor Corporation from 2002 until 2009 and marks the fifth generation of Nissan's Z-car line. The 350Z entered production in 2002 and was sold and marketed as a 2003 model from August 2002. The first year there was only a coupe, as the roadster did not debut until the following year. Initially, the coupe came in Base, Enthusiast, Performance, Touring and Track versions, while the Roadster was limited to Enthusiast and Touring trim levels. The Track trim came with lightweight wheels and Brembo brakes, but its suspension tuning was the same as all other coupes. The Nissan 350Z was succeeded by the 370Z for the 2009 model year.


title: Nissan 350Z

text: After the Nissan 300ZX was withdrawn from the U.S. market in 1996, Nissan initially tried to keep the Z name alive by re-creating the 240Z the following year. The car was conceived by Nissan's North American design team in their free time, and the concept was introduced in a four state Road Show in July 1998 to various car media, dealers, and employees. Yutaka Katayama, regarded as the "Father of the Z" unveiled the Z concept sketch to the public when he received a motor industry award. The design, representing a modern vision of the 240Z, did not please the original 240Z designer Yoshihiko Matsuo, who compared it to the Bluebird and Leopard.


title: Nissan 350Z

text: The 240Z concept was produced for the Detroit Motor Show during the following August and September. Nissan was unhappy with the first design as they felt the original 2.4 L KA24DE engine that was going to be assigned made the car feel underpowered, they also felt the car was considered too "retro" or too "backward" resembling a futuristic 240Z; hence, a redesign was commissioned. During a press conference in February 2000, president Carlos Ghosn announced plans to produce the car as he felt the new model would help to assist the company's recovery.


title: Nissan 350Z

text: The Z Concept was unveiled in Detroit Motor Show two years later, which was similar in body shape but with a new front end. The car then underwent a minor redesign and was eventually assigned the 3.5 L VQ35DE engine, hence becoming known as the "350Z".


title: Nissan 350Z

text: Nissan unveiled the 240Z concept car at the 1999 North American International Auto Show, then later at the Los Angeles Auto Expo. The concept was based primarily on a design sketch by Manny Baker of Nissan's California design studio. In a reference to the original, it was a bright orange two-seater with swept-back styling. It was fully functional car with its 2.4 L 4-cylinder KA24DE engine from the Nissan Altima producing and of torque, and not the Z-car's traditional 6-cylinder engine. It was thought a less than worthy successor to the line. The designers used an original 240Z to provide inspiration and the concept was created in only 12 weeks. Automotive critics described "it would be cool but get a new model." This design served the intended purpose of creating interest, in the public and the corporation, for a new Z car.


title: Nissan 350Z

text: The 350Z is a front-engine, rear-wheel-drive, two-door, two-seat sports car designed by Diane Allen, part of a design team led by Ajay Panchal of Nissan Design America in San Diego, California in 2000. This program was inspired by the successful reception to the 1998 240Z concept model.


title: Nissan 350Z

text: The vehicle has the long-hood short-deck design common to the Z-Car family. External design highlights include: sloping fastback style arched roof line, unique brushed aluminum door handles, high waistline, and bulging fenders that are pushed out to the corners of the vehicle.


title: Nissan 350Z

text: The Interior design has brushed aluminum accents. The main gauge pod is mounted directly to the steering column allowing its movement to coincide with steering wheel adjustments. Additional gauges are mounted in a center triple gauge cluster (similar to the 240Z/260Z/280Z). Touring models are equipped with the Bose sound system get a six CD changer and 8-inch Bose subwoofer mounted behind the driver's seat. The 350Z's interior does not have a conventional glove box, but has storage compartments located behind and between the two seats.


title: Nissan 350Z

text: Released on July 2002 in Japan at reorganized Nissan Japanese dealerships called "Nissan Blue Stage", and August 20, 2002 in the U.S., the 350Z coupé was available in 5 trim packages: '350Z' (Base), 'Enthusiast', 'Performance', 'Touring', and 'Track' editions. In Europe, only the 'Track' trim was available, although it was badged and marketed as '350Z'. The Base model did not include a VLSD or Traction Control and was only available with cloth seats. It did not include cruise control, nor power or heated seats. The Enthusiast model came with traction control, a VLSD, and cruise control. The Performance model came with larger 18-inch wheels, front air dam, rear spoiler, optional Brembo brakes, and VDC instead of Traction Control. Touring was made more of the luxury model. It had power, leather, heated seats, VDC, a VLSD, xenon headlamps, optional Brembo brakes, 18-inch wheels, and optional GPS Navigation. The Track model included Brembo brakes, front air dam, rear spoiler, traction control, cloth seats, 18-inch wheels, VLSD, and optional GPS Navigation.


title: Nissan 350Z

text: In 2004 Nissan introduced the 350Z Roadster with an electrically retractable soft-top roof. In the U.S. market the car was available in two trim packages (Enthusiast and Touring), while in Europe, the same versions as the coupé were offered. Nissan added the Grand Touring (GT) trim to the Roadster trim packages for 2005.


title: Nissan 350Z

text: In 2005 Nissan launched the 35th Anniversary edition, with a revised exterior and interior (see "Special Editions" below). Early 2005 model-year 35th anniversary edition models were equipped with the original VQ35DE engine with 287HP/274TQ and an automatic transmission. In January 2005, Nissan introduced the 35th Anniversary 6-speed manual models and Track models (mid-year introduction), which included the updated VQ35DE 300HP/260TQ 'Rev-up' engine and new updated CD009 manual transmission as well as minor changes to suspension tuning and parts.


title: Nissan 350Z

text: For the 2006 model year, the 350Z received changes for its mid-cycle facelift. The VQ35DE 300HP/260TQ 'Rev-up' engine that was introduced mid-year 2005 on the Track and 35th Anniversary Edition with 6-speed manual transmission models was offered for every trim level that had a manual transmission option. The VQ35DE rated at and of torque continued to be offered with only the 5-speed automatic transmission. Additions included bi-xenon projectors, a revised front fascia, new LED rear lights, changes to the interior trim and speed sensitive steering. Trim levels above the basic enthusiast package received a brake system upgrade including a larger brake booster, front dual piston calipers and larger diameter brake disks. Touring and Grand Touring models had radio-steering controls standard, MP3 CD compatibility, and Satellite Radio became an available option.


title: Nissan 350Z

text: For the 2007 model year, the 350Z was again moderately revised. The VQ35DE V6 was replaced with a new VQ35HR V6. It produced at 6800 rpm with of torque at 4800 rpm using the revised SAE certified power benchmark. The VQ35HR had a raised redline to 7500 rpm and more torque across the rpm range. The hood was redesigned with a bulge reminiscent of the original 240Z to accommodate the raised deck height of the new VQ35HR. In the U.S., trim levels were narrowed down to 350Z (base), Enthusiast, Touring, Grand Touring and NISMO, while in Europe the same trim levels remained. Bluetooth was added for the 2007 model year.


title: Nissan 350Z

text: A total of 5 units, called the Type E, were produced in Japan for homologation requirements to compete in the Super GT series. It has a longer nose and rear overhang, as well as several add-ons for aerodynamic purposes. The Type-E engine is rated at at 6,200 rpm and of torque at 4,800 rpm.


title: Nissan 350Z

text: To commemorate the 35th anniversary of the debut of the Datsun 240Z, Nissan released a tuned version of the 350Z coupé. The 35th Anniversary Z was exhibited at the Specialty Equipment Marketing Association (SEMA) Show in Las Vegas on November 2, followed by the Miami Auto Show in early November. It went on sale in January 2005.


title: Nissan 350Z

text: The 35th Anniversary Edition includes an updated VQ35DE 300 hp (224.99 kW) V6 engine for the six-speed manual transmission model. Other equipment (standard on six-speed manual-equipped versions) includes 18-inch (460 mm) cast aluminum-alloy wheels, front spoilers, Brembo brakes and special Z badging. The car was available in a special "Ultra Yellow" and "Pearl Blue" colors. The interior was also available with a black set configuration. Also included was a Bose 6-speaker premium sound system. A version of the 35th Anniversary Edition with a Gran Turismo 4 video game tie-in was also made.


title: Nissan 350Z

text: During the 2006 Goodwood Festival of Speed, Nissan Technical Centre Europe (NTCE) unveiled the 350Z GT-S Concept. The GT-S had a unique radial flow supercharger that could be turned on or off via a switch on the dashboard, raising the VQ35DE engine output to and without modifications to the engine components. The car also had new body kit for more cooling and downforce and wider 245 and 265/40/18 tires. The car was tested by automotive journalists, but none were marketed.


title: Nissan 350Z

text: The Nissan Fairlady Z Type F, XANAVI NISMO Z (SUPER GT 2007 GT500 Class), ENDLESS ADVAN Z (series winner of the Japan's SUPER TAIKYU 2007 endurance series) and Fairlady Z Version NISMO Type 380RS were all unveiled at the 2008 Tokyo Auto Salon.


title: Nissan 350Z

text: The Fairlady Z Type F is a version of the Nissan Fairlady Z coupe and roadster for the Japanese market with:


title: Nissan 350Z

text: Nissan's performance tuning division, NISMO, began producing modified versions of the 350Z shortly after its introduction.


title: Nissan 350Z

text: The R-Tune was a kit sold directly to customers with modifications including new headers, cams, pulleys. The R-Tune voids the Nissan factory warranty, but gains significant horsepower, intended for track racers.


title: Nissan 350Z

text: The S-Tune GT was released by NISMO to celebrate its success in the Super GT series. The S-Tune GT had revised long nose bodywork as in the Type-E, a modified version of the VQ35DE engine called the S1 which featured more power (300 PS / 221 kW / 296 hp) and a higher redline (7,200 rpm), as well as a sportier NISMO suspension.


title: Nissan 350Z

text: 20 were produced each month in Japan. Although Nissan did not officially sell S-Tune in UK, Nissan Motor (GB) Ltd. imported 1 S-Tune GT to UK.


title: Nissan 350Z

text: The NISMO edition of the Nissan 350Z Coupé debuted at the New York International Auto Show on April 4, 2007. This version had the same engine as the regular 350Z (VQ35HR), but was only available with a 6-speed manual transmission and a Viscous Limited-Slip Differential (VLSD), Traction Control System (TCS) and a NISMO aerodynamics package based on the Super GT championship car, which included an aggressive front fascia with chin spoiler, side skirts, an extended rear fascia with an underbody diffuser and a rear wing. The vehicle also featured NISMO-tuned independent multi-link suspension developed by Yamaha, Brembo brakes with four-piston front and two-piston rear calipers (with front and rear rotors) and NISMO-branded gunmetal grey RAYS forged alloy wheels and a NISMO-branded tuned exhaust. Yamaha also included front and rear dampeners to help with stability of the chassis.


title: Nissan 350Z

text: The conversion process for the Nismo 350Z began with a limited number of chassis being pulled from the assembly line to be sent to Nissan-tuner Autech to have structural seams hand-welded for greater body rigidity. This process made the Nismo 350Z a more capable track car than the other trim levels available at the time.


title: Nissan 350Z

text: The NISMO 350Z went on sale in the USA in July 2007 at Nissan dealers. 1607 were produced for the 2007 and 2008 model years, and it was assumed that if there was a greater demand, more would be produced, limited to 10% of all 350Z sales. The NISMO model 350Z had a manufacturer's suggested retail price of $38,070 for the 2007 model year.


title: Nissan 350Z

text: Released as the road version for Japanese market of the Type 380RS-Competition race car, the Type 380RS includes a detuned version of the 380RS-C race engine, rated at 257 kW (350 PS/348 hp) at 7200 rpm and 397 N·m (40.5 kgf·m/293 lbf·ft) of torque at 4,800 rpm. Brembo disc brakes are fitted, Front and rear dampers from Yamaha and forged RAYS alloy wheels.


title: Nissan 350Z

text: NISMO Type 380RS is priced 5.397 million (5.14 million+tax) yen ($38695 USD). Only 300 units were produced from 2007 through to 2008.


title: Nissan 350Z

text: The NISMO Type 380RS-Competition is the race car on which NISMO Type 380RS is based. The 3,798 cc engine (VQ38HR) is rated at 294 kW (400 PS) at 7500 rpm and 421 N m (43 kgf m) of torque at 5,200 rpm. This in turn is based on the GT 500 race car that Nissan enters into the Super GT championship.


title: Nissan 350Z

text: Since its introduction in 2002, it did not take long for drivers and teams to enter a 350Z for competition when B.J. Zacharias and Michiel Schuitemaker of Schuitemaker Motorsports helped the car to make its début in the Grand-Am Cup Series at the start of the 2003 season. They have taken a few podium finishes with Unitech Racing who is also the other team to field a Z33, but effort was proved to be successful under the name of "Geddings Racing" scoring wins along with the other current Grand-Am entrant East Competition Promotorsport. The Grand-Am Cup car has also been used in the new FIA GT4 European Cup. Schumacher Motorsports with drivers Michael Schumacher and BJ Zacharias won 3rd place in the '03 Grand-Am Cup season. The following year, they improved and finished in 2nd place. After winning 3rd overall in the '03 season, Nissan had Wright Tuning build a new 350Z race car for the '04 season. This car differed from the '03 car in that it was completely stripped and seam welded. The cage was lighter and stiffer by using different diameter tubing where possible. The car used a Menard's built engine with a Pectel engine management system. Overall racing weight was which was the minimum allowable weight for its class. The '04 chassis proved to be the most successful chassis to run in Grand-Am to date. The '03 chassis was sold to a French team with Edouardo Atkatlan as the driver. It still competes in the European "Fun Races" today, winning 2nd place in the inaugural '07 race in Madrid, Spain.


title: Nissan 350Z

text: The 350Z replaced the Skyline GT-R as the car for Nissan's factory and customer teams in the Super GT's GT 500 class. The cars used are heavily modified and had a longer nose and tail (requiring the production of the Type-E homologation special), carbon fiber bodywork, and a tube chassis. In 2004, NISMO won the GT500 championship. Until the 2007 season, the car was powered by a VQ30DETT V6, then a new 4.5L V8 powerplant was developed. The 350Z, with slightly more pedestrian modifications also competed in the GT300 class, having started there even before the Skyline GT-Rs were replaced, by teams such as Endless Sports and Mola. In 2003 Hasemi Sports won the GT300 championship with the 350Z. In the 2008 season, the 350Zs were all replaced by Nissan GT-Rs in the GT500 class, but they continued to be used in the GT300 class as the GT-Rs exceed the class's horsepower limits. Two 350Zs competed in the series and MOLA won both the Drivers' and Teams' championships in the GT300 class.


title: Nissan 350Z

text: The 350Z is a popular choice for amateurs and professionals competing in SCCA events. T.C Kline achieved third place in the 2003 Touring 2 category in one of three Z33s that qualified to the SCCA T-2 runoffs that year. In the SCCA GT2 class, Jim Goughary took the title in the car's debut season.


title: Nissan 350Z

text: The car has also seen success in SCCA solo events. In 2006, Carter Thompson's 350Z lost the SCCA National Championship by 0.1 second over two days of competition. The 350Z has achieved a high level of success at the National Solo Championships since 2006. Although production of the 350Z was discontinued in 2009, the car continues to compete in local and national SCCA events. As recently as 2015, 350Z solo drivers Jeff Stuart and Bryan Heitkotter were rated as the top two SCCA drivers competing in national autocross.


title: Nissan 350Z

text: In 2012, NASA (National Auto Sport Association), created a class of racing specifically for the 350Z. The "Spec Z" class includes all trim levels of the popular 2003-2008 Nissan 350Z in a single class focused on close competition, parity and cost containment that will showcase driving ability and car setup skills. The road racing series is backed by Nissan Motorsports and BFG Tires. The 2012 class rules were in their infant stage, but solidified by mid-2012.


title: Nissan 350Z

text: The 350Z is a popular platform for import events and drifting, where in the latter, drivers including Ryuji Miki, Youichi Imamura, Tyler McQuarrie and Tanner Foust have used them with success in the D1 Grand Prix and Formula D series. During the 2006 D1 Grand Prix exhibition event at the Las Vegas Motor Speedway, Tanner Foust, driving a 350Z, became the first competitor to achieve a perfect score of 100. Two Z33s competed in the non-Japanese domestic D1 Grand Prix spin-off series, D1 Great Britain. In the 2007 season, both SVA Imports and Sumo Power competed using 350Zs in the European Drift Championship. In Formula D, Foust was awarded the runner-up spot in Round 1. In Round 2, Chris Forsberg scored a maiden victory in his 350Z Roadster equipped with a VK56DE from a Nissan Titan. Forsberg's win for the 350Z was followed-up by Youichi Imamura's win during the Las Vegas round of the US D1 Grand Prix series in his RB26DETT-engined car. Foust would eventually take his 350Z to the Formula D title.


title: Nissan 350Z

text: Option magazine founder Daijiro Inada used an extensively modified 350Z, dubbed "Option Stream Z," to compete in the Silver State Classic Challenge. The car was equipped with a GReddy/Trust T88 turbo-charger and was stroked to 3.8 L to produce over . The "Option Stream Z" appeared in the games Gran Turismo 4, Gran Turismo 5, and Gran Turismo (PSP).


title: Nissan 350Z

text: In 2004, the tuner Dandy and magazine Option entered a Z33 known as the "Option Dandy 380Z" with a donor engine from a salvaged Stream Z with a deleted turbo, producing , to compete in the F/GT class for naturally aspirated grand touring sport cars at the Bonneville Speed Week. The car reached a speed of , measured over a fixed distance.


title: Nissan 350Z

text: To promote the 350Z, Nissan released a short film, ""The Run"", with a 2003 model being driven in a high-speed run through city streets of up to . This took place through the narrow cobblestone streets of Prague in the Czech Republic, and lasted six and a half minutes.


title: Nissan 350Z

text: The 350Z has been extremely popular with diecast manufacturers, with companies such as Hot Wheels releasing various colors and styles of the car over the years.


title: Nissan 350Z

text: The 350Z benefitted in popularity by making an appearance in , where it was fitted with a Veilside bodykit, amongst other modifications, and was driven by the fictional character "Drift King" Takashi.


title: Nissan 350Z

text: The 350Z has been given extensive coverage in the automotive press, and has obtained generally positive reviews. Eddie Alterman, senior editor of "Automobile" magazine, said of the 350Z "An outstanding performance value. They got all the important stuff right." While David Swigg of "Motor Trend" said "With a competent driver at the wheel and the traction control switched off, many Boxster drivers would be hard-pressed to post better lap times than with this Z." "Top Gear" magazine later awarded the Nissan Designers with the 2004 "Top Gear" Magazine Car of the year award.


title: Nissan 350Z

text: Automotive journalists tend to praise the 350Z's value, performance, handling, and braking. Criticisms tend to be directed towards the grade of interior plastics, greater curb weight than its competitors, cabin ergonomics and engine refinement. Other reviews have criticised reflections off the back strut in the rear window.


title: Nissan 350Z

text: The 350Z came with front air bags in standard and supplemental side air bags and curtain air bags as an option. It won a NHTSA 5-star safety rating for front and side impact on the driver's side. With 143 deaths per million registrations, the two-door 350Z has been one of the least safe 2005–2008 model cars in the United States.


title: Danny Denzongpa

text: Tshering Phintso "Danny" Denzongpa (born 25 February 1948) is an Indian actor, singer and film director who primarily works in Hindi films. He has acted in over 190 films since 1971. In 2003, Denzongpa was awarded the Padma Shree, India's fourth-highest civilian honour. His film career spans more than 4 decades.


title: Danny Denzongpa

text: He has also starred in some international films, the most famous being "Seven Years in Tibet" where he appeared alongside Brad Pitt. His best known villainous roles are in "Dhund", "36 Ghante", "Bandish", "Jeeo Aur Jeene Do", "Dharm Aur Qanoon" and "Agneepath" whereas his best known positive roles were in "Fakira", "Chor Machaye Shor", "Devata", "Kalicharan", "Bulundi" and "Adhikar". His directorial venture "Phir Wahi Raat" was considered among the top five best horror suspense films of Hindi Cinema.


title: Danny Denzongpa

text: Born as Tshering Phintso Denzongpa to a Nepali speaking Buddhist family in Yuksom, Sikkim, he did his schooling in Birla Vidya Mandir, Nainital and thereafter completed college coursework at St Joseph's College, Darjeeling, in 1964. Denzongpa's love of horses and horse-riding began at an early age, as his family was into horse breeding. He is also a painter, a writer and a sculptor.


title: Danny Denzongpa

text: He had an ambition to join the Indian Army and won the Best Cadet award from West Bengal and participated in the Republic Day parade. In an interview to "The Times of India" newspaper, he said that he had qualified for the Armed Forces Medical College, Pune, but withdrew admission to join the Film and Television Institute of India (FTII), Pune. He decided to change his name to a simpler sounding "Danny", on recommendation from his then-classmate Jaya Bhaduri, as his original name of Tshering Phintso Denzongpa was considered difficult for some to pronounce. His son Rinzing Denzongpa made his acting debut in the action film "Squad".


title: Danny Denzongpa

text: He started out with B.R. Ishara's "Zaroorat" in 1971 (released in 1972), which was his debut film. He got his major break in Gulzar's "Mere Apne (1971)", where he had a positive role. He first played an antagonist in B.R.Chopra's "Dhundh" (1973), where he played the role of a cripple and frustrated husband.


title: Danny Denzongpa

text: He played the second lead hero and had more positive roles in commercially successful critically acclaimed films in the seventies, such as "Chor Machaye Shor", "36 Ghante", "Fakira", "Sangram" (1976), "Kalicharan", "Kaala Sona" and "Devata". After his performance in the film "Devata", he started getting more significant lengthy roles. He was simultaneously part of big budget films such as "Aashiq Hoon Baharon Ka", "Paapi", "Bandish", "The Burning Train" and "Chunoti" in negative roles.


title: Danny Denzongpa

text: In the early 1980s period, he had thought of quitting films. He said in an interview, when asked why he decided to direct a film, "I remember in 80s I was so fed up of the films I was doing. Those days every villain was a dacoit and I remember going on the sets where an actor called Tiwari was my henchmen and my den was a cave with lanterns. Next day I went on another set and I saw Tiwari again as my henchman, and the same lanterns. I asked myself what was I doing? I left Mumbai. I did lot of trekking and did not do films for a couple of years. I told NN Sippy about a script that I had in mind. and he asked me to direct. I made "Phir Wohi Raat" with Rajesh Khanna and my then girlfriend Kim." After the success of his directorial debut, he received offers to act as the hero again in the films such as "Bulundi" and "Hum Se Badkar Kaun" in 1981, which became successful. He played a double role in the film "Bulundi". However, most subsequent films between 1981 and 1983 were not successful. He was disappointed with the failure of his recently released film "Abhi Toh Jee Ley", which had popular songs such as "Tu Laali Hai Saveriwali". Hence, Danny started accepting supporting roles, often playing a character quite older than his real age. He played Kumar Gaurav's father-in-law in "Love Story" (1981) and Mithun Chakraborty's father in "Boxer" (1984).


title: Danny Denzongpa

text: He started getting more frequent offers to play the negative character in Hindi films, after the success of the films "Phir Wahi Raat", "Jeeo Aur Jeene Do" and "Dharm Aur Qanoon". He then went on to play the role of villain many times since 1984. From 1984 and through the 1990s, Danny mainly was featured as the lead negative character opposite all the leading actors of that time such as Rajesh Khanna, Dharmendra, Jeetendra, Mithun Chakraborty, Vinod Khanna, Anil Kapoor and Sunny Deol. He stated in an interview; "Had it not been that I had not done the four special negative roles – with Rajesh Khanna, in the lead – "Phir Wohi Raat", "Dharm Aur Qanoon", "Bandish" and "Aashiq Hoon Baharon Ka", people would not have considered me for villainous roles. In "Adhikar" I had positive role. He holds special place in my heart as he recognized and stood by me in my tough times which was early eighties."


title: Danny Denzongpa

text: His most applauded negative characters are in "Bandish" (1980) as Kapil Kumar, "Phir Wahi Raat" as "Ashok", "Dharm Aur Qanoon" (1984), as SP "Kader", "Kanoon Kya Karega" (1984), as "Raghuvir Singh", "Andar Baahar" (1984), as "Shera", "Oonche Log" (1985), as "Thakur Maan Singh", "Aandhi Toofan" (1986), as "Balbir" "Bhagwaan Dada" (1986), as "Gangwaa", "Agneepath" (1990), as "Kancha Cheena", "Hum" (1991), as "Bakhtawar", "", as "Kaatya", "Krantiveer" (1994), as "Chatur Singh", "Pukar", (2000) as "Abhrush" and Indian, as "Shankar Singhania". He was pitted against Pran in the film "Sanam Bewafa", Paap Ki Duniya, Gurudev and . His command over the Urdu language came in handy in films such as Sawan Kumar's "Sanam Bewafa" and Mukul Anand's "Khuda Gawah".


title: Danny Denzongpa

text: At one time, when he was increasingly doing negative lead roles, Rajkumar Santoshi cast him as the positive role in China Gate. In the early 2000s, Denzongpa appeared in films such as "Asoka" and 16 December. Some of the antihero roles he played included an unscrupulous politician, corrupt policeman, traitor, and stingy landlord. He has also starred in some international films, the most famous being "Seven Years in Tibet", where he appeared. He did positive roles in "Lahu Ke Do Rang", "Bulundi", "Boxer", "Humse Badkar Kaun", "Khuda Gawah", "16 December" and "China Gate".


title: Danny Denzongpa

text: In early 2003 Denzongpa decided to take a break from films as he wanted to do different but strong roles, even if it was a negative character. He appeared in only 10 films between 2003 and 2009.


title: Danny Denzongpa

text: He then made a strong comeback as the villain with his role in "Enthiran". He made his debut in Tamil films with "Enthiran", co-starring Rajinikanth and Aishwarya Rai in the leads. Denzongpa played the antagonist role of Bohra, a prominent scientist who transforms "Chitti", (played by Rajinikanth) into an evil robot. He then started playing villains in big budget movies such as "Jai Ho" (2014), co-starring Salman Khan and "Bang Bang" (2014), co-starring Hrithik Roshan.


title: Danny Denzongpa

text: He has recently played the role of a coordinator, "Feroz Khan" in the 2015 hit "Baby" co-starring Akshay Kumar. He reprised his role of "Feroz Khan" in the film's spin-off prequel "Naam Shabana"


title: Danny Denzongpa

text: He is an accomplished singer, having sung with Kishore Kumar, Lata Mangeshkar, Mohammed Rafi and Asha Bhosle, the stalwarts of Indian music. He was first given a chance to sing by S.D. Burman in the film "Yeh Gulistan Hamara" in 1972. Denzongpa sang a duet with Lata Mangeshkar.


title: Danny Denzongpa

text: Danny Denzongpa has quoted on S.D. Burman, "My dream to be a playback singer in films came with the number, 'Mera Naam Aao' in 'Yeh Gulistan Hamara' (1972). The maestro that he was, S.D. Burman recognised my singing abilities and conducted the daring experiment of making me sing my first duet with Lata Mangeshkar. He advised me to produce a comic effect yet maintain melody whilst singing. The song was a raging hit." This was told to Ranjan Das Gupta in 'The Hindu' on 8 January 2012.


title: Danny Denzongpa

text: He has released Nepalese songs, and has sung for Nepalese movies. His two most famous songs recorded in the 1970s but still popular are "Chiso Chiso Hawama" ("In the cool air") and "Manko kura lai bandhi narakha... ("Do not keep the words of the heart tied").


title: Danny Denzongpa

text: He sang the duet "Suno Suno Kasam Se" in Kaala Sona with Asha Bhosle and sang "Mujhe Doston Tum Gale Lagaa Lo" with Mohammed Rafi, Asha Bhosle and the duet song "Botal Khaali Hone To Do" with Kishore Kumar in the 1978 film "Naya Daur" – all of which were composed by R.D. Burman.


title: Danny Denzongpa

text: "Hiun vanda chiso, Aago vanda taato..." ("Colder than snow, hotter than fire..."), "Naachana hoi maichyan hau nachana", ("Dance o lovely girl"), "Jhimkai deu pareli manma bajchha mitho murali...", ("Please blink your eyes and sweet sound of flute plays in the heart), "Raatko rani phulay jhain sanjhama", "Pani Hai Paryo Jhyaure" etc. are some of his few hit numbers. He gained popularity as a singer in the period 1975–1990 especially in Nepal and parts of India like Darjeeling, Sikkim and Assam.


title: Danny Denzongpa

text: He has sung a Nepali duet with Asha Bhosle, "Aage aage topai ko gola pachhi pachhi machinegun barara" in 1976. This song was shown by Danny to Rajesh Khanna who liked the song tremendously. Then Rajesh Khanna requested R.D. Burman to compose the song – "Sang Mere Nikle The Sajan" from the 1981 film Phir Wohi Raat, which was directed by Danny himself – after getting inspired by the melody of the Nepali folk song sung by Danny – "Aage Aage Topaiko Gola". R. D. Burman changed the interludes and tunes of stanzas but retained the tune at the beginning.


title: Danny Denzongpa

text: Denzongpa wrote and acted in the Nepali film "Saino". His nephew Ugyen Chhopel directed it. He has sung its title song and a duet with Deepa Narayan, wife of Udit Narayan. Later, this film was made in Hindi as "Bandhu" (1992) by Chopel himself and loosely adapted as the Indian television series "Ajnabi" for Doordarshan by Denzongpa.


title: The Vow (2012 film)

text: The Vow is a 2012 American romantic drama film directed by Michael Sucsy and written by Abby Kohn, Marc Silverstein, and Jason Katims, inspired by the true story of Kim and Krickitt Carpenter. The film stars Rachel McAdams and Channing Tatum as Paige and Leo Collins, with Sam Neill, Scott Speedman, Jessica Lange and Jessica McNamee in supporting roles. As of 2013, "The Vow" was the eighth highest-grossing romantic drama film produced since 1980. This was Spyglass Entertainment's last film before the company's closure in 2012, and its revival in 2019.


title: The Vow (2012 film)

text: Paige Collins (Rachel McAdams) and her husband Leo (Channing Tatum) come out of a movie theater. On their way home, at a stop sign, Paige unbuckles her seatbelt to lean over and kiss Leo. At that very moment, a truck rams their car from behind and Paige crashes through the windshield. Both of them are rushed to the emergency room, and as Leo, in a voice-over, talks about how "moments of impact help in finding who we are" the movie cuts to how Paige and Leo first met. The scenes of how they courted, became engaged and married at the Art Institute of Chicago and share a kiss under the Cloud Gate are interwoven with the present.


title: The Vow (2012 film)

text: Paige is put into an induced coma and when she regains consciousness, she thinks Leo is her doctor, having lost all memories of the past few years. When her wealthy parents, Bill and Rita Thornton, learn about this, they visit her. This is the first time that Leo meets them, and they do not appreciate Leo taking their daughter, and not being informed. Paige does not understand why he would not have met her parents, after having been married to her. She finds it even stranger that he did not know why either. Nor did she understand why she left law school, broke her engagement with her previous fiancé, Jeremy, and why she has not been in touch with her family and friends. Her parents insist on taking her home with them and Paige agrees, thinking she might have married Leo for some mutual benefit. She seeks evidence of the marriage. Just as she is about to leave, Leo comes running to play her a voice message in which she sounds very happy and romantic. Paige decides to go back with Leo, hoping it will help her regain her lost memory. Paige is welcomed home with a surprise party by her friends, but as she is not able to remember any of them, she finds it overwhelming and is extremely confused.


title: The Vow (2012 film)

text: The next day Paige ventures out to her regular café, but does not remember having been there and loses her way back. She calls her mother because she does not know or remember Leo's number. That evening Leo and Paige are invited for dinner by her parents. At the dinner and in the bar later, Leo does not fit in with her family and friends. He persists in his attempts to help her regain her lost memory, but Paige is more driven to learn why she left law school and broke her engagement to Jeremy. During the course of one encounter with Jeremy, she kisses him. Her doctor advises her to fill the holes in her memory rather than be afraid of her past. With her sister Gwen's wedding approaching, Paige decides to stay with her parents until the wedding. Though Leo asks her out on a date and spends a night with her, the relationship is further strained when Paige's dad attempts to persuade Leo to divorce his daughter, and by Leo punching Jeremy for talking about chances to bed his wife.


title: The Vow (2012 film)

text: Paige rejoins law school and Leo signs divorce papers. At a store, she meets her old friend Diane who, unaware of her amnesia, apologizes for having had a relationship with Paige's dad, thus alerting Paige as to why she had left her family. When she confronts her mother about this, Rita tells her that she decided to stay with Bill for all the things he had done right instead of leaving him for one wrong act. Paige then asks Leo why he never told her, and he replies he wanted to earn her love instead of driving her away from her parents. Paige, while in class, starts sketching; thus depicting why she first left law school. Despite her father's misgivings about quitting law school, she reassures him that she will always be his daughter no matter what. She continues her interest in art, eventually returning to sculpting and drawing. Though Jeremy confesses he broke up with his present girlfriend, hoping to be back with her, she turns him down stating she needs to know what life would be like without him.


title: The Vow (2012 film)

text: As seasons change, Leo discusses his philosophy about "Moments of impact". "A moment of impact whose potential for change has ripple effects far beyond what we can predict. Sending some particles crashing together, making them closer than before. While sending others, spinning off into great adventures, landing where you never thought you'd find them". Back in her room, Paige finds the menu card on which she had written her wedding vows and is deeply moved. The movie ends with Paige finding Leo at their regular Café Mnemonic and suggesting they go to their backup Cuban restaurant that she knew of because she had been asking her friend about the relationship. Leo then suggests to trying out a new place that they've never been to, which Paige agrees to and film ends as they walk away from the scene.


title: The Vow (2012 film)

text: Rachel McAdams and Channing Tatum's casting was announced by "Variety" in June 2010. Filming took place from August until November 2010 in Toronto and Chicago.


title: The Vow (2012 film)

text: "The Vow" is loosely based on the actual relationship of Kim and Krickitt Carpenter, who wrote a book about their marriage, also known as "The Vow". Ten weeks after their wedding on September 18, 1993, the couple was involved in a serious car accident. Krickitt suffered a brain trauma, which erased all memories of her romance with Kim as well as their marriage. Kim was still deeply in love with his wife, although she viewed him as a stranger after the accident. In 2018, however, he admitted to having an affair and they divorced.


title: The Vow (2012 film)

text: The film was developed as early as 1998, when Spyglass Entertainment was first set up. Stephen Herek was attached to direct at first.


title: The Vow (2012 film)

text: The soundtrack was released on February 7, 2012, through Rhino Records. The film score, written and composed by Rachel Portman and Michael Brook, was released digitally on a separate album on February 7, 2012, through Madison Gate Records.


title: The Vow (2012 film)

text: Review aggregation website Rotten Tomatoes gives the film an approval rating of 31% based on 134 reviews and an average rating of 4.95/10. The site's consensus reads, "Channing Tatum and Rachel McAdams do their best with what they're given, but "The Vow" is too shallow and familiar to satisfy the discriminating date-night filmgoer." On Metacritic, which assigns a weighted mean rating to reviews, the film received an average score of 43 out of 100 based on 28 critics, which indicates "mixed or average reviews".


title: The Vow (2012 film)

text: Emma Dibdin from "Total Film" gave the film a three stars rating out of five, commenting, "there's an essential sweetness at work here, thanks partly to McAdams and partly to an unusually chaste love story that ultimately keeps melodrama at bay." "Empire" critic Helen O'Hara gave the film a three stars rating out of five, also. She found McAdams "excellent" and Tatum "surprisingly heartbreaking" and concluded, "The few weaknesses in the plot can be overlooked as "The Vow" makes for a wonderful – if a bit teary – romance that is brilliantly acted." "The Washington Post"s Stephanie Merry wrote, "It's a shame things are so black and white, because the movie has more promise – and more laughs – than trailers suggest". She added "Tatum, while a bit deficient in the dramatic acting department, delivers some memorable quips. He and McAdams also have chemistry."


title: The Vow (2012 film)

text: Giving the film a 2.5 stars out of 4, Roger Ebert from the "Chicago Sun-Times" found it "pleasant enough as a date movie, but that's all." "USA Today" wrote, "It may appeal to the most rabid fans of tearjerk romances like "The Notebook", but it's a hard-to-swallow, maudlin tale." Betsy Sharkey, film critic from the "Los Angeles Times" wrote, "Despite the sweet story, this is a movie that leaves you wanting more. To care more, to cry more, to love more." ReelViews' James Berardinelli was very negative about the film. He wrote, "with its would-be crowd-pleasing contrivances and rote adherence to formula, [this film] offers almost no redeeming characteristics. [...] This is for young women what "Transformers" is for young men. He concluded describing the film as a "heartless, soulless product".


title: The Vow (2012 film)

text: "The Vow" debuted at #1 in its opening weekend, with $15.4 million on opening day and $41.2 million over the weekend. On the Valentine's Day the film grossed $11.6 million, breaking "Hitch"s record $7.5 million for the highest-grossing mid-week Valentine's Day. It also earned around $9.7 million internationally that weekend.


title: The Vow (2012 film)

text: On the weekend lasting from February 24–26, "The Vow" became the first film of 2012 in North America to cross the $100 million mark, and the third film to cross the $100 million mark worldwide behind "" and "". The film grossed $125 million in North America and $71.1 million in other countries for a worldwide total of $196.1 million. It is the eighth highest-grossing romantic drama film since 1980. Documents from the Sony Pictures hack revealed the film turned a profit of $52 million.


title: Foyle's War

text: Foyle's War is a British detective drama television series set during and shortly after the Second World War, created by "Midsomer Murders" screenwriter and author Anthony Horowitz and commissioned by ITV after the long-running series "Inspector Morse" ended in 2000. It began broadcasting on ITV in October 2002. ITV director of programmes Simon Shaps cancelled "Foyle's War" in 2007, but Peter Fincham (Shaps' replacement) revived the programme after good ratings for 2008's fifth series. The final episode was broadcast on 18 January 2015, after eight series.


title: Foyle's War

text: Detective Chief Superintendent Christopher Foyle (Michael Kitchen), a widower, is quiet, methodical, sagacious, scrupulously honest and frequently underestimated by his foes. Many of his cases concern profiteering, the black market and murder, and he is often called on to catch criminals who are taking advantage of the confusion created by the war. Although Foyle often comes up against high-ranking officials in the British military or intelligence services who would prefer that he mind his own business, he seeks justice tenaciously. Throughout the series, he is assisted by his driver, Samantha "Sam" Stewart (Honeysuckle Weeks), and Detective Sergeant Paul Milner (Anthony Howell).