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Question: What are the three synthetic types of vitamin K?

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Context 1: Vitamin K - Wikipedia
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This article needs more medical references for verification or relies too heavily on primary sources  Please review the contents of the article and add the appropriate references if you can  Unsourced or poorly sourced material may be challenged and removed  (November 2015)
This article is about the family of vitamers  For vitamin K1 the form usually used as a supplement, see Phytomenadione 
Vitamin K structures  MK-4 and MK-7 are both subtypes of K2 
Vitamin K deficiency, Warfarin overdose
Vitamin K is a group of structurally similar, fat-soluble vitamins the human body requires for complete synthesis of certain proteins that are prerequisites for blood coagulation and which the body also needs for controlling binding of calcium in bones and other tissues  The vitamin K-related modification of the proteins allows them to bind calcium ions, which they cannot do otherwise  Without vitamin K, blood coagulation is seriously impaired, and uncontrolled bleeding occurs  Low levels of vitamin K also weaken bones and promote calcification of arteries and other soft tissues[citation needed] 
Chemically, the vitamin K family comprises 2-methyl-1,4-naphthoquinone (3-) derivatives  Vitamin K includes two natural vitamers: vitamin K1 and vitamin K2 [1] Vitamin K2, in turn, consists of a number of related chemical subtypes, with differing lengths of carbon side chains made of isoprenoid groups of atoms 
Vitamin K1, also known as phylloquinone, is made by plants, and is found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis  It may be thought of as the plant form of vitamin K  It is active as a vitamin in animals and performs the classic functions of vitamin K, including its activity in the production of blood-clotting proteins  Animals may also convert it to vitamin K2 
Bacteria in the gut flora can also convert K1 into vitamin K2  In addition, bacteria typically lengthen the isoprenoid side chain of vitamin K2 to produce a range of vitamin K2 forms, most notably the MK-7 to MK-11 homologues of vitamin K2  All forms of K2 other than MK-4 can only be produced by bacteria, which use these forms in anaerobic respiration  The MK-7 and other bacterially derived forms of vitamin K2 exhibit vitamin K activity in animals, but MK-7's extra utility over MK-4, if any, is unclear and is a matter of investigation 
Three synthetic types of vitamin K are known: vitamins K3, K4, and K5  Although the natural K1 and all K2 homologues and synthetic K4 and K5 have proven nontoxic, the synthetic form K3 (menadione) has shown toxicity [2]
1 2 Cardiovascular health
1 4 Coumarin poisoning
4 1 Conversion of vitamin K1 to vitamin K2
4 2 Vitamin K2
6 Absorption and dietary need
7 Dietary reference intake
10 Biochemistry
10 1 Function in animals
10 2 Gamma-carboxyglutamate proteins
10 3 Methods of assessment
10 4 Function in bacteria
11 Injection in newborns
11 3 Controversy
A review of 2014 concluded that there is positive evidence that monotherapy using MK-4, one of the forms of Vitamin K2, reduces fracture incidence in post-menopausal women with osteoporosis, and suggested further research on the combined use of MK-4 with bisphosphonates  In contrast, an earlier review article of 2013 concluded that there is no good evidence that vitamin K supplementation helps prevent osteoporosis or fractures in postmenopausal women [3]
A Cochrane systematic review of 2006 suggested that supplementation with Vitamin K1 and with MK4 reduces bone loss; in particular, a strong effect of MK-4 on incident fractures among Japanese patients was emphasized [4]
A review article of 2016 suggested to consider, as one of several measures for bone health, increasing the intake of foods rich in vitamins K1 and K2 [5]
Cardiovascular health[edit]
Adequate intake of vitamin K is associated with the inhibition of arterial calcification and stiffening,[6] but there have been few interventional studies and no good evidence that vitamin K supplementation is of any benefit in the primary prevention of cardiovascular disease [7]
One 10-year population study, the Rotterdam Study, did show a clear and significant inverse relationship between the highest intake levels of menaquinone (mainly MK-4 from eggs and meat, and MK-8 and MK-9 from cheese) and cardiovascular disease and all-cause mortality in older men and women [8]
Vitamin K has been promoted in supplement form with claims it can slow tumor growth; there is however no good medical evidence that supports such claims [9]
Coumarin poisoning[edit]
Vitamin K is part of the suggested treatment regime for poisoning by rodenticide (coumarin poisoning) [10]
Although allergic reaction from supplementation is possible, no known toxicity is associated with high doses of the phylloquinone (vitamin K1) or menaquinone (vitamin K2) forms of vitamin K, so no tolerable upper intake level (UL) has been set [11]
Blood clotting (coagulation) studies in humans using 45 mg per day of vitamin K2 (as MK-4)[12] and even up to 135 mg per day (45 mg three times daily) of K2 (as MK-4),[13] showed no increase in blood clot risk  Even doses in rats as high as 250 mg/kg, body weight did not alter the tendency for blood-clot formation to occur [14]
Unlike the safe natural forms of vitamin K1 and vitamin K2 and their various isomers, a synthetic form of vitamin K, vitamin K3 (menadione), is demonstrably toxic at high levels  The U S  FDA has banned this form from over-the-counter sale in the United States because large doses have been shown to cause allergic reactions, hemolytic anemia, and cytotoxicity in liver cells [2]
Phylloquinone (K1)[15][16] or menaquinone (K2) are capable of reversing the anticoagulant activity of the anticoagulant warfarin (tradename Coumadin)  Warfarin works by blocking recycling of vitamin K, so that the body and tissues have lower levels of active vitamin K, and thus a deficiency of vitamin K 
Supplemental vitamin K (for which oral dosing is often more active than injectable dosing in human adults) reverses the vitamin K deficiency caused by warfarin, and therefore reduces the intended anticoagulant action of warfarin and related drugs [17] Sometimes small amounts of vitamin K are given orally to patients taking warfarin so that the action of the drug is more predictable [17] The proper anticoagulant action of the drug is a function of vitamin K intake and drug dose, and due to differing absorption must be individualized for each patient [citation needed] The action of warfarin and vitamin K both require two to five days after dosing to have maximum effect, and neither warfarin or vitamin K shows much effect in the first 24 hours after they are given [18]
The newer anticoagulants dabigatran and rivaroxaban have different mechanisms of action that do not interact with vitamin K, and may be taken with supplemental vitamin K [19][20]
Vitamin K2 (menaquinone)  In menaquinone, the side chain is composed of a varying number of isoprenoid residues  The most common number of these residues is four, since animal enzymes normally produce menaquinone-4 from plant phylloquinone 
A sample of phytomenadione for injection, also called phylloquinone
The three synthetic forms of vitamin K are vitamins K3 (menadione), K4, and K5, which are used in many areas, including the pet food industry (vitamin K3) and to inhibit fungal growth (vitamin K5) [21]
Conversion of vitamin K1 to vitamin K2[edit]
Vitamin K1 (phylloquinone) – both forms of the vitamin contain a functional naphthoquinone ring and an aliphatic side chain  Phylloquinone has a phytyl side chain 
The MK-4 form of vitamin K2 is produced by conversion of vitamin K1 in the testes, pancreas, and arterial walls [22] While major questions still surround the biochemical pathway for this transformation, the conversion is not dependent on gut bacteria, as it occurs in germ-free rats[23][24] and in parenterally-administered K1 in rats [25][26] In fact, tissues that accumulate high amounts of MK-4 have a remarkable capacity to convert up to 90% of the available K1 into MK-4 [27][28] There is evidence that the conversion proceeds by removal of the phytyl tail of K1 to produce menadione as an intermediate, which is then condensed with an activated geranylgeranyl moiety (see also prenylation) to produce vitamin K2 in the MK-4 (menatetrione) form [29]
Vitamin K2[edit]
Main article: Vitamin K2
Vitamin K2 (menaquinone) includes several subtypes  The two subtypes most studied are menaquinone-4 (menatetrenone, MK-4) and menaquinone-7 (MK-7) 
Vitamin K1, the precursor of most vitamin K in nature, is a stereoisomer of phylloquinone, an important chemical in green plants, where it functions as an electron acceptor in photosystem I during photosynthesis  For this reason, vitamin K1 is found in large quantities in the photosynthetic tissues of plants (green leaves, and dark green leafy vegetables such as romaine lettuce, kale and spinach), but it occurs in far smaller quantities in other plant tissues (roots, fruits, etc )  Iceberg lettuce contains relatively little  The function of phylloquinone in plants appears to have no resemblance to its later metabolic and biochemical function (as "vitamin K") in animals, where it performs a completely different biochemical reaction 
Vitamin K (in animals) is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate (Gla) residues  The modified residues are often (but not always) situated within specific protein domains called Gla domains  Gla residues are usually involved in binding calcium, and are essential for the biological activity of all known Gla proteins [30]
At this time[update], 17 human proteins with Gla domains have been discovered, and they play key roles in the regulation of three physiological processes:
Blood coagulation: prothrombin (factor II), factors VII, IX, and X, and proteins C, S, and Z[31]
Bone metabolism: osteocalcin, also called bone Gla protein (BGP), matrix Gla protein (MGP),[32] periostin,[33] and the recently discovered Gla-rich protein (GRP) [34][35]
Vascular biology: growth arrest-specific protein 6 (Gas6)[36]
Unknown function: proline-rich γ-carboxyglutamyl proteins (PRGPs) 1 and 2, and transmembrane γ-carboxy glutamyl proteins (TMGs) 3 and 4 [37]
Like other lipid-soluble vitamins (A, D and E), vitamin K is stored in the fatty tissue of the human body 
Absorption and dietary need[edit]
Previous theory held that dietary deficiency is extremely rare unless the small intestine was heavily damaged, resulting in malabsorption of the molecule  Another at-risk group for deficiency were those subject to decreased production of K2 by normal intestinal microbiota, as seen in broad spectrum antibiotic use [38] Taking broad-spectrum antibiotics can reduce vitamin K production in the gut by nearly 74% in people compared with those not taking these antibiotics [39] Diets low in vitamin K also decrease the body's vitamin K concentration [40] Those with chronic kidney disease are at risk for vitamin K deficiency, as well as vitamin D deficiency, and particularly those with the apoE4 genotype [41] Additionally, in the elderly there is a reduction in vitamin K2 production [42]
The National Academy of Medicine (NAM) updated an estimate of what constitutes an adequate intake (AI) for vitamin K in 2001  The NAM does not distinguish between K1 and K2 – both are counted as vitamin K  At that time there was not sufficient evidence to set the more rigorous estimated average requirement (EAR) or recommended dietary allowance (RDA) given for most of the essential vitamins and minerals  The current daily AIs for vitamin K for adult women and men are 90 μg and 120 μg respectively  The AI for pregnancy and lactation is 90 μg  For infants up to 12 months the AI is 2–2 5 μg, and for children aged 1 to 18 years the AI increases with age from 30 to 75 μg  As for safety, the FNB also sets tolerable upper intake levels (known as ULs) for vitamins and minerals when evidence is sufficient  In the case of vitamin K no UL is set, as evidence for adverse effects is not sufficient  Collectively EARs, RDAs, AIs and ULs are referred to as dietary reference intakes [43] The European Food Safety Authority reviewed the same safety question and did not set an UL [44]
For U S  food and dietary supplement labeling purposes, the amount in a serving is expressed as a percentage of daily value (%DV)  For vitamin K labeling purposes the daily value was 80 μg, but as of May 2016 it has been revised upwards to 120 μg  A table of the pre-change adult daily values is provided at reference daily intake  Food and supplement companies have until 28 July 2018 to comply with the change 
See also: Vitamin K2 § Dietary sources
K1 (μg)[45]
Kale, cooked
Collards, cooked
Collards, raw
Swiss chard, cooked
Swiss chard, raw
Turnip greens, raw
Romaine lettuce, raw
Table from "Important information to know when you are taking: Warfarin (Coumadin) and Vitamin K", Clinical Center, National Institutes of Health Drug Nutrient Interaction Task Force [46]
Vitamin K1 is found chiefly in leafy green vegetables such as dandelion greens (which contain 778 4 μg per 100 g, or 741% of the recommended daily amount), spinach, swiss chard, lettuce and Brassica vegetables (such as cabbage, kale, cauliflower, broccoli, and brussels sprouts) and often the absorption is greater when accompanied by fats such as butter or oils; some fruits, such as avocados, kiwifruit and grapes, are also high in vitamin K  By way of reference, two tablespoons of parsley contains 153% of the recommended daily amount of vitamin K [47] Some vegetable oils, notably soybean oil, contain vitamin K, but at levels that would require relatively large calorie consumption to meet the USDA-recommended levels [48] colonic bacteria synthesize a significant portion of humans' vitamin K needs; newborns often receive a vitamin K shot at birth to tide them over until their colons become colonized at five to seven days of age from the consumption of breast milk 
The tight binding of vitamin K1 to thylakoid membranes in chloroplasts makes it less bioavailable  For example, cooked spinach has a 5% bioavailability of phylloquinone, however, fat added to it increases bioavailability to 13% due to the increased solubility of vitamin K in fat [49]
Main article: Vitamin K deficiency
Average diets are usually not lacking in vitamin K, and primary deficiency is rare in healthy adults  Newborn infants are at an increased risk of deficiency  Other populations with an increased prevalence of vitamin K deficiency include those who suffer from liver damage or disease (e g  alcoholics), cystic fibrosis, or inflammatory bowel diseases, or have recently had abdominal surgeries  Secondary vitamin K deficiency can occur in people with bulimia, those on stringent diets, and those taking anticoagulants  Other drugs associated with vitamin K deficiency include salicylates, barbiturates, and cefamandole, although the mechanisms are still unknown  Vitamin K1 deficiency can result in coagulopathy, a bleeding disorder [50]Symptoms of K1 deficiency include anemia, bruising, nosebleeds and bleeding of the gums in both sexes, and heavy menstrual bleeding in women 
Osteoporosis[51][52] and coronary heart disease[53][54] are strongly associated with lower levels of K2 (menaquinone)  Vitamin K2 (as menaquinones MK-4 through MK-10) intake level is inversely related to severe aortic calcification and all-cause mortality [8]
Function in animals[edit]
Mechanism of action of vitamin K1 
The function of vitamin K2 in the animal cell is to add a carboxylic acid functional group to a glutamate (Glu) amino acid residue in a protein, to form a gamma-carboxyglutamate (Gla) residue  This is a somewhat uncommon posttranslational modification of the protein, which is then known as a "Gla protein"  The presence of two −COOH (carboxylic acid) groups on the same carbon in the gamma-carboxyglutamate residue allows it to chelate calcium ions  The binding of calcium ions in this way very often triggers the function or binding of Gla-protein enzymes, such as the so-called vitamin K-dependent clotting factors discussed below 
Within the cell, vitamin K undergoes electron reduction to a reduced form called vitamin K hydroquinone, catalyzed by the enzyme vitamin K epoxide reductase (VKOR) [55] Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of Glu to Gla; this enzyme is called gamma-glutamyl carboxylase[56][57] or the vitamin K-dependent carboxylase  The carboxylation reaction only proceeds if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time  The carboxylation and epoxidation reactions are said to be coupled  Vitamin K epoxide is then reconverted to vitamin K by VKOR  The reduction and subsequent reoxidation of vitamin K coupled with carboxylation of Glu is called the vitamin K cycle [58] Humans are rarely deficient in vitamin K1 because, in part, vitamin K1 is continuously recycled in cells [59]
Warfarin and other 4-hydroxycoumarins block the action of VKOR [60] This results in decreased concentrations of vitamin K and vitamin K hydroquinone in tissues, such that the carboxylation reaction catalyzed by the glutamyl carboxylase is inefficient  This results in the production of clotting factors with inadequate Gla  Without Gla on the amino termini of these factors, they no longer bind stably to the blood vessel endothelium and cannot activate clotting to allow formation of a clot during tissue injury  As it is impossible to predict what dose of warfarin will give the desired degree of clotting suppression, warfarin treatment must be carefully monitored to avoid overdose 
Gamma-carboxyglutamate proteins[edit]
Main article: Gla domain
The following human Gla-containing proteins ("Gla proteins") have been characterized to the level of primary structure: blood coagulation factors II (prothrombin), VII, IX, and X, anticoagulant proteins C and S, and the factor X-targeting protein Z  The bone Gla protein osteocalcin, the calcification-inhibiting matrix Gla protein (MGP), the cell growth regulating growth arrest specific gene 6 protein (Gas6), and the four transmembrane Gla proteins (TMGPs), the function of which is at present unknown  Gas6 can function as a growth factor to activate the Axl receptor tyrosine kinase and stimulate cell proliferation or prevent apoptosis in some cells  In all cases in which their function was known, the presence of the Gla residues in these proteins turned out to be essential for functional activity 
Gla proteins are known to occur in a wide variety of vertebrates: mammals, birds, reptiles, and fish  The venom of a number of Australian snakes acts by activating the human blood-clotting system  In some cases, activation is accomplished by snake Gla-containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones, leading to unwanted and potentially deadly clotting 
Another interesting class of invertebrate Gla-containing proteins is synthesized by the fish-hunting snail Conus geographus [61] These snails produce a venom containing hundreds of neuroactive peptides, or conotoxins, which is sufficiently toxic to kill an adult human  Several of the conotoxins contain two to five Gla residues [62]
Methods of assessment[edit]
Vitamin K status can be assessed by:
The prothrombin time (PT) test measures the time required for blood to clot  A blood sample is mixed with citric acid and put in a fibrometer; delayed clot formation indicates a deficiency  This test is insensitive to mild deficiency, as the values do not change until the concentration of prothrombin in the blood has declined by at least 50% [63]
Undercarboxylated prothrombin (PIVKA-II); in a study of 53 newborns, found "PT (prothrombin time) is a less sensitive marker than PIVKA II",[64] and as indicated above, PT is unable to detect subclinical deficiencies that can be detected with PIVKA-II testing 
Plasma phylloquinone was found to be positively correlated with phylloquinone intake in elderly British women, but not men,[65] but an article by Schurgers et al  reported no correlation between FFQ[further explanation needed] and plasma phylloquinone [66]
Urinary γ-carboxyglutamic acid responds to changes in dietary vitamin K intake  Several days are required before any change can be observed  In a study by Booth et al , increases of phylloquinone intakes from 100 μg to between 377 and 417 μg for five days did not induce a significant change  Response may be age-specific [67]
Undercarboxylated osteocalcin (UcOc) levels have been inversely correlated with stores of vitamin K[68] and bone strength in developing rat tibiae  Another study following 78 post-menopausal Korean women found a supplement regimen of vitamins K and D, and calcium, but not a regimen of vitamin D and calcium, was inversely correlated with reduced UcOc levels [69]
Function in bacteria[edit]
Many bacteria, such as Escherichia coli found in the large intestine, can synthesize vitamin K2 (menaquinone-7 or MK-7, up to MK-11),[70] but not vitamin K1 (phylloquinone)  In these bacteria, menaquinone transfers two electrons between two different small molecules, during oxygen-independent metabolic energy production processes (anaerobic respiration) [71] For example, a small molecule with an excess of electrons (also called an electron donor) such as lactate, formate, or NADH, with the help of an enzyme, passes two electrons to menaquinone  The menaquinone, with the help of another enzyme, then transfers these two electrons to a suitable oxidant, such fumarate or nitrate (also called an electron acceptor)  Adding two electrons to fumarate or nitrate converts the molecule to succinate or nitrite plus water, respectively 
Some of these reactions generate a cellular energy source, ATP, in a manner similar to eukaryotic cell aerobic respiration, except the final electron acceptor is not molecular oxygen, but fumarate or nitrate  In aerobic respiration, the final oxidant is molecular oxygen (O2), which accepts four electrons from an electron donor such as NADH to be converted to water  E  coli, as facultative anaerobes, can carry out both aerobic respiration and menaquinone-mediated anaerobic respiration 
Injection in newborns[edit]
The blood clotting factors of newborn babies are roughly 30–60% that of adult values; this may be due to the reduced synthesis of precursor proteins and the sterility of their guts  Human milk contains 1–4 μg/L of vitamin K1, while formula-derived milk can contain up to 100 μg/L in supplemented formulas  Vitamin K2 concentrations in human milk appear to be much lower than those of vitamin K1  Occurrence of vitamin K deficiency bleeding in the first week of the infant's life is estimated at 0 25–1 7%, with a prevalence of 2–10 cases per 100,000 births [72] Premature babies have even lower levels of the vitamin, so they are at a higher risk from this deficiency 
Bleeding in infants due to vitamin K deficiency can be severe, leading to hospitalization, blood transfusions, brain damage, and death  Supplementation can prevent most cases of vitamin K deficiency bleeding in the newborn  Intramuscular administration is more effective in preventing late vitamin K deficiency bleeding than oral administration [73][74]
As a result of the occurrences of vitamin K deficiency bleeding, the Committee on Nutrition of the American Academy of Pediatrics has recommended 0 5–1 mg of vitamin K1 be administered to all newborns shortly after birth [74]
In the UK vitamin K supplementation is recommended for all newborns within the first 24 hours [75] This is usually given as a single intramuscular injection of 1 mg shortly after birth but as a second-line option can be given by three oral doses over the first month [76]
Controversy arose in the early 1990s regarding this practice, when two studies suggested a relationship between parenteral administration of vitamin K and childhood cancer,[77] however, poor methods and small sample sizes led to the discrediting of these studies, and a review of the evidence published in 2000 by Ross and Davies found no link between the two [78] Doctors reported emerging concerns in 2013,[79] after treating children for serious bleeding problems  They cited lack-of newborn vitamin K administration, as the reason that the problems occurred, and recommended that breastfed babies could have an increased risk unless they receive a preventative dose 
In the early 1930s, Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol-depleted diet [80] He initially replicated experiments reported by scientists at the Ontario Agricultural College (OAC) [81] McFarlane, Graham and Richardson, working on the chick feed program at OAC, had used chloroform to remove all fat from chick chow  They noticed that chicks fed only fat-depleted chow developed hemorrhages and started bleeding from tag sites [82] Dam found that these defects could not be restored by adding purified cholesterol to the diet  It appeared that – together with the cholesterol – a second compound had been extracted from the food, and this compound was called the coagulation vitamin  The new vitamin received the letter K because the initial discoveries were reported in a German journal, in which it was designated as Koagulationsvitamin  Edward Adelbert Doisy of Saint Louis University did much of the research that led to the discovery of the structure and chemical nature of vitamin K [83] Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on vitamin K (K1 and K2) published in 1939  Several laboratories synthesized the compound(s) in 1939 [84]
For several decades, the vitamin K-deficient chick model was the only method of quantifying vitamin K in various foods: the chicks were made vitamin K-deficient and subsequently fed with known amounts of vitamin K-containing food  The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content  Three groups of physicians independently found this: Biochemical Institute, University of Copenhagen (Dam and Johannes Glavind), University of Iowa Department of Pathology (Emory Warner, Kenneth Brinkhous, and Harry Pratt Smith), and the Mayo Clinic (Hugh Butt, Albert Snell, and Arnold Osterberg) [85]
The first published report of successful treatment with vitamin K of life-threatening hemorrhage in a jaundiced patient with prothrombin deficiency was made in 1938 by Smith, Warner, and Brinkhous [86]
The precise function of vitamin K was not discovered until 1974, when three laboratories (Stenflo et al ,[87] Nelsestuen et al ,[88] and Magnusson et al [89]) isolated the vitamin K-dependent coagulation factor prothrombin (factor II) from cows that received a high dose of a vitamin K antagonist, warfarin  It was shown that, while warfarin-treated cows had a form of prothrombin that contained 10 glutamate (Glu) amino acid residues near the amino terminus of this protein, the normal (untreated) cows contained 10 unusual residues that were chemically identified as γ-carboxyglutamate (Gla)  The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla 
The biochemistry of how vitamin K is used to convert Glu to Gla has been elucidated over the past thirty years in academic laboratories throughout the world 
^ "Vitamin K Overview"  University of Maryland Medical Center  ^ a b Higdon, Jane (Feb 2008)  "Vitamin K"  Linus Pauling Institute, Oregon State University  Retrieved 12 Apr 2008  ^ Hamidi, M  S ; Gajic-Veljanoski, O ; Cheung, A  M  (2013)  "Vitamin K and bone health"  Journal of Clinical Densitometry (Review)  16 (4): 409–413  doi:10 1016/j jocd 2013 08 017  PMID 24090644  ^ Cockayne, S ; Adamson, J ; Lanham-New, S ; Shearer, M  J ; Gilbody, S; Torgerson, D  J  (Jun 2006)  "Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials"  Archives of Internal Medicine (Review)  166 (12): 1256–1261  doi:10 1001/archinte 166 12 1256  PMID 16801507  ^ O'Keefe, J  H ; Bergman, N ; Carrera Bastos, P ; Fontes Villalba, M ; Di Nicolantonio, J  J ; Cordain, L  (2016)  "Nutritional strategies for skeletal and cardiovascular health: hard bones, soft arteries, rather than vice versa"  Open Heart (Review)  3 (1): e000325  doi:10 1136/openhrt-2015-000325  PMC 4809188  PMID 27042317  ^ Maresz, K  (Feb 2015)  "Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health"  Integrative Medicine (Review)  14 (1): 34–39  PMC 4566462  PMID 26770129  ^ Hartley, L ; Clar, C ; Ghannam, O ; Flowers, N ; Stranges, S ; Rees, K  (Sep 2015)  "Vitamin K for the primary prevention of cardiovascular disease"  The Cochrane Database of Systematic Reviews (Systematic review)  9 (9): CD011148  doi:10 1002/14651858 CD011148 pub2  PMID 26389791  ^ a b Geleijnse, J  M ; Vermeer, C ; Grobbee, D  E ; Schurgers, L  J ; Knapen, M  H ; van der Meer, I  M ; Hofman, A ; Witteman, J  C  (Nov 2004)  "Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study"  Journal of Nutrition  134 (11): 3100–3105  PMID 15514282  ^ Ades, T  B , ed  (2009)  "Vitamin K"  American Cancer Society Complete Guide to Complementary and Alternative Cancer Therapies (2nd ed )  American Cancer Society  pp  558–563  ISBN 978-0-944235-71-3  ^ Lung, D  (Dec 2015)  Tarabar, A , ed  "Rodenticide Toxicity Treatment & Management"  Medscape  WebMD  ^ Rasmussen, S  E ; Andersen, N  L ; Dragsted, L  O ; Larsen, J  C  (Mar 2006)  "A safe strategy for addition of vitamins and minerals to foods"  European Journal of Nutrition  45 (3): 123–135  doi:10 1007/s00394-005-0580-9  PMID 16200467  ^ Ushiroyama, T ; Ikeda, A ; Ueki, M (Mar 2002)  "Effect of continuous combined therapy with vitamin K2 and vitamin D3 on bone mineral density and coagulofibrinolysis function in postmenopausal women"  Maturitas  41 (3): 211–221  doi:10 1016/S0378-5122(01)00275-4  PMID 11886767  ^ Asakura, H ; Myou, S ; Ontachi, Y ; Mizutani, T ; Kato, M ; Saito, M ; Morishita, E ; Yamazaki, M ; Nakao, S  (Dec 2001)  "Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency"  Osteoporosis International  12 (12): 996–1000  doi:10 1007/s001980170007  PMID 11846334  ^ Ronden, J  E ; Groenen-van Dooren, M  M ; Hornstra, G ; Vermeer, C  (Jul 1997)  "Modulation of arterial thrombosis tendency in rats by vitamin K and its side chains"  Atherosclerosis  132 (1): 61–67  doi:10 1016/S0021-9150(97)00087-7  PMID 9247360  ^ Ansell, J ; Hirsh, J ; Poller, L ; Bussey, H ; Jacobson, A ; Hylek, E (Sep 2004)  "The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy"  Chest  126 (3 Suppl ): 204S–233S  doi:10 1378/chest 126 3_suppl 204S  PMID 15383473  ^ Crowther, M  A ; Douketis, J  D ; Schnurr, T ; Steidl, L ; Mera, V ; Ultori, C ; Venco, A ; Ageno, W  (Aug 2002)  "Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy  A randomized, controlled trial"  Annals of Internal Medicine  137 (4): 251–254  doi:10 7326/0003-4819-137-4-200208200-00009  PMID 12186515  ^ a b "Important Information to Know When You Are Taking: Warfarin (Coumadin) and Vitamin K" (PDF)  National Institute of Health Clinical Center Drug-Nutrient Interaction Task Force  Retrieved 17 Apr 2015  ^ "Guidelines For Warfarin Reversal With Vitamin K" (PDF)  American Society of Health-System Pharmacists  Retrieved 17 Apr 2015  ^ "Pradaxa Drug Interactions"  Pradaxapro com  19 Mar 2012  Retrieved 21 Apr 2013  ^ Bauersachs, R ; Berkowitz, S  D ; Brenner, B ; Buller, H  R ; Decousus, H ; Gallus, A  S ; Lensing, A  W ; Misselwitz, F ; Prins, M  H ; Raskob, G  E ; Segers, A ; Verhamme, P ; Wells, P ; Agnelli, G ; Bounameaux, H ; Cohen, A ; Davidson, B  L ; Piovella, F ; Schellong, S  (Dec 2010)  "Oral rivaroxaban for symptomatic venous thromboembolism"  New England Journal of Medicine  363 (26): 2499–2510  doi:10 1056/NEJMoa1007903  PMID 21128814  ^ McGee, W  (1 Feb 2007)  "Vitamin K"  MedlinePlus  Retrieved 2 Apr 2009  ^ Shearer, M  J ; Newman, P  (Oct 2008)  "Metabolism and cell biology of vitamin K"  Thrombosis and Haemostasis  100 (4): 530–547  doi:10 1160/TH08-03-0147  PMID 18841274  ^ Davidson, R  T ; Foley, A  L ; Engelke, J  A ; Suttie, J  W  (Feb 1998)  "Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria"  Journal of Nutrition  128 (2): 220–223  PMID 9446847  ^ Ronden, J  E ; Drittij-Reijnders, M  J ; Vermeer, C ; Thijssen, H  H  (Jan 1998)  "Intestinal flora is not an intermediate in the phylloquinone–menaquinone-4 conversion in the rat"  Biochimica et Biophysica Acta  1379 (1): 69–75  doi:10 1016/S0304-4165(97)00089-5  PMID 9468334  ^ Thijssen, H   H ; Drittij-Reijnders, M  J  (Sep 1994)  "Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4"  The British Journal of Nutrition  72 (3): 415–425  doi:10 1079/BJN19940043  PMID 7947656  ^ Will, B  H ; Usui, Y ; Suttie, J  W  (Dec 1992)  "Comparative metabolism and requirement of vitamin K in chicks and rats"  Journal of Nutrition  122 (12): 2354–2360  PMID 1453219  ^ Davidson, R  T ; Foley, A  L ; Engelke, J  A ; Suttie, J  W  (Feb 1998)  "Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria"  Journal of Nutrition  128 (2): 220–223  PMID 9446847  ^ Ronden, J  E ; Drittij-Reijnders, M  J ; Vermeer, C ; Thijssen, H  H  (Jan 1998)  "Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat"  Biochimica et Biophysica Acta  1379 (1): 69–75  doi:10 1016/S0304-4165(97)00089-5  PMID 9468334  ^ Al Rajabi, Ala (2011)  The Enzymatic Conversion of Phylloquinone to Menaquinone-4 (PhD thesis)  Tufts University, Friedman School of Nutrition Science and Policy  ^ Furie, B ; Bouchard, B  A ; Furie, B  C  (Mar 1999)  "Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid"  Blood  93 (6): 1798–1808  PMID 10068650  ^ Mann, K  G  (Aug 1999)  "Biochemistry and physiology of blood coagulation"  Thrombosis and Haemostasis  82 (2): 165–174  PMID 10605701  ^ Price, P  A  (1988)  "Role of vitamin-K-dependent proteins in bone metabolism"  Annual Review of Nutrition  8: 565–583  doi:10 1146/annurev nu 08 070188 003025  PMID 3060178  ^ Coutu, D  L ; Wu, J  H ; Monette, A ; Rivard, G  E ; Blostein, M  D ; Galipeau, J (Jun 2008)  "Periostin, a member of a novel family of vitamin K-dependent proteins, is expressed by mesenchymal stromal cells"  Journal of Biological Chemistry  283 (26): 17991–18001  doi:10 1074/jbc M708029200  PMID 18450759  ^ Viegas, C  S ; Simes, D  C ; Laizé, V ; Williamson, M  K ; Price, P  A ; Cancela, M  L  (Dec 2008)  "Gla-rich protein (GRP), a new vitamin K-dependent protein identified from sturgeon cartilage and highly conserved in vertebrates"  Journal of Biological Chemistry  283 (52): 36655–36664  doi:10 1074/jbc M802761200  PMC 2605998  PMID 18836183  ^ Viegas, C  S ; Cavaco, S ; Neves, P  L ; Ferreira, A ; João, A ; Williamson, M  K ; Price, P  A ; Cancela, M  L ; Simes, D  C  (Dec 2009)  "Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications"  American Journal of Pathology  175 (6): 2288–2298  doi:10 2353/ajpath 2009 090474  PMC 2789615  PMID 19893032  ^ Hafizi, S ; Dahlbäck, B  (Dec 2006)  "Gas6 and protein S  Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily"  The FEBS Journal  273 (23): 5231–5244  doi:10 1111/j 1742-4658 2006 05529 x  PMID 17064312  ^ Kulman, J  D ; Harris, J  E ; Xie, L ; Davie, E  W  (May 2007)  "Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that binds to the transcriptional coactivator Yes-associated protein"  Proceedings of the National Academy of Sciences of the United States of America  104 (21): 8767–8772  doi:10 1073/pnas 0703195104  PMC 1885577  PMID 17502622  ^ "Vitamin K"  MedlinePlus  US National Library of Medicine, National Institutes of Health  Sep 2016  Retrieved 26 May 2009  ^ Conly, J; Stein, K  (Dec 1994)  "Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials"  Clinical and Investigative Medicine  17 (6): 531–539  PMID 7895417  ^ Ferland, G ; Sadowski, J  A ; O'Brien, M  E  (Apr 1993)  "Dietary induced subclinical vitamin K deficiency in normal human subjects"  Journal of Clinical Investigation  91 (4): 1761–1768  doi:10 1172/JCI116386  PMC 288156  PMID 8473516  ^ Holden, R  M ; Morton, A  R ; Garland, J  S ; Pavlov, A ; Day, A  G ; Booth, S  L  (Apr 2010)  "Vitamins K and D status in stages 3-5 chronic kidney disease"  Clinical Journal of the American Society of Nephrology  5 (4): 590–597  doi:10 2215/CJN 06420909  PMC 2849681  PMID 20167683  ^ Hodges, S  J ; Pilkington, M  J ; Shearer, M  J ; Bitensky, L ; Chayen, J (Jan 1990)  "Age-related changes in the circulating levels of congeners of vitamin K2, menaquinone-7 and menaquinone-8"  Clinical Science  78 (1): 63–66  PMID 2153497  ^ "Vitamin K"  Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (PDF)  National Academy Press  2001  p  162–196  ^ Tolerable Upper Intake Levels For Vitamins And Minerals (PDF), European Food Safety Authority, 2006 ^ a b Rhéaume-Bleue, p  42
^ "Important information to know when you are taking: Warfarin (Coumadin) and Vitamin K" (PDF)  National Institutes of Health Clinical Center  ^ "Nutrition Facts and Information for Parsley, raw"  Nutritiondata com  Retrieved 21 Apr 2013  ^ "Nutrition facts, calories in food, labels, nutritional information and analysis"  Nutritiondata com  13 Feb 2008  Retrieved 21 Apr 2013  ^ "Vitamin K"  Vivo colostate edu  2 Jul 1999  Retrieved 21 Apr 2013  ^ "Vitamin K"  Micronutrient Data Centre  ^ Ikeda, Y ; Iki, M ; Morita, A ; Kajita, E ; Kagamimori, S ; Kagawa, Y ; Yoneshima, H  (May 2006)  "Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study"  Journal of Nutrition  136 (5): 1323–1328  PMID 16614424  ^ Katsuyama, H ; Ideguchi, S ; Fukunaga, M ; Saijoh, K ; Sunami, S  (Jun 2002)  "Usual dietary intake of fermented soybeans (Natto) is associated with bone mineral density in premenopausal women"  Journal of Nutritional Science and Vitaminology  48 (3): 207–215  doi:10 3177/jnsv 48 207  PMID 12350079  ^ Sano, M ; Fujita, H ; Morita, I ; Uematsu, H ; Murota, S  (Dec 1999)  "Vitamin K2 (menatetrenone) induces iNOS in bovine vascular smooth muscle cells: no relationship between nitric oxide production and gamma-carboxylation"  Journal of Nutritional Science and Vitaminology  45 (6): 711–723  doi:10 3177/jnsv 45 711  PMID 10737225  ^ Gast, G  C ; de Roos, N  M ; Sluijs, I ; Bots, M  L ; Beulens, J  W ; Geleijnse, J  M ; Witteman, J  C ; Grobbee, D  E ; Peeters, P  H ; van der Schouw, Y  T  (Sep 2009)  "A high menaquinone intake reduces the incidence of coronary heart disease"  Nutrition, Metabolism, and Cardiovascular Diseases  19 (7): 504–510  doi:10 1016/j numecd 2008 10 004  PMID 19179058  ^ Oldenburg, J ; Bevans, C  G ; Müller, C  R ; Watzka, M  (2006)  "Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle"  Antioxidants & Redox Signaling  8 (3–4): 347–353  doi:10 1089/ars 2006 8 347  PMID 16677080  ^ Suttie, J  W  (1985)  "Vitamin K-dependent carboxylase"  Annual Review of Biochemistry  54: 459–477  doi:10 1146/annurev bi 54 070185 002331  PMID 3896125  ^ Presnell, S  R ; Stafford, D  W  (Jun 2002)  "The vitamin K-dependent carboxylase"  Thrombosis and Haemostasis  87 (6): 937–946  PMID 12083499  ^ Stafford, D  W  (Aug 2005)  "The vitamin K cycle"  Journal of Thrombosis and Haemostasis  3 (8): 1873–1878  doi:10 1111/j 1538-7836 2005 01419 x  PMID 16102054  ^ Rhéaume-Bleue, p  79 
^ Whitlon, D  S ; Sadowski, J  A ; Suttie, J  W  (Apr 1978)  "Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition"  Biochemistry  17 (8): 1371–1377  doi:10 1021/bi00601a003  PMID 646989  ^ Terlau, H ; Olivera, B  M  (Jan 2004)  "Conus venoms: a rich source of novel ion channel-targeted peptides"  Physiological Reviews  84 (1): 41–68  doi:10 1152/physrev 00020 2003  PMID 14715910  ^ Buczek, O ; Bulaj, G ; Olivera, BM (Dec 2005)  "Conotoxins and the posttranslational modification of secreted gene products"  Cellular and Molecular Life Sciences  62 (24): 3067–3079  doi:10 1007/s00018-005-5283-0  PMID 16314929  ^ "Prothrombin Time"  WebMD  ^ Dituri, F ; Buonocore, G ; Pietravalle, A ; Naddeo, F ; Cortesi, M; Pasqualetti, P; Tataranno M  L ; R , Agostino (Sep 2012)  "PIVKA-II plasma levels as markers of subclinical vitamin K deficiency in term infants"  Journal of Maternal, Fetal & Neonatal Medicine  25 (9): 1660–1663  doi:10 3109/14767058 2012 657273  PMID 22280352  ^ Thane, C  W ; Bates, C  J ; Shearer, M  J ; Unadkat, N; Harrington, D  J ; Paul, A  A ; Prentice, A ; Bolton-Smith, C  (Jun 2002)  "Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in a national sample of British elderly people"  British Journal of Nutrition  87 (6): 615–622  doi:10 1079/BJNBJN2002582  PMID 12067432  ^ McKeown, N  M ; Jacques, P  F ; Gundberg, C  M ; Peterson, J  W ; Tucker, K  L ; Kiel, D  P ; Wilson, P  W ; Booth, SL (Jun 2002)  "Dietary and nondietary determinants of vitamin K biochemical measures in men and women" (PDF)  Journal of Nutrition  132 (6): 1329–1334  PMID 12042454  ^ Yamano, M ; Yamanaka, Y ; Yasunaga, K ; Uchida, K  (Sep 1989)  "Effect of vitamin K deficiency on urinary gamma-carboxyglutamic acid excretion in rats"  Nihon Ketsueki Gakkai Zasshi  52 (6): 1078–1086  PMID 2588957  ^ Matsumoto, T ; Miyakawa, T ; Yamamoto, D  (Mar 2012)  "Effects of vitamin K on the morphometric and material properties of bone in the tibiae of growing rats"  Metabolism  61 (3): 407–414  doi:10 1016/j metabol 2011 07 018  PMID 21944271  ^ Je, S -H ; Joo, N -S ; Choi, B -H ; Kim, K -M ; Kim, B -T ; Park, S -B ; Cho, D -Y ; Kim, K -N ; Lee, D -J  (Aug 2011)  "Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old"  Journal of Korean Medical Science  26 (8): 1093–1098  doi:10 3346/jkms 2011 26 8 1093  PMC 3154347  PMID 21860562  ^ Bentley, R ; Meganathan, R  (Sep 1982)  "Biosynthesis of vitamin K (menaquinone) in bacteria" (PDF)  Microbiological Reviews  46 (3): 241–280  PMC 281544  PMID 6127606  ^ Haddock, B  A ; Jones, C  W  (Mar 1977)  "Bacterial respiration" (PDF)  Bacteriological Reviews  41 (1): 47–99  PMC 413996  PMID 140652  ^ Shearer, M  J  (Jan 1995)  "Vitamin K"  Lancet  345 (8944): 229–234  doi:10 1016/S0140-6736(95)90227-9  PMID 7823718  ^ Greer, J  P ; Foerster, J ; Lukens, J  N ; Rodgers, G  M ; Paraskevas, F ; Glader, B  (eds )  Wintrobe's Clinical Hematology (11th ed )  Philadelphia, Pennsylvania: Lippincott, Williams and Wilkens  ^ a b American Academy of Pediatrics Committee on Fetus Newborn  (Jul 2003)  "Controversies concerning vitamin K and the newborn  American Academy of Pediatrics Committee on Fetus and Newborn" (PDF)  Pediatrics  112 (1 1): 191–192  doi:10 1542/peds 112 1 191  PMID 12837888  ^ Logan, S ; Gilbert, R  (1998)  "Vitamin K For Newborn Babies" (PDF)  Department of Health  Retrieved 12 Oct 2014  ^ "Postnatal care: Routine postnatal care of women and their babies [CG37]"  www nice org uk  NICE  Jul 2006  Retrieved 12 Oct 2014  ^ Parker, L ; Cole, M ; Craft, A  W ; Hey, E  N  (1998)  "Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study"  BMJ (Clinical Research Edition)  316 (7126): 189–193  doi:10 1136/bmj 316 7126 189  PMC 2665412  PMID 9468683  ^ McMillan, D  D  (1997)  "Routine administration of vitamin K to newborns"  Paediatric Child Health  2 (6): 429–431  ^ "Newborns get rare disorder after parents refused shots"  Having four cases since February just at Vanderbilt was a little bit concerning to me ^ Dam, C  P  H  (1935)  "The Antihaemorrhagic Vitamin of the Chick: Occurrence And Chemical Nature"  Nature  135 (3417): 652–653  doi:10 1038/135652b0  ^ Dam, C  P  H  (1941)  "The discovery of vitamin K, its biological functions and therapeutical application" (PDF)  Nobel Prize Laureate Lecture  ^ McAlister, V  C  (2006)  "Control of coagulation: a gift of Canadian agriculture" (PDF)  Clinical and Investigative Medicine  29 (6): 373–377  ^ MacCorquodale, D  W ; Binkley, S  B ; Thayer, S  A ; Doisy, E  A  (1939)  "On the constitution of Vitamin K1"  Journal of the American Chemical Society  61 (7): 1928–1929  doi:10 1021/ja01876a510  ^ Fieser, L  F  (1939)  "Synthesis of Vitamin K1"  Journal of the American Chemical Society  61 (12): 3467–3475  doi:10 1021/ja01267a072  ^ Dam, C  P  H  (12 Dec 1946)  "The discovery of vitamin K, its biological functions and therapeutical application" (PDF)  Nobel Prize lecture  ^ Warner, E  D ; Brinkhous, K  M ; Smith, H  P  (1938)  "Bleeding Tendency of Obstructive Jaundice"  Proceedings of the Society of Experimental Biology and Medicine  37 (4): 628–630  doi:10 3181/00379727-37-9668P  ^ Stenflo, J; Fernlund, P ; Egan, W ; Roepstorff, P  (Jul 1974)  "Vitamin K dependent modifications of glutamic acid residues in prothrombin"  Proceedings of the National Academy of Sciences of the United States of America  71 (7): 2730–2733  doi:10 1073/pnas 71 7 2730  PMC 388542  PMID 4528109  ^ Nelsestuen, G  L ; Zytkovicz, T  H ; Howard, J  B  (Oct 1974)  "The mode of action of vitamin K  Identification of gamma-carboxyglutamic acid as a component of prothrombin" (PDF)  Journal of Biological Chemistry  249 (19): 6347–6350  PMID 4214105  ^ Magnusson, S ; Sottrup-Jensen, L ; Petersen, T  E ; Morris, H  R ; Dell, A  (Aug 1974)  "Primary structure of the vitamin K-dependent part of prothrombin"  FEBS Letters  44 (2): 189–193  doi:10 1016/0014-5793(74)80723-4  PMID 4472513  Bibliography[edit]
Rhéaume-Bleue, Kate (2012)  Vitamin K2 and the Calcium Paradox  John Wiley & Sons, Canada  ISBN 1-118-06572-7  External links[edit]
"Vitamin K: Another Reason to Eat Your Greens"  v
TPP / ThDP (B1)
FMN, FAD (B2)
NAD+, NADH, NADP+, NADPH (B3)
Coenzyme A (B5)
PLP / P5P (B6)
THFA / H4FA, DHFA / H2FA, MTHF (B9)
AdoCbl, MeCbl (B12)
Phylloquinone (K1), Menaquinone (K2)
non-vitamins
Coenzyme B
Heme / Haem (A, B, C, O)
Molybdopterin/Molybdenum cofactor
THMPT / H4MPT
Fe2+, Fe3+
vitamins: see vitamins
Antihemorrhagics (B02)
(coagulation)
Phytomenadione (K1)
Menadione (K3)
intrinsic: IX/Nonacog alfa
VIII/Moroctocog alfa/Turoctocog alfa
extrinsic: VII/Eptacog alfa
common: X
II/Thrombin
I/Fibrinogen
XIII/Catridecacog
combinations: Prothrombin complex concentrate (II, VII, IX, X, protein C and S)
Carbazochrome
thrombopoietin receptor agonist (Romiplostim
Eltrombopag)
Tetragalacturonic acid hydroxymethylester
Epinephrine/Adrenalone
amino acids (Aminocaproic acid
Aminomethylbenzoic acid)
serpins (Aprotinin
Alfa1 antitrypsin
Camostat) 
Context 2: \section{Introduction}

Despite the rise of graphene and other 2D materials, semiconducting single-walled carbon nanotubes (SWNT) are still regarded as strong candidates for the next generation of high-performance ultrascaled transistors~\cite{Cao_IBM_2015,IBM_2017,3D_CNT_FET} as well as for opto-electronic devices~\cite{Review_Avouris,CNT_photonics} such as chip-scale electronic-photonic platforms~\cite{Pernice_2016} or low-threshold near-infrared tunable micro-lasers~\cite{Graf_2017}  
Engineering a quantum dot (QD) along a (suspended) semiconducting SWNT foreshadows promising opportunities in the field of quantum information processing and sensing through recently proposed schemes such as detection and manipulation of single spins via coupling to vibrational motion~\cite{Palyi_2012}, optomechanical cooling~\cite{Wilson_Rae_2012} as well as all optical manipulation of electron spins~\cite{Galland_all_optical_2008}  Furthermore, the quasi one-dimensional geometry of SWNTs allows for defining tunable p-n junctions induced by electrostatic doping through local gates~\cite{Buchs_JAP,tunable_pn_2011}  Combining a well-defined QD within such a p-n junction structure could constitute a crucial building-block for the realization of highly desirable electrically driven, on-demand single photon emitters operating at telecom wavelength, based $e g $ on a turnstile device architecture~\cite{turnstile_1994,turnstile_1999} 
In practice, QDs in carbon nanotubes have been reported predominantly for two different confinement structures: i) Engineered tunneling barriers at metal-nanotube contacts~\cite{Pablo04nat} and/or by gate electrodes, used \emph{e g } to manipulate single electron spins~\cite{Laird:2015}, ii) Unintentional localization potentials stemming from environmental disorder~\cite{Hofmann_2016}, allowing for single-photon emission mediated by localization of band-edge excitons to QD states~\cite{CNT_photonics,Hoegele_2008,Walden_Newman_2012,Hofmann_2013,Pernice_2016_2}  Both types of structures are usually operated at cryogenic temperature due to small energy scales ranging from a few to few tens of millielectronvolts 
\\
\indent Another technique for achieving confinement in SWNTs makes use of artificial defects such as covalently bound oxygen or aryl functionalization groups on the side walls of semiconducting SWNTs, inducing deep exciton trap states allowing for single-photon emission at room temperature~\cite{Htoon_2015,tunable_QD_defects}  Also, carrier confinement between defect pairs acting as strong scattering centers has been reported for mechanically induced defects~\cite{Postma_SET} as well as for ion-induced defects with reported level spacings up to 200 meV in metallic SWNTs~\cite{Buchs_PRL}  The latter technique, combined with recent progress in controlling defects structure and localization~\cite{Robertson_2012,Yoon_2016,Laser_writing_2017} offers a high potential for engineering a broad set of SWNT-based quantum devices operating at room temperature  
\\
\indent Here, we demonstrate confinement of electrons and holes in sub-10 nm QD structures defined by ion-induced defect pairs along the axis of semiconducting SWNTs  Using low temperature scanning tunneling microscopy and spectroscopy (STM/STS), bound states with level spacings of the order of 100 meV and larger are resolved in energy and space  By solving the one-dimensional Schr\"odinger equation over a piecewise constant potential model, the effects of asymmetric defect scattering strength as well as the influence of the Au(111) substrate such as terrace edges on the bound states structure are remarkably well reproduced  By means of ab-initio calculations based on density functional theory and Green's functions, we find that single (SV) and double vacancies (DV) as well as chemisorbed nitrogen ad-atoms are good candidates to produce QDs with the experimentally observed features  These simulations also allow to study the scattering profile as a function of energy for different defect combinations 

\section{Experimental section}

The experiments have been performed in a commercial (Omicron) low temperature STM setup operating at $\sim5$~K in ultra high vacuum  Topography images have been recorded in constant current mode with a grounded sample, using mechanically cut Pt/Ir tips  Differential conductance $dI/dV$ spectra, proportional in first approximation to the local density of states (LDOS)~\cite{Tersoff85} have been recorded using a lock-in amplifier technique  The LDOS spatial evolution along a nanotube axis is obtained by $dI/dV(x,V)$ maps built by a series of equidistant $dI/dV$ spectra  Spatial extent mismatches between topography images and consecutive $dI/dV(x,V)$ maps have been systematically corrected~\cite{Buchs_Ar}, and the metallic nature of the tip has been systematically checked on the gold substrate to prevent any tip artefacts before recording STM or/and STS data sets  
\\
\indent Nanotube samples were made of extremely pure high-pressure CO conversion (HiPCo) SWNTs~\cite{Smalley01} with a diameter distribution centered around 1 nm, FWHM $\sim$ 0 3 nm~\cite{Buchs_conf}  The measured intrinsic defect density was below one defect every 200 nm  SWNTs were deposited on atomically flat Au(111) surfaces from a 1,2-dichloroethane suspension, followed by an in-situ annealing process~\cite{Buchs_APL_07,Buchs_Ar} 
\\
\indent Local defects in SWNTs have been created in-situ by exposure to: (i) Medium energy $\sim$ 200 eV argon ions (Ar$^{+}$) produced by an ion gun \cite{Buchs_Ar,Buchs_PRL}, (ii) Low energy (few eV's) nitrogen ions (N$^{+}$) produced by a 2 45 GHz ECR plasma source~\cite{Buchs_APL_07,Buchs_NJP_07}  In both cases, the exposure parameters have been calibrated to reach an average defect separation along the SWNTs of about 10 nm~\cite{Buchs_Ar,Buchs_APL_07} 

\section{Results and discussion}
\subsection{Experimental LDOS patterns}
\begin{figure}
  \includegraphics[width=8cm]{Figure_1 pdf}
  \caption{\label{exp_data_1} (a)-(b) 3D topography images (processed with WSXM~\cite{WSXM}) of SWNT I with Ar$^{+}$ ions-induced defects, with sample-tip bias voltage ($V_\mathrm{S}$) 1 V and tunneling current $I_\mathrm{S}$ 0 1 nA  (c) Corresponding $dI/dV(x,V)$ map recorded along the horizontal dashed lines in (b), with $V_\mathrm{S}=1$ V, $I_\mathrm{S}=0 2$ nA  Spatial resolution $\sim$ 0 3 nm  (d) 3D topography image of SWNT II with N$^{+}$ ions-induced defects, with $V_\mathrm{S}=1$ V, $I_\mathrm{S}=128$ pA  (e) Corresponding $dI/dV(x,V)$ map recorded along the horizontal dashed lines in (d), with $V_\mathrm{S}=1 5$ V, $I_\mathrm{S}=0 3$ nA  Spatial resolution $\sim$ 0 2 nm }
\end{figure}
In Fig ~\ref{exp_data_1} (a) and (b), we show 3D STM images of the same semiconducting SWNT (referred as SWNT I in the following) with Ar$^{+}$ ions-induced defect sites labeled $d1-d5$   Panel (d) shows a 3D STM image of a second semiconducting SWNT (referred as SWNT II) with N$^{+}$ ions-induced defect sites labeled $d6-d7$  In both cases, defect sites typically appear as hillock-like protrusions with an apparent height ranging from 0 5~{\AA} to 4~{\AA} and an apparent lateral extension varying between 5~{\AA} and 30~{\AA}~\cite{Buchs_NJP_07,Buchs_Ar,Thesis_Buchs}  
\\
\indent The resulting $dI/dV(x,V)$ maps recorded along the horizontal dashed line drawn in the STM images (b) and (d) are displayed in panels (c) and (e) in Fig ~\ref{exp_data_1}, respectively  Defect signatures in the LDOS in both cases are characterized by deep in-gap states at the defects positions  This is consistent with the expected defect structures, $i e $ mainly SVs, DVs and combinations thereof for collisions with Ar$^{+}$ ions~\cite{Buchs_Ar} and bridgelike N ad-atom for collisions with N$^{+}$ ions~\cite{Thesis_Buchs,Nitrogen_prb_07}  Note that gap states at energy levels $\sim$~0 2 eV and $\sim$~0 05 eV in panels (c) and (e), respectively, are shifted to the right from $d3$ by about 1 nm and to the right from $d6$ by about 2 nm  This indicates the presence of intrinsic or ion-induced defects on the lateral or bottom side wall of the SWNTs~\cite{Kra01prb}, not visible in the topographic images  These defects are labelled $d3'$ and $d6'$, respectively   
\\
\begin{figure}
  \includegraphics[width=12cm]{Figure_2 pdf}
  \caption{\label{exp_data_Ar} (a)-(b) QD I detailed $dI/dV(x,V)$ maps in conduction and valence bands  Lower subpanels contain QD states linecut profiles and stationary wave-like fits in left and right QD parts  Right subpanels contain experimental energy dispersion relation data sets $k_\mathrm{n}(E_\mathrm{n})$ and tight-binding calculations  (c)-(d) Resulting LDOS calculated from a one-dimensional piecewise constant potential model featuring potential barriers and a potential step (gray area), with position of the potential step: 5 09 nm from the right barrier's center, potential step heigth: $U_\mathrm{C}=V_\mathrm{L}-V_\mathrm{R}=60$ meV, barrier heights: $V_\mathrm{d3'}=1$ eV, $V_\mathrm{d4}=0 85$ eV, barrier widths: $a_\mathrm{d3'}=a_\mathrm{d4}=3 4$ nm   Valence band: $V_\mathrm{d3'}=-0 4$ eV, $a_\mathrm{d3'}=a_\mathrm{d4}=2 5$ nm, $V_\mathrm{d4}=-0 4$ eV  $E_\mathrm{g}$ stands for bandgap energy }
\end{figure}
\begin{figure}
  \includegraphics[width=12cm]{Figure_3 pdf}
  \caption{\label{exp_data_N} (a) QD II detailed $dI/dV(x,V)$ map  Lower subpanels contain QD states linecut profiles and stationary wave-like fits in the left and right QD parts  Right subpanel contains experimental energy dispersion relation data sets $k_\mathrm{n}(E_\mathrm{n})$ and tight-binding calculations  (b) Resulting LDOS calculated from a one-dimensional piecewise constant potential model featuring potential barriers and a potential step (gray area) with position of the potential step: 4 7 nm from the right barrier's center, potential step heigth: $U_\mathrm{C}=V_\mathrm{L}-V_\mathrm{R}=60$ meV, barrier heights: $V_\mathrm{d6'}=0 6$ eV, $V_\mathrm{d7}=0 6$ eV, barrier widths: $a_\mathrm{d6'}=1 5$ nm, $a_\mathrm{d7}=2 6$ nm }
\end{figure}
\indent Remarkably, the $dI/dV(x,V)$ maps in Fig ~\ref{exp_data_1} exhibit several broad discrete states in the conduction bands of SWNT I, II (white dashed boxes in panel (c) and (e), respectively) and in the valence band of SWNT I (white dashed box in panel (c)), characterized by a modulation of the $dI/dV$ signals in the spatial direction between pairs of consecutive defect sites $d3'-d4$ and $d6'-d7$  Enlarged plots of these boxed regions are displayed in Fig ~\ref{exp_data_Ar}(a)-(b) and Fig ~\ref{exp_data_N}(a) for SWNTs I and II, respectively  In the conduction bands, cross-sectional curves recorded along the black horizontal dashed lines labelled m1--m3 in Fig ~\ref{exp_data_Ar}(a) and m1--m4 in Fig ~\ref{exp_data_N}(a) are plotted below the LDOS panels  These clearly reveal one to three and respectively one to four spatially equidistant maxima  The number of maxima increases for increasing $\left|V_\mathrm{bias}\right|$ and the measured level spacings between consecutive discrete states is of the order of 100 meV and larger for both cases  This indicates that defect sites $d3'-d4$ and $d6'-d7$, respectively separated by 12 1 nm and 11 2 nm, act as strong scattering centers able to confine carriers in semiconducting SWNTs~\cite{Buchs_PRL,Bercioux_prb_2011}  Such intrananotube QD structures will be referred as QD I (in SWNT I) and QD II (in SWNT II) in the following  We estimated the level spacings in the conduction band of QD I to 98 meV (m1-m2) and 116 meV (m2-m3)  For QD II, we measured 122 meV (m1-m2), 185 meV (m2-m3) and 210 meV (m3-m4) 
\\
\indent In the valence band of SWNT I, discrete states with level spacings of the order of 80-90 meV, with one clear maximum at the level m-1, can also be distinguished between defect sites $d3'-d4$ in Fig ~\ref{exp_data_Ar}(b)  The discretization of the states indicates that this QD structure also confines holes  Discrete states starting from m-2 and lower show less well defined structures compared to the conduction band states  In the case of SWNT II, no clear discrete states are observed in the valence band (see supplementary information)  These observations are most probably the result of an energy dependent scattering strength of the defects, respectively $d3'$-$d4$ and $d6'$-$d7$, leading here to a weaker confinement in the valence band  Such energy dependence is well known for metallic SWNTs~\cite{Chico96,vac_2007,mayrhofer:2011,Bockrath_Science01} and is corroborated by our ab-initio calculations  Note that mixing effects with defect states and substrate-induced effects~\cite{substrate_effects} cannot be ruled out 
\\
\indent Another remarkable feature in the LDOS is the strong spatial asymmetry of the lowest energy states m1 and m-1 in QD I and m1 in QD II  In QD I, m1 is shifted to the right side of the dot while m-1 is shifted to the left side  Higher states m2 and m3 show more symmetry in terms of position of the maxima relative to the center of the QD  In QD II, m1 is shifted to the right side of the QD  We attribute the observed lowest energy states asymmetry (for electrons as well as for holes) in part to their strong sensitivity to weak potential modulations within the QD structure (as we will show in section \ref{1D})  For QD I, this assertion is supported by the observation of a 0 25 nm high Au(111) terrace edge located around the center of the QD, leading to a supported-suspended interface (see white dashed lines in Fig ~\ref{exp_data_1}(b) and more topographic details in Fig ~S2(a)-(d) in supplementary information)  Such configurations have been reported to induce a rigid shift in the SWNT bands~\cite{Clair_2011}, for instance here a down-shift in the right side of QD I corresponding to the "suspended" portion between two terraces  In QD II, we attribute the spatial shift of m1 to a potential modulation induced by a layer of disordered impurities, most probably residua from the 1,2-dichloroethane suspension, lying between the gold substrate and the SWNT (see Fig ~\ref{exp_data_1}(d) and Fig ~S2(e)-(h) in supplementary information)  
\\
\indent Also, the LDOS in QD I and II (Fig ~\ref{exp_data_Ar}(a) and Fig ~\ref{exp_data_N}(a), respectively) reveals asymmetric patterns with curved stripes oriented from top left to bottom right for QD I and from bottom left to top right for QD II  These are characteristic signatures for defect pairs with different scattering strengths~\cite{Bercioux_prb_2011,Buchs_PRL}  For instance here, the left defect in QD I ($d3'$) has a larger scattering strength than the right one ($d4$), while the right defect in QD II ($d7$) has a larger scattering strength than the left one ($d6'$)
Context 3: KSTP (1500 AM; SKOR North) is a commercial AM radio station licensed to Saint Paul, Minnesota  It is the flagship AM radio station of Hubbard Broadcasting, which also owns several other television and radio stations across the United States   KSTP has a sports radio format and is the ESPN Radio Network affiliate for Minneapolis-St  Paul   The radio studios are  on University Avenue in Minneapolis, shared with sister stations KSTP-FM, KSTP-TV, KTMY, and KSTC-TV  On weekdays, KSTP airs local sports shows from 9 a m  to 9 p m  and carries ESPN programming weekday mornings, late nights and weekends  Some KSTP shows are simulcast on other sports radio stations in the region 

KSTP runs the maximum power for AM stations, 50,000 watts   It shares clear-channel, Class A status on 1500 AM with WFED in Washington, D C   KSTP broadcasts a directional signal at night, using a three-tower array, with its transmitter on U S  Route 61 at Beam Avenue in Maplewood   Programming is also heard on 250 watt FM translator K235BP at 94 9 MHz in Bemidji 

History

WAMD and KFOY
KSTP's start in 1928 was the product of a merger between two pioneering Twin Cities stations: WAMD ("Where All Minneapolis Dances") in Minneapolis, first licensed on February 16, 1925 to Stanley E  Hubbard, and KFOY in St  Paul, first licensed on March 12, 1924 to the Beacon Radio Service in St  Paul 

Following a few test transmissions, WAMD made its formal debut broadcast on February 22, 1925  (In later interviews Stanley Hubbard traced WAMD's start to April 1924 ) It was located at the Marigold Dance Garden, and featured nightly "Midnight Frolics" broadcasts by the ballroom's orchestra  It is claimed that WAMD was the first radio station to be completely supported by running paid advertisements  Effective June 15, 1927, WAMD was assigned to 1330 kHz 

On November 11, 1927 WAMD's transmitter site at Oxboro Heath on Lyndale Avenue South burned down, two weeks after the station had been sold to the National Battery Company  An initial arrangement was made to carry WAMD's programs over WRHM (now WWTC), transmitting on WAMD's 1330 kHz frequency  Beginning on November 24, 1927 the WAMD broadcasts, still on 1330 kHz, were shifted to KFOY's facility in St  Paul  (At this time KFOY was assigned to 1050 kHz)  The next day it was announced that National Battery had purchased KFOY, and as of December 1, 1927 both KFOY and WAMD were reassigned to 1350 kHz  WAMD continued making regular broadcasts until the end of March 1928, while KFOY, although it continued to be licensed for a few more months on a time-sharing basis with WAMD, ceased operations at this point 

National Battery Company
In mid-December 1927, the National Battery Company announced it had received permission from the Federal Radio Commission (FRC) to build a new station, with the call letters KSTP, operating from a transmitter site to be constructed three miles south of Wescott



ground_truth: Vitamins K3, K4, and K5.

prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: What experimental techniques were used to study the quantum dot structures in this research?

Read the following text and answer briefly.

Context 2:  
\\
\indent The exact atomic structure of the defects could in principle be determined from a comparison of $dI/dV$ spectra with simulated first-principle LDOS signatures of expected defect types  In reality, this is hampered by the large number of possible geometries to simulate, including complex multiple defect structures~\cite{Buchs_Ar}, together with the large unit cells of the semiconducting chiral SWNTs studied here 
\\
\subsection{1D piecewise constant potential model}
\label{1D}
To better understand the physical origins of the non-trivial signatures of the quantized states, we model the experimental $dI/dV$ maps by solving the time independent one-dimensional Schr\"odinger equation over a piecewise constant potential model of QD I and QD II  The scattering centers are approximated by semi-transparent rectangular tunneling barriers leading to a square confinement potential~\cite{Laird:2015}  This is supported by previous results on defect-induced confinement in metallic SWNTs using the same experimental conditions~\cite{Buchs_PRL} and is consistent with ab-initio simulations presented later in this work  The potential modulation within the QD is approximated by a potential step  The resulting potential geometries are illustrated with gray shaded areas in Fig ~\ref{exp_data_Ar} (c) and (d) and Fig ~\ref{exp_data_N}(b)  Dispersion relations $E(k)$ can be extracted experimentally from the quantized states wavefunctions by measuring the energy and corresponding momenta in the left and right sides of the QDs  The wavevectors $k$ are determined using stationary wave-like fitting functions~\cite{Buchs_PRL} displayed with dashed red curves in Figs ~\ref{exp_data_Ar}(a)-(b) and ~\ref{exp_data_N}(a))  From this procedure, the potential step height and position can be estimated (see supplementary information)  The experimental data sets $E(k)$ are plotted in the right panels of Figs ~\ref{exp_data_Ar}(a) and \ref{exp_data_N}(a) together with dispersion relations from a third-nearest neighbor tight-binding calculation closely approximating ab-initio results~\cite{Reich_TB_2002}  These chirality-dependent tight-binding dispersion relations, calculated within an extended Brillouin zone resulting from the defect-induced breaking of the translation invariance~\cite{Bercioux_prb_2011}, are used in the Hamiltonian of our one-dimensional model  Taking into account the measured chiral angle, diameter distribution~\cite{Buchs_conf} and measured bandgaps, we find the best match with chiralities $(7,6)$ for QD I and $(11,1)$ for QD II (see supplementary information)  
\\
\indent Once chiralities together with potential step heights and positions are optimized, one can fit the height and width of the rectangular tunneling barriers in order to reproduce the experimental level spacings and general LDOS patterns  On a qualitative ground, a symmetric double barrier system results in the formation of spatially symmetric discrete bound states  Increasing both barrier heights simultaneously shifts the bound state energy levels and level spacings up  This leads to sharper bound states as the confinement in the QD is made stronger thus increasing the lifetime of the confined electrons  Increasing the barrier thickness with constant inner edge separation does not affect much the level spacings but further sharpens the bound states  Any asymmetry introduced by a change in the width or height of one single barrier leads to broader bound states  The presence of a potential step modifies the LDOS in lifting the levels of the bound states, with a more pronounced effect on the lower states  In QD I and II, the center of each barrier is aligned with the center of the gap states ($d3'$-$d4$ for QD I and $d6'$-$d7$ in QD II) and the width ratio is kept proportional to the ratio of the spatial extent of the gap states  Thus, by increasing the width of the barriers, we decrease the length of the QD leading to higher level spacings, and vice versa  The experimental level spacings can then be approximated by tuning both barrier widths in the same ratio and the heights individually, knowing that the scattering strength of $d3'$ ($d7$) is larger than $d4$ ($d6'$) according to the observed asymmetry in the LDOS described above \footnote{The transmission probability through a rectangular tunneling barrier is given by $T=\left( 1+\frac{V^{2}\sinh^{2}\left( a \cdot \sqrt{2m^{*}(V-E)}/\hbar \right)}{4E(V-E)} \right)^{-1}$, where $V$ and $a$ are respectively the barrier height and width  For the argument in the $\sinh$ sufficiently small such that $\sinh(x)\simeq x$, it can be shown that $a$ and $V$ can be coupled such that the transmission probability becomes a function of the area under the barrier $A=a\cdot V$, with $T=\left( 1+ \frac{m^{*}A^{2}}{2\hbar^{2}E} \right)^{-1}$  In our case, this condition is not satisfied and thus the barrier geometries are tuned empirically to fit the experimental level spacings }  
\\
\indent For QD I, we find a good match in the conduction band for the barrier heights $V_\mathrm{d3'}=1$ eV and $V_\mathrm{d4}=0 85$ eV, widths $a_\mathrm{d3'}=a_\mathrm{d4}=$ 3 4 nm,  and potential step $V_\mathrm{L}-V_\mathrm{R}=60$ meV  With these parameters, the spatial profile of the obtained quantized states (see lower subpanels in Fig ~\ref{exp_data_Ar}(a) and (c)) reproduces the experimental modulation features remarkably well  Also, the simulated LDOS displays a pattern with curved stripes oriented from top left to bottom right, as observed experimentally, due to a left barrier with a larger scattering strength  In the valence band, although modes m-2 and lower do not show a well defined structure in the spatial direction, thinner barriers with dimensions $a_\mathrm{d3'/d4}=2 5$ nm, $V_\mathrm{d3'/d4}=-0 4$ eV, leading to a slightly longer QD length (9 6 nm compared to 8 7 nm in the conduction band) can reproduce the measured level spacings very well  
\\
\indent For QD II, we observed that the measured energy levels are overestimated by a factor $\alpha\sim1 29$, presumably due to a voltage division effect induced by the impurity layer mentioned above (see details in supplementary information)  We find a good agreement with the experimental LDOS with the parameters: $V_{d3'}=V_{d4}\simeq$ 0 47 eV, $a_\mathrm{d6'}=1 5$ nm, $a_\mathrm{d7}=2 6$ nm and $U_\mathrm{C}=V_\mathrm{L}-V_\mathrm{R}\simeq 47$ meV  Note that in Fig ~\ref{exp_data_N}(b) the barrier and potential heights are multiplied by $\alpha$ to allow a direct comparison with the experimental LDOS  The simulated LDOS shows a pattern with curved stripes oriented from bottom left to top right, as observed experimentally, due to a right barrier exhibiting a larger scattering strength  Also, the spatial profile of the obtained bound states (see lower subpanels in Fig ~\ref{exp_data_N}(a) and (b)) reproduces the experimental features quite well  Note also that one can distinguish an isolated state in the experimental LDOS at an energy level between m1 and m2, about in the middle of the QD  This state that prevented an accurate fit of the state m2 in the right QD part is attributed to a spatial feature visible in the STM topography image in Fig ~\ref{exp_data_Ar}(d) (see also supplementary information, Fig S2(f)), probably a physisorbed impurity which does not affect the LDOS significantly 
\\
\subsection{Ab-initio calculations}
\begin{figure}
  \includegraphics[width=16cm]{Figure_4 pdf}
  \caption{\label{num_data} (a)-(c) LDOS ab-initio simulations of a semiconducting $(16,0)$ SWNT with combinations of vacancies defects separated by 11 1 nm  Subpanels display QD state linecut profiles  (d) Tight-binding (black curve) and ab-initio dispersion relations (green circles) for a pristine $(16,0)$ SWNT with $E_\mathrm{n}(k_\mathrm{n})$ data sets extracted from (a)-(c)  (e)-(g) LDOS ab-initio simulations of a semiconducting $(17,0)$ SWNT with combinations of N ad-atoms and vacancies defects separated by 10 7 nm  (h) Tight-binding (black curve) and ab-initio dispersion relations (green circles) for a pristine $(17,0)$ SWNT with $E_\mathrm{n}(k_\mathrm{n})$ data sets extracted from (e)-(g) }
\end{figure}
In order to elucidate the physical nature of the electron/hole confining scattering centers, we performed ab-initio simulations based on a combination of density functional theory~\cite{pbe,paw,vasp_paw,VASP2}, maximally localized Wannier orbitals~\cite{transportwannier90} and Green's functions (see supplementary information)  Without loss of generality, we have simulated short unit cell semiconducting zigzag SWNTs with different combinations of the most probable defect structures  Results for vacancy defects likely being induced by 200 eV Ar$^{+}$ ions, separated by about 11 nm in a $(16,0)$ SWNT are shown in Fig ~\ref{num_data}(a)-(c) with DV-DV, DV-SV and SV-SV pairs, respectively  The LDOS displays midgap states at the defect positions as expected as well as defect states in the valence band~\cite{Buchs_Ar}  Most importantly, clear quantized states with a number of maxima increasing with energy are observed between the defects in the conduction band, emphasizing the ability of SVs and DVs to confine carriers  For the asymmetric configuration DV-SV, one can distinguish faint curved stripe patterns oriented from top left to bottom right, indicating a larger scattering strength for DVs compared to SVs  This is consistent with observations in transport experiments~\cite{Gomez05nm}  On the other hand, the patterns in the valence band strongly depend on the defect types  Discrete states can be distinguished for the DV-DV case, with m-2 being mixed with defect states  For the DV-SV case, clear curved stripe patterns oriented from bottom left to top right indicate again a stronger scattering strength for DV  Also, broader states are observed, indicating that the scattering strength of DVs and SVs is weaker in the valence band compared to the conduction band 
\\
\indent More insight on the energy dependent scattering strength for each defect pair configuration can be obtained by extracting the wavevector $k_\mathrm{n}(E_\mathrm{n})$ for each resonant state  This data set is plotted in Fig ~\ref{num_data}(d) for the conduction and valence bands together with the $(16,0)$ dispersion relations calculated from the third-nearest neighbor TB model and from the ab-initio calculation for the pristine nanotube  A first observation is the excellent agreement between TB and ab-initio results, further validating the method used in Figs ~\ref{exp_data_Ar}(a)-(b) and ~\ref{exp_data_N}(a)  The vertical dashed lines indicate the limiting $k_\mathrm{n,\infty}=\frac{\pi \cdot n}{L}$ values corresponding to the closed system (infinite hard walls potential) with $L=11 1$ nm being the defect-defect distance  In the conduction band, we find that $k_\mathrm{n}(E_\mathrm{n})=\frac{\pi \cdot n}{L_\mathrm{eff}(n)} < k_\mathrm{n,\infty}$, indicating that the effective lengths $L_\mathrm{eff}(n)$ of the QD are larger than $L$ ($i e $ the resonant states wavefunctions are characterized by penetrating evanescent modes inside the defect scattering potential), as expected for an open system  The shortest $L_\mathrm{eff}(n)$ are obtained for the DV-DV configuration with 12 1 nm (m1), 13 1 nm (m2) and 12 9 nm (m3), which we attribute to wider scattering potential profiles for DVs compared to SVs  In the valence band, we find that $k_\mathrm{n}(E_\mathrm{n})=\frac{\pi \cdot n}{L_\mathrm{eff}(n)} > k_\mathrm{n,\infty}$, with $L_\mathrm{eff}(n)$ values between 7 9 nm (DV-DV, m-1) and 9 66 nm (DV-SV, m-2)  We attribute this pronounced QD shortening to wider scattering potential profiles of both DVs and SVs in the valence band, probably due to mixing with wide spread defect states in the valence band 
\\
\indent Ab-initio calculations for different defect pairs combinations containing at least one N ad-atom, $i e $ N-DV, N-SV and N-N, are presented in Fig ~\ref{num_data}(e)-(h) for a $(17,0)$ SWNT, along with details on the defects geometries  Remarkably, clear QD states are generated for all three configurations, underlining the potential of N ad-atoms to confine carriers in semiconducting SWNTs and thus to generate intrananotube QDs  
\\
\indent In order to demonstrate the scattering strengths of the different defects, we calculated the energy dependent conductance in addition to the LDOS for the different combinations of the QD defining scattering defects on the $(16,0)$ and $(17,0)$ SWNTs, see supplementary information  Generally we can observe strong conductance modulation of the order of 30-40\% with regard to the pristine CNT for all three tested defects (double vacancies DV, single vacancies SV and chemisorbed C-N) with the DVs having the largest scattering strength in the CB and VB   
\\
\indent Note that the choice of the zigzag SWNT chiralities in the two different ab-initio scenarios is motivated by the different effective masses of both chiralities ($m^{*}_{(17,0)}>m^{*}_{(16,0)}$) which is typical for chirality families $(3n-1,0)$ and $(3n-2,0)$~\cite{ZZ_families}  Taking advantage of recent reports on SWNT chirality control~\cite{chirality_control_EMPA,chirality_control_chinese,chirality_chemistry}, this property could be used in practice to design QDs with different level spacings for the same QD length  From an application point of view, however, QDs generated by DVs will have far superior stability at room temperature due to their high migration barrier above 5 eV ($\sim$~1 eV for single vacancy)~\cite{Kra06vm}  This value drops down by at least 2 eV for N ad-atoms depending on their chemisorption configuration~\cite{Nitrogen_prb_07,Yma05nitr} 
\\
\indent Our ab-initio simulations do not take into account any substrate effect  In the experimental case, the carriers can decay through the substrate, thus limiting their lifetime  This leads to state broadening, measured between about 60 meV up to 120 meV in QD I and II, while the quantized states widths in ab-initio simulations vary between about 5 meV and 45 meV  This suggests that a better contrast of the experimental quantized states, especially in the valence band, could be achieved by lowering the nanotubes-substrate interaction through $e g $ the insertion of atomically thin insulating NaCl films~\cite{Ruffieux_Nature_2016}  This would allow to gain more insight on the electronic structure of the QDs as well as in the associated scattering physics at the confining defects~\cite{Buchs_PRL}  

\section{Conclusions and outlook}
In summary, using low-temperature STM/STS measurements supported by an analytical model and ab-initio simulations, we have demonstrated that intrananotube quantum dots with confined electron and hole states characterized by energy level spacings well above thermal broadening at room temperature can be generated in semiconducting SWNTs by structural defects such as vacancies and di-vacancies, as well as nitrogen ad-atoms  These results, combined with recent progresses in type and spatial control in the formation of defects~\cite{Robertson_2012,Yoon_2016,Laser_writing_2017} as well as chirality control~\cite{tunable_QD_defects}, hold a high potential for applications in the design of SWNT based quantum devices  These include $e g $ electrically driven single-photon emitters operating at room temperature and telecom wavelength  In this context, the observation of quantum confinement effects in the emitted light of cut, sub-10 nm, semiconducting SWNTs~\cite{Dai_2008} shall be seen as an additional motivation for investigating the optical properties of our "QD with leads" building-blocks  These would include $e g $ studying optical transitions selection rules for different types and configurations of defect pairs~\cite{sel_rules_2006} associated with experimental studies such as photoluminescence~\cite{Lefebvre06} combined to $g^{(2)}$ correlation measurements~\cite{Hofmann_2013} in suspended SWNT devices as well as photocurrent imaging~\cite{Buchs_Nat_comm} and spectroscopy~\cite{Gabor_2009} 

\section*{Acknowledgements}
The authors thank Ethan Minot, Lee Aspitarte, Jhon Gonzalez, Andres Ayuela, Omjoti Dutta and Arkady Krasheninnikov for fruitful discussions 
The work of DB is supported by Spanish Ministerio de Econom\'ia y Competitividad (MINECO) through the project  FIS2014-55987-P and by the (LTC) QuantumChemPhys  LM acknowledges support from the BMBF-project WireControl (FKZ16ES0294) and computing time for the supercomputers JUROPA and JURECA at the J\"ulich Supercomputer Centre (JSC) 


\clearpage

\section*{References}



Context 3:  The next month it was reported that the new station, still under construction, had been assigned to 1360 kHz  KSTP made its debut broadcast on March 29, 1928  Although technically it was a separate station from WAMD and KFOY, both of which were formally deleted on April 30, 1928, overall KSTP was treated as the direct successor to a consolidated WAMD and KFOY 

Hubbard became the merged station's general manager, acquiring controlling interest in 1941  A month after the merger, KSTP became an affiliate for the NBC Red Network   It remained with NBC for 46 years  On November 11, 1928, under the provisions of the FRC's General Order 40, KSTP was assigned to a "high-powered regional" frequency of 1460 kHz  The only other station assigned to this frequency was WTFF in Mount Vernon Hills, Virginia (later WJSV, now WFED, Washington, D C )  On February 7, 1933, the FRC authorized KSTP to increase its daytime power to 25 KW  In 1938 and 1939 KSTP also operated a high-fidelity AM "experimental audio broadcasting station" Apex station, W9XUP, originally on 25,950 kHz and later on 26,150 kHz  In 1941, as part of the implementation of the North American Regional Broadcasting Agreement, KSTP was assigned to its current "clear channel" frequency of 1500 kHz, with the provision that it and WJSV, as "Class I-B" stations, had to maintain directional antennas at night in order to mutually protect each other from interference  An FM station, KSTP-FM, was founded in 1946 but shut down in 1952 

Hubbard reportedly acquired an RCA TV camera in 1939, and started experimenting with television broadcasts   But World War II put a hold on the development of television   In 1948, with the war over, KSTP-TV became the first television station in Minnesota   With KSTP 1500 already associated with NBC Radio, KSTP-TV became an NBC Television Network affiliate   From 1946 to 1952, KSTP also had an FM counterpart   KSTP-FM 102 1 was only on the air four years   There were few radios equipped to receive FM signals in that era, and management decided to discontinue FM broadcasts 

MOR and Top 40
As network programming moved from radio to television, KSTP programmed a full service Middle of the Road (MOR) radio format, in the shadow of its chief competitor, CBS Radio affiliate 830 WCCO  In 1965, a new FM station, reviving the KSTP-FM call sign, was put on the air, largely simulcasting the AM station   But by the late 1960s, KSTP-FM began a separate format of beautiful music   KSTP was the radio home of the Minnesota Vikings football team from 1970 to 1975  

In 1973, KSTP broke away from its longtime adult MOR sound and became one of four area stations at the time to program a Top 40 format  "15 KSTP, The Music Station" competed with Top 40 AM rivals WDGY, KDWB and later, WYOO  The competition would eventually shake itself out, with outrageous rocker WYOO dropping out after being sold in 1976, and then the staid WDGY switching to country music the following year   As for uptempo hits station 15 KSTP, it went from a tight Top 40 format to leaning adult rock in 1978, to leaning adult contemporary in 1979, to evolving into adult contemporary/talk by 1980   In 1982, it officially shifted to talk   Most Top 40 rock music, by this time, had moved to the FM band 

Past Personalities

Notable hosts who have been on KSTP include John Hines, Jesse Ventura, Larry Carolla, Tom Barnard, Big Al Davis, Don Vogel, John MacDougall, Griff, Mike Edwards, Geoff Charles, Joe Soucheray, James Lileks, Leigh Kamman, Barbara Carlson, Peter Thiele, Tom Mischke, Jason Lewis, Chuck Knapp, Machine Gun Kelly, Charle Bush, Mark O'Connell and Paul Brand  These broadcasters were supported by producers such as Bruce Huff, Rob Pendleton, Alison Brown, Jean Bjorgen, David Elvin (who Vogel dubbed the "Steven Spielberg of Talk Radio"), Mitch Berg and others 

The station has, for the most part, emphasized local hosts over the years   But in 1988, KSTP was one of Rush Limbaugh's first affiliates when his conservative talk show was rolled out for national syndication



ground_truth: Low temperature scanning tunneling microscopy and spectroscopy (STM/STS).

prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: When did KSTP switch to a sports radio format?

Read the following text and answer briefly.

Context 3:   (Clear Channel-owned KTLK-FM took over rights to Limbaugh's show in January 2006)  Other syndicated hosts previously heard on KSTP include Sean Hannity, Bruce Williams, Larry King, and Owen Spann 

Sports Radio
KSTP switched to Sports Radio on February 15, 2010   As the station had to wait for ESPN's contract with rival KFAN and its sister station KFXN to expire, it did not become an ESPN Radio affiliate until April 12, the same day that the Minnesota Twins were scheduled to play the first game in their new ball park, Target Field, against the Boston Red Sox   As a result Coast to Coast AM and Live on Sunday Night, it's Bill Cunningham were retained during this period   One ESPN Radio network program, The Herd with Colin Cowherd, was picked up by KSTP immediately following the format change 

In 2018, the station was approved for an FM translator on 94 1 FM, broadcasting from a transmitter atop the IDS Center in downtown Minneapolis  The two-watt signal threw most of its power to the west, preventing interference to low powered FM stations on the same channel including WFNU-LP in St  Paul  With only two watts of power, however, the signal was limited to the immediate downtown area surrounding the IDS Center   It later acquired a 250 watt translator, K235BP at 94 9 MHz   The original translator was discontinued 

On January 15, 2019, KSTP rebranded as "SKOR North" (a reference to the Vikings team song/chant, "Skol, Vikings"), with local programming between 12 noon and 7 pm  About a year later, in May of 2020, KSTP suspended most of its local programming and laid off nearly all of its local staff  Station management cited the economic toll of the coronavirus for the changes  Sports broadcasting continues, primarily composed of ESPN radio network broadcasts 

Sports Teams

KSTP-AM served as the radio flagship for the Minnesota Vikings football team from 1970 to 1975 

On August 1, 2006, the station announced that it would be the new flagship station for the Minnesota Twins baseball team, effective with the start of the 2007 season  The Twins had been on rival WCCO since arriving in Minnesota in 1961   KSTP served as the flagship for the Twins until the end of the 2012 season, when games moved to 96 3 KTWN-FM (now KMWA)   The Twins have since returned to WCCO 830 

The switch to a fairly weak FM station caused dissent among some listeners, particularly in communities that had trouble picking up KSTP 1500   Although KSTP is the state's second most powerful AM station, it must operate directionally at night, delivering a reduced signal to parts of the market  WCCO, by comparison, offers a signal with a wider coverage area during the day than KSTP does, with WCCO's non-directional 50,000 watt signal  In response, the Twins have expanded the number of affiliates 

On March 9, 2011, KSTP announced it would be the new flagship for the University of Minnesota Golden Gophers men's and women's basketball and men's ice hockey, ending a 68-year run on WCCO  The rights have since moved to KFXN-FM, which already aired Gopher football 

On March 2, 2017, KSTP announced it would be the first radio broadcaster for Minnesota United FC   The move brings live soccer action to 1500 AM 

Previous logos

References

External links
KSTP website

FCC History Cards for KSTP (covering 1928-1980)
Radiotapes com Historic Minneapolis/St  Paul airchecks dating back to 1924 including KSTP and other Twin Cities radio stations 
Rick Burnett's TwinCitiesRadioAirchecks com has additional airchecks of KSTP and other Twin Cities radio stations from the '60s and '70s, including Chuck Knapp's 2nd show on KSTP 

Hubbard Broadcasting
ESPN Radio stations
Peabody Award winners
Radio stations in Minneapolis–Saint Paul
Radio stations established in 1925
1925 establishments in Minnesota
Minnesota Kicks
Sports radio stations in the United States
Clear-channel radio stations



ground_truth: KSTP switched to a sports radio format on February 15, 2010.