title: Fortepiano

text: A number of modern harpsichordists and pianists have achieved distinction in fortepiano performance, including Susan Alexander-Max, Paul Badura-Skoda, Malcolm Bilson, Hendrik Bouman, Ronald Brautigam, Wolfgang Brunner, Gary Cooper, Jörg Demus, Ursula Dütschler. Richard Egarr, Richard Fuller, Tuija Hakkila, Christoph Hammer, Robert Hill, Knut Jacques, Jenny Soonjin Kim, Piet Kuijken, Geoffrey Lancaster, Gustav Leonhardt, Trudelies Leonhardt, Morgane Le Corre, Robert Levin, Alexei Lubimov, Steven Lubin, Yury Martynov, Costantino Mastroprimiano, Zvi Meniker, Bart van Oort, Olga Pashchenko, Trevor Pinnock, David Schrader, Viviana Sofronitsky, Andreas Staier, Melvyn Tan, Natalia Valentin, Jos van Immerseel, Andras Schiff, Kristian Bezuidenhout, Katia and Marielle Labèque, Duo Pégase, Vladimir Feltsman.


title: Fortepiano

text: People's opinions about fortepiano sound vary widely, both from person to person and from instrument to instrument. Here are three representative opinions about fortepianos:


title: Fortepiano

text: "Fortepiano" is Italian for "loud-soft", just as the formal name for the modern piano, "pianoforte", is "soft-loud". Both are abbreviations of Cristofori's original name for his invention: "gravicembalo col piano e forte", "harpsichord with soft and loud".


title: Fortepiano

text: The term "fortepiano" is somewhat specialist in its connotations, and does not preclude using the more general term "piano" to designate the same instrument. Thus, usages like "Cristofori invented the piano" or "Mozart's piano concertos" are currently common and would probably be considered acceptable by most musicians. "Fortepiano" is used in contexts where it is important to make the precise identity of the instrument clear, as in (for instance) "a fortepiano recital by Malcolm Bilson".


title: Fortepiano

text: The use of "fortepiano" to refer specifically to early pianos appears to be recent. Even the authoritative Oxford English Dictionary does not record this usage, noting only that "fortepiano" is "an early name of the pianoforte". During the age of the fortepiano, "fortepiano" and "pianoforte" were used interchangeably, as the OED's attestations show. Jane Austen, who lived in the age of the fortepiano and herself played the instrument, used "pianoforte" (also: "piano-forte", "piano forte") for the many occurrences of the instrument in her writings.


title: Graham Young

text: Graham Frederick Young (7 September 1947 – 1 August 1990), best known as the Teacup Poisoner and later the St Albans Poisoner, was an English serial killer who used poison to kill his victims.


title: Graham Young

text: Obsessed with poisons from an early age, Young began poisoning relatives and school friends by lacing their food and drink with thallium and antimony. He was caught when his schoolteacher became concerned by his interest in poisons and contacted the police. In 1962, at the age of 14, Young was charged with administering poison to his father, sister and schoolfriend and detained at Broadmoor Hospital. Young would later claim responsibility for the death of his stepmother, although he was never charged with this crime. The presiding judge stipulated that Young should not be released without the Home Secretary's authorization for 15 years.


title: Graham Young

text: In 1971, Young was deemed rehabilitated and released from Broadmoor. He found a job as a storekeeper at a factory in Bovingdon, Hertfordshire, where his duties included making tea for his colleagues. Soon afterwards, Young began poisoning his workmates, resulting in two fatalities and several others left critically ill. The deaths were initially attributed to a mysterious bug, but Young's odd behaviour and his penchant for showing off his considerable knowledge of poisons aroused suspicions and he was arrested. Large quantities of poison were found in his bedsit along with a diary detailing his poisonings. In 1972, he was convicted on two counts of murder and two counts of attempted murder and sentenced to life imprisonment. He served most of his sentence at HM Prison Parkhurst, where he died of a heart attack in 1990.


title: Graham Young

text: The Young case made headlines in Britain and led to a public debate over the release of mentally ill offenders. Within hours of his conviction, the British Government announced two inquiries into the issues it raised. The Butler Committee led to widespread reforms in mental health services. The outcry over the ease with which Young was able to obtain deadly poisons led to the passage of the 1972 Poisons Act. Young's life story inspired the 1995 film "The Young Poisoner's Handbook".


title: Graham Young

text: Young was born in Neasden in Middlesex on 7 September 1947 to Frederick and Molly Young. He had an older sister, Winifred. Molly died of tuberculous pleurisy when Graham was 14 weeks old. He was sent by his father to live with an uncle and aunt, while his sister went to live with their grandparents. Several years later, Frederick Young remarried, to another woman named Molly, and the family were re-united.


title: Graham Young

text: He was fascinated from an early age by poisons and their effects. He read extensively about Adolf Hitler and Nazi Germany. William Palmer, the Victorian poisoner, also became a hero of Young's. In 1959 Young passed his eleven-plus, and went to grammar school. He also started to read books on advanced toxicology.


title: Graham Young

text: In 1961, Young acquired antimony from a local chemist; his knowledge of chemistry and poisons convinced the chemist that he was older than he appeared. He signed the poisons register in the name "M.E. Evans". He began poisoning his stepmother, father and sister. Beginning in February, Molly Young suffered vomiting, diarrhoea and excruciating stomach pain, which she initially dismissed as bilious attacks. Before long his father was also suffering, with similar stomach cramps debilitating him for days at a time. Then Young's sister was violently ill on a couple of occasions that summer. Shortly afterwards, Young himself was violently sick at home. It even seemed as if the mystery bug had spread beyond their household: a couple of Young's school friends had also been off school ill a couple of times with similar painful symptoms.


title: Graham Young

text: In November 1961, Winifred Young was served a cup of tea by her brother one morning, but found its taste so sour she took only one mouthful before she threw it away. While on the train to work an hour later, she began to hallucinate, had to be helped out of the station and was eventually taken to hospital, where doctors came to the conclusion that she had somehow been exposed to the poisonous "Atropa belladonna". Fred Young confronted his son, but Graham blamed Winifred, whom he claimed had been using the family's teacups to mix shampoo. Unconvinced, Fred searched Graham's room, but found nothing incriminating. Nevertheless, he warned his son to be more careful in future when "messing about with those bloody chemicals".


title: Graham Young

text: On Easter Saturday, 21 April 1962, Molly Young died. Her death was attributed to a prolapsed cervical disc, which was believed to have resulted from a road accident. Much later, Young told police that he poisoned her with a lethal dose of thallium. At her wake, Young poisoned a male relative after lacing a jar of mustard pickle with antimony. Shortly afterwards his father became seriously ill and was taken to hospital where he was told that he was suffering from antimony poisoning and one more dose would have killed him. Young's aunt, who knew of his fascination with chemistry and poisons, became suspicious, as did his science teacher (Mr Hughes) who discovered several bottles of poison in Young's desk and spoke to the school's headmaster about his concerns. They arranged for Young to be interviewed by a psychiatrist, posing as a careers advisor, who contacted the police after Young revealed his extensive knowledge of poisons and toxicology.


title: Graham Young

text: Young was arrested on 23 May 1962 after returning home from school. Vials of thallium and antimony were found in his possession. When questioned by police, he confessed to poisoning his father, stepmother, sister and school friend Chris Williams. Psychiatrist Dr Christopher Fysh testified that Young had a psychopathic disorder rather than a mental illness, and had failed "to develop a normal moral sense." He felt it was "extremely likely" that Young would re-offend, and recounted a conversation in which Young said: "I am missing my antimony. I miss the power it gives me." Fysh recommended that Young be detained at Broadmoor Hospital, an institution for patients with mental disorders who have committed offences. Dr Donald Blair, another psychiatrist, concurred with Fysh's viewpoint.


title: Graham Young

text: Young pleaded guilty to three charges of poisoning his father, sister and Chris Williams and was convicted of "malicious administration of a noxious thing to inflict grievous bodily harm". He was not charged for murdering his stepmother, as her autopsy report did not list poison as the cause of death. The judge, Justice Melford Stevenson, ruled that Young was to be detained under section 60 of the Mental Health Act in Broadmoor Hospital. Furthermore, he was not to be released for 15 years without the approval of the Home Secretary.


title: Graham Young

text: At 14, Young was among Broadmoor's youngest ever inmates. During his time at Broadmoor, there were a number of poisoning incidents. Soon after his arrival, John Berridge, a fellow inmate, died of cyanide poisoning. Young was suspected by some staff and inmates, not least because he enjoyed explaining in detail how cyanide can be extracted from laurel leaves; the grounds around Broadmoor were covered with laurel bushes. However, Young's involvement was never proven and the death was officially ruled a suicide. Later, Harpic was found in a nurse's coffee and the contents of a missing packet of sugar soap were discovered in a tea urn.


title: Graham Young

text: He continued to read medical and toxicology textbooks, obtained from Broadmoor's library. He also continued his interest in Nazism, reading William Shirer's "The Rise and Fall of the Third Reich" and Lord Russell's "The Scourge of the Swastika". At one point, he grew a toothbrush moustache and took to mimicking the speeches of Hitler and listening to composer Richard Wagner, who had been one of Hitler's idols.


title: Graham Young

text: Young first applied for release from Broadmoor in 1965. His father and sister attended the tribunal and stated that if Young was released, none of his relatives would be willing to house him. Fred Young also told the hearing that his son should "never be released". Young's application was rejected.


title: Graham Young

text: In June 1970, after Young had spent nearly eight years in Broadmoor, Edgar Udwin, the prison psychiatrist, wrote to the Home Secretary to recommend his release, announcing that Young "is no longer obsessed with poisons, violence and mischief. And he is no longer a danger to others." However, Young remarked to a Broadmoor nurse: "When I get out, I'm going to kill one person for every year I've spent in this place."


title: Graham Young

text: One of Young's fellow patients at Broadmoor was the criminal Roy Shaw. In his autobiography "Pretty Boy" (2003), Shaw recounted his friendship with Young.


title: Graham Young

text: After his release from Broadmoor in February 1971, Young initially stayed with his sister Winifred and her husband in Hemel Hempstead. Within weeks he had resumed his interest in poisons. An attempt to acquire poison from John Bell & Croyden in Wigmore Street was unsuccessful, as the chemist refused to sell them without written authorization. Young duly returned with the required authorization on Bedford College headed notepaper and was sold 25 g of antimony potassium tartrate. He told the chemist that he needed it for a qualitative and quantitative analysis. He later returned to the same chemist to purchase 25 g of thallium.


title: Graham Young

text: Young attended a store keeping training course in Slough and stayed at a hostel in nearby Cippenham. He befriended 34-year-old Trevor Sparkes, another resident of the hostel, and the two occasionally visited the pub together or shared a bottle of wine in Sparkes' room. Young would later confess to poisoning Sparkes with antimony sodium tartrate. On the night of February 10, Sparkes was violently sick, had diarrhoea, pins and needles in his legs and pains in his testicles; earlier in the evening he had accepted a glass of water from Young. Sparkes' symptoms returned periodically over the following months. He felt so ill during a football match that he had to leave the pitch after a few minutes. Specialists were unable to pinpoint the cause, variously diagnosing it as a kidney infection, bowel infection, urinary tract infection or stomach infection. Sparkes left Slough in April 1971 and gradually recovered, though he never played football again.


title: Graham Young

text: Young secured a job as assistant storekeeper at John Hadland Laboratories in Bovingdon, Hertfordshire, near his sister's home in Hemel Hempstead. The company manufactured thallium bromide-iodide infrared lenses, which were used in military equipment. However, no thallium was stored on site, and Young obtained his supplies of the poison from a London chemist. On his application, Young stated that he had studied chemistry and toxicology. He explained that his lack of employment history was because he had suffered a nervous breakdown following the death of his mother in a car accident. His employers received references as part of Young's rehabilitation from Broadmoor, but were not informed of his past as a convicted poisoner. Young's probation officer never visited Young's home or place of work. Young left Slough and rented a room in Maynard Road, Hemel Hempstead, at £4 per week.


title: Graham Young

text: His new colleagues found him unpredictable; he could be surly and kept to himself, but on other days he was more cheery. During breaks he usually sat alone reading, invariably a book on one of his favourite subjects: war, chemistry, Nazi Germany or famous murderers. He was not talkative, unless one of his favourite topics was being discussed. Young's duties at Hadland included collecting drinks from the tea trolley in the corridor and bringing them to the storeroom. Each employee had their own mug, which made it easier for him to target specific individuals for poisoning.


title: Graham Young

text: Soon after Young's arrival at Hadland, he started poisoning his co-workers, mostly focusing on his immediate colleagues in the store rooms. His "modus operandi" was to slip poison, usually antimony or thallium, into their tea or coffee. Victims would fall ill with symptoms that included vomiting, stomach pains, nausea and diarrhoea. Initially, the mysterious illness was assumed to be a virus and was nicknamed the "Bovingdon Bug". Other explanations put forward were contamination of the local water supply and radioactivity from a disused airfield nearby.


title: Graham Young

text: 59-year-old Bob Egle was storeroom manager at Hadland and Young's immediate superior. Egle was a Dunkirk veteran and Young - a Second World War enthusiast - often asked about his wartime experiences. Young began poisoning Egle in June, weeks after his arrival at the company. Egle had several days off work with diarrhoea and severe stomach pains. His health improved after a week-long holiday, but on his return Young put a lethal dose of thallium in his afternoon tea. Egle's condition deteriorated rapidly from this point. He complained of intense back pain and numbness in his fingers and feet. He was transferred to the intensive care unit at St Albans City Hospital, where paralysis set in. Young showed a strong concern for Egle, repeatedly contacting the hospital for updates on his progress. Egle finally died on 7 July 1971. A post-mortem attributed Egle's death to a rare form of polyneuritis known as Guillain–Barré syndrome. Young was chosen to accompany managing director Godfrey Foster to Egle's funeral, as a representative of the department Egle managed. Foster recalled Young remarking how sad it was that "Bob should come through the terrors of Dunkirk only to fall victim to some strange virus."


title: Graham Young

text: During Egle's absences, Young targeted Egle's assistant Ron Hewitt, poisoning his tea with antimony. Hewitt had already accepted a job at another company and was working his notice (Young was specifically hired as his replacement). After leaving the company, he suffered no further symptoms. As a result of Egle's death and Hewitt's departure, Young was promoted to head storeman for a probationary period. For the next few months, his poisonings were limited to small doses of antimony in his co-worker Diana Smart's tea, usually when she annoyed him. Young wrote in his diary: "Di [Diana Smart] irritated me yesterday so I packed her off home with an attack of sickness. I only gave her something to shake her up. I now regret that I didn't give her a larger dose, capable of laying her up for a few days."


title: Graham Young

text: On 8 October 1971, Young put thallium acetate in David Tilson's tea. Tilson found the tea too sweet for his liking (Young had added sugar to disguise any unusual taste from the thallium) and therefore did not drink it all. Young administered a second dose of thallium a week later. Tilson was admitted to hospital with numb legs, breathing difficulties and chest pains. His skin was so tender he could not endure the weight of the bedsheets, and all his hair then fell out. Young had a back-up plan to visit Tilson in hospital and offer him a bottle of brandy laced with more thallium. Subsequently, Tilson recovered, though he was left permanently impotent by the poisoning.


title: Graham Young

text: At the same time he was poisoning Tilson, Young also began poisoning another Hadland employee, Jethro Batt. Batt had become friendly with Young and would give him a ride home to Hemel Hempstead. Young admitted to administering 4 g of thallium to Batt in two doses, enough to kill him. However, he found the coffee Young had made for him too strong and did not drink it all. Nevertheless, Batt was admitted to hospital with stomach and chest pains, and his hair fell out. The thallium made him suicidal. Batt ultimately recovered, but like Tilson he was also left impotent. Young apparently felt some remorse for poisoning Batt, writing in his diary: "I feel rather ashamed in my action in harming J [Batt]."


title: Graham Young

text: Fred Biggs was a 56-year-old local councillor and part-time employee at Hadland's. Young poisoned him with antimony, prompting the typical "Bovingdon bug" symptoms. Then, on 30 October 1971, Young put three doses of thallium acetate in Biggs' tea. By the following day, Biggs had developed chest pains and had trouble walking. Within days, he was admitted to Hemel Hempstead General Hospital, then transferred to the Whittington Hospital in North London, followed by the London National Hospital for Nervous Diseases (now part of the National Hospital for Neurology and Neurosurgery). His central nervous system deteriorated to the point that he could not speak and had trouble breathing. His skin also began to peel off. Young showed concern for Biggs' condition, continually telephoning Biggs' wife and the hospital directly to make enquiries. Biggs finally died on 19 November 1971.


title: Graham Young

text: The management at Hadland became so concerned about the mysterious sickness that they initiated an investigation. Moreover, some of Young's co-workers began to have suspicions about him. Diana Smart noticed that he was never affected by the bug and suggested he might be a carrier of the virus. Philip Doggett informed the management of Young's unhealthy interest in poisons. The firm's medical officer, Dr Iain Anderson, told staff that he had ruled out heavy metal poisoning as a possible cause, which led to an argument with Young, who insisted that the symptoms displayed by victims pointed to this diagnosis. Intrigued by the young storeman who seemed knowledgeable about medicine, Anderson sought out Young after the meeting and quizzed him further. He quickly discovered that Young had a deep knowledge of poisons and toxicology, which prompted John Hadland, the firm's owner, to contact the police. The investigating officers noticed that the onset of the "Bovingdon bug" coincided with Young's arrival at the company. A police background check revealed Young's earlier poisoning convictions.


title: Graham Young

text: Young was arrested at the home of his aunt and uncle in Sheerness, Kent, on 20 November 1971. Nothing incriminating was found on his person. He denied any wrongdoing, but as he was being led away his aunt overheard him ask the officers "which one is it you're doing me for?" When police searched his bedsit, they discovered a large stash of bottles containing poisons, including 434 milligrams of thallium and 32.33 grams of antimony, the latter 200 times a lethal dose. Other poisons in his possession included atropine, aconitine and digitalis. His lodgings were covered in swastikas and pictures of Hitler and other Nazis. Police also discovered a detailed diary that Young had kept, noting the doses he had administered, their effects, and whether he was going to allow each person to live or die. Upon further questioning by police, he admitted that the initials in the diary referred to his co-workers ('F' was Fred Biggs, 'D' was David Tilson and so on).


title: Graham Young

text: He confessed to poisoning Egle, Biggs, Batt, Tilson and Trevor Sparkes, and said that he deliberately used different poisons in order to confuse doctors. He also boasted of having committed the "perfect murder" by killing his stepmother Molly. He spent twenty minutes explaining to the officers the effects that thallium has on the human body. When asked why he had poisoned people who were his friends and colleagues, Young responded: "I suppose I had ceased to see them as a people - at least, a part of me had. They were simply guinea pigs."


title: Graham Young

text: Young was charged with two counts of murder, two counts of attempted murder, four counts of administering poison with intent to injure and four alternative counts of administering poison with intent to cause grievous bodily harm. He pleaded not guilty, which made it difficult to find a barrister willing to represent him and the trial date had to be postponed several times. Eventually, Sir Arthur Irvine QC agreed to defend him. John Leonard QC led the prosecution for the Crown. The judge was Mr Justice Eveleigh. The trial was held at St Albans Crown Court and started on 19 June 1972.


title: Graham Young

text: Due to safeguards protecting defendants, the jury could not be told of Young's previous convictions for poisoning. Young retracted his earlier confession to the police, claiming he had only made it in order to get some rest. Nevertheless, the evidence against him was strong. The prosecution called 75 witnesses to testify against him. Young himself was the only witness in his defence. Excerpts from Young's diary were read out in court. Young claimed the diary was a fantasy for a novel. Examination of Fred Biggs' internal organs found thallium in his intestines, kidneys, muscles, bones and brain tissue. The cremated remains of Bob Egle, which had not yet been scattered, were also analysed and found to contain 9 mg of thallium. The latter was the first instance of cremated ashes being used as evidence in a murder conviction.


title: Graham Young

text: On 29 June 1972, after one hour and 38 minutes of deliberation, the jury found Young guilty of two counts of murder (Bob Egle and Fred Biggs), two counts of attempted murder (Jethro Batt and David Tilson) and two counts of administering poison with intent to injure (Diana Smart and Ronald Hewitt). He was found not guilty of administering poison to Trevor Sparkes and Peter Buck, and was acquitted on all four counts of administering poison with intent to cause grievous bodily harm. Through his counsel, Young requested that he be sent to a conventional prison rather than return to Broadmoor. His request was granted, and he was sentenced to life imprisonment, to be served at HM Prison Park Lane in Maghull later changing to Ashworth Hospital.


title: Graham Young

text: During his stay at Ashworth he was moved from cells due to him being able to make a poison out of seven common household items with no antidote for it, so was moved regularly and cells searched. He would have regular visits from the medical director and during these visits Young said to the medical director that he had seen on the medical journals that a trial drug from America would be beneficial to him; they looked into this and ordered a batch from America and got him on a two week course. After the two weeks another interview with Young was arranged, during which Young informed the medical director that it seemed to be working but the effects wore off and asked for the dose to be increased. This was done and after a further two weeks another review was arranged. During this review, Young asked for his solicitor to be notified as Park Lane had been overdosing him; he was later transferred to HMP Parkhurst.


title: Graham Young

text: While in prison, Young befriended Moors murderer Ian Brady, with whom he shared a fascination for Nazi Germany. Brady's 2001 book, "The Gates of Janus", in which he discusses various serial killers, includes a chapter on Young. Brady wrote that Young "was genuinely asexual, finding even discussion of sexual matters not only uninteresting but also distinctly distasteful... Power and death were his aphrodisiacs and raisons d’être." Elsewhere Brady stated that "it was difficult not to empathise with Graham Young."


title: Graham Young

text: Young died in his cell at Parkhurst prison on the evening of 1 August 1990, one month before his 43rd birthday. The cause of death was listed as myocardial infarction at an inquest, after a postmortem. As Young had no history of heart disease, it has been speculated that he either committed suicide, or was murdered by prisoners or prison staff who did not feel safe around him.


title: Graham Young

text: On 29 June 1972, the day Young's trial ended, Home Secretary Reginald Maudling gave a statement in the House of Commons about the case and the issues it raised. He confirmed that more safeguards were to be introduced governing the release of mentally ill offenders. Henceforth, no patient at a special hospital was to be discharged without two concurring recommendations from psychiatrists. Supervision of released patients was also to be improved.


title: Graham Young

text: Maudling ordered a review of current procedures for releasing offenders from psychiatric hospitals. The review was to be carried out by a three man committee headed by Sir Carl Aarvold, Recorder of London. Their findings were published in January 1973. Maudling also announced an inquiry to review the management of mentally ill offenders in the criminal justice system, to be chaired by Lord Butler of Saffron Walden. This led to the Butler Committee's recommendations in 1975, which resulted in the expansion in forensic mental health services with the development of regional (now referred to as medium) secure units in most of the health regions in England and Wales. Prior to that there had been only the high security hospitals of Broadmoor, Rampton and Ashworth.


title: Graham Young

text: Soon after Young's conviction, reports of copycat poisonings appeared in the British press. In April 1973, Howard Grodnow of Ealing, London, committed suicide. Grodnow became convinced that he had been poisoned by Young after reading about the case. For the previous 18 months he had suffered from severe chest pains, which he traced back to an encounter, in a Hemel Hempstead pub, with a young man obsessed with poisons and chemicals. In November 2005, a 16-year-old Japanese schoolgirl was arrested for poisoning her mother with thallium. She claimed to be fascinated by Young, having seen the 1995 film (see below), and kept an online blog, similar to Young's diary, recording dosage and reactions.


title: Graham Young

text: Young was the subject of an episode of the ITV series "Crime Story", entitled "Terrible Coldness". It was broadcast on 6 October 1993. Young was portrayed by Mark Womack.


title: Graham Young

text: During his trial, Young expressed his hope that his waxwork would appear in Madame Tussauds' Chamber of Horrors. He later got his wish and his likeness appeared in the exhibit near those of his boyhood heroes Hawley Harvey Crippen and John Haigh.


title: Robbie Ray

text: Robert Glenn Ray (born October 1, 1991) is an American professional baseball pitcher for the Seattle Mariners of Major League Baseball (MLB). He previously played for the Detroit Tigers, Arizona Diamondbacks, and Toronto Blue Jays. Ray was an MLB All-Star in 2017 and won the American League Cy Young Award in 2021, when he led the league in earned run average and strikeouts.


title: Robbie Ray

text: Ray was born on October 1, 1991, in Brentwood, Tennessee. Growing up in the Nashville area, Ray often played youth baseball on travel teams alongside future Major League Baseball (MLB) All-Star Mookie Betts. Although he and Betts were on the same travel teams, they played against each other at their respective high schools, with Ray attending Brentwood and Betts at John Overton. During his senior year of high school, Ray posted a 7–1 win–loss record and a 0.50 earned run average (ERA), striking out 95 batters while walking only 13. He also pitched three no-hitters that year, including one perfect game against Centennial High School.


title: Robbie Ray

text: After de-committing from Vanderbilt University, Ray had planned to play college baseball for the Arkansas Razorbacks when he was selected by the Washington Nationals in the 12th round of the 2010 MLB Draft. He signed with the team on August 14, just before the deadline for draftees, and accepted a signing bonus of $799,000, an amount typically allotted for fourth-round draft picks. Because he signed so late in the season, Ray had limited time to play in the minor leagues in 2010. He pitched only one inning that season, striking out two batters in an appearance for the Vermont Lake Monsters of the New York–Penn League. After spending five weeks at extended spring training Ray's first professional baseball start came on May 10, 2011, when he pitched five innings for the Class A Hagerstown Suns, striking out six and walking none. Although Hagerstown missed the South Atlantic League playoffs, Ray had a standout season, going 2–3 with a 3.13 ERA in 20 starts.


title: Robbie Ray

text: Promoted to the Potomac Nationals for the 2012 season, Ray struggled with the jump to Class A-Advanced. He went 4–12 with a 6.56 ERA, walking 49 and striking out 86 in innings. Ray described the season as "put[ting] me in my place and show[ing] me what I needed to work on", and he spent the offseason adjusting his pitching mechanics with the help of minor league pitching coach Chris Michalak. By turning his hip mid-pitch and lifting his arm slot, Ray was able to isolate the strike zone, and increase his confidence as a pitcher. Leading the Carolina League (CAR) with 93 strikeouts and tying for fourth with an ERA of 2.84 in the first half, Ray was named to the CAR All-Star Team. After going 6–3 with a 3.11 ERA in 16 starts and striking out 100 batters in 84 innings, Ray was promoted to the Double-A Harrisburg Senators on July 5, 2013. He recorded a complete game shutout in only his second Double-A start, allowing just three singles and striking out 11 in a victory over the Erie SeaWolves. In 11 starts for Harrisburg, Ray went 5–2 with a 3.72 ERA, striking out 60 batters in 58 innings.


title: Robbie Ray

text: On December 3, 2013, the Nationals traded Ray, Ian Krol, and Steve Lombardozzi Jr. to the Detroit Tigers for Doug Fister, a move that was part of general manager Dave Dombrowski's larger plan to cut the Tigers' payroll and invest in pitching prospects. Ray received an invitation to join the Tigers for spring training, with the stipulation that he would only be considered for the major league starting rotation if Justin Verlander was not yet ready to return from core muscle surgery. Ray ultimately began the season with the Triple-A Toledo Mud Hens, serving as the No. 3 starter in a rotation that alternated between left- and right-handed pitchers. When Aníbal Sánchez was placed on the disabled list with a middle finger laceration, Ray, who had gone 3–2 with a 1.59 ERA in five starts for Toledo, was called up to fill his spot in the rotation. Ray made his MLB debut on May 6, 2014, allowing only one run on five hits in innings of an 11–4 rout of the Houston Astros. He was the first Tigers pitcher to win his first major league start at the age of 22 or younger since Jeff Weaver in 1999.


title: Robbie Ray

text: After two spot starts for Detroit, Ray was sent back down to Toledo, where he remained until August 10, when he was once again called up to fill in for Sánchez. Ray struggled during this second call-up, which was extended after Sánchez's strained pectoral muscle turned out to be a more severe injury than anticipated. Ray pitched in nine games for the Tigers, starting six, during which he went 1–4 with an 8.16 ERA. He found more success in Toledo, posting a 7–6 record and 4.22 ERA in 20 games (19 starts). After the regular season ended, Ray showed signs of improvement in the Arizona Fall League, where he allowed only one run and struck out 12 in his first two starts for the Glendale Desert Dogs. In four starts for Glendale, Ray went 1–1 with a 2.45 ERA, striking out 13 batters in 11 innings of work.


title: Robbie Ray

text: The Tigers traded Ray to the Arizona Diamondbacks on December 5, 2014, as part of a three-team trade also involving the New York Yankees: Ray and Domingo Leyba went from Detroit to Arizona, Didi Gregorius went from Arizona to New York, and Shane Greene went from New York to Detroit. Once there, he was assigned to the Triple-A Reno Aces to open the 2015 season. When Archie Bradley was hit in the face with a line drive, Ray was called up for a spot start in the second game of a doubleheader against the Colorado Rockies on May 6. He allowed one run on five hits in six innings and took Arizona to a 5–1 victory. When Bradley suffered another injury on June 4, Ray was once again recalled to take his place in the rotation. With a 5–12 record and 3.52 ERA, Arizona Chief Baseball Officer Tony La Russa was confident in Ray's development over the course of the 2015 season, with his increased command leading to 108 strikeouts in innings.


title: Robbie Ray

text: Ray was named to a major league opening day roster for the first time in 2016, serving as the Diamondbacks' No. 5 starter. He started the season in a slump, going over a month between his first and second wins of the season, with the second coming in a 12–2 rout of the Yankees on May 16. He hit his first career home run on June 7, a solo shot against Chris Archer of the Tampa Bay Rays. In 32 starts for the Diamondbacks, Ray was 8–15 with a 4.90 ERA in 2016. His season was marked by inconsistency: Ray had 11.3 strikeouts per nine innings (K/9), becoming only the 11th pitcher in MLB history to do so, and he recorded 218 strikeouts in innings, but his ERA was also the third-worst of any pitcher with 200 or more strikeouts in a single season. In terms of Wins Above Replacement (WAR), he was at 0.7 by Baseball-Reference.com, 3.0 by FanGraphs, and 4.8 by Baseball Prospectus.


title: Robbie Ray

text: Ray had an unremarkable start to the 2017 season, with a 4.57 ERA through eight starts. At that point, Randy Johnson, who was serving as a special assistant to the Diamondbacks' president, spoke with Ray and told him, "You better figure this out, because you never know what your last pitch is going to be." From there, Ray went on a -inning scoreless streak, including his first major league complete game shutout, coming on May 30 against the Pittsburgh Pirates. As the Diamondbacks' No. 2 starter behind Zack Greinke, Ray finished the first half of the season with eight wins and a 2.97 ERA, leading to his first All-Star Game selection. Ray's season was interrupted on July 28, when he was hit in the head with a line drive from Luke Voit of the St. Louis Cardinals. Ray fell to the ground and was placed on concussion protocols, only returning to the mound on August 24. Ray made 28 regular-season starts for Arizona, going 15–5 with a 2.89 ERA in the process. The Diamondbacks propelled to 93 wins, the best record since the franchise began, while Ray boasted 12.1 K/9 and held his opponents to a batting average of .199, the best of any Diamondback since Johnson's .197 in 2004. Ray made his first postseason start with innings of relief in the 2017 National League Wild Card Game against the Colorado Rockies. Although the Diamondbacks won that game and advanced to the 2017 National League Division Series (NLDS), the need to use Ray in the Wild Card Game pushed his start from Game 1 to Game 2 of the NLDS. There, he surrendered three runs in innings of an eventual 8–5 defeat at the hands of the Los Angeles Dodgers. The Dodgers swept the Diamondbacks in three games, eliminating Arizona from postseason contention.


title: Robbie Ray

text: After going 2–0 with a 4.88 ERA in his first four starts of the 2018 season, Ray left his April 30 start against the Nationals with a strained oblique muscle and no timetable for his return. He returned on June 27, pitching six innings and allowing two hits in a 2–1 victory over the Miami Marlins. Upon his return, Ray struggled with going deep into games: on his third time through the order, batters would hit .286 against him; the season prior, it would take four times through the lineup before his opposing batting average would be that high, He finished the season 6–2 with an ERA of 3.93 in 24 starts. In innings, he struck out 165 batters, and gave up 70 walks.


title: Robbie Ray

text: Ray pitched a career high 33 starts in 2019 despite averaging less than 6 innings per start. He was 12–8 with a 4.34 ERA in innings, tying his career best innings pitched from 2016. He also struck out a career-high 235 batters.


title: Robbie Ray

text: On August 31, 2020, the Diamondbacks traded Ray along with cash considerations to the Toronto Blue Jays in exchange for Travis Bergen. On September 1, 2020, he made his Blue Jays debut. With the 2020 Toronto Blue Jays, Ray appeared in 5 games, compiling a 1–1 record with 4.79 ERA and 25 strikeouts in 20.2 innings pitched. He re-signed with the Blue Jays for the 2021 season, signing a 1 year, $8 million contract. On July 11, 2021, Ray took a no-hitter into the 7th inning against the Tampa Bay Rays when a one-out double by Yandy Díaz broke it up.


title: Robbie Ray

text: On August 30, he struck out 10 Orioles and reached 1,000 career innings pitched. His 1,244 strikeouts are the most in Major League history through a player's first 1,000 career innings pitched.


title: Robbie Ray

text: Ray finished the 2021 season with a 13–7 record and led the American League in ERA (2.84), strikeouts (248), innings pitched (), and WHIP (1.04). He left 90.1% of runners on base, tops in the majors. Ray won the American League Cy Young Award in a near-unanimous vote, receiving 29 of 30 first-place votes. He also won the Players Choice Award for AL Outstanding Pitcher.


title: Robbie Ray

text: On November 30, 2021, the Seattle Mariners signed Ray to a five-year contract worth $115 million, with an opt-out after three years and a no-trade clause.


title: Robbie Ray

text: In 2022 he was 12-12 with a 3.71 ERA in 187 innings, and led the majors in pickoffs at first base, with six.


title: Robbie Ray

text: Ray throws a fastball in the range, topping out at . His primary off-speed pitches are a slider that averages about and tops out at , and a curveball that he throws at about .


title: FLA Live Arena

text: FLA Live Arena (previously known as the National Car Rental Center, Office Depot Center, BankAtlantic Center, and BB&T Center) is an indoor arena located next to Sawgrass Mills in Sunrise, Florida. It is the home venue for the Florida Panthers of the National Hockey League. It was completed in 1998, at a cost of US$185 million, almost entirely publicly financed, and features 70 suites and 2,623 club seats.


title: FLA Live Arena

text: In 1992, Wayne Huizenga obtained a new NHL franchise that would eventually become the Florida Panthers. Until the team had an arena of their own, they initially played at the now-demolished Miami Arena, sharing the venue with the NBA's Miami Heat. Sunrise City Manager Pat Salerno made public a $167-million financing and construction plan for a civic center near the Sawgrass Expressway in December 1995, and Broward County approved construction in February 1996. In June 1996, the site was chosen by the Panthers, and in July, Alex Muxo gathered more than a dozen architects, engineers and contractors for the first major design brainstorming session. Architects Ellerbe Becket were given 26 months to build the arena, which had to be ready by August 30, 1998, to accommodate the 1998–99 NHL season. Despite never having designed a facility that had taken less than 31 months from start to finish, they accepted the job.


title: FLA Live Arena

text: Seventy suites were completed with wet bars, closed circuit monitors and leather upholstery. Averaging over , the suites are the largest in the country for this type of facility. Also home to private lounge box seating, all construction activity was generated by over fifty subcontractors and 2.3 million man hours without a single injury. Known as the Broward County Civic Center during construction, the naming rights were won in July 1998 by National Car Rental — a company purchased by Huizenga in January 1997 — leading to the venue being named the National Car Rental Center. A certificate of occupancy was given on September 12, 1998, and the arena opened on October 3, 1998, with a Celine Dion concert. The next day, Elton John performed, and on October 9, 1998, the Florida Panthers had their first home game at their new arena.


title: FLA Live Arena

text: As NRC's new parent company, ANC Rental, went bankrupt in 2002, the Panthers sought a new sponsor for the arena. It became the Office Depot Center in the summer of 2002. (Office Depot is an office supply retailing company, which is headquartered in nearby Boca Raton.) Just over three years later, the arena's name changed again; it became the BankAtlantic Center on September 6, 2005. (BankAtlantic was headquartered in nearby Fort Lauderdale.)


title: FLA Live Arena

text: The arena is currently the largest in Florida and second-largest in the Southeastern United States, behind Greensboro Coliseum. During the 2011 offseason, the BB&T Center replaced the original green seats in the lower bowl with new red seats, as a part of the Panthers' "We See Red" campaign.


title: FLA Live Arena

text: In October 2012, Sunrise Sports and Entertainment completed installation of the Club Red seating sections encompassing the center ice seats during hockey games. It is an all-inclusive nightclub experience following the trend of other sports and entertainment venues in incorporating high-end seating sections and clubs.


title: FLA Live Arena

text: The ADT Club, located on the club level, offers food and beverage. The Duffy's Sky Club at the BB&T Center encompasses approximately and can cater to a maximum of about 500 guests. The Penalty Box offers fans another seating and dining option inside the BB&T Center. The Legends Lounge is a restaurant located on the Lexus Suite Level, and offers sit down service.


title: FLA Live Arena

text: On May 14, 2013, Broward County voted to fund a new scoreboard for the county-owned arena. On October 11, 2013, the scoreboard made its debut for the Panthers' 2013–14 home opener.


title: FLA Live Arena

text: In February 2019, it was announced that BB&T would be merging with SunTrust Banks to form Truist Financial Corporation. The merged company decided to not renew the naming rights agreement after it expired in 2021; the arena will thus have the temporary name of FLA Live Arena until a new rights partner is found.


title: FLA Live Arena

text: The arena has held boxing and mixed martial arts events such as featuring the main event of Seth Petruzelli and Kimbo Slice took place on October 4, 2008. On February 15, 2009, a lightweight bout between Nate Campbell and Ali Funeka took place in the arena.


title: FLA Live Arena

text: The Professional Bull Riders brought their Built Ford Tough Series tour to the BB&T Center in September 2005 for a bull riding event, which was won by Kody Lostroh (who ultimately became the Rookie of the Year that same year).


title: FLA Live Arena

text: In addition to the Panthers, the arena was formerly home to the Florida Pit Bulls of the American Basketball Association, the Miami Caliente of the Lingerie Football League, and the Florida Bobcats of the AFL, along with the only season of the Florida ThunderCats. This arena also serves as the host for the Orange Bowl Basketball Classic held every December in conjunction with the namesake college football game.


title: Cas9

text: Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna.


title: Cas9

text: More technically, Cas9 is a dual RNA-guided DNA endonuclease enzyme associated with the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) adaptive immune system in "Streptococcus pyogenes". "S. pyogenes" utilizes CRISPR to memorize and Cas9 to later interrogate and cleave foreign DNA, such as invading bacteriophage DNA or plasmid DNA. Cas9 performs this interrogation by unwinding foreign DNA and checking for sites complementary to the 20 nucleotide spacer region of the guide RNA (gRNA). If the DNA substrate is complementary to the guide RNA, Cas9 cleaves the invading DNA. In this sense, the CRISPR-Cas9 mechanism has a number of parallels with the RNA interference (RNAi) mechanism in eukaryotes.


title: Cas9

text: Apart from its original function in bacterial immunity, the Cas9 protein has been heavily utilized as a genome engineering tool to induce site-directed double-strand breaks in DNA. These breaks can lead to gene inactivation or the introduction of heterologous genes through non-homologous end joining and homologous recombination respectively in many laboratory model organisms. Alongside zinc finger nucleases and Transcription activator-like effector nuclease (TALEN) proteins, Cas9 is becoming a prominent tool in the field of genome editing.


title: Cas9

text: Cas9 has gained traction in recent years because it can cleave nearly any sequence complementary to the guide RNA. Because the target specificity of Cas9 stems from the guide RNA:DNA complementarity and not modifications to the protein itself (like TALENs and zinc fingers), engineering Cas9 to target new DNA is straightforward. Versions of Cas9 that bind but do not cleave cognate DNA can be used to locate transcriptional activator or repressors to specific DNA sequences in order to control transcriptional activation and repression. Native Cas9 requires a guide RNA composed of two disparate RNAs that associate – the CRISPR RNA (crRNA), and the trans-activating crRNA (tracrRNA). Cas9 targeting has been simplified through the engineering of a chimeric single guide RNA (chiRNA). Scientists have suggested that Cas9-based gene drives may be capable of editing the genomes of entire populations of organisms. In 2015, Cas9 was used to modify the genome of human embryos for the first time.


title: Cas9

text: To survive in a variety of challenging, inhospitable habitats that are filled with bacteriophages, bacteria and archaea have evolved methods to evade and fend off predatory viruses. This includes the CRISPR system of adaptive immunity. In practice, CRISPR/Cas systems act as self-programmable restriction enzymes. CRISPR loci are composed of short, palindromic repeats that occur at regular intervals composed of alternate CRISPR repeats and variable CRISPR spacers between 24 and 48 nucleotides long. These CRISPR loci are usually accompanied by adjacent CRISPR-associated (cas) genes. In 2005, it was discovered by three separate groups that the spacer regions were homologous to foreign DNA elements, including plasmids and viruses. These reports provided the first biological evidence that CRISPRs might function as an immune system.


title: Cas9

text: Cas9 has been used often as a genome-editing tool. Cas9 has been used in recent developments in preventing viruses from manipulating hosts' DNA. Since the CRISPR-Cas9 was developed from bacterial genome systems, it can be used to target the genetic material in viruses. The use of the enzyme Cas9 can be a solution to many viral infections. Cas9 possesses the ability to target specific viruses by the targeting of specific strands of the viral genetic information. More specifically the Cas9 enzyme targets certain sections of the viral genome that prevents the virus from carrying out its normal function. Cas9 has also been used to disrupt the detrimental strand of DNA and RNA that cause diseases and mutated strands of DNA. Cas9 has already showed promise in disrupting the effects of HIV-1. Cas9 has been shown to suppress the expression of the long terminal repeats in HIV-1. When introduced into the HIV-1 genome Cas9 has shown the ability to mutate strands of HIV-1. Cas9 has also been used in the treatment of Hepatitis B through targeting of the ends of certain of long terminal repeats in the Hepatitis B viral genome. Cas9 has been used to repair the mutations causing cataracts in mice.


title: Cas9

text: CRISPR-Cas systems are divided into three major types (type I, type II, and type III) and twelve subtypes, which are based on their genetic content and structural differences. However, the core defining features of all CRISPR-Cas systems are the cas genes and their proteins: cas1 and cas2 are universal across types and subtypes, while cas3, cas9, and cas10 are signature genes for type I, type II, and type III, respectively.


title: Cas9

text: Adaptation involves recognition and integration of spacers between two adjacent repeats in the CRISPR locus. The "Protospacer" refers to the sequence on the viral genome that corresponds to the spacer. A short stretch of conserved nucleotides exists proximal to the protospacer, which is called the protospacer adjacent motif (PAM). The PAM is a recognition motif that is used to acquire the DNA fragment. In type II, Cas9 recognizes the PAM during adaptation in order to ensure the acquisition of functional spacers.


title: Cas9

text: Loss of spacers and even groups of several have also been observed by Aranaz et al. 2004 and Pourcel et al. 2007. This probably occurs through homologous recombination of the between-repeat material.


title: Cas9

text: CRISPR expression includes the transcription of a primary transcript called a CRISPR RNA (pre-crRNA), which is transcribed from the CRISPR locus by RNA polymerase. Specific endoribonucleases then cleave the pre-crRNAs into small CRISPR RNAs (crRNAs).


title: Cas9

text: Interference involves the crRNAs within a multi-protein complex called CASCADE, which can recognize and specifically base-pair with regions of inserting complementary foreign DNA. The crRNA-foreign nucleic acid complex is then cleaved, however if there are mismatches between the spacer and the target DNA, or if there are mutations in the PAM, then cleavage will not be initiated. In the latter scenario, the foreign DNA is not targeted for attack by the cell, thus the replication of the virus proceeds and the host is not immune to viral infection. The interference stage can be mechanistically and temporally distinct from CRISPR acquisition and expression, yet for complete function as a defense system, all three phases must be functional.


title: Cas9

text: Stage 1: CRISPR spacer integration. Protospacers and protospacer-associated motifs (shown in red) are acquired at the "leader" end of a CRISPR array in the host DNA. The CRISPR array is composed of spacer sequences (shown in colored boxes) flanked by repeats (black diamonds). This process requires Cas1 and Cas2 (and Cas9 in type II), which are encoded in the cas locus, which are usually located near the CRISPR array.


title: Cas9

text: Stage 2: CRISPR expression. Pre-crRNA is transcribed starting at the leader region by the host RNA polymerase and then cleaved by Cas proteins into smaller crRNAs containing a single spacer and a partial repeat (shown as hairpin structure with colored spacers).


title: Cas9

text: Stage 3: CRISPR interference. crRNA with a spacer that has strong complementarity to the incoming foreign DNA begins a cleavage event (depicted with scissors), which requires Cas proteins. DNA cleavage interferes with viral replication and provides immunity to the host. The interference stage can be functionally and temporarily distinct from CRISPR acquisition and expression (depicted by white line dividing the cell).


title: Cas9

text: dCas9, also referred to as endonuclease deficient Cas9 can be utilized to edit gene expression when applied to the transcription binding site of the desired section of a gene. The optimal function of dCas9 is attributed to its mode of action. Gene expression is inhibited when nucleotides are no longer added to the RNA chain and therefore terminating elongation of that chain, and as a result affects the transcription process. This process occurs when dCas9 is mass-produced so it is able to affect the most genes at any given time via a sequence specific guide RNA molecule. Since dCas9 appears to down regulate gene expression, this action is amplified even more when it is used in conjunction with repressive chromatin modifier domains. The dCas9 protein has other functions outside of the regulation of gene expression. A promoter can be added to the dCas9 protein which allows them to work with each other to become efficient at beginning or stopping transcription at different sequences along a strand of DNA. These two proteins are specific in where they act on a gene. This is prevalent in certain types of prokaryotes when a promoter and dCas9 align themselves together to impede the ability of elongation of polymer of nucleotides coming together to form a transcribed piece of DNA. Without the promoter, the dCas9 protein does not have the same effect by itself or with a gene body.


title: Cas9

text: When examining the effects of repression of transcription further, H3K27, an amino acid component of a histone, becomes methylated through the interaction of dCas9 and a peptide called FOG1. Essentially, this interaction causes gene repression on the C + N terminal section of the amino acid complex at the specific junction of the gene, and as a result, terminates transcription.


title: Cas9

text: dCas9 also proves to be efficient when it comes to altering certain proteins that can create diseases. When the dCas9 attaches to a form of RNA called guide-RNA, it prevents the proliferation of repeating codons and DNA sequences that might be harmful to an organism's genome. Essentially, when multiple repeat codons are produced, it elicits a response, or recruits an abundance of dCas9 to combat the overproduction of those codons and results in the shut-down of transcription. dCas9 works synergistically with gRNA and directly affects the DNA polymerase II from continuing transcription.


title: Cas9

text: Further explanation of how the dCas9 protein works can be found in their utilization of plant genomes by the regulation of gene production in plants to either increase or decrease certain characteristics. The CRISPR-CAS9 system has the ability to either upregulate or downregulate genes. The dCas9 proteins are a component of the CRISPR-CAS9 system and these proteins can repress certain areas of a plant gene. This happens when dCAS9 binds to repressor domains, and in the case of the plants, deactivation of a regulatory gene such as AtCSTF64, does occur.


title: Cas9

text: Bacteria are another focus of the usage of dCas9 proteins as well. Since eukaryotes have a larger DNA makeup and genome; the much smaller bacteria are easy to manipulate. As a result, eukaryotes use dCas9 to inhibit RNA polymerase from continuing the process of transcription of genetic material.


title: Cas9

text: Cas9 features a bi-lobed architecture with the guide RNA nestled between the alpha-helical lobe (blue) and the nuclease lobe (cyan, orange, and gray). These two lobes are connected through a single bridge helix. There are two nuclease domains located in the multi-domain nuclease lobe, the RuvC (gray) which cleaves the non-target DNA strand, and the HNH nuclease domain (cyan) that cleaves the target strand of DNA. The RuvC domain is encoded by sequentially disparate sites that interact in the tertiary structure to form the RuvC cleavage domain (See right figure).


title: Cas9

text: A key feature of the target DNA is that it must contain a protospacer adjacent motif (PAM) consisting of the three-nucleotide sequence- NGG. This PAM is recognized by the PAM-interacting domain (PI domain, orange) located near the C-terminal end of Cas9. Cas9 undergoes distinct conformational changes between the apo, guide RNA bound, and guide RNA:DNA bound states.


title: Cas9

text: Cas9 recognizes the stem-loop architecture inherent in the CRISPR locus, which mediates the maturation of crRNA-tracrRNA ribonucleoprotein complex. Cas9 in complex with CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) further recognizes and degrades the target dsDNA. In the co-crystal structure shown here, the crRNA-tracrRNA complex is replaced by a chimeric single-guide RNA (sgRNA, in red) which has been proved to have the same function as the natural RNA complex. The sgRNA base paired with target ssDNA is anchored by Cas9 as a T-shaped architecture. This crystal structure of the DNA-bound Cas9 enzyme reveals distinct conformational changes in the alpha-helical lobe with respect to the nuclease lobe, as well as the location of the HNH domain. The protein consists of a recognition lobe (REC) and a nuclease lobe (NUC). All regions except the HNH form tight interactions with each other and sgRNA-ssDNA complex, while the HNH domain forms few contacts with the rest of the protein. In another conformation of Cas9 complex observed in the crystal, the HNH domain is not visible. These structures suggest the conformational flexibility of HNH domain.


title: Cas9

text: To date, at least three crystal structures have been studied and published. One representing a conformation of Cas9 in the apo state, and two representing Cas9 in the DNA bound state.


title: Cas9

text: In sgRNA-Cas9 complex, based on the crystal structure, REC1, BH and PI domains have important contacts with backbone or bases in both repeat and spacer region. Several Cas9 mutants including REC1 or REC2 domains deletion and residues mutations in BH have been tested. REC1 and BH related mutants show lower or none activity compared with wild type, which indicate these two domains are crucial for the sgRNA recognition at repeat sequence and stabilization of the whole complex. Although the interactions between spacer sequence and Cas9 as well as PI domain and repeat region need further studies, the co-crystal demonstrates clear interface between Cas9 and sgRNA.


title: Cas9

text: Previous sequence analysis and biochemical studies have posited that Cas9 contains two nuclease domains: an McrA-like HNH nuclease domain and a RuvC-like nuclease domain. These HNH and RuvC-like nuclease domains are responsible for cleavage of the complementary/target and non-complementary/non-target DNA strands, respectively. Despite low sequence similarity, the sequence similar to RNase H has a RuvC fold (one member of RNase H family) and the HNH region folds as T4 Endo VII (one member of HNH endonuclease family).


title: Cas9

text: Wild-type "S. pyogenes" Cas9 requires magnesium (Mg) cofactors for the RNA-mediated DNA cleavage; however, Cas9 has been shown to exhibit varying levels of activity in the presence of other divalent metal ions. For instance, Cas9 in the presence of manganese (Mn) has been shown to be capable of RNA-independent DNA cleavage. The kinetics of DNA cleavage by Cas9 have been of great interest to the scientific community, as this data provides insight into the intricacies of the reaction. While the cleavage of DNA by RNA-bound Cas9 has been shown to be relatively rapid ("k" ≥ 700 s), the release of the cleavage products is very slow ("t" = ln(2)/"k" ≈ 43-91 h), essentially rendering Cas9 a single-turnover enzyme. Additional studies regarding the kinetics of Cas9 have shown engineered Cas9 to be effective in reducing off-target effects by modifying the rate of the reaction.


title: Cas9

text: The cleavage efficiency of Cas9 depends on numerous factors. A key requirement is the presence of a valid PAM at the non-target strand 3 nucleotides downstream from the cleavage site. The canonical PAM sequence for "S. Pyogenes" Cas9 is NGG, but alternative motifs are tolerated with lower cleavage activity. The most efficient alternative PAM motifs for the wild-type "S. Pyogenes" Cas9 are NAG and NGA. The sequence composition at the target DNA site complementary to the 20 nucletode spacer region of the gRNA also affects cleavage efficiency. The most relevant nucleotide composition properties that impact efficiency are those in the PAM-proximal region. Free energy changes of nucleic acids are also highly relevant in defining cleavage activity. Guide RNAs that bind to the DNA forming a duplex that falls into a restricted range of binding free energy changes that excludes extremely weak or stable bindings generally perform efficiently. Stable guide RNA folding conformations can also impair cleavage.


title: Cas9

text: Most archaea and bacteria stubbornly refuse to allow a Cas9 to edit their genome. This is because they can attach foreign DNA, that does not affect them, into their genome. Another way that these cells defy Cas9 is by process of restriction modification (RM) system. When a bacteriophage enters a bacteria or archaea cell it is targeted by the RM system. The RM system then cuts the bacteriophages DNA into separate pieces by restriction enzymes and uses endonucleases to further destroy the strands of DNA. This poses a problem to Cas9 editing because the RM system also targets the foreign genes added by the Cas9 process.


title: Cas9

text: Due to the unique ability of Cas9 to bind to essentially any complement sequence in any genome, researchers wanted to use this enzyme to repress transcription of various genomic loci. To accomplish this, the two crucial catalytic residues of the RuvC and HNH domain can be mutated to alanine abolishing all endonuclease activity of Cas9. The resulting protein coined 'dead' Cas9 or 'dCas9' for short, can still tightly bind to dsDNA. This catalytically inactive Cas9 variant has been used for both mechanistic studies into Cas9 DNA interrogative binding and as a general programmable DNA binding RNA-Protein complex.


title: Cas9

text: The interaction of dCas9 with target dsDNA is so tight that high molarity urea protein denaturant can not fully dissociate the dCas9 RNA-protein complex from dsDNA target. dCas9 has been targeted with engineered single guide RNAs to transcription initiation sites of any loci where dCas9 can compete with RNA polymerase at promoters to halt transcription. Also, dCas9 can be targeted to the coding region of loci such that inhibition of RNA Polymerase occurs during the elongation phase of transcription. In Eukaryotes, silencing of gene expression can be extended by targeting dCas9 to enhancer sequences, where dCas9 can block assembly of transcription factors leading to silencing of specific gene expression. Moreover, the guide RNAs provided to dCas9 can be designed to include specific mismatches to its complementary cognate sequence that will quantitatively weaken the interaction of dCas9 for its programmed cognate sequence allowing a researcher to tune the extent of gene silencing applied to a gene of interest.


title: Cas9

text: This technology is similar in principle to RNAi such that gene expression is being modulated at the RNA level. However, the dCas9 approach has gained much traction as there exist less off-target effects and in general larger and more reproducible silencing effects through the use of dCas9 compared to RNAi screens. Furthermore, because the dCas9 approach to gene silencing can be quantitatively controlled, a researcher can now precisely control the extent to which a gene of interest is repressed allowing more questions about gene regulation and gene stoichiometry to be answered.


title: Cas9

text: Beyond direct binding of dCas9 to transcriptionally sensitive positions of loci, dCas9 can be fused to a variety of modulatory protein domains to carry out a myriad of functions. Recently, dCas9 has been fused to chromatin remodeling proteins (HDACs/HATs) to reorganize the chromatin structure around various loci. This is important in targeting various eukaryotic genes of interest as heterochromatin structures hinder Cas9 binding. Furthermore, because Cas9 can react to heterochromatin, it is theorized that this enzyme can be further applied to studying the chromatin structure of various loci. Additionally, dCas9 has been employed in genome wide screens of gene repression. By employing large libraries of guide RNAs capable of targeting thousands of genes, genome wide genetic screens using dCas9 have been conducted.


title: Cas9

text: Another method for silencing transcription with Cas9 is to directly cleave mRNA products with the catalytically active Cas9 enzyme. This approach is made possible by hybridizing ssDNA with a PAM complement sequence to ssRNA allowing for a dsDNA-RNA PAM site for Cas9 binding. This technology makes available the ability to isolate endogenous RNA transcripts in cells without the need to induce chemical modifications to RNA or RNA tagging methods.


title: Cas9

text: In contrast to silencing genes, dCas9 can also be used to activate genes when fused to transcription activating factors. These factors include subunits of bacterial RNA Polymerase II and traditional transcription factors in eukaryotes. Recently, genome-wide screens of transcription activation have also been accomplished using dCas9 fusions named 'CRISPRa' for activation.


title: The Pale Horse

text: The Pale Horse is a work of detective fiction by British writer Agatha Christie, first published in the UK by the Collins Crime Club on 6 November 1961, and in the US by Dodd, Mead and Company the following year. The UK edition retailed at fifteen shillings (15/- = 75p) and the US edition at $3.75. The novel features her novelist detective Ariadne Oliver as a minor character, and reflects in tone the supernatural novels of Dennis Wheatley who was then at the height of his popularity. The Pale Horse is mentioned in Revelation 6:8, where it is ridden by Death.


title: The Pale Horse

text: A dying woman, Mrs Davis, gives her last confession to Father Gorman, a Roman Catholic priest, but along with her confession she gives him a list of names and a terrible secret. Before he can take action, however, he is struck dead in the fog. As the police begin to investigate, a young hero begins to piece together evidence that sets him upon a converging path.


title: The Pale Horse

text: Mark Easterbrook, the central character of the book and its principal narrator, sees a fight between two girls in a Chelsea coffee bar, during which one pulls out some of the other's hair at the roots. Soon afterwards, he finds out that one of the girls, Thomasina Tuckerton, has died. At dinner with a friend, a woman named Poppy Stirling mentions something called the Pale Horse that arranges deaths, but is suddenly scared at having mentioned it and will say no more.


title: The Pale Horse

text: When Mark encounters the police surgeon, Corrigan, he learns of the list of surnames found in the shoe of a murdered priest called Father Gorman. The list includes the names Corrigan, Tuckerton and Hesketh-Dubois (the same name as Mark's godmother who has recently died of what appear to be natural causes). He begins to fear that the list contains the names of those who are dead or are shortly to die.


title: The Pale Horse

text: When Mark goes to a village fete, organised by his cousin, at Much Deeping, with the famous mystery writer, Ariadne Oliver, he hears about a house which has been converted from an old inn called the Pale Horse. The house is inhabited by three modern "witches", led by Thyrza Grey. Visiting houses in the area, he meets Mr Venables, a man who uses a wheelchair and has no apparent explanation for his substantial wealth.


title: The Pale Horse

text: Mark also visits the Pale Horse, and Thyrza Grey discusses with him the ability to kill at a distance, which she claims to have developed. In retrospect, it seems to Mark that she has been outlining to him a service that she would be willing to provide. As part of the police investigation, a witness, Zachariah Osborne, describes a man seen following Father Gorman shortly before the murder. Later, Osborne tells the police that he has seen the same man in a wheelchair. Even though he finds out that the man, Venables, is crippled by polio, and is incapable of standing due to the atrophy of his legs, Osborne remains certain of his identification and suggests that Venables could have faked his disability.


title: The Pale Horse

text: Mark's girlfriend, Hermia, does not take his growing fears seriously and he becomes disaffected with her. He does, however, receive support from Ariadne Oliver, and from a vicar's wife, Dane Calthrop, who wants him to stop whatever evil might be taking place. Mark also makes an ally of Katherine "Ginger" Corrigan, a girl whom he has met in the area, and who successfully draws Poppy out about the Pale Horse organisation. Ginger obtains from Poppy an address in Birmingham, where Mark meets Mr Bradley, a disbarred lawyer, who outlines the means by which the Pale Horse functions without breaking the law - that Bradley bets someone will die within a certain period of time and the client bets otherwise. If the person in question does die within that time, the client must pay. (One client who refused fell in front of an oncoming train and was killed).


title: The Pale Horse

text: With the agreement of Inspector Lejeune and the co-operation of Ginger, Mark agrees to solicit the murder of his first wife, who will be played by Ginger. At a ritual of some kind at the Pale Horse, Mark witnesses Thyrza apparently channel a malignant spirit through an electrical apparatus. Shortly afterwards, Ginger falls ill and begins to decline rapidly. In desperation, Mark turns to Poppy again, who mentions that friend (Eileen Brandon) resigned from a research organisation called CRC (Customers' Reactions Classified) that seems to be connected with the Pale Horse. When Mrs Brandon is interviewed, she reveals that both she and Mrs Davis worked for the organisation, which surveyed targeted people about what foods, cosmetics and proprietary medicines they used.


title: The Pale Horse

text: Ariadne Oliver contacts Mark with a key connection that she has made: another victim of the Pale Horse (Mary Delafontaine) has lost her hair during her illness. The same thing happened to Lady Hesketh-Dubois, and Thomasina's hair was easily pulled out during the fight. Moreover, Ginger has begun to shed her own hair. Mark recognises the symptoms are of thallium poisoning, not some sort of satanic assassination.


title: The Pale Horse

text: It is revealed that Osborne has been the brains behind the Pale Horse organisation, and that black magic element was a piece of misdirection on his part. The murders were committed by replacing products the victims had named in the CRC survey with poisoned ones. Osborne's clumsy attempt to implicate Venables was a vital mistake. After Osborne's arrest, Mark and Ginger, who is recovering, become engaged.


title: The Pale Horse

text: Francis Iles (Anthony Berkeley Cox) praised the novel in the 8 December 1961 issue of "The Guardian": "Mrs Agatha Christie is our nearest approach to perpetual motion. And not only does she never stop, but she drops the ball into the cup nearly every time; and if one is sometimes reminded of those automatic machines where one pulls a handle and out pops the finished product, that is a compliment to the automatic machine and not by any means a reflection on Mrs Christie. For the latest tug on the Christie handle produces a product which is not only up to the standard but even above it. "The Pale Horse" is in fact the best sample from this particular factory for some time, and that is saying plenty. The black magic theme is handled in a masterly and sinister fashion, and to give away what lay behind it would be unforgivable. This is a book which nobody (repeat, nobody) should miss." Iles further named the novel as his favourite in the paper's "Critic's choice" for the end of the year, published one week later, writing that "It has not been an outstanding year for crime fiction, but as usual there have been one or two first-class items. The best puzzle has certainly been Agatha Christie's "The Pale Horse"."


title: The Pale Horse

text: Robert Barnard: "Goodish late example – loosely plotted, but with intriguing, fantastical central idea. Plot concerns a Murder-Inc.-type organisation, with a strong overlay of black magic. Also makes use of 'The Box,' a piece of pseudo-scientific hocus-pocus fashionable in the West Country in the 'fifties (one of the things which drove Waugh to the verge of lunacy, as narrated in "Pinfold")."


title: The Pale Horse

text: In the "Binge!" article of "Entertainment Weekly" Issue #1343-44 (26 December 2014–3 January 2015), the writers picked "The Pale Horse" as an "EW favorite" on the list of the "Nine Great Christie Novels".


title: The Pale Horse

text: Several of Christie's earlier characters reappear in this book. In addition to Ariadne Oliver, Major Despard and his wife Rhoda (who met and fell in love in "Cards on the Table") also participate in the plot. Mrs Dane Calthrop from "The Moving Finger" also reappears in approximately the same role as she played in that book: the rational but devoted Christian who wants the evil stopped.


title: The Pale Horse

text: Mrs Oliver is apprehensive of attending a fete, for reasons that will be apparent to readers of her previous appearance in a Christie novel: "Dead Man's Folly".


title: The Pale Horse

text: Mrs Lancaster from "By the Pricking of My Thumbs" may have been mentioned in a conversation, when one of the characters, David Ardingly, mentions how he met an old lady in a mental home who says exactly the same phrase which chilled Tuppence to the bone, and which had a similar effect on Ardingly. Mrs Lancaster mentioned "ten past eleven", though, while Ardingly's recollection placed the mentioned time at "12.10".


title: The Pale Horse

text: This novel is notable among Christie's books as it is credited with having saved at least two lives after readers recognised the symptoms of thallium poisoning from its description in the book.


title: The Pale Horse

text: The novel is also cited to have been the "inspiration" of what was dubbed "The Mensa Murder". In 1988, George Trepal, a Mensa Club member, poisoned his neighbours, Pye and Peggy Carr and their children, with thallium introduced in a Coca-Cola Classic bottles eight-pack. Peggy Carr succumbed while the others survived the attack.


title: The Pale Horse

text: The novel was first adapted for TV by ITV in 1996, in a 100-minute TV film with Colin Buchanan as Mark Easterbrook. This version omitted the character of Ariadne Oliver. It makes Easterbrook the suspect in the killing of Father Gorman. At first it seems that the murders are masterminded by Venables, who it transpires is not disabled, but ultimately Osbourne is still revealed as the murderer.


title: The Pale Horse

text: A second adaptation was later made by the same network, done by Russell Lewis for the fifth series of ITV's "Agatha Christie's Marple" starring Julia McKenzie in 2010. As the character of Miss Marple was made the chief sleuth of the plot, several changes were made for the adaptation:


title: The Pale Horse

text: It was adapted as a 2016 episode of the French television series "Les Petits Meurtres d'Agatha Christie".


title: The Pale Horse

text: In June 2019, it was announced that Sarah Phelps, who had written several Christie adaptations for BBC and Mammoth Screen, would write a new adaptation of "The Pale Horse". The two-part series was broadcast on 9 and 16 February 2020 on BBC One. The cast included Rufus Sewell as Mark Easterbrook, Sean Pertwee as Inspector Lejeune, Bertie Carvel as Zachariah Osborne, Kaya Scodelario as Hermia, and Sheila Atim, Rita Tushingham and Kathy Kiera Clarke as the “witches” of Much Deeping. It was only very loosely based on the novel, deviating in many significant ways, including the portrayal of Mark Easterbrook as a twice-married antihero. "The Independent" noted that it had a "satisfying conclusion despite traditional whodunnit thrills", while "The Telegraph" asserted that it chucked "the rat-filled kitchen sink into this rewrite of Agatha Christie".


title: The Pale Horse

text: The novel was first serialised in the British weekly magazine "Woman’s Mirror" in eight abridged instalments from 2 September to 21 October 1961 with illustrations by Zelinski.


title: The Pale Horse

text: In the US a condensed version of the novel appeared in the April 1962 (Volume LXXIX, Number 4) issue of the "Ladies Home Journal" with an illustration by Eugenie Louis.


title: Samarium

text: Samarium is a chemical element with symbol Sm and atomic number 62. It is a moderately hard silvery metal that slowly oxidizes in air. Being a typical member of the lanthanide series, samarium usually has the oxidation state +3. Compounds of samarium(II) are also known, most notably the monoxide SmO, monochalcogenides SmS, SmSe and SmTe, as well as samarium(II) iodide. The last compound is a common reducing agent in chemical synthesis. Samarium has no significant biological role, and some samarium salts are slightly toxic.


title: Samarium

text: Samarium was discovered in 1879 by French chemist Paul-Émile Lecoq de Boisbaudran and named after the mineral samarskite from which it was isolated. The mineral itself was named after a Russian mine official, Colonel Vassili Samarsky-Bykhovets, who thus became the first person to have a chemical element named after him, albeit indirectly. Though classified as a rare-earth element, samarium is the 40th most abundant element in Earth's crust and more common than metals such as tin. Samarium occurs in concentration up to 2.8% in several minerals including cerite, gadolinite, samarskite, monazite and bastnäsite, the last two being the most common commercial sources of the element. These minerals are mostly found in China, the United States, Brazil, India, Sri Lanka and Australia; China is by far the world leader in samarium mining and production.


title: Samarium

text: The main commercial use of samarium is in samarium–cobalt magnets, which have permanent magnetization second only to neodymium magnets; however, samarium compounds can withstand significantly higher temperatures, above , without losing their magnetic properties, due to the alloy's higher Curie point. The radioisotope samarium-153 is the active component of the drug samarium (Sm) lexidronam (Quadramet), which kills cancer cells in lung cancer, prostate cancer, breast cancer and osteosarcoma. Another isotope, samarium-149, is a strong neutron absorber and so is added to control rods of nuclear reactors. It also forms as a decay product during the reactor operation and is one of the important factors considered in the reactor design and operation. Other uses of samarium include catalysis of chemical reactions, radioactive dating and X-ray lasers.


title: Samarium

text: Samarium is a rare earth element with hardness and density similar to zinc. With boiling point 1794 °C, samarium is the third most volatile lanthanide after ytterbium and europium; this helps separation of samarium from ore. At ambient conditions, samarium normally has a rhombohedral structure (α form). Upon heating to 731 °C, its crystal symmetry changes to hexagonal close-packed ("hcp"), but transition temperature depends on metal purity. Further heating to 922 °C transforms the metal into a body-centered cubic ("bcc") phase. Heating to 300 °C plus compression to 40 kbar results in a double-hexagonally close-packed structure ("dhcp"). Higher pressure of the order of hundreds or thousands of kilobars induces a series of phase transformations, in particular with a tetragonal phase appearing at about 900 kbar. In one study, the "dhcp" phase could be produced without compression, using a nonequilibrium annealing regime with a rapid temperature change between about 400 and 700 °C, confirming the transient character of this samarium phase. Also, thin films of samarium obtained by vapor deposition may contain the "hcp" or "dhcp" phases at ambient conditions.


title: Samarium

text: Samarium and its sesquioxide are paramagnetic at room temperature. Their corresponding effective magnetic moments, below 2μ, are the 3rd lowest among lanthanides (and their oxides) after lanthanum and lutetium. The metal transforms to an antiferromagnetic state upon cooling to 14.8 K. Individual samarium atoms can be isolated by encapsulating them into fullerene molecules. They can also be doped between the C molecules in the fullerene solid, rendering it superconductive at temperatures below 8 K. Samarium doping of iron-based superconductors – the most recent class of high-temperature superconductor – allows enhancing their transition temperature to 56 K, which is the highest value achieved so far in this series.


title: Samarium

text: Freshly prepared samarium has a silvery luster. In air, it slowly oxidizes at room temperature and spontaneously ignites at 150 °C. Even when stored under mineral oil, samarium gradually oxidizes and develops a grayish-yellow powder of the oxide-hydroxide mixture at the surface. The metallic appearance of a sample can be preserved by sealing it under an inert gas such as argon.


title: Samarium

text: Samarium is quite electropositive and reacts slowly with cold water and quite quickly with hot water to form samarium hydroxide:


title: Samarium

text: Samarium dissolves readily in dilute sulfuric acid to form solutions containing the yellow to pale green Sm(III) ions, which exist as complexes:


title: Samarium

text: Samarium is one of the few lanthanides that exhibit oxidation state +2. ions are blood-red in aqueous solution.


title: Samarium

text: The most stable oxide of samarium is the sesquioxide SmO. Like many samarium compounds, it exists in several crystalline phases. The trigonal form is obtained by slow cooling from the melt. The melting point of SmO is high (2345 °C), so it is usually melted not by direct heating, but with induction heating, through a radio-frequency coil. SmO crystals of monoclinic symmetry can be grown by the flame fusion method (Verneuil process) from SmO powder, that yields cylindrical boules up to several centimeters long and about one centimeter in diameter. The boules are transparent when pure and defect-free and are orange otherwise. Heating the metastable trigonal SmO to 1900 °C converts it to the more stable monoclinic phase. Cubic SmO has also been described.


title: Samarium

text: Samarium is one of the few lanthanides that form a monoxide, SmO. This lustrous golden-yellow compound was obtained by reducing SmO with samarium metal at high temperature (1000 °C) and pressure above 50 kbar; lowering the pressure resulted in incomplete reaction. SmO has cubic rock-salt lattice structure.


title: Samarium

text: Samarium forms a trivalent sulfide, selenide and telluride. Divalent chalcogenides SmS, SmSe and SmTe with cubic rock-salt crystal structure are also known. They are remarkable by converting from semiconducting to metallic state at room temperature upon application of pressure. Whereas the transition is continuous and occurs at about 20–30 kbar in SmSe and SmTe, it is abrupt in SmS and requires only 6.5 kbar. This effect results in spectacular color change in SmS from black to golden yellow when its crystals of films are scratched or polished. The transition does not change lattice symmetry, but there is a sharp decrease (~15%) in the crystal volume. It exhibits hysteresis, i.e., when the pressure is released, SmS returns to the semiconducting state at a much lower pressure of about 0.4 kbar.


title: Samarium

text: Their further reduction with samarium, lithium or sodium metals at elevated temperatures (about 700–900 °C) yields dihalides. The diiodide can also be prepared by heating SmI, or by reacting the metal with 1,2-diiodoethane in anhydrous tetrahydrofuran at room temperature:


title: Samarium

text: In addition to dihalides, the reduction also produces many non-stoichiometric samarium halides with a well-defined crystal structure, such as SmF, SmF, SmF, SmBr, SmBr and SmBr.


title: Samarium

text: As reflected in the table above, samarium halides change their crystal structures when one type of halide atom is substituted for another, which is an uncommon behavior for most elements (e.g. actinides). Many halides have two major crystal phases for one composition, one being significantly more stable and another being metastable. The latter is formed upon compression or heating, followed by quenching to ambient conditions. For example, compressing the usual monoclinic samarium diiodide and releasing the pressure results in a PbCl-type orthorhombic structure (density 5.90 g/cm), and similar treatment results in a new phase of samarium triiodide (density 5.97 g/cm).


title: Samarium

text: Sintering powders of samarium oxide and boron, in vacuum, yields a powder containing several samarium boride phases, and their volume ratio can be controlled through the mixing proportion. The powder can be converted into larger crystals of a certain samarium boride using arc melting or zone melting techniques, relying on the different melting/crystallization temperature of SmB (2580 °C), SmB (about 2300 °C) and SmB (2150 °C). All these materials are hard, brittle, dark-gray solids with the hardness increasing with the boron content. Samarium diboride is too volatile to be produced with these methods and requires high pressure (about 65 kbar) and low temperatures between 1140 and 1240 °C to stabilize its growth. Increasing the temperature results in the preferential formations of SmB.


title: Samarium

text: Samarium hexaboride is a typical intermediate-valence compound where samarium is present both as Sm and Sm ions in a 3:7 ratio. It belongs to a class of Kondo insulators, that is at high temperatures (above 50 K), its properties are typical of a Kondo metal, with metallic electrical conductivity characterized by strong electron scattering, whereas at low temperatures, it behaves as a non-magnetic insulator with a narrow band gap of about 4–14 meV. The cooling-induced metal-insulator transition in SmB is accompanied by a sharp increase in the thermal conductivity, peaking at about 15 K. The reason for this increase is that electrons themselves do not contribute to the thermal conductivity at low temperatures, which is dominated by phonons, but the decrease in electron concentration reduced the rate of electron-phonon scattering.


title: Samarium

text: Samarium carbides are prepared by melting a graphite-metal mixture in an inert atmosphere. After the synthesis, they are unstable in air and are studied also under inert atmosphere. Samarium monophosphide SmP is a semiconductor with the bandgap of 1.10 eV, the same as in silicon, and high electrical conductivity of n-type. It can be prepared by annealing at 1100 °C an evacuated quartz ampoule containing mixed powders of phosphorus and samarium. Phosphorus is highly volatile at high temperatures and may explode, thus the heating rate has to be kept well below 1 °C/min. Similar procedure is adopted for the monarsenide SmAs, but the synthesis temperature is higher at 1800 °C.


title: Samarium

text: Numerous crystalline binary compounds are known for samarium and one of the group-14, 15 or 16 element X, where X is Si, Ge, Sn, Pb, Sb or Te, and metallic alloys of samarium form another large group. They are all prepared by annealing mixed powders of the corresponding elements. Many of the resulting compounds are non-stoichiometric and have nominal compositions SmX, where the b/a ratio varies between 0.5 and 3.


title: Samarium

text: Samarium forms a cyclopentadienide and its chloroderivatives and . They are prepared by reacting samarium trichloride with in tetrahydrofuran. Contrary to cyclopentadienides of most other lanthanides, in some rings bridge each other by forming ring vertexes η or edges η toward another neighboring samarium, thus creating polymeric chains. The chloroderivative has a dimer structure, which is more accurately expressed as . There, the chlorine bridges can be replaced, for instance, by iodine, hydrogen or nitrogen atoms or by CN groups.


title: Samarium

text: The () ion in samarium cyclopentadienides can be replaced by the indenide () or cyclooctatetraenide () ring, resulting in or . The latter compound has a structure similar to uranocene. There is also a cyclopentadienide of divalent samarium, a solid that sublimates at about 85 °C. Contrary to ferrocene, the rings in are not parallel but are tilted by 40°.


title: Samarium

text: Naturally occurring samarium is composed of five stable isotopes: Sm, Sm, Sm, Sm and Sm, and two extremely long-lived radioisotopes, Sm (half-life "t" = 1.06 years) and Sm (7 years), with Sm being the most abundant (26.75%). Sm is listed by various sources either as stable or radioactive, but only a lower bound for its half-life is given. Some observationally stable samarium isotopes are predicted to decay to isotopes of neodymium.


title: Samarium

text: The long-lived isotopes Sm, Sm, and Sm, primarily alpha decay to neodymium. Lighter unstable isotopes of samarium mainly decay by electron capture to promethium, while heavier ones beta decay to europium. Natural samarium has a radioactivity of 127 Bq/g, mostly due to Sm. Sm can be used as an extinct radionuclide in radiometric dating.


title: Samarium

text: The half-lives of Sm and Sm are 90 years and 340 days, respectively. All remaining radioisotopes, which range from Sm to Sm, have half-lives that are less than 2 days, and most these have half-life less than 48 seconds. Samarium also has twelve known nuclear isomers, the most stable of which are Sm (half-life 22.6 minutes), Sm ("t" = 66 seconds), and Sm ("t" = 10.7 seconds).


title: Samarium

text: Detection of samarium and related elements was announced by several scientists in the second half of the 19th century; however, most sources give priority to French chemist Paul-Émile Lecoq de Boisbaudran. Boisbaudran isolated samarium oxide and/or hydroxide in Paris in 1879 from the mineral samarskite ) and identified a new element in it via sharp optical absorption lines. Swiss chemist Marc Delafontaine announced a new element "decipium" (from meaning "deceptive, misleading") in 1878, but later in 1880–1881 demonstrated that it was a mix of several elements, one being identical to Boisbaudran's samarium. Though samarskite was first found in the remote Russian region of Urals, by the late 1870s it had been found in other places, making it available to many researchers. In particular, it was found that the samarium isolated by Boisbaudran was also impure and had a comparable amount of europium. The pure element was produced only in 1901 by Eugène-Anatole Demarçay.


title: Samarium

text: Boisbaudran named his element "samaria" after the mineral samarskite, which in turn honored Vassili Samarsky-Bykhovets (1803–1870). Samarsky-Bykhovets, as the Chief of Staff of the Russian Corps of Mining Engineers, had granted access for two German mineralogists, the brothers Gustav and Heinrich Rose, to study the mineral samples from the Urals. Samarium was thus the first chemical element to be named after a person. Later the name "samaria" used by Boisbaudran became "samarium", to conform with other element names. Samaria is now sometimes used to mean samarium oxide, by analogy with yttria, zirconia, alumina, ceria, holmia, etc. The symbol "Sm" was suggested for samarium, but an alternative "Sa" was often used instead until the 1920s.


title: Samarium

text: Before the advent of ion-exchange separation technology in the 1950s, pure samarium had no commercial uses. However, a by-product of fractional crystallization purification of neodymium was a mix of samarium and gadolinium that got the name "Lindsay Mix" after the company that made it. This material is thought to have been used for nuclear control rods in some early nuclear reactors. Nowadays, a similar commodity product has the name "samarium-europium-gadolinium" (SEG) concentrate. It is prepared by solvent extraction from the mixed lanthanides isolated from bastnäsite (or monazite). Since heavier lanthanides have more affinity for the solvent used, they are easily extracted from the bulk using relatively small proportions of solvent. Not all rare-earth producers who process bastnäsite do so on a large enough scale to continue by separating the components of SEG, which typically makes up only 1-2% of the original ore. Such producers therefore make SEG with a view to marketing it to the specialized processors. In this manner, the valuable europium in the ore is rescued for use in making phosphor. Samarium purification follows the removal of the europium. , being in oversupply, samarium oxide is cheaper on a commercial scale than its relative abundance in the ore might suggest.


title: Samarium

text: With the average concentration of about 8 parts per million (ppm), samarium is the 40th most abundant element in the Earth's crust. It is the fifth most abundant lanthanide and is more common than elements such as tin. Samarium concentration in soils varies between 2 and 23 ppm, and oceans contain about 0.5–0.8 parts per trillion. Distribution of samarium in soils strongly depends on its chemical state and is very inhomogeneous: in sandy soils, samarium concentration is about 200 times higher at the surface of soil particles than in the water trapped between them, and this ratio can exceed 1,000 in clays.


title: Samarium

text: Samarium is not found free in nature, but, like other rare earth elements, is contained in many minerals, including monazite, bastnäsite, cerite, gadolinite and samarskite; monazite (in which samarium occurs at concentrations of up to 2.8%) and bastnäsite are mostly used as commercial sources. World resources of samarium are estimated at two million tonnes; they are mostly located in China, US, Brazil, India, Sri Lanka and Australia, and the annual production is about 700 tonnes. Country production reports are usually given for all rare-earth metals combined. By far, China has the largest production with 120,000 tonnes mined per year; it is followed by the US (about 5,000 tonnes) and India (2,700 tonnes). Samarium is usually sold as oxide, which at the price of about US$30/kg is one of the cheapest lanthanide oxides. Whereas mischmetal – a mixture of rare earth metals containing about 1% of samarium – has long been used, relatively pure samarium has been isolated only recently, through ion exchange processes, solvent extraction techniques, and electrochemical deposition. The metal is often prepared by electrolysis of a molten mixture of samarium(III) chloride with sodium chloride or calcium chloride. Samarium can also be obtained by reducing its oxide with lanthanum. The product is then distilled to separate samarium (boiling point 1794 °C) and lanthanum (b.p. 3464 °C).


title: Samarium

text: Domination of samarium in minerals is unique. Minerals with essential (dominant) samarium include monazite-(Sm) and florencite-(Sm). They are very rare.


title: Samarium

text: Samarium-151 is produced in nuclear fission of uranium with a yield of about 0.4% of all fissions. It is also made by neutron capture by samarium-149, which is added to the control rods of nuclear reactors. Therefore, Sm is present in spent nuclear fuel and radioactive waste.


title: Samarium

text: One of the most important uses of samarium is samarium–cobalt magnets, which are nominally or . They have high permanent magnetization, about 10,000 times that of iron and second only to neodymium magnets. However, samarium magnets resist demagnetization better; they are stable to temperatures above 700 °C (cf. 300–400 °C for neodymium magnets). These magnets are found in small motors, headphones, and high-end magnetic pickups for guitars and related musical instruments. For example, they are used in the motors of a solar-powered electric aircraft, the Solar Challenger, and in the Samarium Cobalt Noiseless electric guitar and bass pickups.


title: Samarium

text: Another important use of samarium and its compounds is as catalyst and chemical reagent. Samarium catalysts help decomposition of plastics, dechlorination of pollutants such as polychlorinated biphenyls (PCB), as well as dehydration and dehydrogenation of ethanol. Samarium(III) triflate , that is , is one of the most efficient Lewis acid catalysts for a halogen-promoted Friedel–Crafts reaction with alkenes. Samarium(II) iodide is a very common reducing and coupling agent in organic synthesis, for example in desulfonylation reactions; annulation; Danishefsky, Kuwajima, Mukaiyama and Holton Taxol total syntheses; strychnine total synthesis; Barbier reaction and other reductions with samarium(II) iodide.


title: Samarium

text: In its usual oxidized form, samarium is added to ceramics and glasses where it increases absorption of infrared light. As a (minor) part of mischmetal, samarium is found in "flint" ignition device of many lighters and torches.