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Fibrinogen

Fibrinogen is a glycoprotein complex that circulates in the blood of vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and to a fibrin-based blood clot. Fibrin clots function to occlude blood vessels to stop bleeding. Fibrin binds and reduces the activity of thrombin; this activity, sometimes referred to as antithrombin I, limits clotting. Fibrin mediates blood platelet and endothelial cell spreading, tissue fibroblast proliferation, capillary tube formation, angiogenesis and thereby promotes revascularization and wound healing. Reduced and/or dysfunctional fibrinogens occur in various congenital and acquired human fibrinogen-related disorders; these disorders represent a group of rare conditions in which individuals may present with severe episodes of pathological bleeding and thrombosis. These disorders may be the cause of certain liver and kidney diseases. Fibrinogen is a "positive" acute-phase protein, i.e. its blood levels rise in response to systemic inflammation, tissue injury, certain other events.

It is elevated in various cancers. Elevated levels of fibrinogen in inflammation as well as cancer and other conditions have been suggested to be the cause of thrombosis and vascular injury that accompanies these conditions. Fibrinogen is made and secreted into the blood by liver hepatocyte cells. Endothelium cells are reported to make small amounts of fibrinogen, but this fibrinogen has not been characterized; the final secreted, hepatocyte-derived glycoprotein is composed of two trimers, with each trimer composed of three different polypeptide chains, the fibrinogen alpha chain encoded by the FGA gene, the fibrinogen beta chain encoded by the FGB gene, the fibrinogen gamma chain encoded by the FGG gene. All three genes are located on the long or "p" arm of human chromosome 4. Alternate splicing of the FGA gene produces a minor expanded isoform of Aα termed AαE which replaces Aα in 1–3% of circulating fibrinogen. Hence, the final fibrinogen product is composed principally of Aα, Bβ, γ chains with a small percentage of it containing AαE and/or γ' chains in place of Aα and/or γ chains, respectively.

The three genes are transcribed and translated in co-ordination by a mechanism which remains incompletely understood. The coordinated transcription of these three fibrinogen genes is and increased by systemic conditions such as inflammation and tissue injury. Cytokines produced during these systemic conditions, such as interleukin 6 and interleukin 1β, appear responsible for up-regulating this transcription; the Aα, Bβ, γ chains are transcribed and translated coordinately on the endoplasmic reticulum, with their peptide chains being passed into the ER while their signal peptide portions are removed. Inside the ER, the three chains are assembled into Aαγ and Bβγ dimers to AαBβγ trimers, to 2 heximers, i.e. two AαBβγ trimers joined together by numerous disulfide bonds. The heximer is transferred to the Golgi where it is glycosylated, hydroxylated and phosphorylated to form the mature fibrinogen glycoprotein, secreted into the blood. Mature fibrinogen is arranged as a long flexible protein array of three nodules held together by a thin thread, estimated to have a diameter between 8 and 15 Ångstrom.

The two end nodules are alike in consisting of Bβ and γ chains, while the center smaller nodule consists of two intertwined Aα alpha chains. Measurements of shadow lengths indicate that nodule diameters are in the range 50 to 70 Å; the length of the dried molecule is 475 ± 25 Å. The fibrinogen molecule circulates as a soluble plasma glycoprotein with a typical molecular weight of ~340 kDa, it has a rod-like shape with dimensions of 9 × 47.5 × 6 nm and has a negative net charge at physiological pH. The normal concentration of fibrinogen in blood plasma is 150–400 mg/dl, with levels appreciably below or above this range associated with pathological bleeding and/or thrombosis. Fibrinogen has a circulating half-life of ~4 days. During blood clotting, thrombin attacks the N-terminus of the Aα and Bβ chains in fibrinogen to form individual fibrin strands plus two small polypeptides, fibrinopeptides A and B derived from these respective chains; the individual fibrin strands polymerize and are crosslinked with other fibrin stands by blood factor XIIIa to form an extensive interconnected fibrin network, the basis for the formation of a mature fibrin clot.

In addition to forming fibrin, fibrinogen promotes blood clotting by forming bridges between, activating, blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor. Fibrin participates in limiting blood clot formation and degraging formed blood clots by at least two important mechanisms. First, it possesses three low affinity binding sites for thrombin. Second, fibrin's Aα chain accelerates by at least 100-fold the amount of plasmin act

Damien Karras

Father Damien Karras, SJ is a fictional character from the novel The Exorcist, its sequel Legion, one of the main protagonists in The Exorcist and a supporting character in the film adaptation of Legion. He is portrayed by Jason Miller. In William Peter Blatty's The Exorcist, Father Karras was one of the priests who exorcises the demon from young Regan MacNeil, he is a Jesuit psychiatrist suffering a crisis of faith. He searches for proof to lead an exorcism, yet during his investigation he comes to realize that there is no better way for God to prove His own existence than to reveal the foul presence of a demon. During the exorcism, the demon brings up the subject of Karras's mother's death and how he wasn't there to see her die, which seems to trouble Karras emotionally. Father Karras dies by throwing himself down a flight of stone steps in order to purge the demon from his own body after having coaxed it out of Regan's. In the sequel, Legion, it is revealed that after the demon departed, another evil spirit invaded Karras's body.

Karras was found wandering and amnesiac and was placed in the care of a mental hospital near Washington, D. C. While incarcerated there, the spirit suppresses Karras's personality and makes forays into the bodies of other patients in order to commit a series of ritual murders. In the films The Exorcist and The Exorcist III, he is played by Jason Miller. Jack Nicholson was up for the part of Karras. According to The Exorcist director William Friedkin, Paul Newman wanted to portray Karras. Friedkin spotted Miller following a performance of Miller's play That Championship Season in New York. Though Miller had never acted in a film, Keach's contract was bought out by Warner Brothers, Miller was signed. In the 2014 BBC Radio dramatisation Karras is voiced by Robert Glenister. Damien Karras was born on April 1933 to a Greek family, he became a Jesuit priest on July 30, 1957. Over the years, the priest began to doubt the existence of God, the Devil, many Biblical and supernatural beings. Still a Jesuit, he decided to become a psychiatrist.

Along with fellow-Jesuit Father Lankester Merrin, Karras attempts to exorcise 12-year-old Regan MacNeil. In the process, Merrin suffers a fatal heart attack and an embittered Karras provokes the possessed child, forcing the demon to channel itself into him instead. Karras dominated by the demon, throws himself out the window of the MacNeils' residence, seeing it as his chance to purge the world of the evil being. At the same time that Karras died, a criminal by the name of James Venamun was executed; the demon left the body of the dead Karras and placed Venamun's soul into Karras's body as a means of revenge for having been thrown out of Regan MacNeil's. The body was switched prior to interment and an amnesiac Karras was found roaming the streets of Washington DC. Soon, he was placed under the care of a mental hospital, he remained in cell #11 for 15 years. His brain and bone tissues mended over time, but he alternated between his own personality and that of Venamun; the spirit of Venamun left Karras's body by night to invade the other patients in the ward, making them commit murders for him without Venamun taking the blame.

The Gemini Killer had come back to wreak havoc. In the film, during the course of an exorcism, Venamun is forced to abandon Karras's body and Lt. William Kinderman shoots Karras several times, ending Karras's life for the final time. In the book, Venamun's father passes away from natural causes and Venamun wills Karras' body to die as he sees no more reason to remain in the world if he cannot continue to shame his father. Damien Karras at The Exorcist Damien Karras at Heroes

Bethel Regional High School shooting

The Bethel Regional High School shooting was a school shooting that occurred on February 19, 1997, when student Evan Ramsey shot and killed two people and wounded two others at Bethel Regional High School in Bethel, Alaska. Ramsey is serving two 99-year prison sentences and will be eligible for parole in 2066 when he is 85. Reports say in the two weeks prior to the incident, more than 15 students knew of Ramsey's intention to commit a school shooting, two assisted him. One student named James Randall taught him how to load and fire a shotgun, another named Matthew Charles told him of the infamy that would come. Reports say that several students brought cameras to school on the day of the shooting, that many students were watching the shooting from a library balcony overlooking the student commons area. On February 19, 1997, Ramsey armed himself with a Mossberg 500 12-gauge shotgun, arrived at Bethel Regional High School by school bus, he approached the student commons area, brandishing the shotgun, shot 15-year-old Josh Palacios in the abdomen, who died after emergency surgery.

He shot and injured two other students. Reyne Athanas, an art teacher, entered the commons area after hearing the gunshots. Athanas said she failed to convince Ramsey to surrender, he entered the main lobby, where he shot principal Ron Edwards twice, killing him. Ramsey retreated to the commons area, shooting once at police. Ramsey placed the shotgun barrel under his chin, but reportedly said, "I don't want to die," laid the shotgun on the ground, surrendered without further incident. Ramsey was believed to be bullied at school. According to his friends, Ramsey complained of being harassed and teased by other students to the extent of only addressing him as "Screech", a character from the TV series Saved by the Bell. In addition to being picked on by peers, Ramsey had a long history of abuse, his mother lived with a series of violent men who abused his brothers. He was physically and sexually abused by an older boy in one of the foster homes he was placed. Evan Ramsey was identified as the gunman.

When he was five years old, his father was imprisoned after a police standoff and his mother became an alcoholic. Ramsey and his family soon after were forced to relocate to the Anchorage area after their house was set on fire; when he was seven, the Anchorage Department of Youth and Family Services removed Ramsey and his two brothers from his mother's custody and placed them in foster care. He was soon separated from his older brother and lived in eleven different foster homes between 1988 and 1991. Ramsey and his younger brother were abused by several foster parents, his younger brother, claimed that their foster brothers would pay other children to beat Evan for their amusement. Ramsey was adopted with his brother at age 10, settled in Bethel, with their foster mother. Ramsey has suffered from depression since early childhood, attempted suicide when he was 10 years old. Ramsey was not the first in his family to take a firearm into a public place. In October 1986, his father, Don Ramsey, went to the Anchorage Times newspaper office armed with an Armalite AR-18 rifle, a revolver, more than 210 rounds of ammunition.

While inside the building, Don Ramsey began taking hostages and was involved in a brief standoff with police until he surrendered. His motive for doing this was because he was angered that the Times refused to publish a political letter he had written, he was sentenced to 10 years in prison, was paroled just several weeks before his son Evan perpetrated the school shooting. A week before Evan's attack, his older brother was arrested for armed robbery. Following his arrest, Ramsey claimed, his trial was delayed as prosecutors discussed whether Ramsey should be tried as a juvenile or as an adult. Prosecutors decided to try Ramsey as an adult in Anchorage. On Dec. 2, 1998, Ramsey was found guilty of two counts of first-degree murder, three counts of first-degree attempted murder, fifteen counts of third-degree assault. Judge Mark Isaac Wood sentenced him to 210 years in prison, he is imprisoned at the Spring Creek Correctional Center in Seward, will be eligible for parole in 2066, when he will be 85 years old.

On February 15, 2006, Ramsey participated in an interview with Anderson Cooper titled In the Mind of a Killer, in which his father Don Ramsey blamed the video game Doom for the shooting. His crime was profiled on the Court TV series Anatomy of a Crime. Ramsey's actions were covered in the program Kids Who Kill which featured interviews with Ramsey. Violence goes to School Young lives at risk Court case of Evan E. Ramsey Portrait Of A High School Killer