Generic top-level domain

Generic top-level domains (gTLDs) are one of the categories of top-level domains (TLDs) maintained by the Internet Assigned Numbers Authority (IANA) for use in the Domain Name System of the Internet. A top-level domain is the last label of every fully qualified domain name. They are called generic for historic reasons; initially, they were contrasted with country-specific TLDs in RFC 920.

The core group of generic top-level domains consists of the com, info, net, and org domains. In addition, the domains biz, name, and pro are also considered generic; however, these are designated as restricted, because registrations within them require proof of eligibility within the guidelines set for each.

Historically, the group of generic top-level domains included domains, created in the early development of the domain name system, that are now sponsored by designated agencies or organizations and are restricted to specific types of registrants. Thus, domains edu, gov, int, and mil are now considered sponsored top-level domains, much like the themed top-level domains (e.g., jobs). The entire group of domains that do not have a geographic or country designation (see country-code top-level domain) is still often referred to by the term generic TLDs.

Pilot (House)

"Pilot", also known as "Everybody Lies", is the first episode of the U.S. television series House. The episode premiered on the Fox network on November 16, 2004. It introduces the character of Dr. Gregory House (played by Hugh Laurie)—a maverick antisocial doctor—and his team of diagnosticians at the fictional Princeton-Plainsboro Teaching Hospital in New Jersey. The episode features House's attempts to diagnose a kindergarten teacher after she collapses in class.

House was created by David Shore, who got the idea for the curmudgeonly title character from a doctor's visit. Initially, producer Bryan Singer wanted an American to play House, but British actor Hugh Laurie's audition convinced him that a foreign actor could play the role. Shore wrote House as a character with parallels to Sherlock Holmes—both are drug users, aloof, and largely friendless. The show's producers wanted House handicapped in some way and gave the character a damaged leg arising from an improper diagnosis.

House (1995 film)

House is a Canadian drama film, released in 1995. Written and directed by Laurie Lynd as an adaptation of Daniel MacIvor's one-man play House, the film stars MacIvor as Victor, an antisocial drifter with some hints of paranoid schizophrenia, who arrives in the town of Hope Springs and invites ten strangers into the local church to watch him perform a monologue about his struggles and disappointments in life.

The original play was performed solely by MacIvor. For the film, Lynd added several other actors, giving the audience members some moments of direct interaction and intercutting Victor's monologue with scenes which directly depict the stories he describes. The extended cast includes Anne Anglin, Ben Cardinal, Patricia Collins, Jerry Franken, Caroline Gillis, Kathryn Greenwood, Nicky Guadagni, Joan Heney, Rachel Luttrell, Stephen Ouimette, Simon Richards, Christofer Williamson and Jonathan Wilson.

The film premiered at the 1995 Toronto International Film Festival in the Perspectives Canada series, before going into general release in 1996.

SOD1

Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or SOD1 is an enzyme that in humans is encoded by the SOD1 gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis and amyotrophic lateral sclerosis.

Structure

SOD1 is a 32 kDa homodimer which forms a β-barrel and contains an intramolecular disulfide bond and a binuclear Cu/Zn site in each subunit. This Cu/Zn site holds the copper and a zinc ion and is responsible for catalyzing the disproportionation of superoxide to hydrogen peroxide and dioxygen. The maturation process of this protein is complex and not fully understood, involving the selective binding of copper and zinc ions, formation of the intra-subunit disulfide bond between Cys-57 and Cys-146, and dimerization of the two subunits. The copper chaperone for Sod1 (CCS) facilitates copper insertion and disulfide oxidation. Though SOD1 is synthesized in the cytosol can mature there, the fraction of expressed, and still immature, SOD1 targeted to the mitochondria must be inserted into the intermembrane space. There, it forms the disulfide bond, though not metallation, required for its maturation. The mature protein is highly stable, but unstable when in its metal-free and disulfide-reduced forms. This manifests in vitro, as the loss of metal ions results in increased SOD1 aggregation, and in disease models, where low metallation is observed for insoluble SOD1. Moreover, the surface-exposed reduced cysteines could participate in disulfide crosslinking and, thus, aggregation.