A board of directors is a group of people who jointly supervise the activities of an organization, which can be either a for-profit business, nonprofit organization, or a government agency. Such a board's powers and responsibilities are determined by government regulations and the organization's own constitution and bylaws; these authorities may specify the number of members of the board, how they are to be chosen, how they are to meet. In an organization with voting members, the board is accountable to, might be subordinate to, the organization's full membership, which vote for the members of the board. In a stock corporation, non-executive directors are voted for by the shareholders, with the board having ultimate responsibility for the management of the corporation; the board of directors appoints the chief executive officer of the corporation and sets out the overall strategic direction. In corporations with dispersed ownership, the identification and nomination of directors are done by the board itself, leading to a high degree of self-perpetuation.
In a non-stock corporation with no general voting membership, the board is the supreme governing body of the institution, its members are sometimes chosen by the board itself. Other names include board of directors and advisors, board of governors, board of managers, board of regents, board of trustees, or board of visitors, it may be called "the executive board" and is simply referred to as "the board". Typical duties of boards of directors include: governing the organization by establishing broad policies and setting out strategic objectives. For companies with publicly trading stock, these responsibilities are much more rigorous and complex than for those of other types; the board chooses one of its members to be the chairman, who holds whatever title is specified in the by-laws or articles of association. However, in membership organizations, the members elect the president of the organization and the president becomes the board chair, unless the by-laws say otherwise; the directors of an organization are the persons.
Several specific terms categorize directors by the presence or absence of their other relationships to the organization. An inside director is a director, an employee, chief executive, major shareholder, or someone connected to the organization. Inside directors represent the interests of the entity's stakeholders, have special knowledge of its inner workings, its financial or market position, so on. Typical inside directors are: A chief executive officer who may be chairman of the board Other executives of the organization, such as its chief financial officer or executive vice president Large shareholders Representatives of other stakeholders such as labor unions, major lenders, or members of the community in which the organization is locatedAn inside director, employed as a manager or executive of the organization is sometimes referred to as an executive director. Executive directors have a specified area of responsibility in the organization, such as finance, human resources, or production.
An outside director is a member of the board, not otherwise employed by or engaged with the organization, does not represent any of its stakeholders. A typical example is a director, president of a firm in a different industry. Outside directors are not affiliated with it in any other way. Outside directors bring outside experience and perspectives to the board. For example, for a company that serves a domestic market only, the presence of CEOs from global multinational corporations as outside directors can help to provide insights on export and import opportunities and international trade options. One of the arguments for having outside directors is that they can keep a watchful eye on the inside directors and on the way the organization is run. Outside directors are unlikely to tolerate "insider dealing" between inside directors, as outside directors do not benefit from the company or organization. Outside directors are useful in handling disputes between inside directors, or between shareholders and the board.
They are thought to be advantageous because they can be objective and present little risk of conflict of interest. On the other hand, they might lack familiarity with the specific issues connected to the organization's governance, they might not know about the industry or sector in which the organization is operating. Director – a person appointed to serve on the board of an organization, such as an institution or business. Inside director – a director who, in addition to serving on the board, has a meaningful connection to the organization Outside director – a director who, other than serving on the board, has no meaningful connections to the organization Executive director – an insi
HIV-1 protease is a retroviral aspartyl protease, an enzyme involved with peptide bond hydrolysis in retroviruses, essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV protease cleaves newly synthesized polyproteins at nine cleavage sites to create the mature protein components of an HIV virion, the infectious form of a virus outside of the host cell. Without effective HIV protease, HIV virions remain uninfectious. Mature HIV protease exists with each subunit made up of 99 amino acids. A single active site lies between the identical subunits and has the characteristic Asp-Thr-Gly catalytic triad sequence common to aspartic proteases; as HIV-1 PR can only function as a dimer, the mature protease contains two Asp25 amino acids, one from each monomer, that act in conjunction with each other as the catalytic residues. Additionally, HIV protease has two molecular "flaps" which move a distance of up to 7 Å when the enzyme becomes associated with a substrate; this can be visualized with animations of the flaps closing.
The Gag-Pol polyprotein, which contains premature coding proteins, including HIV-1 PR. PR is located between the p6pol of the transframe region. In order for this precursor to become a functional protein, each monomer must associate with another HIV-1 PR monomer to form a functional catalytic active site by each contributing the Asp25 of their respective catalytic triads; when viral HIV-RNA enters the cell, it is accompanied by a reverse transcriptase, an integrase, a mature HIV-1 PR. The reverse transcriptase converts viral RNA into DNA, facilitating the integrase's role in incorporating viral genetic information with the host cell DNA; the viral DNA can either remain dormant in the nucleus or be transcribed into mRNA and translated by the host cell into the Gag-Pol polyprotein, which would be cleaved into individual functional proteins by the mature HIV-1 PR. The HIV-1 PR precursor catalyzes its own production by facilitating its cleavage from the Gag-Pol polyprotein in a mechanism known as auto-processing.
Auto-processing of HIV-1 PR is characterized by two sequential steps: the intramolecular cleavage of the N-terminus at the p6pol-protease cleavage site, which serves to finalize PR processing and increase enzymatic activity with the newly formed PR-reverse transcriptase intermediate, the intermolecular cleavage of the C-terminus at the protease-reverse transcriptase cleavage site, leading to the assembly of two PR subunits into mature dimers. Dimerization of the two subunits allows for functional, combined active site, characterized by two Asp25 catalytic residues, to form. HIV-1 PR serves a dual purpose. Precursor HIV-1 PR is responsible for catalyzing its own production into mature PR enzymes via PR auto-processing. Mature protease is able to hydrolyze peptide bonds on the Gag-Pol polyproteins at nine specific sites, processing the resulting subunits into mature functional proteins; these cleaved proteins, including reverse transcriptase, RNaseH, are encoded by the coding region components necessary for viral replication.
As an aspartic protease, the dimerized HIV-1 PR functions through the aspartyl group complex, in order to perform hydrolysis. Of the two Asp25 residues on the combined catalytic active site of HIV-1 PR, one is deprotonated while the other is protonated, due to pKa differences from the micro-environment. In a general aspartic protease mechanism, once the substrate is properly bound to the active site of the enzyme, the deprotonated Asp25 catalytic amino acid undergoes base catalysis, rendering the incoming water molecule a better nucleophile by deprotonating it; the resulting hydroxyl ion attacks the carbonyl carbon of the peptide bond, forming an intermediate with a transient oxyanion, stabilized by the protonated Asp25. The oxyanion re-forms a double bond, leading to the cleavage of the peptide bond between the two amino acids, while the deprotonated Asp25 undergoes acid catalysis to donate its proton to the amino group, making the amino group a better leaving group for complete peptide bond cleavage and returning to its original deprotonated state.
While HIV-1 PR shares many of the same characteristics as a non-viral aspartic protease, some evidence has shown that HIV-1 PR catalyzes hydrolysis in a concerted manner. With its integral role in HIV replication, HIV protease has been a prime target for drug therapy. HIV protease inhibitors work by binding to the active site by mimicking the tetrahedral intermediate of its substrate and becoming “stuck,” disabling the enzyme. After assembly and budding, viral particles lacking active protease cannot mature into infectious virions. Several protease inhibitors have been licensed for HIV therapy. There are ten HIV-1 PR inhibitors that are approved by the Food and Drug Administration; these include indinavir, ritonavir, lopinavir, fosamprenevir, atazanavir and darunavir. Many of the inhibitors have different molecular components and thus different mechanistic actions, such as blocking the active site, their functional roles extend to influencing circulation concentrations of other inhibitor drugs and being used only for certain circumstances in which the virus exhibits tolerance of other inhibitors.
Killer Be Killed is the debut studio album from the supergroup Killer Be Killed featuring Greg Puciato of The Dillinger Escape Plan, Max Cavalera of Soulfly/ex-Sepultura, Troy Sanders of Mastodon, Dave Elitch of the Mars Volta. It was recorded in September 2013 at Fortress Studio in Los Angeles, CA and released May 9, 2014 on Nuclear Blast Records; the album reached No. 58 on the U. S. sold around 5,500 copies. Greg Puciato – vocals, guitar Max Cavalera – vocals, guitar Troy Sanders – vocals, bass guitar David Elitch – drums, percussion Juan Montoya – additional guitar Josh Wilbur – production, mastering, engineering Paul Suarez – engineering Monte Conner – A&R Ryan Clark – art direction, design Glen La Ferman – band photography Killer Be Killed has been well received by critics. Writing for All About The Rock, Zack Slabbert said "From the opening track till the closing track this album thrusts into your mind and takes over; the vocals, guitaring and bass on this album is flawless." Alkahest of MetalSucks writes that Killer be Killed "is a proper culmination of influences that represents each member’s artistic lineage and talents in a manner that does each act’s legacy justice."
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