SCIENTIFIC BACKGROUND Sample Clauses

SCIENTIFIC BACKGROUND. The enzyme IDO catalyzes tryptophan degradation. IDO can be a potent effector of immunosuppression and of tolerance induction in certain settings; for example, expression of IDO in the placenta maintains maternal tolerance towards the fetus. Tumors create a state of immunologic unresponsiveness (tolerance) toward their own antigens, which allows tumors to escape the host’s immune system. This also imposes a barrier to effective anti-tumor immunotherapy. One molecular mechanism contributing to this tolerance is expression of the immunosuppressive enzyme IDO, leading to inhibition of T-cell response. Expression of IDO by human and mouse antigen-presenting cells inhibits T cell mediated immune responses in vitro and in vivo. Tumor cells transfected with IDO become immunosuppressive in vivo, and expression of IDO has been reported in tumor cells from a variety of human tumors. IDO is also expressed by a population of host antigen-presenting cells (dendritic cells) found in tumor-draining lymph nodes of melanoma, breast cancer, and a variety of other tumors, which may act to create tolerance to tumor antigens. Therefore, IDO may be a primary molecular target for cancer immunotherapy and inhibition of the IDO pathway may assist in breaking tumor tolerance. Studies have shown that the small-molecule 1MT possesses immune-enhancing activity by inhibiting IDO in a variety of animal models. 1MT can inhibit IDO enzyme activity in vitro and can prevent IDO-mediated immunosuppression in vivo. 1MT has also been shown to be synergistic with a number of commonly used chemotherapeutic agents. Thus, 1MT may potentially be used as a novel immune modulator in cancer immunotherapy.
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SCIENTIFIC BACKGROUND. Tumors rely on angiogenesis to grow and metastasize, and angiogenesis inhibitors have demonstrated clinical benefit in patients with cancer. CD105 is a member of the transforming growth factor beta (TGF-b) receptor family that is selectively expressed by proliferating endothelial cells and is essential for endothelial cell proliferation. Expression of CD105 is induced by cellular hypoxia through hypoxia-inducible factor-1-. CD105 is highly expressed on tumor vessel endothelium of all types of solid cancer and exerts its effect by modulating the signaling of multiple TGF-b receptor signaling complexes. In the absence of CD105, TGF- b receptor activation inhibits endothelial cell proliferation and angiogenesis. However, in the presence of CD105, TGF-b receptor signaling is modified to promote endothelial cell proliferation and angiogenesis.
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SCIENTIFIC BACKGROUND. Base-excision repair (BER) is a key resistance mechanism employed by cancer cells to survive chemotherapy-induced DNA damage, and inhibiting BER improves the therapeutic index of these agents in preclinical models. TRC102 (methoxyamine hydrochloride) is an inhibitor of BER with a unique mechanism of action. TRC102 exerts its effect by rapidly and covalently binding to chemotherapy-induced apurinic/apyrimidinic (AP) sites generated by glycosylase removal of abnormal bases. TRC102-bound DNA is no longer a substrate for BER enzymes and is instead irreversibly cleaved by topoisomerase II resulting in double-strand DNA breaks that trigger cellular apoptosis. The induction of apoptosis by TRC102 is selective for cancer cells because they express high levels of topoisomerase II. In normal cells with low topoisomerase II expression, TRC102-bound DNA is predominantly excised and replaced with normal DNA by the long patch DNA repair system. The efficacy of TRC102 is independent of tumor O-6-methylguanine-DNA methyltransferase (MGMT) expression, mismatch repair status, or p53 status. TRC102 is synergistic with a wide variety of cancer therapies including antimetabolites, oxidizing agents, alkylating agents, and poly ADP ribose polymerase (PARP) inhibitors. The active molecule is a small organic amine that is highly water soluble and nearly completely bioavailable after oral administration.
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SCIENTIFIC BACKGROUND. Clinical depression is one of the most common mental disorders. The condition is characterized mostly by a combination of a number of symptoms such as pessimism, loss of interest or pleasure, major weight change or change in appetite, fatigue or loss of energy, sleep disorder, loss of concentration, feelings of guilt, thoughts of death, etc. that last at least two weeks. In various studies, the average incidence of this disorder worldwide is between 5% and 15% annually. This situation adversely affects many areas of a person’s life, such as family, work and studies, quality of life and general health. It can be a considerable burden on the health services and at the same time can cause major functional damage, including loss of ability to work and alcoholism. The most accepted treatments in situations of depression are currently therapeutic treatment and psychotherapeutic treatment (on their own or in combination). However, there are cases in which these treatments do not lead to the desired results and to the patient’s remission (1-3). Between 20% and 40% of patients do not respond to the existing therapeutic treatment or to a combination of therapeutic treatment and psychotherapeutic treatment (4). In cases of persistent depression, patients who do not respond to the standard treatment occasionally switch to treatment with electro convulsive therapy. This treatment is considered the most effective (5) but is administered under general anesthetic, and apart from the risks of the anesthesia, it involves side effects, including a risk of developing cognitive disorders and permanent damage (6). Transcranial Magnetic Stimulation (TMS) is a non-invasive method in which the nerve cells in specific regions of the brain can be stimulated. This method, which has been in use for 20 years, works by means of a coil into which flows a pulsating electrical current. During pulsation, the current in the coil causes electromagnetic induction that permeates into the brain and creates an electrical field that arouses the nerve cells in the brain in the region at which the coil is directed. In the last few years, use has been made of Repetitive Transcranial Magentic Stimulation (rTMS) in the treatment of depression, whereby the TMS device is operated at a number of consecutive pulses at a certain frequency. This treatment is non-invasive, is administered when the patient is fully conscious, and has few side effects. In depressive patients with no psychotic component it is ev...
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Related to SCIENTIFIC BACKGROUND

  • BACKGROUND 1.1. The “Work” is the research article, review article, letter, clinical trial study, report, article, or other copyright work, as identified in the Copyright Letter and further detailed in Schedule 1: Details of the Work (including such form of the copyright work submitted to Xxxxxxx Science for publication pursuant to clause 4, below), but excluding (except where context otherwise requires) any diagrams, figures or illustration specifically identified to Xxxxxxx Science pursuant to clause 3.2, below.

  • Background Screening VENDOR shall comply with all requirements of Sections 1012.32 and 1012.465, Florida Statutes, and all of its personnel who (1) are to be permitted access to school grounds when students are present, (2) will have direct contact with students, or (3) have access or control of school funds, will successfully complete the background screening required by the referenced statutes and meet the standards established by the statutes. This background screening will be conducted by SBBC in advance of VENDOR or its personnel providing any services under the conditions described in the previous sentence. VENDOR shall bear the cost of acquiring the background screening required by Section 1012.32, Florida Statutes, and any fee imposed by the Florida Department of Law Enforcement to maintain the fingerprints provided with respect to VENDOR and its personnel. The parties agree that the failure of VENDOR to perform any of the duties described in this section shall constitute a material breach of this Agreement entitling SBBC to terminate immediately with no further responsibilities or duties to perform under this Agreement. VENDOR agrees to indemnify and hold harmless SBBC, its officers and employees from any liability in the form of physical or mental injury, death or property damage resulting from VENDOR’s failure to comply with the requirements of this section or with Sections 1012.32 and 1012.465, Florida Statutes.

  • Project Background 6.1.1. Brief description of Contracting Agency’s project background and/or situation leading to this Project

  • Technology Discoveries, innovations, Know-How and inventions, whether patentable or not, including computer software, recognized under U.S. law as intellectual creations to which rights of ownership accrue, including, but not limited to, patents, trade secrets, maskworks and copyrights developed under this Agreement.

  • General Background Ecuador is part of the United Nations Convention of 1951 relating to the Status of Refugees and its 1967 Protocol, as well as major international and regional human rights instruments that recognize the right to asylum. It is also part of the United Nations Convention of 1954 relating to the Status of Stateless Persons and the United Nations Convention of 1961 on the Reduction of Statelessness. The asylum procedure in Ecuador is regulated by the Organic Law of Human Mobility, effective February 6, 2017. Ecuador is a country of transit and destination for people who need international protection. In the last two decades, Ecuador hosted more than 68,708 recognized refugees (mainly Colombian) and has become one of the leading countries of transit and destination for Venezuelan refugees and migrants. Ecuador receives the third highest number of Venezuelans after Colombia and Peru. Since 2016, more than 4.7 million Venezuelans have left their country, making it the biggest exodus in the history of Latin America. Of these, 2.2 million have entered Ecuador, of which estimated 500,000 have been established in the country according to the R4V. In 2019, approximately 2,100 Venezuelans per day entered Ecuador (with peaks of 6,000) until 26 August, when Ecuador began requiring visas for Venezuelans. Since 2018, the number of Venezuelan asylum seekers exceeded the number of asylum seekers from Colombia. The Office of the United Nations High Commissioner for Refugees works in Ecuador supporting the Ecuadorian government to protect refugees and looking for durable solutions. UNHCR's operation in Ecuador began in 2000 as part of the strategy of the organization to protect and provide assistance, particularly to the victims of the Colombian conflict. The Ecuadorian 2023-2025 Multiyear Strategy aims to support the Government of Ecuador to: (i) the development of protection mechanisms, (ii) strengthening national asylum system, (iii) and identification of durable solutions, including alternative pathways. The operation is coordinated at the national level by the country office in Quito. In addition, UNHCR has Sub- Offices in Quito (Solanda), Xxxxxx and Guayaquil; Field Offices in Esmeraldas, Huaquillas, Tulcán, Lago Agrio, and Field Units in Manta, Cuenca and Ambato.

  • Introduction and Background 1.1 The purpose of this Schedule 2 (Contract Services and Contract Supplies) is to set out the characteristics of the Contract Services and/or Contract Supplies (as the case may be) and Funding that the Provider will be required to make available to all Contracting Authorities in relation to Lot 1 and/or Lot 2 (as the case may be) and to provide a description of what the Contract Services and/or Contract Supplies (as the case may be) and Funding will entail.

  • Investment Analysis and Commentary The Subadviser will provide quarterly performance analysis and market commentary (the “Investment Report”) during the term of this Agreement. The Investment Reports are due within 10 days after the end of each quarter. In addition, interim Investment Reports shall be issued at such times as may be mutually agreed upon by the Adviser and Subadviser; provided however, that any such interim Investment Report will be due within 10 days of the end of the month in which such agreement is reached between the Adviser and Subadviser. The subject of each Investment Report shall be mutually agreed upon. The Adviser is freely able to publicly distribute the Investment Report.

  • Clinical 2.1 Provides comprehensive evidence based nursing care to patients including assessment, intervention and evaluation.

  • Product Development Attach all requested documentation and attach additional pages as necessary. For all requirements include efforts of all Sublicensees. If not applicable, please so indicate by N/A.

  • Technical Information The Employer agrees to provide to the Union such information that is available relating to employees in the bargaining unit, as may be required by the Union for collective bargaining purposes.

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