Background and Significance. The human genome comprises three billion base pairs of DNA. In order to sequence the entire genome, a phased approach has been implemented by the NIH and DOE. The first requirement is the production of a conceptual array of large contiguous DNA sequences (large insert clones) spanning the 23 chromosomes. These "physical maps" must accurately represent the human genome and be in a form amenable to DNA sequencing. To make these physical maps amenable to sequencing, the individual large-insert clones will be further sub-divided into templates (either physically by subcloning or by primer walking) for direct DNA sequencing. Once the precise sequence of these templates is determined (by Sanger sequencing and fluorescent detection) they will be "assembled" into accurate ("finished" sequence) virtual representations of the original large-insert clones. The sequences of these large-insert clones are then assembled to form the full finished sequence of the human genome.
Background and Significance. Sleep Duration in U.S. Adults
Background and Significance. Maternal mortality, defined as obstetric deaths that occur during pregnancy, childbirth, or within 42 days of delivery or end of a pregnancy is a significant global health issue (The DHS Program
Background and Significance. The background and significance section responds to PCORI Methodology Standard 1:RQ-1 “Gap analysis to support the need for the proposed study”.1
1.1 African Americans, Hypertension, and the Region known as the ‘Black Belt’. Figure 1. Areas of the US where HTN affects
Background and Significance. Introduction The systolic and diastolic blood pressures have a strong, continuous and significant effect on the development of cardiovascular disease in the future. This significant association has been proven in many epidemiological studies done on patients with optimal or high blood pressure (Xxxxxxx Xxxxxxxxxxx & Subcommittee, 2015) (Xxxx Xxxxxxx MD, 1988) (Xxxxx
Background and Significance. The apparent need for the timely development of a P. vivax vaccine has become glaringly evident as research begins to show the widespread global distribution of P. vivax, the significant difficulties currently faced in elimination efforts, combined with the rapid development of multidrug-resistant malaria in the GMS. These factors highlight the urgent need for a vaccine for
Background and Significance. Briefly sketch the background to the research project. Indicate the importance of the project to long-‐term research goals. Include relevant references. Do not exceed two pages (not including references).
Background and Significance. Pancreatic adenocarcinoma affects approximately 10 per 100,000 persons annually in the United States, and is the fourth leading cause of cancer related-mortality,1-3 occurring in approximately 43,140 patients per year (2010), with 36,800 patients expected to die in the US from the disease. Pancreatic cancer is generally diagnosed in advanced stages, with a 5-year survival rate of 1.3-3%.4 It is known that 30% of all human cancers have a RAS allele activated by mutation. At least 93% of pancreatic cancers have the identical position 12-activating mutation in the K-RAS gene. We previously discovered that over-activity of RAS signaling sensitizes tumor cells to apoptosis when PKCδ activity is suppressed, and this effect can be exploited as a targeted cancer therapeutic. We have demonstrated that mutated, constitutively-activated RAS is lethal to the cell unless a survival pathway, also driven by Ras, is active.5-14 Over-activity of RAS signaling sensitizes tumor cells to apoptosis when PKCδ activity is suppressed. We have shown that this cancer-specific susceptibility can be exploited as a targeted cancer therapeutic.15 Importantly, PKCδ inhibition is not toxic to cells with normal levels of RAS activity. Unlike the classical PKC isozymes, PKCδ is not required for the survival of normal cells, and its inhibition or down-regulation in normal cells and organisms has no adverse effects.5-8 Inhibition of PKCδ by a variety of means in human and murine cells containing a mutated, activated RAS allelle, however, initiates rapid and profound apoptosis.5 This molecular approach, targeting tumor cells containing a mutated oncogenic protein (and sparing normal cells), by altering a second protein or its activity required for survival of the tumor (“non-oncogene addiction”) is now sometimes termed “synthetic lethality.” While activation of Ras itself renders tumor cells absolutely dependent upon PKCδ activity, aberrant activation of Ras effector pathways such as the Raf/Mek pathway causes the same sensitization. Up to 70% of melanomas have activating mutations of Raf. We have shown that Raf mutant melanoma cells are dependent upon PKCδ for survival and our inhibitors are extremely cytotoxic to these cells. Very recently, a Raf inhibitor has been approved for the treatment of Raf-mutant melanomas. While demonstrating unprecedented activity against these tumors, resistance and relapse invariably occurs within 6-8 months. These resistant tumors have developed activating mut...
Background and Significance. Briefly sketch the background leading to the present application, critically evaluate existing knowledge, and specifically identify the gaps the proposed project is intended to fill. State concisely the importance and Pediatric Health relevance of the research described in this application by relating the specific aims to the broad, long-term objectives. Recommended Length of Section -Grant-in-Aid Awards: 1/2-3/4 page (total application not to exceed 3 pages)
Background and Significance. UConn/UConn Health may use or disclose Protected Health Information (PHI) as a limited data-set for purposes of public health, research, and health care operations only if UConn/UConn Health enters into a DUA with the recipient/covered entity. A limited data set is PHI that may be used without obtaining either an individual’s Authorization, a waiver or an alteration of Authorization for its use and disclosure with a data use agreement. A data use agreement excludes the following direct identifiers of the individual or of relatives, employers, or household members of the individual:
