Background and Significance Clause Samples

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. 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. Related Previous Studies

Background and Significance. Evidence-Based Practice

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. ‌ 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. Sexual and reproductive health first became a true area of focus and concern to humanitarian actors in the early 1990s; up until this point, it was truly only pregnant women that received targeted health care and interventions, many of which only focused on the woman’s health in terms of her pregnancy (▇▇▇▇▇▇, ▇▇▇▇▇, ▇▇▇▇▇▇ & ▇▇▇▇▇, 2004). The first truly influential document released that brought attention to the specific challenges female refugees faced was the United Nations High Commissioner for Refugees’ (UNHCR) 1990 ‘Policy on Refugee Women and International Protection’ (▇▇▇▇▇▇ et al., 2004). The policy, although not specific about the reproductive health services that should be allotted to women refugees, did state that the needs of refugee women should be actively considered and accounted for in all aspects of humanitarian programming (UNHCR, 1990). The policy also made sure to emphasize that is UNHCR’s responsibility to prevent and address physical and sexual abuse, and more specifically, physical and sexual abuse against women refugees (UNHCR, 1990; ▇▇▇▇▇▇ et al., 2004). Following the release of this policy The Lancet released their own equally influential editorial arguing in favor of the vital need for sexual and reproductive health services for refugee women (Black, ▇▇▇▇▇▇▇ & ▇▇▇▇▇, 1993). The editorial, ‘Reproductive Freedom for Refugees’ was one of the first literature pieces to note just how poor reproductive health was for refugee women: it in its review of different refugee populations located throughout the world, it reported on the extremely limited amount of options refugees had for sexual and reproductive health care and the devastating health effects resulting from the unmet needs of women. The article concluded with a pleading call for action, stating that although “refugees are a nation lacking borders, surely they deserve reproductive freedom” (Black et al., 1993). This call to action was only further intensified when the following year, in 1994, the Women’s Commission for Refugee Women and Children released their own study illuminating the truly shocking limited amount of reproductive health resources available for refugees (▇▇▇▇▇▇ et al, 2004). That same year, following these reports and declarations, the United Nations Internal Conference on Population and Development (ICPD) was held and, in what many credit to be the most influential moment for sexual and reproductive health of refugee populations, 179 countries came together ...

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 (▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇ & Subcommittee, 2015) (▇▇▇▇ ▇▇▇▇▇▇▇ MD, 1988) (▇▇▇▇▇

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).