Analyzing the costs/tradeoffs involved between layer 2, layer 3, layer 4 and layer 5 switching

The switching function was primarily entrusted to Layer 2 of the OSI model, i.e. the Data Link Layer. A Layer 2 switch performs forwarding decisions by analyzing the MAC (Media Access Control) address of the destination segment in the frame. The Layer 2 switch checks for the destination address and transmits the packet to the appropriate segment if the address is present in its table of known destinations. If the entry for that address is not present, the switch then forwards the packet to all segments except the one on which it came from. This is known as flooding. When it gets a reply from the destination segment, it learns the location of the new address and adds it to its table of known destinations. As number of users are increasing on the network, the speed and the bandwidth of the network is being stretched to its limits. Earlier, switching was primarily entrusted to Layer 2 (Data Link Layer) of the OSI model, but now there are switches that operate at Layer 3 (Network Layer), Layer 4 (Transport Layer) and Layer 5 (Session Layer) of the OSI model. Going from one layer to the other layer does involve some costs/tradeoffs. My thesis explores the costs and tradeoffs involved with switching based on layers 2, 3, 4 and 5 of the OSI reference model

Improving promotional effectiveness through supplier-retailer collaboration

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2007.Includes bibliographical references (leaves 60-61).In the consumer products industry, retail chains and manufacturers run promotions to maintain consumer and brand loyalty. The two major issues in planning and executing promotions are to accurately forecast demand and to control Out-of-Stock at the shelf. This thesis addresses both these issues. At the strategic level, "Collaborative, Planning, Forecasting and Replenishment" is used to define a process for two companies to collaboratively plan and execute promotions. At an operational level, the single period multi-item newsboy concept with a budget constraint is used to define an optimization model that helps determine the right budget and order quantities for products under a promotion at a targeted service level to improve profit or sales. The concept of Supply Contracts is researched to identify some ways that can be used to optimize the whole supply chain rather than just the retailer's. The value of optimal collaboration was confirmed in the results shown by the model. When optimizing the entire chain, the maximize profit optimization model achieved combined profit improvements of 37% as compared to an actual promotion.(cont.) When only the retailer profit was maximized, the optimization model resulted in 5.9% profit improvements for the retailer and 0.3% profit improvements for the supplier as compared to an actual promotion. Finally, the revenue maximization model showed that after a certain point, increasing the budget did not result in increased service levels. This research can also be applied to new product launches, seasonality of products as well as daily replenishments.by Gautam Kapur and Bin Liu.M.Eng.in Logistic

Association of biomarkers for human papillomavirus with survival among adults with Barrett high-grade dysplasia and esophageal adenocarcinoma

Importance: The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. Objective: To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. Design, Setting, and Participants: This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017. Main Outcomes and Measures: Disease-free survival and overall survival. Results: Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04). Conclusions and Relevance: This study's findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status

Class IA PI3Kinase Regulatory Subunit, p85α, Mediates Mast Cell Development through Regulation of Growth and Survival Related Genes

Stem cell factor (SCF) mediated KIT receptor activation plays a pivotal role in mast cell growth, maturation and survival. However, the signaling events downstream from KIT are poorly understood. Mast cells express multiple regulatory subunits of class 1A PI3Kinase (PI3K) including p85α, p85β, p50α, and p55α. While it is known that PI3K plays an essential role in mast cells; the precise mechanism by which these regulatory subunits impact specific mast cell functions including growth, survival and cycling are not known. We show that loss of p85α impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85α regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85α-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85α-deficient cells in response to SCF stimulation compared to WT cells. Functional categorization based on DAVID bioinformatics tool and Ingenuity Pathway Analysis (IPA) software relates the altered genes due to lack of p85α to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85α is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Evaluation of Cyclooxygenase-2, P53, Vascular Endothelial Growth Factor, and Nitric Oxide Synthase-2 in Angiogenesis and Growth of Tobacco-Related Malignancies

Introduction In India, tobacco consumption is responsible for half of all the cancers in men and a quarter in women. The present study focuses on the expression of cyclooxygenase-2 (COX-2), P53, vascular endothelial growth factor (VEGF), and nitric oxide synthase (NOS) and their relationship with the growth and angiogenesis of tobacco-related malignancies of the oral cavity, esophagus, lungs, and stomach. It further evaluates the carcinogenic action of nicotine and examines whether COX-2 and NOS-2 overexpression is responsible for tumor growth and associated angiogenic VEGF expression via its receptor

Convulsive threshold in humans and rats and magnetic field changes: observations during total solar eclipse

Convulsive thresholds were measured in 26 psychiatric patients who were receiving electroconvulsive treatment, and in 8 rats subjected to electroconvulsive shocks, during the recent total solar eclipse day (February 16th, 1980) and on control days. Our results showed that there was a significant reduction in the convulsive thresholds of both humans and rats at the time of solar eclipse, probably occurring due to the observed geomagnetic field variation of 19 Gammas