DESIGN AND MOLECULAR DOCKING OF SULFONAMIDE DERIVATIVES

Objective: Sulfonamides are a sulfa-related group of antibiotics, which are used to treat bacterial infections and some fungal infections. Some sulfonamides are also devoid of antibacterial activity, such as thiazide diuretics, etc. In this study, an effort was made to find out some novel and potent Sulfonamide derivatives as diuretic agents. Methods: Here, 30 three-dimensional sulphonamides are designed and docking simulation with PDB ID 1AZM which was downloaded from www. rcsb. org. All the molecules were also screened through a preliminary property filter (Molinspiration Property Calculator). Results: Among the 30 different molecules designed, 5 molecules were found to have a very good affinity towards the target protein. Conclusion: These molecular properties define if a molecule can be orally active in our body

Linear and Branched Glyco-Lipopeptide Vaccines Follow Distinct Cross-Presentation Pathways and Generate Different Magnitudes of Antitumor Immunity

Glyco-lipopeptides, a form of lipid-tailed glyco-peptide, are currently under intense investigation as B- and T-cell based vaccine immunotherapy for many cancers. However, the cellular and molecular mechanisms of glyco-lipopeptides (GLPs) immunogenicity and the position of the lipid moiety on immunogenicity and protective efficacy of GLPs remain to be determined.We have constructed two structural analogues of HER-2 glyco-lipopeptide (HER-GLP) by synthesizing a chimeric peptide made of one universal CD4(+) epitope (PADRE) and one HER-2 CD8(+) T-cell epitope (HER(420-429)). The C-terminal end of the resulting CD4-CD8 chimeric peptide was coupled to a tumor carbohydrate B-cell epitope, based on a regioselectively addressable functionalized templates (RAFT), made of four alpha-GalNAc molecules. The resulting HER glyco-peptide (HER-GP) was then linked to a palmitic acid moiety, attached either at the N-terminal end (linear HER-GLP-1) or in the middle between the CD4+ and CD8+ T cell epitopes (branched HER-GLP-2). We have investigated the uptake, processing and cross-presentation pathways of the two HER-GLP vaccine constructs, and assessed whether the position of linkage of the lipid moiety would affect the B- and T-cell immunogenicity and protective efficacy. Immunization of mice revealed that the linear HER-GLP-1 induced a stronger and longer lasting HER(420-429)-specific IFN-gamma producing CD8(+) T cell response, while the branched HER-GLP-2 induced a stronger tumor-specific IgG response. The linear HER-GLP-1 was taken up easily by dendritic cells (DCs), induced stronger DCs maturation and produced a potent TLR- 2-dependent T-cell activation. The linear and branched HER-GLP molecules appeared to follow two different cross-presentation pathways. While regression of established tumors was induced by both linear HER-GLP-1 and branched HER-GLP-2, the inhibition of tumor growth was significantly higher in HER-GLP-1 immunized mice (p<0.005).These findings have important implications for the development of effective GLP based immunotherapeutic strategies against cancers

DECO: Data replication and Execution CO-scheduling for Utility Grids

Abstract. Vendor strategies to standardize grid computing as the IT backbone for service-oriented architectures have created business opportunities to offer grid as a utility service for compute and data– intensive applications. With this shift in focus, there is an emerging need to incorporate agreements that represent the QoS expectations (e.g. response time) of customer applications and the prices they are willing to pay. We consider a utility model where each grid application (job) is associated with a function, that captures the revenue accrued by the provider on servicing it within a specified deadline. The function also specifies the penalty incurred on failing to meet the deadline. Scheduled execution of jobs on appropriate sites, along with timely transfer of data closer to compute sites, collectively work towards meeting these deadlines. To this end, we present DECO, a grid meta-scheduler that tightly integrates the compute and data transfer times of each job. A unique feature of DECO is that it enables differentiated QoS – by assigning profitable jobs to more powerful sites and transferring the datasets associated with them at a higher priority. Further, it employs replication of popular datasets to save on transfer times. Experimental studies demonstrate that DECO earns significantly better revenue for the grid provider, when compared to alternative scheduling methodologies.

Organizational models for service delivery

The organizations in the business of IT service delivery have conventionally adopted the team structure of dedicated customer teams to deliver services. A dedicated team is assigned to address all requirements that are specific to the customer. However, this way of organizing service delivery leads to inefficiencies in using expertise and available resources across teams in a flexible manner. In contrast the shared services model became very popular in the last decade, but soon faced challenges of losing customer focus. This gives rise to the question of what is the best way of grouping shared resources across customers. Especially, with the large variations in the technical and domain skills required to address customer requirements, what should be the service delivery model for diverse customer profile? This chapter looks at different dimensions one can organize delivery by and recommends patterns based on customer profiles, business functions technologies, geographies and operational characteristics.</p

Does one-size-fit-all suffice for service delivery clients?

The traditional mode of delivering IT services has been through customer-specific teams. A dedicated team is assigned to address all (and only those) requirements that are specific to the customer. However, this way of organizing service delivery leads to inefficiencies due to inability to use expertise and available resources across teams in a flexible manner. To address some of these challenges, in recent times, there has been interest in shared delivery of services, where instead of having customer specific teams working in silos, there are cross-customer teams (shared resource pools) that can potentially service more than one customer. However, this gives rise to the question of what is the best way of grouping the shared resources across customer? Especially, with the large variations in the technical and domain skills required to address customer requirements, what should be the service delivery model for diverse customer workloads? Should it be customer-focused? Business domain focused? Or Technology focused? This paper simulates different delivery models in face of complex customer workload, diverse customer profiles, stringent service contracts, and evolving skills, with the goal of scientifically deriving principles of decision making for a suitable delivery model. Results show that workload arrival pattern, customer work profile combinations and domain skills, all play a significant role in the choice of delivery model. Specifically, the complementary nature of work arrivals and degree of overlapping skill requirements among customers play a crucial role in the choice of models. Interestingly, the impact of skill expertise level of resources is overshadowed by these two factors.</p

Behavioral analysis of service delivery models

Enterprises and IT service providers are increasingly challenged with the goal of improving quality of service while reducing cost of delivery. Effective distribution of complex customer workloads among delivery teams served by diverse personnel under strict service agreements is a serious management challenge. Challenges become more pronounced when organizations adopt ad-hoc measures to reduce operational costs and mandate unscientific transformations. This paper simulates different delivery models in face of complex customer workload, stringent service contracts, and evolving skills, with the goal of scientifically deriving design principles of delivery organizations. Results show while Collaborative models are beneficial for highest priority work, Integrated models works best for volume-intensive work, through up-skilling the population with additional skills. In repetitive work environments where expertise can be gained, these training costs are compensated with higher throughput. This return-on-investment is highest when people have at most two skills. Decoupled models work well for simple workloads and relaxed service contracts.</p

Delusion of pregnancy and other pregnancy-mimicking conditions: Dissecting through differential diagnosis

The delusion of pregnancy is defined as the belief of being pregnant despite factual evidence to the contrary. Even being more common in a developing country, the literature about delusion of pregnancy from India is meager. The present article reports the case of delusion of pregnancy in an unmarried female associated with subclinical hypothyroidism and prominent sibling rivalry from psychological aspect. The literature in this field has addressed for the organic and psychodynamic, psychosocial aspect of this disorder and its difference from other disorders mimicking pregnancy and its relevance to the treatment plan