53 research outputs found
Optimal deployment of components of cloud-hosted application for guaranteeing multitenancy isolation
One of the challenges of deploying multitenant cloud-hosted
services that are designed to use (or be integrated with) several
components is how to implement the required degree
of isolation between the components when there is a change
in the workload. Achieving the highest degree of isolation
implies deploying a component exclusively for one tenant;
which leads to high resource consumption and running cost
per component. A low degree of isolation allows sharing of
resources which could possibly reduce cost, but with known
limitations of performance and security interference. This
paper presents a model-based algorithm together with four
variants of a metaheuristic that can be used with it, to provide
near-optimal solutions for deploying components of a
cloud-hosted application in a way that guarantees multitenancy
isolation. When the workload changes, the model based
algorithm solves an open multiclass QN model to
determine the average number of requests that can access
the components and then uses a metaheuristic to provide
near-optimal solutions for deploying the components. Performance
evaluation showed that the obtained solutions had
low variability and percent deviation when compared to the
reference/optimal solution. We also provide recommendations
and best practice guidelines for deploying components
in a way that guarantees the required degree of isolation
Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen
Superantigens activate T-cells by linking the T-cell receptor to MHC class II on antigen-presenting cells, and novel reactivity can be introduced by fusing the superantigen to a targeting molecule. Thus, an antibody-targeted superantigen, which activates T cells to destroy tumour cells, might be used as cancer therapy. A suitable target is the 5T4 oncofetal antigen, which is expressed on many carcinomas. We constructed a fusion protein from a Fab of a monoclonal antibody recognizing the 5T4 antigen, and an engineered superantigen. The recombinant product 5T4FabV13-SEAD227A bound the 5T4 antigen expressed on the human non-small-cell lung cancer cell line Calu-1 with a Kd of 1.2 nM while the substitution of Asp227 to Ala in the superantigen moiety reduced binding activity to MHC class II. 5T4FabV13-SEAD227A tumour reactivity was demonstrated in 7/7 NSCLC samples by immunohistochemistry, while normal tissue reactivity was low to moderate. 5T4FabV13-SEAD227A induced significant T-cell-dependent in vitro killing of sensitive 5T4 bearing Calu-1 cells, with maximum lysis at 10β10M, while the capacity to lyse MHC class II expressing cells was approximately 1000 times less effective. Immunotherapy of 5T4FabV13-SEAD227A against human NSCLC was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells. Mice carrying intreperitoneally growing Calu-1 cells showed significant reduction in tumour mass and number after intravenous therapy with 5T4FabV13-SEAD227A. Thus, 5T4FabV13-SEAD227A has highly attractive properties for therapy of human NSCLC. Β© 2001 Cancer Research Campaign http://www.bjcancer.co
Is Promiscuity Associated with Enhanced Selection on MHC-DQΞ± in Mice (genus Peromyscus)?
Reproductive behavior may play an important role in shaping selection on Major Histocompatibility Complex (MHC) genes. For example, the number of sexual partners that an individual has may affect exposure to sexually transmitted pathogens, with more partners leading to greater exposure and, hence, potentially greater selection for variation at MHC loci. To explore this hypothesis, we examined the strength of selection on exon 2 of the MHC-DQΞ± locus in two species of Peromyscus. While the California mouse (P. californicus) is characterized by lifetime social and genetic monogamy, the deer mouse (P. maniculatus) is socially and genetically promiscuous; consistent with these differences in mating behavior, the diversity of bacteria present within the reproductive tracts of females is significantly greater for P. maniculatus. To test the prediction that more reproductive partners and exposure to a greater range of sexually transmitted pathogens are associated with enhanced diversifying selection on genes responsible for immune function, we compared patterns and levels of diversity at the Class II MHC-DQΞ± locus in sympatric populations of P. maniculatus and P. californicus. Using likelihood based analyses, we show that selection is enhanced in the promiscuous P. maniculatus. This study is the first to compare the strength of selection in wild sympatric rodents with known differences in pathogen milieu
Engineering Cloud-based Applications: Towards an Application Lifecycle
The adoption of cloud computing by organizations of all sizes and types in the recent years has created multiple opportunities and challenges for the development of software to be used in this environment. In this work-in-progress paper, the focus is on the latter part, providing a view on the main research challenges that are created for software engineering by cloud computing. These challenges stem from the inherent characteristics of the cloud computing paradigm, and require a multi-dimensional approach to address them. Towards this goal, a lifecycle for cloud-based applications is presented, as the foundation for further work in the area
A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo
Aqueous Viscum album L. extracts are widely used in complementary cancer
medicine. Hydrophobic triterpene acids also possess anti-cancer properties,
but due to their low solubility they do not occur in significant amounts in
aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes
(mainly oleanolic acid) and investigated the effect of a mistletoe whole plant
extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo.
Single Viscum album L. extracts containing only solubilised triterpene acids
(TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in
a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT
extracts (viscumTT) enhanced the induction of apoptosis synergistically. The
experiments demonstrated that all three extracts are able to induce apoptosis
via caspase-8 and -9 dependent pathways with down-regulation of members of the
inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute
myeloid leukaemia mouse model experiment confirmed the therapeutic
effectiveness of viscumTT-treatment resulting in significant tumour weight
reduction, comparable to the effect in cytarabine-treated mice. These results
suggest that the combination viscumTT may have a potential therapeutic value
for the treatment AML
Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation
A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules
Staphylococcal enterotoxin H contrasts closely related enterotoxins in species reactivity
Staphylococcus aureus enterotoxin H (SEH) belongs to the staphylococcal enterotoxin (SE) family of superantigens (SAgs). SEH has structural similarities to other SE; however, its biological properties are less well characterized. SEH binds with high affinity to human major histocompatibility complex (MHC) class II and exhibits strong mitogenic activity in human T cells, although it was found to be less potent than the related SEA. Surprisingly and in sharp contrast to related SEs, SEH did not possess superantigen activity in murine T cells and T cells from three investigated rat strains. However, SEH bound to a high extent to murine MHC class II expressing cells and when presented by these cells SEH stimulated human T cells to proliferate. Thus, SEH interacts with the murine MHC class II molecule in a functional manner. Notably, SEH had an inhibitory effect on murine SEA response, demonstrating that SEH interferes with the SEA interactions with murine cells. Despite this, murine T cells did not proliferate regardless of whether SEH was presented on human or murine MHC class II expressing cells. Consequently, SEH differs in species reactivity as compared to related SEs and lacks critical properties for T-cell activation in mice. We propose that unlike other SEs, SEH does not interact with murine T cells since it is not recognized by murine T-cell receptors
Recreational Amenities, Rural Migration Patterns, and the Great Recession
Natural and recreational amenities have played an important role in drawing migrants to rural areas in the USA over the past 40 years. However, less is known about the independent role of desirable recreational amenities in recent migration patterns, whether these patterns vary by age, and how the most recent economic recession affected them. I find that counties with desirable recreational amenities experienced net in-migration from 2000 to 2010 regardless of other county-level attributes, although the direction and magnitude of the effect varied when taking the age group of migrants into account. The recreation status of a county was a predictor of out-migration among emerging adults and in-migration for all other age groups. The Great Recession had a significant impact on migration trends in rural areas, including reducing the effect of recreational amenities in migration. These findings highlight the importance of refining the definition of βamenities,β how broader economic trends impact growth patterns in rural places, and the age-specific nature of the amenity migration trend. Knowledge about the current drivers of population patterns in rural places can help stakeholders better plan for future population trends and accommodate new or existing residents in rural recreation destinations. This study builds on existing amenity growth literature by providing a more contextual analysis of this demographic trend
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