Scalable architectures for platform-as-a-service clouds: performance and cost analysis

Scalability is a significant feature of cloud computing, which ad-dresses to increase or decrease the capacities of allocated virtual resources at application, platform, database and infrastructure level on demand. We investigate scalable architecture solutions for cloud PaaS that allow services to utilize the resources dynamically and effectively without directly affecting users. We have implemented scalable architectures with different session state management solutions, deploying an online shopping cart application in a PaaS solution, and measuring the performance and cost under three server-side session state providers: Caching, SQL database and NoSQL database. A commercial solution with its supporting state management components has been used. Particularly when re-architecting software for the cloud, the trade-off between performance, scalability and cost implications needs to be discussed

Using Performance Forecasting to Accelerate Elasticity

Cloud computing facilitates dynamic resource provisioning. The automation of resource management, known as elasticity, has been subject to much research. In this context, monitoring of a running service plays a crucial role, and adjustments are made when certain thresholds are crossed. On such occasions, it is common practice to simply add or remove resources. In this paper we investigate how we can predict the performance of a service to dynamically adjust allocated resources based on predictions. In other words, instead of “repairing” because a threshold has been crossed, we attempt to stay ahead and allocate an optimized amount of resources in advance. To do so, we need to have accurate predictive models that are based on workloads. We present our approach, based on the Universal Scalability Law, and discuss initial experiments

CAR T-Cell-Based gene therapy for cancers: new perspectives, challenges, and clinical developments

Chimeric antigen receptor (CAR)-T cell therapy is a progressive new pillar in immune cell therapy for cancer. It has yielded remarkable clinical responses in patients with B-cell leukemia or lymphoma. Unfortunately, many challenges remain to be addressed to overcome its ineffectiveness in the treatment of other hematological and solidtumor malignancies. The major hurdles of CAR T-cell therapy are the associated severe life-threatening toxicities such as cytokine release syndrome and limited anti-tumor efficacy. In this review, we briefly discuss cancer immunotherapy and the genetic engineering of T cells and, In detail, the current innovations in CAR T-cell strategies to improve efficacy in treating solid tumors and hematologic malignancies. Furthermore, we also discuss the current challenges in CAR T-cell therapy and new CAR T-cell-derived nanovesicle therapy. Finally, strategies to overcome the current clinical challenges associated with CAR T-cell therapy are included as well

Comparative analysis of homology models of the Ah receptor ligand binding domain: Verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness. © 2013 American Chemical Society

Morphometric analysis of a triple negative breast cancer cell line in hydrogel and monolayer culture environments

Triple negative breast cancer (TNBC) is a belligerent carcinoma that is unresponsive to targeted receptor therapies. Development of new treatment strategies would benefit from an expanded repertoire of in vitro cell culture systems, such as those that support tridimensional growth in the presence of hydrogel scaffolds. To this end, we established protocols for maintenance of the TNBC cell line HCC70 in monolayer culture and in a commercially available basement membrane matrix hydrogel. We evaluated the general morphology of cells grown in both conditions with light microscopy, and examined their subcellular organization using transmission electron microscopy (TEM). Phase contrast and confocal microscopy showed the prevalence of irregularly shaped flattened cells in monolayer cultures, while cells maintained in hydrogel organized into multi-layered spheroids. A quantitative ultrastructural analysis comparing cells from the two culture conditions revealed that cells that formed spheroids comprised a greater number of mitochondria, autophagic vacuoles and intercellular junctions than their monolayer counterparts, within the equivalent area of sampled tissue. These observations suggest that triple negative breast cancer cells in culture can alter their organelle content, as well as their morphology, in response to their microenvironment. Methods presented here may be useful for those who intend to image cell cultures with TEM, and for investigators who seek to implement diverse in vitro models in the search for therapeutic molecular targets for TNBC

On the Impact of Management on the Performance of a Managed System: A JMX-Based Management Case Study

http://www.springerlink.com/(j5rieh45rj1s1e55eqi3w2uq)/app/home/contribution.asp?referrer=parent&backto=issue,3,23;journal,14,2293;linkingpublicationresults,1:105633,1Studying the performance of a distributed system without taking care on the impact of its management system will falsify the understanding of its overall performance, especially its productivity. We propose a metric called MIM (Management Impact Metric) to evaluate this impact by varying one or several impact factors related to the management system within a management strategy of the managed system. We show the accuracy and interest of our metric on a managed J2EE application server that uses a management architecture based on the JMX standard

Online Gaming Scalability

Online gaming scalability refers to all those techniques that aim at supporting online game sessions with a variable amount of participants. No matter the amount of players, the online game session must provide a fluid, compelling, and responsive game evolution