Secure Efficient On-Demand Insider Attacks Multicast Routing Protocol in Wireless Networks

Wireless multicast routing send and receives the data source to destination. High error rates, unfixed and changeable self of the signal power and broadcast change with time and environment regularly result in not effective links. These services more weak to internal attacks coming from compromised nodes that behave randomly to disrupt the network, also referred to as Inside attacks. Our method ensures that as long as a fault-free path exists between two node or multi nodes in multicast group they can communicate reliably even if an destroy majority of the network acts in a complex mode. Multicast Group is the link on different Multicast Group’s Group Leader in multi hops networks

Adenylate Kinase 3 Sensitizes Cells to Cigarette Smoke Condensate Vapor Induced Cisplatin Resistance

Background: The major established etiologic risk factor for bladder cancer is cigarette smoking and one of the major antineoplastic agents used for the treatment of advanced bladder cancer is cisplatin. A number of reports have suggested that cancer patients who smoke while receiving treatment have lower rates of response and decreased efficacy of cancer therapies. Methodology/Principal Findings: In this study, we investigated the effect of cigarette smoke condensate (CSC) vapor on cisplatin toxicity in urothelial cell lines SV-HUC-1 and SCaBER cells. We showed that chronic exposure to CSC vapor induced cisplatin resistance in both cell lines. In addition, we found that the expression of mitochondrial-resident protein adenylate kinase-3 (AK3) is decreased by CSC vapor. We further observed that chronic CSC vapor-exposed cells displayed decreased cellular sensitivity to cisplatin, decreased mitochondrial membrane potential (DYm) and increased basal cellular ROS levels compared to unexposed cells. Re-expression of AK3 in CSC vapor-exposed cells restored cellular sensitivity to cisplatin. Finally, CSC vapor increased the growth of the tumors and also curtail the response of tumor cells to cisplatin chemotherapy in vivo. Conclusions/Significance: The current study provides evidence that chronic CSC vapor exposure affects AK3 expression an

Efficient optimal policy and resource allocation to provide qos services in multi-cloud

ABSTRACT: we propose a novel Service Level Agreement (SLA) framework  for cloud computing, in which a value control parameter is utilized to satisfy QoS needs for all classes in the market. The framework  utilizes reinforcement learning (RL) to infer a VM enlisting approach that can adjust to changes in the framework to ensure the QoS for all User classes. These progressions include: administration cost, framework limit, and the interest for administration. In displaying arrangements, when the CP rents more VMs to a class of Users, the QoS is debased for different classes because of a deficient number of VMs. In any case, our methodology coordinates processing assets adjustment with administration affirmation control dependent on the RL show. To the best of our insight, this investigation is the principal endeavor that encourages this mix to upgrade the CP's benefit and maintain a strategic distance from SLA infringement

CLINICAL PHARMACIST-LED PROGRAM ON MEDICATION RECONCILIATION AND PATIENT COUNSELING IN THE DEPARTMENT OF GASTROENTEROLOGY

Objective: To study the effects of medication reconciliation and patient counseling on the overall health benefits of the patients in the department of gastroenterology. Methods: This study is a prospective interventional study, was conducted in a 500 bedded MNR Hospital. The sample size taken was 150 patients and the study population comprised of patients aged 18-80 y, admitted in the hospital during the study period of six months. Results: Out of 150 patients, there were 98 (65.33%) male patients and 52 (34.67%) female patients. Patients between 18 and 30 y of age were 29(19.33%), between the age of 30 and 50 y were 71 (47.33%) and above 50 were 50(33.33%). Pancreatitis was most prevalent with 21% of total prevalence, followed by CLD and cholelithiasis with 17%, then IBD 16%, PUD and Gastritis 5%, GERD 4% and other diseases 15%. Conclusion: The basic role of the pharmacist, is to help in minimizing the errors and to perform medication reconciliation. In patient counseling, pharmacists provide information about the disease, and the medications to increase patient safety and the changes in the behavior for the better outcome

EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma.

Squamous cell carcinoma (SCC) and malignant pleural mesothelioma (MPM) are thoracic malignancies with very poor prognosis and limited treatment options. It is an established fact that most of the solid tumors have overexpression of EPHA2 receptor tyrosine kinase. EPHA2 is known to exhibit opposing roles towards cancer progression. It functions in inhibiting cancer survival and migration via a ligand and tyrosine kinase dependent signaling (Y772). Whereas it is known to promote tumor progression and cell migration through a ligand-independent signaling (S897). We analyzed the expression profile and mutational status of the ephrin receptor A2 (EPHA2) in SCC and MPM cell lines and primary patient specimens. The EPHA2 receptor was found to be either overexpressed, mutated or amplified in SCC and MPM. In particular, the EPHA2 mutants A859D and T647M were interesting to explore, A859D Y772 dead mutant exhibited lower levels of phosphorylation at Y772 compared to T647M mutant. Molecular Dynamics simulations studies suggested that differential changes in conformation might form the structural basis for differences in the level of EPHA2 activation. Consequently, A859D mutant cells exhibited increased proliferation as well as cell migration compared to controls and T647M mutant. Kinomics analysis demonstrated that the STAT3 and PDGF pathways were upregulated whereas signaling through CBL was suppressed. Considered together, the present work has uncovered the oncogenic characteristics of EPHA2 mutations in SSC and MPM reinstating the dynamics of different roles of EPHA2 in cancer. This study also suggests that a combination of doxazosin and other EPHA2 inhibitors directed to inhibit the pertinent signaling components may be a novel therapeutic strategy for MPM and Non-small cell lung cancer patients who have either EPHA2 or CBL alterations

MET and PI3K/mTOR as a Potential Combinatorial Therapeutic Target in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis. Studies have shown that both MET and its key downstream intracellular signaling partners, PI3K and mTOR, are overexpressed in MPM. Here we determined the combinatorial therapeutic efficacy of a new generation small molecule inhibitor of MET, ARQ 197, and dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 in mesothelioma cell and mouse xenograft models. Cell viability results show that mesothelioma cell lines were sensitive to ARQ 197, NVP-BEZ235 and GDC-0980 inhibitors. The combined use of ARQ 197 with either NVP-BEZ235 or GDC-0980, was synergistic (CI<1). Significant delay in wound healing was observed with ARQ 197 (p<0.001) with no added advantage of combining it with either NVP-BEZ235 or GDC-0980. ARQ 197 alone mainly induced apoptosis (20±2.36%) that was preceded by suppression of MAPK activity, while all the three suppressed cell cycle progression. Both GDC-0980 and NVP-BEZ235 strongly inhibited activities of PI3K and mTOR as evidenced from the phosphorylation status of AKT and S6 kinase. The above observation was further substantiated by the finding that a majority of the MPM archival samples tested revealed highly active AKT. While the single use of ARQ 197 and GDC-0980 inhibited significantly the growth of MPM xenografts (p<0.05, p<0.001 respectively) in mice, the combination of the above two drugs was highly synergistic (p<0.001). Our results suggest that the combined use of ARQ 197/NVP-BEZ235 and ARQ 197/GDC-0980 is far more effective than the use of the drugs singly in suppressing MPM tumor growth and motility and therefore merit further translational studies

RNA Interference: An Overview

In the course of transgenic experiments on the nematode Caenorhabditis elegans, RNA interference, usually abbreviated as RNAi, was discovered first. It is a gene-silencing effect and is found to be widely distributed in eukaryotes. It was observed that control injections of sense RNA were just as effective as antisense RNA, directed at specifically inhibiting target genes in C. elegans by the injection of antisense RNA during an experiment causing the reduction or elimination of expression from the gene under investigation. Subsequently, by injecting double-stranded RNA (dsRNA) corresponding to the target gene, it was discovered that the effect could be most potently elicited, and contamination of the single-stranded RNA (ssRNA; either sense or antisense) by traces of dsRNA could explain the earlier results. By post-transcriptional mechanism, substantial or complete inhibition of expression from any gene can be done using dsRNA corresponding to part or all of the mature mRNA from any given gene. An attempt was made here to describe the basic underlying molecular mechanism of RNAi, the methodology and various experimental requirements, and its advantages and disadvantages. In relation to CRISPR/Cas9 technology, the future prospects of virus-induced gene silencing (VIGS) are considered finally. For the cutting-edge CRISPR/Cas9 genome editing technology, VIGS has emerged as the preferred delivery system besides using it to overexpress or silence genes

MET and PI3K/mTOR as a Potential Combinatorial Therapeutic Target in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis. Studies have shown that both MET and its key downstream intracellular signaling partners, PI3K and mTOR, are overexpressed in MPM. Here we determined the combinatorial therapeutic efficacy of a new generation small molecule inhibitor of MET, ARQ 197, and dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 in mesothelioma cell and mouse xenograft models. Cell viability results show that mesothelioma cell lines were sensitive to ARQ 197, NVP-BEZ235 and GDC-0980 inhibitors. The combined use of ARQ 197 with either NVP-BEZ235 or GDC-0980, was synergistic (CI<1). Significant delay in wound healing was observed with ARQ 197 (p<0.001) with no added advantage of combining it with either NVP-BEZ235 or GDC-0980. ARQ 197 alone mainly induced apoptosis (20±2.36%) that was preceded by suppression of MAPK activity, while all the three suppressed cell cycle progression. Both GDC-0980 and NVP-BEZ235 strongly inhibited activities of PI3K and mTOR as evidenced from the phosphorylation status of AKT and S6 kinase. The above observation was further substantiated by the finding that a majority of the MPM archival samples tested revealed highly active AKT. While the single use of ARQ 197 and GDC-0980 inhibited significantly the growth of MPM xenografts (p<0.05, p<0.001 respectively) in mice, the combination of the above two drugs was highly synergistic (p<0.001). Our results suggest that the combined use of ARQ 197/NVP-BEZ235 and ARQ 197/GDC-0980 is far more effective than the use of the drugs singly in suppressing MPM tumor growth and motility and therefore merit further translational studies.</p