Evaluation Comparison of Mesh-Based routing Protocols in MANET

A multicast routing protocol manages group membership and controls the path that multicast data takes over the network in mobile ad hoc network. This process is done through either tree-based or mesh-based protocols. The mesh-based protocols are more reliable and robust against the tree based protocols. One of the most used on-demand multicast routing protocol is ODMRP (On-Demand Routing Protocol). However, it has the significant overhead due to redundant data delivery group and path maintenance. This overhead has been eliminated through the forwarding node reduction and link break time prediction algorithm (FNRLP). This work aims to exhibit the performance characteristics of mesh-based on-demand multicast routing protocols ODMRP and ODMRP-FNRLP

PHARMACOGNOSTIC AND HPTLC BASED COMPARATIVE STUDY ON LEAVES OF MERREMIA EMARGINATA BURM. F. AND CENTELLA ASIATICA (L.) URBAN

Objective: In this study, an attempt was made to generate information based on botanical, physicochemical and HPTLC data needed for proper identification and authentication of M. emarginata and C. asiatica belonging to two different families. Methods: Botanical study comprises of macroscopy, microscopy and powder microscopy of leaves of both crude drugs. The physicochemical parameters such as water-soluble extractive, alcohol soluble extractive and loss on drying at 105℃, total ash, acid insoluble ash, and volatile oil were determined according to standard methods. HPTLC studies of chloroform extracts of leaves of both drugs were conducted at 254 nm, 366 nm and 575 nm after derivatisation using vanillin-sulphuric acid and the results were documented. Results: The present study reveals that microscopy and most of the physicochemical parameters of both the plant materials are different. Anatomy of the leaves showed two main characteristic differences. First plenty of trichome with trichome base and calcium oxalate crystal is common in M. emarginata, which is not observed in C. asiatica. Both plants have different venation patterns and leaf constants. The total ash content and the solubility in alcohol and water for leaves of C. asiatica are higher than that of M. emarginata. The HPTLC fingerprinting pattern obtained for both drugs are different. Conclusion: All the results obtained from this study help in determining differences and similarities of leaves of M. emarginata and C. asiatica and thereby preventing adulteration and substitution and emphasizing the importance of standardization

Pharmacognostic Investigation and HPTLC Fingerprinting of a Siddha Polyherbal Drug, Padai chankaran

The present study aims to establish the quality and purity of a Siddha formulation, Padai chankaran by laying down various pharmacognostic parameters, physico-chemical constants and HPTLC fingerprint profiles. Padai chankaran is a Siddha polyherbal preparation comprised of Catunaregum spinosa – root bark, C. spinosa – seed and Alangium salvifolium – root bark as the ingredients. The formulation is used as an external application, having astringent, anthelmintic and antiseptic activities that supports in healing of ulcers and dermatological diseases. Powder microscopy studies and physico-chemical analysis were carried out. Also, an attempt has been made to develop a HPTLC method for phytochemical fingerprinting and the mobile phase Toluene: Ethyl acetate: Formic acid (5: 2: 0.1) gave the best resolution for various components. Hence, the aforesaid analyses confirmed the purity and quality of the Siddha formulation for their future applications. Keywords: Padai chankaran, powder microscopy, physico-chemical, HPTLC studie

X-Linked Inhibitor of Apoptosis Protein-Mediated Attenuation of Apoptosis, Using a Novel Cardiac-Enhanced Adeno-Associated Viral Vector

Successful amelioration of cardiac dysfunction and heart failure through gene therapy approaches will require a transgene effective at attenuating myocardial injury, and subsequent remodeling, using an efficient and safe delivery vehicle. Our laboratory has established a well-curated, high-quality repository of human myocardial tissues that we use as a discovery engine to identify putative therapeutic transgene targets, as well as to better understand the molecular basis of human heart failure. By using this rare resource we were able to examine age- and sex-matched left ventricular samples from (1) end-stage failing human hearts and (2) nonfailing human hearts and were able to identify the X-linked inhibitor of apoptosis protein (XIAP) as a novel target for treating cardiac dysfunction. We demonstrate that XIAP is diminished in failing human hearts, indicating that this potent inhibitor of apoptosis may be central in protecting the human heart from cellular injury culminating in heart failure. Efforts to ameliorate heart failure through delivery of XIAP compelled the design of a novel adeno-associated viral (AAV) vector, termed SASTG, that achieves highly efficient transduction in mouse heart and in cultured neonatal rat cardiomyocytes. Increased XIAP expression achieved with the SASTG vector inhibits caspase-3/7 activity in neonatal cardiomyocytes after induction of apoptosis through three common cardiac stresses: protein kinase C-γ inhibition, hypoxia, or β-adrenergic receptor agonist. These studies demonstrate the potential benefit of XIAP to correct heart failure after highly efficient delivery to the heart with the rationally designed SASTG AAV vector

Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2

<p>Abstract</p> <p>Background</p> <p>The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses.</p> <p>Methods</p> <p>Subjects with stage II (≥ 6 +LN), III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3), mature cultured DC (n = 3), or mature Flt3-ligand mobilized peripheral blood DC (n = 1) loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact.</p> <p>Results</p> <p>All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH) reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up.</p> <p>Conclusion</p> <p>Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00005956</p

Arm-specific dynamics of chromosome evolution in malaria mosquitoes

<p>Abstract</p> <p>Background</p> <p>The malaria mosquito species of subgenus <it>Cellia </it>have rich inversion polymorphisms that correlate with environmental variables. Polymorphic inversions tend to cluster on the chromosomal arms 2R and 2L but not on X, 3R and 3L in <it>Anopheles gambiae </it>and homologous arms in other species. However, it is unknown whether polymorphic inversions on homologous chromosomal arms of distantly related species from subgenus <it>Cellia </it>nonrandomly share similar sets of genes. It is also unclear if the evolutionary breakage of inversion-poor chromosomal arms is under constraints.</p> <p>Results</p> <p>To gain a better understanding of the arm-specific differences in the rates of genome rearrangements, we compared gene orders and established syntenic relationships among <it>Anopheles gambiae, Anopheles funestus</it>, and <it>Anopheles stephensi</it>. We provided evidence that polymorphic inversions on the 2R arms in these three species nonrandomly captured similar sets of genes. This nonrandom distribution of genes was not only a result of preservation of ancestral gene order but also an outcome of extensive reshuffling of gene orders that created new combinations of homologous genes within independently originated polymorphic inversions. The statistical analysis of distribution of conserved gene orders demonstrated that the autosomal arms differ in their tolerance to generating evolutionary breakpoints. The fastest evolving 2R autosomal arm was enriched with gene blocks conserved between only a pair of species. In contrast, all identified syntenic blocks were preserved on the slowly evolving 3R arm of <it>An. gambiae </it>and on the homologous arms of <it>An. funestus </it>and <it>An. stephensi</it>.</p> <p>Conclusions</p> <p>Our results suggest that natural selection favors specific gene combinations within polymorphic inversions when distant species are exposed to similar environmental pressures. This knowledge could be useful for the discovery of genes responsible for an association of inversion polymorphisms with phenotypic variations in multiple species. Our data support the chromosomal arm specificity in rates of gene order disruption during mosquito evolution. We conclude that the distribution of breakpoint regions is evolutionary conserved on slowly evolving arms and tends to be lineage-specific on rapidly evolving arms.</p

Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract

Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was 1252.4 ml per year in the nintedanib group and 1293.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P=0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of 120.21 (95% CI, 120.94 to 0.53; P=0.58) and 1.69 (95% CI, 120.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo