131 research outputs found
Stabilisation of Deep Soil Cut Using Micropiles and Soil Nailing
The Railway route through south-west part of India (Konkan Railway) is passing through a hilly terrain. The route is developed by cutting the mountains in slopes and construction of tunnels. Many slopes along this route are very deep and steep. The region is characterized by lateritic soil. A heavy monsoon initiates some of the deep slope failures resulting in large magnitude of loss – both in money and life. The initial failure of one of the slope at Chainage 344/900 Km was stabilized by Gabion walls. West side of the Soil cutting was about 100 m long and a lateritic hilly slope steeply rises to 20 m above the track level at the collapse location. Initially the cutting line was 15m away from external track edge. However, after the heavy monsoon in June 2000, the soil slope collapses causing the lateral movement of the gabion wall and lateral shifting of the nearby railway track. The investigation was carried out to study the failure. The scheme of combination of conventional Soil Nails and Micropiles in addition to Gabion wall was proposed. The scheme was executed in Jan 2001 to May 2001. Load Tests were performed on Micropiles and Nails to verify the design. The slope is successfully stable for last 10 years
Ethnomedical Knowledge of Plants used by the Tribal people of Purandhar in Maharashtra, India
This study presents the results of a field survey of the plants used medically by the tribal people of Purandhar in Maharashtra, India. Tribes like Dhangars and Gowlis inhabit the dry deciduous forests of the region. This is an effort to record the valuable ethnomedical knowledge of these Purandhar tribes. A total of 77 species belonging to 30 families and 56 genera were included. These plants are used to treat various aliments, discomforts and diseases like whooping cough, asthma, diabetes, diphtheria, conjunctivitis, snake bite, scorpion bite, etc
Genetic Divergence for Yield, Physiological and Quality Traits in Super-Early Pigeon pea (Cajanus cajan. (l.) Millsp.)
The present investigation aimed to study genetic divergence and clustering pattern of 37super-early pigeon pea genotypes. Analysis of variance and hierarchical cluster analysis of tocher’s method revealed significant differences among the genotypes for all the traits under study. Based on genetic distance (D2 value), the 37 genotypes were grouped into 9 distinctive clusters, of which cluster I and II formed the largest clusters with 10 genotypes in each. Among all the characters understudy, leaf area index(LAI) at 60 DAS contributed more to the divergence followed by leaf area (17.02) and leaf area index (12.71) at maturity. Based on the average inter-cluster distance, the cluster III and IX (66.93) tailed by cluster III and VIII (64.86) and cluster VI and VIII (64.06) showed higher inter-cluster distance depicting the wider divergence. Trait-wise selection of diverse parents from the above clusters aids in exploitation of heterosis in superearly pigeon pea
Genetic Variability for Yield, Physiological and Quality Traits in Novel Super-Early Pigeonpea (Cajanus cajan (L.) Millsp.)
Super-early pigeonpea are novel genotypes that are reported to be photoperiod insensitive making it possible to grow it in non-traditional regions. Estimation of genetic parameters would be useful in developing appropriate selection and breeding strategies. A study was conducted to evaluate 37 super-early pigeonpea genotypes to access the magnitude of variability and to study heritable component of variation present in the yield, physiological and quality traits. The results revealed that traits leaf area duration between 60 DAS & maturity followed by leaf area & leaf area index at maturity, net assimilation between 60 DAS & maturity, leaf area index & leaf area at 60 DAS, leaf area duration between 60 DAS & maturity and plant height had high had higher PCV and GCV values. In general, phenotypic coefficients of variation (PCV) estimates were higher than genotypic coefficients of variation (GCV) estimates for all the characters under study, but the difference was relatively small indicating that these characters were less influenced by the environment and selection to improve those traits might be effective. High heritability combined with high genetic advance as a percent of mean was noted for all the traits except protein content conveying the governance of additive gene on trait expression. Anticipating these traits as selection index reaps competent improvement in yield, physiological and quality traits in early maturing pigeonpea
Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit.
Background We have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection for phase I trials based on albumin, number of disease sites and LDH. Patients with mesothelioma are often selected for phase I trials as the disease remains localised for long periods of time. We have now reviewed the clinical outcomes of patients with relapsed malignant mesothelioma (MM) and propose a specific mesothelioma prognostic score (m-RPS) that can help identify patients who are most likely to benefit from early referral.Methods Patients who participated in 38 phase I trials between September 2003 and November 2015 were included in the analysis. Efficacy was assessed by response rate, median overall survival (OS) and progression-free survival (PFS). Univariate (UVA) and multivariate analyses (MVA) were carried out to develop the m-RPS.Results A total of 65 patients with advanced MM were included in this retrospective study. The PFS was 2.5 months (95% confidence interval [CI] 2.0-3.1 months) and OS was 8 months (95% CI 5.6-9.8 months). A total of four (6%) patients had RECIST partial responses, whereas 26 (40%) patients had RECIST stable disease >3 months. The m-RPS was developed comprising of three different prognostic factors: a neutrophil: lymphocyte ratio greater than 3, the presence of more than two disease sites (including lymph nodes as a single site of disease) and albumin levels less than 35 from the MVA. Patients each received a score of 1 for the presence of each factor. Patients in group A (m-RPS 0-1; n = 35) had a median OS of 13.4 months (95% CI 8.5-21.6), whereas those in group B (m-RPS 2-3; n = 30) had a median OS of 4.0 months (95% CI 2.9-7.1, P < 0.0001). A total of 56 (86%) patients experienced G1-2 toxicities, whereas reversible G3-4 toxicities were observed in 18 (28%) patients. Only 10 (15%) patients discontinued phase I trials due to toxicity.Conclusions Phase I clinical trial therapies were well tolerated with early signals of antitumour activity in advanced MM patients. The m-RPS is a useful tool to assess MM patient suitability for phase I trials and should now be prospectively validated
Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-Induced Suppression of Cytokine Production
BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-alpha production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin
Antibody Responses against Xenotropic Murine Leukemia Virus-Related Virus Envelope in a Murine Model
Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC). Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV.Immunization elicited Env-specific binding and neutralizing antibodies (NAb) against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans
Preparação e caracterização de um biocompósito obtido pela mistura de hidreto de titânio com nitrato de cálcio para implantes dentários
RESUMO Neste trabalho foram realizados estudos sobre a fabricação de um biocompósito à base de titânio para implantes dentários a partir da mistura de pó de hidreto de titânio (92%) com nitrato de cálcio (8% em volume). O pó de hidreto de titânio foi adicionado na solução aquosa de nitrato de cálcio, dissolvido por agitação mecânica, e em seguida os precursores foram misturados e dispersados/homogeneizados por ultrassom. Posteriormente, a mistura foi secada em evaporador rotativo, compactada com 600 MPa à temperatura ambiente, desmoldada e sinterizada em alto vácuo a 1200 oC durante 2 horas. Foi analisada a microestrutrura e fases formadas, as propriedades mecânicas, a rugosidade da superfÃcie, a porosidade aberta, a molhabilidade da superfÃcie e a citotoxicidade do biocompósito. As fases identificadas após a sinterização foram α-Ti e CaTiO3. O limite de resistência em compressão, o módulo de Young (E) e o ângulo de contato do biocompósito diminuÃram significativamente com relação ao hidreto de titânio puro sinterizado nas mesmas condições. O limite médio de resistência em compressão do hidreto de titânio foi de 1794,67 MPa e do biocompósito foi de 481,36 MPa. O módulo de Young e o ângulo de contato do hidreto de titânio e do biocompósito foram de aproximadamente 112 GPa e 94 graus, e de 75 GPa e 83 graus, respectivamente. A rugosidade de superfÃcie foi da mesma ordem de grandeza entre os materiais e ficou aproximadamente entre 1,4 e 1,5 µm (Ra) e 1,4 e 1,9 µm (Ra e Sa), medidas com rugosÃmetro de contato e com microscópio confocal a laser, respectivamente. A porosidade aberta do biocompósito sinterizado foi de aproximadamente três vezes maior do que aquela do hidreto de titânio sinterizado. Nos ensaios de citotoxicidade a porcentagem de células viáveis do biocompósito foi superior à quela do controle negativo e à quela do hidreto de titânio sinterizado
Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review
<p>Abstract</p> <p>Background</p> <p>Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality.</p> <p>Methods</p> <p>We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted.</p> <p>Results</p> <p>Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group.</p> <p>Conclusion</p> <p>The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.</p
Curation of viral genomes: challenges, applications and the way forward
BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies
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