Paper Session III-C - Considerations for Large-Scale Construction in Orbit

To sustain and expand the human presence in space, a space-based economy must be developed. This in turn requires the development of infrastructure to utilize extra-terrestrial resources. This paper revisits concepts for large-scale construction in space from the 1970s, in the context of developing a space-based economy. Developments in robotics, solar power generation, microgravity manufacturing and earth-based launch costs significantly alter the models envisaged in the ‘70s. These changes are illustrated by considering the assembly of the outer shell of a 1 km-radius rotating cylindrical habitat

2nd Zonal Workshop on Fisheries and Aquaculture Policy: Ecosystem and Livelihood Perspectives in East Coast States

2nd Zonal Workshop on Fisheries and Aquaculture Policy: Ecosystem and Livelihood Perspectives in East Coast States Andhra Pradesh, Andaman & Nikobar Islands, Orissa. Pondichery, Tamilnadu and West Bengal Hyderabad 22-24 March, 2007 (CIFE, MUMBAI

Studies on interaction of nematode, Pratylenchus delattrei and fungal pathogen, Fusarium incarnatum associated with crossandra wilt in Tamil Nadu, India

ABSTRACT Investigations were under taken in pot culture experiment to assess a possible interaction between fungal pathogen of crossandra, Fusarium incarnatum and lesion nematode Pratylenchus delattrei, at various population density combinations, time of inoculation and their effect on plant growth and wilt incidence of crossandra. Among varies pathogen and nematode population densities tested, the inoculation of pathogen load @3% w/v and nematode @ 1/g soil resulted in maximum reduction of plant growth parameters viz., shoot length (49.8%), shoot dry weight (52.6%), root length (47.0%), root dry weight (47.4%), and flower yield (82.6%). More over maximum root lesion index of 3.9/1-5 scale, wilt disease incidence of (50%) and nematode population up to 365 per 200 cc soil, were also recorded. Other experimental results revealed that the treatment involving inoculation of nematode prior to fungal pathogen recorded more disease incidence (58.3%), nematode (381/200cc) and pathogen (12.1×10 3 ), populations and there was significant reduction in root length, root weight, shoot height and shoot weight when compared with inoculation of pathogen and nematode simultaneously or inoculation of pathogen prior to nematode

A cell based high-throughput screening approach for the discovery of new inhibitors of respiratory syncytial virus

Background: Human respiratory syncytial virus (hRSV) is a highly contagious pathogen and is the most common cause of bronchiolitis and pneumonia for infants and children under one year of age. Worldwide, greater than 33 million children under five years of age are affected by hRSV resulting in three million hospitalizations and 200,000 deaths. However, severe lower respiratory tract disease may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems. There is no vaccine commercially available. Existing therapies for the acute infection are ribavirin and the prophylactic humanized monoclonal antibody (Synagis® from MedImmune) that is limited to use in high risk pediatric patients. Thus, the discovery of new inhibitors for hRSV would be clinically beneficial. Results: We have developed and validated a 384-well cell-based, high-throughput assay that measures the cytopathic effect of hRSV (strain Long) in HEp-2 cells using a luminescent-based detection system for signal endpoint (Cell Titer Glo®). The assay is sensitive and robust, with Z factors greater than 0.8, signal to background greater than 35, and signal to noise greater than 24. Utilizing this assay, 313,816 compounds from the Molecular Libraries Small Molecule Repository were screened at 10 μM. We identified 7,583 compounds that showed greater than 22% CPE inhibition in the primary screen. The top 2,500 compounds were selected for confirmation screening and 409 compounds showed at least 50% inhibition of CPE and were considered active. We selected fifty-one compounds, based on potency, selectivity and chemical tractability, for further evaluation in dose response and secondary assays Several compounds had SI50 values greater than 3, while the most active compound displayed an SI50 value of 58.9. Conclusions: A robust automated luminescent-based high throughput screen that measures the inhibition of hRSV-induced cytopathic effect in HEp-2 cells for the rapid identification of potential inhibitors from large compound libraries has been developed, optimized and validated. The active compounds identified in the screen represent different classes of molecules, including aryl sulfonylpyrrolidines which have not been previously identified as having anti-hRSV activity

(S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a Small Molecule Inhibitor Probe for the Study of Respiratory Syncytial Virus Infection

A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of infection (EC50 = 2.3 ± 0.8 µM) with marginal cytotoxicity (CC50 = 30.9 ± 1.1 µM) and reduced viral titer by 100-fold. Compared to ribavirin, sulfonylpyrrolidine 5o demonstrated an improved in vitro potency and selectivity index

Exploration of Molecular Factors Impairing Superoxide Dismutase Isoforms Activity in Human Senile Cataractous Lenses

PURPOSE. To explore different molecular factors impairing the activities of superoxide dismutase (SOD) isoforms in senile cataractous lenses. METHODS. Enzyme activity of SOD isoforms, levels of their corresponding cofactors copper (Cu), manganese (Mn), zinc (Zn), and expression of mRNA transcripts and proteins were determined in the lenses of human subjects with and without cataract. DNA from lens epithelium (LE) and peripheral blood was isolated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by sequencing was carried out to screen somatic mutations. The impact of intronic insertion/deletion (INDEL) variations on the splicing process and on the resultant transcript was evaluated. Genotyping of IVS4þ42delG polymorphism of SOD1 gene was done by PCR-restriction fragment length polymorphism (RFLP). RESULTS. A significant decrease in Cu/Zn-and Mn-SOD activity (P < 0.001) and in Cu/Zn-SOD transcript (P < 0.001) and its protein (P < 0.05) were found in cataractous lenses. No significant change in the level of copper (P ¼ 0.36) and an increase in the level of manganese (P ¼ 0.01) and zinc (P ¼ 0.02) were observed in cataractous lenses. A significant positive correlation between the level of Cu/Zn-SOD activity and the levels of Cu (P ¼ 0.003) and Zn (P ¼ 0.005) was found in the cataractous lenses. DNA sequencing revealed three intronic INDEL variations in exon4 of SOD1 gene. Splice-junction analysis showed the potential of IVS4þ42delG in creating a new cryptic acceptor site. If it is involved in alternate splicing, it could result in generation of SOD1 mRNA transcripts lacking exon4 region. Transcript analysis revealed the presence of complete SOD1 mRNA transcripts. Genotyping revealed the presence of IVS4þ42delG polymorphism in all subjects. CONCLUSIONS. The decrease in the activity of SOD1 isoform in cataractous lenses was associated with the decreased level of mRNA transcripts and their protein expression and was not associated with either modulation in the level of enzyme cofactors or with INDEL variations

Large-eddy simulation sensitivities to variations of configuration and forcing parameters in canonical boundary-layer flows for wind energy applications

The sensitivities of idealized large-eddy simulations (LESs) to variations of model configuration and forcing parameters on quantities of interest to wind power applications are examined. Simulated wind speed, turbulent fluxes, spectra and cospectra are assessed in relation to variations in two physical factors, geostrophic wind speed and surface roughness length, and several model configuration choices, including mesh size and grid aspect ratio, turbulence model, and numerical discretization schemes, in three different code bases. Two case studies representing nearly steady neutral and convective atmospheric boundary layer (ABL) flow conditions over nearly flat and homogeneous terrain were used to force and assess idealized LESs, using periodic lateral boundary conditions. Comparison with fast-response velocity measurements at 10 heights within the lowest 100&thinsp;m indicates that most model configurations performed similarly overall, with differences between observed and predicted wind speed generally smaller than measurement variability. Simulations of convective conditions produced turbulence quantities and spectra that matched the observations well, while those of neutral simulations produced good predictions of stress, but smaller than observed magnitudes of turbulence kinetic energy, likely due to tower wakes influencing the measurements. While sensitivities to model configuration choices and variability in forcing can be considerable, idealized LESs are shown to reliably reproduce quantities of interest to wind energy applications within the lower ABL during quasi-ideal, nearly steady neutral and convective conditions over nearly flat and homogeneous terrain.</p

Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is a contagious disease caused by <it>Mycobacterium tuberculosis </it>(Mtb), affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR) and extensively drug-resistant (XDR) strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes.</p> <p>Results</p> <p>We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO) on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures.</p> <p>Conclusions</p> <p>This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.</p

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

The Identification of Protein Kinase C Iota as a Regulator of the Mammalian Heat Shock Response Using Functional Genomic Screens

BACKGROUND: The heat shock response is widely used as a surrogate of the general protein quality control system within the cell. This system plays a significant role in aging and many protein folding diseases as well as the responses to other physical and chemical stressors. METHODS/PRINCIPAL FINDINGS: In this study, a broad-based functional genomics approach was taken to identify potential regulators of the mammalian heat shock response. In the primary screen, a total of 13724 full-length genes in mammalian expression vectors were individually co-transfected into human embryonic kidney cells together with a human HSP70B promoter driving firefly luciferase. A subset of the full-length genes that showed significant activation in the primary screen were then evaluated for their ability to hyper-activate the HSP70B under heat shock conditions. Based on the results from the secondary assay and gene expression microarray analyses, eight genes were chosen for validation using siRNA knockdown. Of the eight genes, only PRKCI showed a statistically significant reduction in the heat shock response in two independent siRNA duplexes compared to scrambled controls. Knockdown of the PRKCI mRNA was confirmed using quantitative RT-PCR. Additional studies did not show a direct physical interaction between PRKCI and HSF1. CONCLUSIONS/SIGNIFICANCE: The results suggest that PRKCI is an indirect co-regulator of HSF1 activity and the heat shock response. Given the underlying role of HSF1 in many human diseases and the response to environmental stressors, PRKCI represents a potentially new candidate for gene-environment interactions and therapeutic intervention