Ground-based salt seeding in Tamil nadu state, south India, 1973-1977

A long series of ground-based salt seeding experiments in north India during the southwest monsoonseasons (June-September) of 1957-66 showed significant increases of about 20 percent in rainfall on seeded days (Ramana Murty and Biswas, 1968). In September of 1974, salt seeding from aircraft on isolated maritime warm cumulus clouds within 50 km off the coast at Bombay(18 15’N, 72v 49’D, II m ASL) was followed by increases in radar echo area coverage in the vertical and in echo intensity (Chatterjee et al., 1978). seek similar results in a different area, a randomized salt-seeding experiment, using a single ground-based generator, was conducted in 1973 and 1975-77 just west of Madras, on the Bengal coast 1,000 km southeast of Bombay. There in the state of Tamil Nadu, South India, the main rainy season is during the northeast monsoon(Oct-Dec), whereas in most parts of India, about 75 percent of the annual rainfall is received during the southwest monsoon(Ananthakrishnan, 1977

Cysteamine Attenuates the Decreases in TrkB Protein Levels and the Anxiety/Depression-Like Behaviors in Mice Induced by Corticosterone Treatment

OBJECTIVE: Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders. MATERIALS AND METHODS: We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure. RESULTS: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine. CONCLUSIONS: The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders

A two-phase flow model to simulate mold filling and saturation in Resin Transfer Molding

The final publication is available at Springer via http://dx.doi.org/10.1007/s12289-015-1225-zThis paper addresses the numerical simulation of void formation and transport during mold filling in Resin Transfer Molding (RTM). The saturation equation, based on a two-phase flow model resin/air, is coupled with Darcy s law and mass conservation to simulate the unsaturated filling flow that takes place in a RTM mold when resin is injected through the fiber bed. These equations lead to a system composed of an advection diffusion equation for saturation including capillary effects and an elliptic equation for pressure taking into account the effect of air residual saturation. The model introduces the relative permeability as a function of resin saturation. When capillary effects are omitted, the hyperbolic nature of the saturation equation and its strong coupling with Darcy equation through relative permeability represent a challenging numerical issue. The combination of the constitutive physical laws relating permeability to saturation with the coupled system of the pressure and saturation equations allows predicting the saturation profiles. The model was validated by comparison with experimental data obtained for a fiberglass reinforcement injected in a RTM mold at constant flow rate. The saturation measured as a function of time during the resin impregnation of the fiber bed compared very well with numerical predictions.The authors acknowledge financial support of the Spanish Government (Projects DPI2010-20333 and DPI2013-44903-R-AR), of the National Science and Research Council of Canada (NSERC) and of the Canada Reseach Chair (CRC) program.Gascón Martínez, ML.; García Manrique, JA.; Lebel, F.; Ruiz, E.; Trochu, F. (2016). A two-phase flow model to simulate mold filling and saturation in Resin Transfer Molding. International Journal of Material Forming. 9(2):229-239. doi:10.1007/s12289-015-1225-zS22923992Patel N, Lee LJ (1996) Modeling of void formation and removal in liquid composite molding. Part I: wettability analysis. Polym Compos 17(1):96–103Ruiz E, Achim V, Soukane S, Trochu F, Bréard J (2006) Optimization of injection flow rate to minimize micro/macro-voids formation in resin transfer molded composites. Compos Sci Technol 66(3–4):475–486Trochu F, Ruiz E, Achim V, Soukane S (2006) Advanced numerical simulation of liquid composite molding for process analysis and optimization. Compos A: Appl Sci Manuf 37(6):890–902Park CH, Lee W (2011) Modeling void formation and unsaturated flow in liquid composite molding processes: a survey and review. J Reinf Plast Compos 30(11):957–977Pillai KM (2004) Modeling the unsaturated flow in liquid composite molding processes: a review and some thoughts. J Compos Mater 38(23):2097–2118Breard J, Saouab A, Bouquet G (2003) Numerical simulation of void formation in LCM. Compos A: Appl Sci Manuf 34:517–523Breard J, Henzel Y, Trochu F, Gauvin R (2003) Analysis of dynamic flows through porous media. Part I: comparison between saturated and unsaturated flows in fibrous reinforcements. Polym Compos 24(3):391–408Parnas RS, Phelan FR Jr (1991) The effect of heterogeneous porous media on mold filling in Resin Transfer Molding. SAMPE Q 22(2):53–60Parseval DY, Pillai KM, Advani SG (1997) A simple model for the variation of permeability due to partial saturation in dual scale porous media. Transp Porous Media 27(3):243–264Pillai KM (2002) Governing equations for unsaturated flow through woven fiber mats. Part 1. Isothermal flows. Compos A: Appl Sci Manuf 33(7):1007–1019Simacek P, Advani SG (2003) A numerical model to predict fiber tow saturation during Liquid Composite Molding. 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A DNMT3B Alternatively Spliced Exon and Encoded Peptide Are Novel Biomarkers of Human Pluripotent Stem Cells

A major obstacle in human stem cell research is the limited number of reagents capable of distinguishing pluripotent stem cells from partially differentiated or incompletely reprogrammed derivatives. Although human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) express numerous alternatively spliced transcripts, little attention has been directed at developing splice variant-encoded protein isoforms as reagents for stem cell research. In this study, several genes encoding proteins involved in important signaling pathways were screened to detect alternatively spliced transcripts that exhibited differential expression in pluripotent stem cells (PSCs) relative to spontaneously differentiated cells (SDCs). Transcripts containing the alternatively spliced exon 10 of the de novo DNA methyltransferase gene, DNMT3B, were identified that are expressed in PSCs. To demonstrate the utility and superiority of splice variant specific reagents for stem cell research, a peptide encoded by DNMT3B exon 10 was used to generate an antibody, SG1. The SG1 antibody detects a single DNMT3B protein isoform that is expressed only in PSCs but not in SDCs. The SG1 antibody is also demonstrably superior to other antibodies at distinguishing PSCs from SDCs in mixed cultures containing both pluripotent stem cells and partially differentiated derivatives. The tightly controlled down regulation of DNMT3B exon 10 containing transcripts (and exon 10 encoded peptide) upon spontaneous differentiation of PSCs suggests that this DNMT3B splice isoform is characteristic of the pluripotent state. Alternatively spliced exons, and the proteins they encode, represent a vast untapped reservoir of novel biomarkers that can be used to develop superior reagents for stem cell research and to gain further insight into mechanisms controlling stem cell pluripotency

Likely Role of APOBEC3G-Mediated G-to-A Mutations in HIV-1 Evolution and Drug Resistance

The role of APOBEC3 (A3) protein family members in inhibiting retrovirus infection and mobile element retrotransposition is well established. However, the evolutionary effects these restriction factors may have had on active retroviruses such as HIV-1 are less well understood. An HIV-1 variant that has been highly G-to-A mutated is unlikely to be transmitted due to accumulation of deleterious mutations. However, G-to-A mutated hA3G target sequences within which the mutations are the least deleterious are more likely to survive selection pressure. Thus, among hA3G targets in HIV-1, the ratio of nonsynonymous to synonymous changes will increase with virus generations, leaving a footprint of past activity. To study such footprints in HIV-1 evolution, we developed an in silico model based on calculated hA3G target probabilities derived from G-to-A mutation sequence contexts in the literature. We simulated G-to-A changes iteratively in independent sequential HIV-1 infections until a stop codon was introduced into any gene. In addition to our simulation results, we observed higher ratios of nonsynonymous to synonymous mutation at hA3G targets in extant HIV-1 genomes than in their putative ancestral genomes, compared to random controls, implying that moderate levels of A3G-mediated G-to-A mutation have been a factor in HIV-1 evolution. Results from in vitro passaging experiments of HIV-1 modified to be highly susceptible to hA3G mutagenesis verified our simulation accuracy. We also used our simulation to examine the possible role of A3G-induced mutations in the origin of drug resistance. We found that hA3G activity could have been responsible for only a small increase in mutations at known drug resistance sites and propose that concerns for increased resistance to other antiviral drugs should not prevent Vif from being considered a suitable target for development of new drugs

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Ureteral Stent Retrieval Using the Crochet Hook Technique in Females

INTRODUCTION: We developed a method for ureteral stent removal in female patients that requires no cystoscopy or fluoroscopic guidance using a crochet hook. In addition, we also investigated the success rate, complications and pain associated with this procedure. METHODS: A total of 40 female patients (56 stents) underwent the removal of ureteral stents. All procedures were carried out with the patients either under anesthesia, conscious sedation, or analgesic suppositories as deemed appropriate for each procedure including Shock Wave Lithotripsy (SWL), Ureteroscopy (URS), Percutaneous Nephrolithotomy (PCNL), and ureteral stent removal. At the time of these procedures, fluoroscopy and/or cystoscopy were prepared, but they were not used unless we failed to successfully remove the ureteral stent using the crochet hook. In addition, matched controls (comprising 50 stents) which were removed by standard ureteral stent removal using cystoscopy were used for comparison purposes. RESULTS: A total of 47 of the 56 stents (83.9%) were successfully removed. In addition, 47 of 52 (90.4%) were successfully removed except for two migrated stents and two heavily encrusted stents which could not be removed using cystoscopy. Ureteral stent removal using the crochet hook technique was unsuccessful in nine patients, including two encrustations and two migrations. Concerning pain, ureteral stent removal using the crochet hook technique showed a lower visual analogue pain scale (VAPS) score than for the standard technique using cystoscopy. CONCLUSIONS: Ureteral stent removal using a crochet hook is considered to be easy, safe, and cost effective. This technique is also easy to learn and is therefore considered to be suitable for use on an outpatient basis

Use of Tissue-Specific MicroRNA to Control Pathology of Wild-Type Adenovirus without Attenuation of Its Ability to Kill Cancer Cells

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 39 UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5610 10 viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral disease