Pituitary gonadotropins regulate spermatogonial differentiation and proliferation in the rat

The relative regulatory roles of the pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone in the spermatogonial proliferation has been studied using specific antibodies against these hormones in the immature rats. Immunoneutralization of luteinizing hormone for 7 days resulted in significant reduction in tetraploid cells and total absence of haploid cells, while there was a relative increase in the diploid population. This was also accomopanied by a decrease in spermatogonial proliferation as indicated by a decrease in [H-3] thymidine incorporation into DNA by purified spermatogonia. Administration bf follicle stimulating hormone als for 7 days also caused a significant decrease in the rate of spermatogonial proliferation. Withdrawal of follicle stimulating hormone led to a significant reduction in tetraploid and haploid cells However interestingly, it failed to totally abolish the appearance of these cells. Administration of testosterone (3mg/day/rat) for 2 days along with the gonadotropin a/s could partially reverse the effect on spermatogonial proliferation. It is concluded that (i) both luteinizing hormone and follicle stimulating hormone are involved in spermatogonial proliferation, (ii) lack of testosterone consequent of the neutralization of luteinizing hormone prevented the entry of spermatogonial cells into meiosis, (iii) testosterone may be involved in spermatogonial proliferation providing a mitotic signal and (v) both follicle stimulating hormone and testosterone act synergistically and lack of any one of the hormones results in impairment of spermatogonial proliferation.

Efficiency enhancement in DSSC using metal nanoparticles: A size dependent study

The photoelectrode of Eosin-Y sensitised DSSC was modified by incorporating Au-nanoparticles to enhance the power conversion efficiency via scattering from surface plasmon polaritons. Size dependence of Au nanoparticle on conversion efficiency was performed in DSSC for the first time by varying the particle size from 20 to 94 nm. It was found that, the conversion efficiency is highly dependent on the size of the Au nanoparticles. For larger particles (>50 nm), the efficiency was found to be increased due to constructive interference between the transmitted and scattered waves from the Au nanoparticle while for smaller particles, the efficiency decreases due to destructive interference. Also a reduction in the V-oc was observed in general, due to the negative shifting of the TiO2 Fermi level on the adsorption of Au nanoparticle. This shift was negligible for larger particles. When 94 nm size particles were employed the conversion efficiency was doubled from 0.74% to 1.52%. This study points towards the application of the scattering effect of metal nanoparticle to enhance the conversion efficiency in DSSCs. (C) 2011 Elsevier Ltd. All rights reserved.

Transition due to base roughness in a dense granular flow down an inclined plane

Particle simulations based on the discrete element method are used to examine the effect of base roughness on the granular flow down an inclined plane. The base is composed of a random configuration of fixed particles, and the base roughness is decreased by decreasing the ratio of diameters of the base and moving particles. A discontinuous transition from a disordered to an ordered flow state is observed when the ratio of diameters of base and moving particles is decreased below a critical value. The ordered flowing state consists of hexagonally close packed layers of particles sliding over each other. The ordered state is denser (higher volume fraction) and has a lower coordination number than the disordered state, and there are discontinuous changes in both the volume fraction and the coordination number at transition. The Bagnold law, which states that the stress is proportional to the square of the strain rate, is valid in both states. However, the Bagnold coefficients in the ordered flowing state are lower, by more than two orders of magnitude, in comparison to those of the disordered state. The critical ratio of base and moving particle diameters is independent of the angle of inclination, and varies very little when the height of the flowing layer is doubled from about 35 to about 70 particle diameters. While flow in the disordered state ceases when the angle of inclination decreases below 20 degrees, there is flow in the ordered state at lower angles of inclination upto 14 degrees. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4710543]

Stochastic Simulations Suggest that HIV-1 Survives Close to Its Error Threshold

The use of mutagenic drugs to drive HIV-1 past its error threshold presents a novel intervention strategy, as suggested by the quasispecies theory, that may be less susceptible to failure via viral mutation-induced emergence of drug resistance than current strategies. The error threshold of HIV-1, mu(c), however, is not known. Application of the quasispecies theory to determine mu(c) poses significant challenges: Whereas the quasispecies theory considers the asexual reproduction of an infinitely large population of haploid individuals, HIV-1 is diploid, undergoes recombination, and is estimated to have a small effective population size in vivo. We performed population genetics-based stochastic simulations of the within-host evolution of HIV-1 and estimated the structure of the HIV-1 quasispecies and mu(c). We found that with small mutation rates, the quasispecies was dominated by genomes with few mutations. Upon increasing the mutation rate, a sharp error catastrophe occurred where the quasispecies became delocalized in sequence space. Using parameter values that quantitatively captured data of viral diversification in HIV-1 patients, we estimated mu(c) to be 7 x 10(-5) -1 x 10(-4) substitutions/site/replication, similar to 2-6 fold higher than the natural mutation rate of HIV-1, suggesting that HIV-1 survives close to its error threshold and may be readily susceptible to mutagenic drugs. The latter estimate was weakly dependent on the within-host effective population size of HIV-1. With large population sizes and in the absence of recombination, our simulations converged to the quasispecies theory, bridging the gap between quasispecies theory and population genetics-based approaches to describing HIV-1 evolution. Further, mu(c) increased with the recombination rate, rendering HIV-1 less susceptible to error catastrophe, thus elucidating an added benefit of recombination to HIV-1. Our estimate of mu(c) may serve as a quantitative guideline for the use of mutagenic drugs against HIV-1.

A finite population model of mlecular evolution: theory and computation

This article is concerned with the evolution of haploid organisms that reproduce asexually. In a seminal piece of work, Eigen and coauthors proposed the quasispecies model in an attempt to understand such an evolutionary process. Their work has impacted antiviral treatment and vaccine design strategies. Yet, predictions of the quasispecies model are at best viewed as a guideline, primarily because it assumes an infinite population size, whereas realistic population sizes can be quite small. In this paper we consider a population genetics-based model aimed at understanding the evolution of such organisms with finite population sizes and present a rigorous study of the convergence and computational issues that arise therein. Our first result is structural and shows that, at any time during the evolution, as the population size tends to infinity, the distribution of genomes predicted by our model converges to that predicted by the quasispecies model. This justifies the continued use of the quasispecies model to derive guidelines for intervention. While the stationary state in the quasispecies model is readily obtained, due to the explosion of the state space in our model, exact computations are prohibitive. Our second set of results are computational in nature and address this issue. We derive conditions on the parameters of evolution under which our stochastic model mixes rapidly. Further, for a class of widely used fitness landscapes we give a fast deterministic algorithm which computes the stationary distribution of our model. These computational tools are expected to serve as a framework for the modeling of strategies for the deployment of mutagenic drugs.

Single-Molecule DNA Analysis Reveals That Yeast Hop1 Protein Promotes DNA Folding and Synapsis: Implications for Condensation of Meiotic Chromosomes

During meiosis, long-range interaction between homologous chromosomes is thought to be crucial for homology recognition, exchange of DNA strands, and production of normal haploid gametes. However, little is known about the identity of the proteins involved and the actual molecular mechanism(s) by which chromosomes recognize and recombine with their appropriate homologous partners. Single-molecule analyses have the potential to provide insights into our understanding of this fascinating and long-standing question. Using atomic force microscopy and magnetic tweezers techniques, we discovered that Hop1 protein, a key structural component of Saccharomyces cerevisiae synaptonemal complex, exhibits the ability to bridge noncontiguous DNA segments into intramolecular stem-loop structures in which the DNA segments appear to be fully synapsed within the filamentous protein stems. Additional evidence suggests that Hop1 folds DNA into rigid protein DNA filaments and higher-order nucleoprotein structures. Importantly, Hop1 promotes robust intra- and intermolecular synapsis between double-stranded DNA molecules, suggesting that juxtaposition of DNA sequences may assist in strand exchange between homologues by recombination-associated proteins. Finally, the evidence from ensemble experiments is consistent with the notion that Hop1 causes rigidification of DNA molecules. These results provide the first direct evidence for long-range protein-mediated DNA DNA synapsis, independent of crossover recombination, which is presumed to occur during meiotic recombination.

Salt and cocrystals of sildenafil with dicarboxylic acids: solubility and pharmacokinetic advantage of the glutarate salt

Sildenafil is a drug used to treat erectile dysfunction and pulmonary arterial hypertension. Because of poor aqueous solubility of the drug, the citrate salt, with improved solubility and pharmacokinetics, has been marketed. However, the citrate salt requires an hour to reach its peak plasma concentration. Thus, to improve solubility and bioavailability characteristics, cocrystals and salts of the drug have been prepared by treating aliphatic dicarboxylic acids with sildenafil; the N-methylated piperazine of the drug molecule interacts with the carboxyl group of the acid to form a heterosynthon. Salts are formed with oxalic and fumaric acid; salt monoanions are formed with succinic and glutaric acid. Sildenafil forms cocrystals with longer chain dicarboxylic acids such as adipic, pimelic, suberic, and sebacic acids. Auxiliary stabilization via C-H center dot center dot center dot O interactions is also present in these cocrystals and salts. Solubility experiments of sildenafil cocrystal/salts were carried out in 0.1N HCl aqueous medium and compared with the solubility of the citrate salt. The glutarate salt and pimelic acid cocrystal dissolve faster than the citrate salt in a two hour dissolution experiment. The glutarate salt exhibits improved solubility (3.2-fold) compared to the citrate salt in water. Solubilities of the binary salts follow an inverse correlation with their melting points, while the solubilities of the cocrystals follow solubilities of the coformer. Pharmacokinetic studies on rats showed that the glutarate salt exhibits doubled plasma AUC values in a single dose within an hour compared to the citrate salt. The high solubility of glutaric acid, in part originating from the strained conformation of the molecule and its high permeability, may be the reason for higher plasma levels of the drug.

Molecular Dynamics Perspective on the Protein Thermal Stability: A Case Study Using SAICAR Synthetase

The enzyme SAICAR synthetase ligates aspartate with CAIR (5'-phosphoribosyl-4-carboxy-5-aminoimidazole) forming SAICAR (5-amino-4-imidazole-N-succinocarboxamide ribonucleotide) in the presence of ATP. In continuation with our previous study on the thermostability of this enzyme in hyper-/thermophiles based on the structural aspects, here, we present the dynamic aspects that differentiate the mesophilic (E. coli, E. chaffeensis), thermophilic (G. kaustophilus), and hyperthermophilic (M. jannaschii, P. horikoshii) SAICAR synthetases by carrying out a total of 11 simulations. The five functional dimers from the above organisms were simulated using molecular dynamics for a period of 50 ns each at 300 K, 363 K, and an additional simulation at 333 K for the thermophilic protein. The basic features like root-mean-square deviations, root-mean-square fluctuations, surface accessibility, and radius of gyration revealed the instability of mesophiles at 363 K. Mean square displacements establish the reduced flexibility of hyper-/thermophiles at all temperatures. At the simulations time scale considered here, the long-distance networks are considerably affected in mesophilic structures at 363 K. In mesophiles, a comparatively higher number of short-lived (having less percent existence time) C alpha, hydrogen bonds, hydrophobic interactions are formed, and long-lived (with higher percentage existence time) contacts are lost. The number of time-averaged salt-bridges is at least 2-fold higher in hyperthermophiles at 363 K. The change in surface accessibility of salt-bridges at 363 K from 300 K is nearly doubled in mesophilic protein compared to proteins from other temperature classes.

Rapid reduction of GO by hydrogen spill-over mechanism by in situ generated nanoparticles at room temperature and their catalytic performance towards 4-nitrophenol reduction and ethanol oxidation

Here, we report the clean and facile synthesis of Pt and Pd nanoparticles decorated on reduced graphene oxide (rGO) by the simultaneous reduction of graphene oxide (GO) and the metal ions in Mg/acid medium. As-generated Pt and Pd nanoparticles serve as a heterogeneous catalyst for the further reduction of the rGO by the hydrogen spill-over process. The C/O ratio is much higher as compared to the rGO obtained by the reduction of GO by only Mg/acid. Overall, the process is rapid, facile and green that does not require any toxic chemical agent or any rigorous chemical reactions. We perform the catalytic reduction of 4-nitophenol (4-NP) to 4-aminophenol (4-AP) at room temperature by Pd@rGO and Pt@rGO. The reduction is complete within 35 s for Pd@rGO and 60 s for Pt@rGO when 50 mu g of hybrid catalyst is used for 0.5 ml of 1 mM of 4-NP. In case of ethanol oxidation, the current density for Pd@rGO is comparable to commercial Pt/C but is doubled for Pt@rGO. Overall, both structures show highly stable catalytic activity compared to commercial Pt/C. (C) 2014 Elsevier B.V. All rights reserved.

Self-assembled ZnO nanoparticles on ZnO microsheet: ultrafast synthesis and tunable photoluminescence properties

We report on the tunable photoluminescence characteristics of porous ZnO microsheets fabricated within 1-5 min of microwave irradiation in the presence of a capping agent such as citric acid, and mixture of citric acid with polyvinylpyrrolidone (PVP). The UV emission intensity reduces to 60% and visible emission increases tenfold when the molar concentration of citric acid is doubled. Further diminution of the intensity of UV emission (25%) is observed when PVP is mixed with citric acid. The addition of nitrogen donor ligands to the parent precursor leads to a red shift in the visible luminescence. The deep level emission covers the entire visible spectrum and gives an impression of white light emission from these ZnO samples. The detailed luminescence mechanism of our ZnO samples is described with the help of a band diagram constructed by using the theoretical models that describe the formation energy of the defect energy levels within the energy band structure. Oxygen vacancies play the key role in the variation of the green luminescence in the ZnO microsheets. Our research findings provide an insight that it is possible to retain the microstructure and simultaneously introduce defects into ZnO. The growth of the ZnO microsheets may be due to the self assembly of the fine sheets formed during the initial stage of nucleation.

InGaN/GaN LEDs grown on Si(111): Dependence of device performance on threading dislocation density and emission wavelength

We demonstrate the growth of crack-free blue and greenemitting LED structures grown on 2-inch and 6-inch Si(111) substrates by metalorganic vapour phase epitaxy (MOVPE), using AlN nucleation layers and AlGaN buffer layers for stress management. LED device performance and its dependence on threading dislocation (TD) density and emission wavelength were studied. Despite the inherently low light extraction efficiency, an output power of 1.2 mW at 50 mA was measured from a 500 μm square planar device, emitting at 455 nm. The light output decreases dramatically as the emission wavelength increases from 455 nm to 510 nm. For LED devices emitting at similar wavelength, the light output was more than doubled when the TD density was reduced from 5×1 09 cm-2 to 2×109 cm-2. Our results clearly show that high TD density is detrimental to the overall light output, highlighting the need for further TD reduction for structures grown on Si. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

Curvature and wrinkling of premixed flame Kernels comparison between planar laser induced fluorescence (PLIF) and 3D direct numerical simulations (DNS)

A direct comparison between time resolved PLIF measurements of OH and two dimensional slices from a full three dimensional DNS data set of turbulent premixed flame kernels in lean methane/air mixture was presented. The local flame structure and the degree of flame wrinkling were examined in response to differing turbulence intensities and turbulent Reynolds numbers. Simulations were performed using the SEGA DNS code, which is based on the solution of the compressible Navier Stokes, species, and energy equations for a lean hydrocarbon mixture. For the OH PLIF measurements, a cluster of four Nd:YAG laser was fired sequentially at high repetition rates and used to pump a dye laser. The frequency doubled laser beam was formed into a sheet of 40 mm height using a cylindrical telescope. The combination of PLIF and DNS has been demonstrated as a powerful tool for flame analysis. This research will form the basis for the development of sub-grid-scale (SGS) models for LES of lean-premixed combustion systems such as gas turbines. This is an abstract of a paper presented at the 30th International Symposium on Combustion (Chicago, IL 7/25-30/2004).

Approximate knowledge of rationality and correlated equilibria

We extend Aumann's [3] theorem deriving correlated equilibria as a consequence of common priors and common knowledge of rationality by explicitly allowing for non-rational behavior. We replace the assumption of common knowledge of rationality with a substantially weaker notion, joint p-belief of rationality, where agents believe the other agents are rational with probabilities p = (pi)i2I or more. We show that behavior in this case constitutes a constrained correlated equilibrium of a doubled game satisfying certain p-belief constraints and characterize the topological structure of the resulting set of p-rational outcomes. We establish continuity in the parameters p and show that, for p su ciently close to one, the p-rational outcomes are close to the correlated equilibria and, with high probability, supported on strategies that survive the iterated elimination of strictly dominated strategies. Finally, we extend Aumann and Dreze's [4] theorem on rational expectations of interim types to the broader p-rational belief systems, and also discuss the case of non-common priors.

Dynamics of Streptococcus pneumoniae Serotypes Causing Acute Otitis Media Isolated from Children with Spontaneous Middle-Ear Drainage over a 12-Year Period (1999–2010) in a Region of Northern Spain

10 p.

On the climatology, oceanography and fisheries of the Panama Bight

ENGLISH: Seasonal changes in the climatology, oceanography and fisheries of the Panama Bight are determined mainly by the latitudinal movements of the ITCZ over the region. Evaporation is about 980 mm annually. Rainfall is probably much less than previous estimates because of a discontinuity in the ITCZ. Freshwater runoff from the northern watershed varies from 22 X 109 m3/mo in October-November to 11 X 109 m3/mo in February-March; from the southeastern watershed it varies from 16 X 109 m3/mo in April-June to 9 X 109 m3/mo in October-December. Total annual runoff is about 350 X 109m3. A marked salinity front is found at all seasons off the eastern shore. In the northern part of the Bight temperatures in the upper layers remained fairly constant from May to November; by February the mean temperature had decreased by 4°C and sharp gradients existed in the geographic distributions. Salinities in the upper layers decreased steadily from May to November; by February the mean salinity had increased by 2.5‰. The mean depth of the mixed layer increased from 27 m in May to 40 m in November; by February upwelling decreased it to 18 m. Between November and February upwelling had doubled the amount of P04-P and tripled that of NO3-N in the euphotic zone; surface phytoplankton production and standing crop, and zooplankton concentrations also doubled during this period. Upwelling was about 1.5 m/mo during May-November and about 9.0 m/mo during November-February, the annual total is about 48 m, Mean primary production is about 0.3 gC/m2day during May-December and about 0.6 gC/m2day during January-April; annual production is about 140 gC/m2. A thermal ridge occurred in February running from the northern to the southwestern part of the Bight. Within this ridge was a marked thermal dome coinciding with the center of the cyclonic circulation cell. Upwelling in the dome averaged 16 m/mo in November-February. The fisheries of the Panama Bight annually produce about 30,000 metric tons of food species and about 68,000 m.t. of species used for reduction. Most attempts to further the understanding of tuna ecology were unsuccessful. The apparent abundances of yellowfin and skipjack in the northern part of the Bight appear to be related to the seasonal cycle of upwelling and enrichment, as abundances are greatest in April and May when food appears to be plentiful. The life-cycle of the anchoveta in the Gulf of Panama also appears to be related to upwelling; the species mass varies from about 39,000 m.t. in December to about 169,000 m.t, in April. About 19.1 X 1012 anchoveta eggs are spawned annually. The life-cycles of shrimp in the Panama Bight appear to be related to upwelling as catches are greatest in May-July, about 3-5 months after peak upwelling, and annual catches are inversely correlated with sea level. SPANISH: Los cambios estacionales en la climatología, oceanografía y pesquerías del Panamá Bight están determinados principalmente por el movimiento latitudinal sobre la región de la Zona de Convergencia Intertropical (ZCIT). La evaporación es de unos 980 mm al año. La pluviosidad es probablemente muy inferior a las estimaciones previas a causa de la descontinuidad en la ZCIT. El drenaje de agua dulce, de la vertiente septentrional, varía de 22 x 109m3/mes en octubre-noviembre hasta 11 x 109m3/mes en febreromarzo; el de la vertiente sudeste varía de 16 x 109m3/mes en abril-junio a 9 x 109m3/mes en octubre-diciembre. El drenaje total, anual, es alrededor de 350 x 109m3. En todas las estaciones frente al litoral oriental se encuentra un frente de salinidad marcada. En la parte septentrional del Bight las temperaturas en las capas superiores permanecieron más bien constantes de mayo a noviembre; en febrero la temperatura media había disminuido en unos 4°C y existieron gradientes agudos en las distribuciones geográficas. Las salinidades en las capas superiores disminuyeron constantemente de mayo a noviembre; en febrero la salinidad media había aumentado en 2.5‰. La profundidad media de la capa mixta aumentó de 27 m en mayo a 40 m en noviembre; en febrero el afloramiento disminuyó el espesor de la capa mixta hasta 18 m. Entre noviembre y febrero el afloramiento había duplicado la cantidad de PO4-P y triplicado la de NO3-N en la zona eufótica; la producción superficial de fitoplancton y la biomasa primaria y las concentraciones de zooplancton también se duplicaron durante este período. El afloramiento era cerca de 1.5 mimes durante mayo-noviembre y de unos 9.0 mimes durante noviembre-febrero, el total anual es de unos 48 m. La producción media primaria es aproximadamente de 0.3 gC/m2 al día durante mayo-diciembre y cerca de 0.6 gC/m2 al día durante enero-abril; la producción anual es de unos 140 gC/m2. En febrero apareció una convexidad termal que se extendió de la parte norte a la parte sudoeste del Bight. Dentro de esta convexidad se encontró un domo termal marcado el cual coincidió con el centro de la circulación ciclonal de la célula. El afloramiento en el domo tuvo un promedio de 16 mimes en noviembre-febrero. Las pesquerías del Panamá Bight producen anualmente de cerca 30,000 toneladas métricas de especies alimenticias y unas 68,000 t.m. de especies usadas para la reducción. La mayoría de los esfuerzos realizados con el fin de adquirir más conocimiento sobre la ecología del atún no tuvo éxito. La abundancia aparente del atún aleta amarilla y del barrilete en la parte septentrional del Bight parece estar relacionada con el ciclo estacional del afloramiento y del enriquecimiento, ya que la abundancia mayor en abril y mayo cuando parece que hay abundancia es de alimento. El ciclo de vida de la anchoveta en el Golfo de Panamá parece también que está relacionada al afloramiento. La masa de la especie varía de unas 39,000 t.m. en diciembre a cerca de 169,000 t.m. en abril. Aproximadamente 19.1 x 1012 huevos de anchoveta son desovados anualmente. Los ciclos de vida del camarón en el Panamá Bight parecen estar relacionados con el afloramiento ya que las capturas son superiores en mayo-julio, unos 3-5 meses después del ápice del afloramiento, y las capturas anuales se correlacionan inversamente con el nivel del mar. (PDF contains 340 pages.)