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Empirical correlations are developed for rewetting velocity and maximum heat transfer coefficient during rewetting phase of single hot vertical Fuel Pin Simulator (FPS) by using radial jet impingement and falling film. Emergency Core Cooling System (ECCS) has been designed for Advance Heavy water Reactor (AHWR) to rewet the hot fuel pin under the loss of coolant accident. Coolant injection takes place from a water rod which is located at the center of the fuel bundle in form of jets to rewet hot surface of fuel pin under loss of coolant accident. This kind of design to reflood the fuel bundle is different than bottom and top spray reflooding practiced in PWR and BWR type of nuclear reactors. There are two different kinds of rewetting found during radial jet induced cooling. The first one is due to radial jet impingement and the second one is due to falling film which is below the jet impingement point. Rewetting velocity has been predicted along the length of fuel pin due to radial jet impingement cooling. Temperature of FPS has been varied from 400°C to 700°C with help of different powers supply, simulating decay heat of reactor. A variation of coolant radial jet mass flow rate is from 0.5 lpm to 1.8 lpm. It is considered during ECCS injection. It has been observed from the experiments that rewetting velocity decreases with increasing the clad surface temperature and increases with increasing the coolant mass flow rate. The rewetting velocity in falling film is found to be nearly 1.8 times higher than rewetting velocity predicted in circumferential direction. Further, it is found that maximum heat transfer coefficient increases with increasing the radial jet coolant mass flow rate. The maximum heat transfer coefficient in case of radial jet impingement is found to be nearly 1.5 times the falling film rewetting. Developed correlation predicts the maximum heat transfer coefficient with experimental data well within the error band of ±10%.

Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism.

Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors.

The Advanced Heavy water Reactor (AHWR) is a natural circulation vertical pressure tube type boiling light water cooled and heavy water moderated reactor. As the AHWR fuel bundle quenching under accident condition is designed primarily with radial jets at several axial locations, bottom re-flooding still remain open as another option. Radial direction injection of emergency core cooling leads to rewetting of AHWR fuel cluster in circumferential direction. A 3D fuel pin model has been developed by using Finite Difference Method (FDM) of transient heat conduction equation. Alternating Direction Implicit technique of Finite Difference Method (FDM) has been used for discretisation of numerical equation in different time step at different direction. Sensitivity numerical study with respect to direction of ADI method has been carried out to optimize the time step during the transient as well as steady state and is found that it is insensitivity with direction of solution. Further, to assess influence of circumferential rewetting vis-à-vis axial rewetting. Both the analyses are carried out with same fluid temperature and heat transfer coefficients as boundary conditions. It has been found from the analyses that for radial jet, the circumferential conduction is significant and overall the fuel temperature falls in the quench plane with the initiation of quenching event. The paper discusses the sensitivity study with respect to direction of ADI solution and comparison of numerical results for circumferential and axial rewetting for single pin.

Rewetting of a hot surface is the process of establishing direct liquid contact with a large portion of the surface whose initial temperature exceeds that required to maintain film boiling for prescribed surface and flow conditions. The Advanced Heavy water Reactor (AHWR) is a natural circulation vertical pressure tube type boiling light water cooled and heavy water moderated reactor. In case of a loss of coolant accident, the clad surface temperature goes up very high and comes down due to coolant injection from the Emergency Core Coolant System (ECCS). The rewetting takes place in Boiling Water Reactors (BWR) due to top flooding and Pressurised Water Reactors (PWR) due to bottom flooding. But in AHWR, the emergency coolant enters into the reactor core in radial direction and after this, cross flow phenomenon takes place from one fuel pin ring to next. The study is being carried out on the effect of cross flow on rewetting of AHWR fuel bundle. This paper will discuss the modeling of the experimental setup having pressure tube, fuel cluster, steam generator, accumulator etc and study the effect of radial flow on rewetting of fuel pins. An analysis of the model, considering with and without cross flow, has been carried out and shows that the pick fuel temperature is sensitive to cross flow. The thermal hydraulic safety analysis code Relap5/3.2 is being used for modeling of experimental setup for rewetting study.

Experiments have been carried out to study the heatup behavior of a submerged debris bed constituted of segmented reactor channels of Pressurized Heavy Water Reactors (PHWR). The study has been done for under fully submerged, partially submerged and nearly exposed conditions. This situation may arise from a severe accident scenario of PHWR where full or segmented reactor channels are likely to be disassembled and form a submerged debris bed. An assembly of electrical heater rod, simulating fuel bundle and channel components like Pressure tube and calandria tube constitute each segmented reactor channels. Ten such reactor channels constitute the debris bed. Heatup of this debris bed is observed with respect to different water levels and at power levels of 10, 20 and 30?kW, typical to decay power levels of 0.25?%, 0.5?% and 0.75?% of reactor full power respectively. It has been observed from the set of experiments that fully submerged debris bed does not get heated up and fuel rod temperature remains at saturation temperature. Heatup is observed for exposed channels only, however the heatup rate is limited with steam and radiative cooling. For exposed debris bed, channels surrounded by neighboring channels get heated up as compared to channels at the periphery of the debris bed.

Experiments have been carried out to study the heatup behavior of a single segmented reactor channel for Pressurized Heavy Water Reactor under submerged, partially submerged and exposed conditions. This situation may arise from a severe accident scenario of Pressurised Heavy Water Reactors where full or segmented reactor channels are likely to be disassembled and form a submerged debris bed. An assembly of electrical heater rod, simulating fuel bundle and channel components like Pressure Tube and Calandria Tube constitutes the segmented reactor channel. Heatup of this assembly is observed with respect to different water levels ranging from full submergence to totally exposed and power levels of 6–8 kW, typical to decay power level. It has been observed from the set of experiment that fuel bundle local dry out followed by heatup does not happen till the bundle is partially submerged. Temperature excursion of the bundle is evident when the bundle is exposed to steam-air environment.

Several applications of optical micromirrors need synchronization of its mechanical oscillation with an external control signal. Self-sustained oscillation of micromirrors is a prerequisite for achieving such synchronization. To suppress its mechanical deformation these micromirrors are operated under atmospheric or controlled pressure environment. Operation under this environment leads to increase in driving voltages to achieve required deflections. However, significant parasitic crosstalk due to these high driving voltages presents a challenge for achieving their self-sustained oscillations. In this paper, stable self-sustained oscillation of a 13.5kHz micromirror is achieved at atmospheric pressure by actively suppressing its crosstalk. Frequency stability of 7.2ppm is obtained for this micromirror's self-sustained oscillation at atmospheric pressure.

Amidst the Meso- to Neoproterozoic South Delhi Fold Belt (SDFB) of Rajasthan, India, a sheet-like body of megacrystic Anasagar Granite Gneiss (AGG) embedded in a supracrustal unit consisting of metapelites, quartzite and calc gneiss is exposed. Detailed analyses of mesoscopic and microscopic structures identify four phases of deformation. Lithological relationships coupled with U–Pb dates of zircon indicate that the protolith of the AGG was emplaced within the supracrustal unit during D1folding at approximately 1.85 Ga. This event is significantly older than the age of volcanism in the SDFB (0.99 Ga) but probably synchronous with Aravalli Orogeny. Thrusts associated with the easterly-vergent D2folds have a ramp–flat geometry and are refolded by coaxial D3folds. The petrology of the metapelites indicates that porphyroblasts of staurolite and/or garnet were formed as a function of bulk-rock composition between D1and D3folding, at the time of the culmination of metamorphism (5.7±1.5 kbar, 560±50 °C). Combining the petrological and structural attributes, it is proposed that the AGG and its enveloping supracrustals might represent the basement of the Delhi Supergroup, which was folded, thrusted and domed up during the South Delhi Orogeny. The cause of the thermal perturbation that triggered the growth of the porphyroblasts in the metapelites is explored.

Layered anorthosite, chromiferous pyroxenite, and spatially associated mafic and felsic rocks of the 2.9 Ga Sittampundi layered complex (SLC), South India, underwent high-grade metamorphism at ca. 2.5 Ga and were subjected to amphibolite-facies metamorphism accompanied by intrusion of granitoid plutons during late-Neoproterozoic tectonothermal activity (0.72-0.45 Ga). During the latter event, anorthosite developed millimeter- to centimeter-thick compositional layers rich in clinopyroxene+amphibole+clinozoisite+chlorite±chromite and corundum+spinel+chlorite. Tiny grains of högbomite replaced only the grains of corundum and spinel and are in textural equilibrium with chlorite. The studied högbomite contains appreciable TiO2(>4.4 wt%) but insignificant NiO and ZnO. Cr2O3content reaches up to 0.35 wt% only in chromite-bearing samples. Systematic partitioning of Fe and Mg between högbomite and associated Fe-Mg minerals demonstrate attainment of chemical equilibrium among these phases. Integrating textural relations and algebraic analyses of the phase compositions, several reactions were constructed involving the associated oxide phases (spinel, corundum, högbomite), calcite, and silicates (amphibole, chlorite, anorthite, clinozoisite). Interpretation of the reaction reveals that (1) Mg2+and Ti4+were mobile for more than 2 cm during the formation of högbomite and chlorite, and (2) chloritization of amphibole in the clinopyroxene+amphibole-bearing layers released Ti that was transported to the spinel+corundum-bearing layers to develop högbomite. Stability fields of some critical mineral assemblages in P-XCO₂and T-XCO₂space combined with geothermobarometry in the associated rocks tightly constrain the growth of högbomite in the presence of aqueous fluids (XCO₂< 0.15) to the P-T range of 7 ± 1 kbar, 650 ± 50 °C. These aqueous fluids, presumably derived from the Pan-African granitoid batholiths, chloritized amphibole grains, and transported the released Ti4+ to the spinel+corundum-bearing layers to develop högbomite. Topological relations in isothermal-isobaric fugacity diagrams (log fO₂-log fS₂ and log fO₂-log fH₂O) in the system FeO-Al2O3- TiO2-O2-S2-H2O-CO2(+MgO, Cr2O3) indicate that the stability and compositional characteristics of natural högbomite are strongly influenced by fO₂, fS₂, fH₂O, and concentrations of other soluble species (Ti, Mg, Cr, etc.) in the metamorphic fluids

This paper describes the synthesis of an aqueous colloidal solution of Eu(OH) 3nanoparticles stabilized by polyvinylalcohol or polyvinylpyrolidone prepared in a sonication bath. These nanoparticles were used as nanolabeling agents for living sperm cells. The nanoparticles retain their desirable optical properties, which are typical of europium inside the sperm cell. The nanoparticles did not affect the sperm cell motility or the sperm’s ability to undergo an acrosome reaction. Furthermore, this work demonstrates for the first time the localization and the quantification of the loaded nanoparticles in the subcellular fractions, cytosol, plasma membrane, nucleus, and cytoskeleton, using ICP measurements.

An area of considerable current interest is the development of a practical approach for assembling inorganic nanoparticles into well‐defined arrays because such a technique would offer immense opportunities leading to applications in microimaging, optoelectronics, therapeutics, etc. This paper illustrates a new, simple one‐step process in which proteins act as templates to assemble gold nanoparticles in a shape‐selective fashion. We show, for the first time, that antibodies to vascular endothelial growth factor 165 isoform, 2C3, and epidermal growth factor receptor can act as templates when present in solution during the synthesis of gold nanoparticles. These proteins direct the assembly of the gold nanoparticles into rod‐like shapes when cooled to –20 °C followed by thawing at room temperature. Immunoglobulin G and bovine serum albumin can also direct the assembly process in a similar fashion; however, small molecules, such as poly(L‐lysine) and lysine, cannot. The formation of a self‐assembled structure in the form of a continuous rod, or the assembly of discrete nanoparticles in a rod‐like fashion, can be tailored by controlling the ratio of the precursor gold salt, HAuCl4, to the antibody/protein used as the template. The nanoconjugates are characterized using UV‐vis spectroscopy, transmission electron microscopy, and infrared spectroscopy. The nano‐bioconjugates obtained via this process may find wide application in areas ranging from optoelectronics and biosensors to therapeutics in neoplastic disorders.

The microwave incremental mobility values of GaN have been calculated at 77K in presence of dc field and found that, the mobility values decreases monotonically with field. Frequency dependence of the real part of microwave conductivity is constant up to milimeter wavelength range of frequencies and the imaginary part shows a peak in submilimeter wavelength range.

Abstract: New mineralogical, bulk chemical and oxygen isotope data on the Palaeoproterozoic Bijli Rhyolite, the basal unit of a bimodal volcanic sequence (Dongargarh Group) in central India, and one of the most voluminous silicic volcanic expressions in the Indian Shield, are presented. The Bijli Rhyolite can be recognized as a poorly sorted pyroclastic deposit, and comprises of phenocrystic K-feldspar + albite ± anorthoclase set in fine-grained micro-fragmental matrix of quartz-feldspar-sericite-chlorite-iron-oxide ± calcite. The rocks are largely metaluminous with high SiO2, Na2O + K2O, Fe/Mg, Ga/Al, Zr, Ta, Sn, Y, REE and low CaO, Ba, Sr contents; the composition points to an ‘A-type granite’ melt. The rocks show negative Cs-, Sr-, Eu- and Ti- anomalies with incompatible element concentrations 2–3 times more than the upper continental crust (UCC). LREE is high (La/Yb ∼ 20) and HREE 20–30 times chondritic. δ18Owhole-rock varies between 4.4 and 7.8‰ (mean 5.87±1.26‰). The Bijli melt is neither formed by fractionation of a basaltic magma, nor does it represent a fractionated crustal melt. It is shown that the mantle-derived high temperature basaltic komatiitic melts/high Mg basalts triggered crustal melting, and interacted predominantly with deep crust compositionally similar to the Average Archaean Granulite (AAG), and a shallower crustal component with low CaO and Al2O3 to give rise to the hybrid Bijli melts. Geochemical mass balance suggests that ∼ 30% partial melting of AAG under anhydrous condition, instead of the upper continental crust (UCC) including the Amgaon granitoid gneiss reported from the area, better matches the trace element concentrations in the rocks. The similar Ta/Th of the rhyolites (0.060) and average granulite (0.065) vs. UCC (0.13) also support a deep crustal protolith. Variable contributions of crust and mantle, and action of hydrothermal fluid are attributed for the spread in δ18Owhole-rock values. The fast eruption of high temperature (∼ 900°C) rhyolitic melts suggests a rapid drop in pressure of melting related to decompression in an extensional setting.

Background & Aims: This study aimed to determine the role of the RNA binding protein apobec-1 in radioprotection of the intestine. Methods: Apobec-1-deleted mice (APOBEC-1^-^/^-) and wild-type controls were treated with 12 Gy of whole-body @c-irradiation in a cesium irradiator. The number of surviving intestinal crypts was assessed 3.5 days after irradiation by using a clonogenic assay. Cyclooxygenase-2 messenger RNA and protein expression were determined by real-time polymerase chain reaction and Western blot, respectively. RNA stability was studied by examining the turnover of a chimeric transcript containing the cyclooxygenase-2 3' untranslated region cloned downstream of luciferase complementary DNA. Apobec-1 binding to the cyclooxygenase-2 3' untranslated region was studied by electrophoretic mobility shift and UV crosslinking assays. Results: After @c-irradiation, the survival of intestinal stem cells decreased significantly in APOBEC-1^-^/^- mice. In wild-type mice treated with lipopolysaccharide before @c-irradiation, intestinal stem cells were protected by marked increases in prostaglandin E"2 mediated by cyclooxygenase-2. No such effect was observed in the APOBEC-1^-^/^- mice. The mechanism of this radioprotective effect involves the binding of apobec-1 to AU-rich sequences in the first 60 nucleotides of the 3' untranslated region of cyclooxygenase-2. Upon binding to the AU-rich sequences, apobec-1 stabilizes cyclooxygenase-2 messenger RNA. This stabilization process does not seem to be mediated by p38 mitogen-activated protein kinase pathways. Conclusions: Lipopolysaccharide increases intestinal stem cell survival through apobec-1-mediated regulation of cyclooxygenase-2 messenger RNA stability.

Soil organic fractions were extracted from 2 surface soils of West Bengal, one of which was arsenic-contaminated, and were fractionated into fulvic and humic acid fractions following standard procedures. These, and one humic acid sample synthesised in the laboratory, were characterised by pH-potentiometric titrations, viscometric measurements, visible spectrophotometry, and surface tension determinations. The results have been correlated with coiling?decoiling behaviour, as well as aliphatic/aromatic balance of these acids. The stability constant (logK) of the complexes formed by these natural humic/fulvic and synthetic humic acids with arsenic in aqueous phase was evaluated by the ion-exchange method. These logK values tend to suggest that the organo-arsenic complexes were quite stable. Further, the logK values displayed an approximately inverse relationship with the viscosity-average molecular weight, excess time needed to attain a stable higher pH during the pH-potentiometric titration, and also the surface excess (in water) of the given humic/fulvic acid samples. These trends were explained in terms of the relative hydrophobic character of the acids, and their resultant tendencies to complex arsenic in the aqueous phase.  The release potential of arsenic from the arsenic?humic/fulvic complexes by soluble phophate and nitrate salts was also examined in terms of the appropriate exchange isotherms. In general, phosphate demonstrated a greater degree of exchangeability with arsenic than did nitrate, at both the lower and higher concentrations.

Substantial evidence exists in literature to suggest that placental protein 14 (PP14) (recently renamed glycodelin A), exhibits immunosuppressive properties and is an indispensable macromolecule in the maternal system for the establishment, maintenance, and progression of pregnancy. Though there are several reports substantiating the above, the mechanism of its action at the molecular level has not been elucidated as yet. In this paper we provide data that suggest that amniotic fluid PP14 and recombinant PP14 expressed in Pichia pastoris induce apoptosis in human peripheral blood lymphocytes upon activation, independent of monocytes. That PP14 has a direct apoptotic action on T cells but not on monocytes was also demonstrated by utilizing human cell lines. PP14 was shown to induce apoptosis in the human T cell lines, Jurkat and MOLT-4 cells, but not in the human monocytic cell line, U937.

AbstractInstitutions are the controlled mechanism to monitor the functions of the social system. Institutions and its activities contribute substantially to the cause of deforestation or afforestation. Reversal of deforestation processes need strengthening of the Forest Protection Committee (FPC) institutions which facilitates the effectiveness of Joint Forest Management (JFM) where the community and foresters work towards a common goal of forest conservation. The paper describes the problem and process of strengthening institution with illustrations from West Bengal JFM. The authors have used systemic approach to forest conservation where structured intervention made in a planned sequence has produced synergic action where the community has not only conserved forest but also made their own self-help group.

Aberrant expression of the potent angiogenic cytokine, vascular endothelial growth factor (VEGF), has been demonstrated to be associated with most human solid tumors. Both transcriptional and post-transcriptional mechanisms have been shown to modulate VEGF expression in a multitude of cell types. Here we report that when protein kinase C (PKC) pathways were activated in human glioblastoma U373 cells by phorbol 12-myristate 13-acetate (PMA), VEGF mRNA expression was up-regulated via a post-transcriptional mRNA stabilization mechanism. PMA treatment exhibited no increase in VEGF-specific transcriptional activation as determined by run-off transcription assays and VEGF promoter-luciferase reporter assays. However, PMA increased VEGF mRNA half-life from 0.8 to 3.6 h which was blocked by PKC inhibitors but not by protein kinase A or cyclic nucleotide-dependent protein kinase inhibitors. When U373 cells were transfected with antisense oligonucleotide sequences to the translation start sites of PKC-alpha, -beta, -gamma, -delta, -epsilon, or -zeta isoforms, both PKC-alpha and -zeta antisense oligonucleotides showed substantial inhibition of PMA-induced VEGF mRNA. In addition, overexpression of PKC-zeta resulted in a strong constitutive up-regulation of VEGF mRNA expression. This study demonstrates for the first time that specific PKC isoforms regulate VEGF mRNA expression through post-transcriptional mechanisms.

The dimensional and mechanical properties of plain knitted fabrics from open-end and ring spun acrylic-viscose blended yams are investigated. The fabric area shrinkage (%), thickness, and areal density of open-end spun yarns are greater but the bursting strength is less in comparison to ring-spun yarns. Knitted fabrics from ring spun yarns have a greater propensity to pill.

We studied the role of tyrosine kinase in the regulation of Ca2+ entry in single smooth muscle cells of the rabbit colonic muscularis mucosae using the whole cell patch-clamp technique. Step depolarization to +10 mV from a holding potential of -60 mV produced inward currents that were abolished by 1 microM nifedipine, consistent with the activation of L-type Ca2+ channels. The tyrosine kinase inhibitors, genistein and tyrphostin B42, dose dependently inhibited these Ca2+ currents. The inactive analogue of tyrphostins, tyrphostin A1, did not affect the currents at concentrations of up to 100 microM. Conversely, the tyrosine phosphatase inhibitor, orthovanadate, enhanced peak Ca2+ currents by 30%. Spontaneous transient outward currents (STOCs) (50-600 pA) were elicited with high K+ in the pipette and at 0-mV holding potential. STOCs were activated due to release of Ca2+ from intracellular stores, required the presence of extracellular Ca2+ concentration, and were insensitive to nifedipine. Genistein abolished STOCs; however, in its presence, outward currents activated by caffeine or carbachol were not affected. The refilling of the Ca2+ stores was studied by first depleting intracellular Ca2+ with carbachol in Ca(2+)-free media followed by reperfusing with a Ca(2+)-containing solution for 3-5 min. Under these conditions, a second application of carbachol evoked an outward current due to Ca2+ release. However, this effect was abolished when the refilling of the stores was carried out in the presence of genistein. Carbachol-evoked currents were not attenuated when the refilling was examined in the presence of orthovanadate. Epidermal growth factor (200 ng/ml) enhanced Ca2+ currents by 60% and markedly increased STOCs by over 200%. Western blot analysis, using an anti-phosphotyrosine antibody, showed a tyrosine phosphorylated protein of 60 kDa in control conditions. This was markedly increased after treatment with epidermal growth factor and carbachol. These results suggest that 1) tyrosine kinase modulates the entry of Ca2+ through L-type channels and through nifedipine-resistant pathways involved in refilling of intracellular stores and 2) stimulation of the kinase by agonists enhances Ca2+ entry in the smooth muscle cells of the rabbit colonic muscularis mucosae.

Electron mobility has been calculated in a number of binary II–VI compound semiconductors using a displaced Maxwellian distribution function and taking the various scattering mechanisms into consideration at different lattice temperatures and for various amounts of ionized impurity concentrations. It is observed that the low field mobility values can be expressed by a cubic power relationship with lattice temperature and with ionized impurity concentration using a least mean square fit technique with an accuracy better than 5 per cent. Similarly, the field dependence of mobility can also be expressed as a power series of the applied electric field. It is suggested that these equations can be profitably used for a quick estimation of mobility values as a check on experiments and also as sufficiently accurate formulae for simulation and modelling purposes.

RNase-sensitive DNA polymerase activity (RSDP) was tested in different cell fractions of Neurospora crassa cell types and its morphological mutants. This RSDP was found localized in the microsomal pellet fraction and absent in the purified nuclear pellets isolated from different N. crassa cell types: conidia, germinated conidia, and mycelia. This enzyme is capable of synthesizing a DNA product only in the presence of all four deoxyribonucleoside-5'-triphosphates and Mg2+. Removal of RNA from the pellet fraction by RNase strongly inhibited the DNA synthesis. The endogenous synthesis of DNA in the microsomal pellet fraction was associated with the formation of an RNA:DNA hybrid as analyzed by Cs2SO4 equilibrium density gradient centrifugation. The DNA product after alkali hydrolysis hybridizes with the RNA isolated from the same pellet fraction, as analyzed by elution from hydroxylapatite column at 60 C. This DNA product did not hybridize with poly(A). A few mutants tested showed this RNase-sensitive DNA polymerase activity.

This study examines the expression of the multi-functional cytokine, vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the rat uterus during early proestrus, proestrus, estrus and diestrus. Groups of ovariectomized or hypophysectomized rats served as endocrine controls. Expression of VPF/VEGF mRNA was 2-fold greater in uteri during proestrus and estrus than in other phases of the estrous cycle. In situ hybridization techniques indicated that VPF/VEGF mRNA expression was confined to the luminal epithelium during proestrus, but shifted to the stromal compartment during estrus. Ovariectomized, hypophysectomized or diestrus rats exhibited scattered localization of VPF/VEGF mRNA among glandular epithelium and endometrial stromal compartments. Although VPF/VEGF mRNA was expressed throughout the estrous cycle, but in different compartments of the endometrium depending on the stage of the estrous cycle, VPF/VEGF protein expression appears to be restricted to the epithelial compartment during proestrus and estrus. Results indicate that circulating levels of gonadal steroids and LH may be associated with the differential expression of VPF/VEGF mRNA and its translation activity in the endometrium during different stages of the estrous cycle.

The transcription factor Sp1 is ubiquitously expressed and plays a significant role in the constitutive and induced expression of a variety of mammalian genes and may even contribute to tumorigenesis. Here, we describe a novel pathway whereby Sp1 promotes the transcription of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), a potent angiogenic factor, by interacting directly and specifically with protein kinase C zeta (PKC zeta) isoform in renal cell carcinoma. PKC zeta binds and phosphorylates the zinc finger region of Sp1. Moreover, in the presence of the wild type von Hippel-Lindau gene product, the interaction of Sp1 with PKC zeta is inhibited, and in this manner steady state levels of Sp1 phosphorylation are decreased significantly. Co-transfection of renal cell carcinoma cells and human fibrosarcoma cells with a plasmid overexpressing PKC zeta and VPF/VEGF promoter luciferase constructs results in activation of Sp1-mediated transcription, whereas expression of a dominant-negative mutant of PKC zeta repressed this activation. Taken together, our results suggest a new pathway of cell signaling through PKC zeta and provide an insight into PKC zeta and Sp1-dependent transcriptional regulation of VPF/VEGF expression and thus tumor angiogenesis.

Mutation or loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is regularly found in sporadic renal cell carcinomas (RCC), well vascularized malignant tumors that characteristically overexpress vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). The wild-type VHL (wt-VHL) gene product acts to suppress VPF/VEGF expression, which is overexpressed when wt-VHL is inactive. The present study investigated the pathways by which VHL regulates VPF/VEGF expression. We found that inhibition of protein kinase C (PKC) represses VPF/VEGF expression in RCC cells that regularly overexpress VPF/VEGF. The wt-VHL expressed by stably transfected RCC cells forms cytoplasmic complexes with two specific PKC isoforms, zeta and delta, and prevents their translocation to the cell membrane where they otherwise would engage in signaling steps that lead to VPF/VEGF overexpression. Other experiments implicated mitogen-activated protein kinase (MAPK) phosphorylation as a downstream step in PKC regulation of VPF/VEGF expression. Taken together, these data demonstrate that wt-VHL, by neutralizing PKC isoforms zeta and delta and thereby inhibiting MAPK activation, plays an important role in preventing aberrant VPF/VEGF overexpression and the angiogenesis that results from such overexpression.

The Sirankatte granite gneiss, an oval-shaped body within the metasedimentary rocks of the Chitradurga Group in the Dharwar tectonic province of Early Precambrian age, occupies the core of a slightly overturned antiform with axial culmination. This antiform, with steep and moderate ENE dips of the western and eastern limbs, respectively, and with axes plunging gently NNW in the northern part and SSE to ESE in the southern part, represents a second generation fold. Isoclinal folds on stratification in the cover rocks as well as on gneissic banding in the granite gneiss have been involved in this folding coaxially. An associated axial planar cleavage dipping steeply towards ENE has been superimposed on both the granitic and metasedimentary rocks. Although conglomerates with pebbles, cobbles and boulders of quartz and granite gneiss at the contact of the granite at a number of places suggest the granite to be the basement, synkinematic migmatization and ductile deformation during the first folding show that the original granitic basement must have been extensively remobilized during the first deformation. Coaxial second folding due to compression in an almost horizontal WSW-ENE direction resulted in the development of an antiform with granite core resembling a mantled gneiss dome. Late folds on ENE-WSW axial planes accentuated the culminations and depressions of the folds of the first and second phases.

In the Dharwar tectonic province, the Peninsular Gneiss was considered to mark an event separating the deposition of the older supracrustal Sargur Group and the younger supracrustal Dharwar Supergroup. Compelling evidence for the evolution of the Peninsular Gneiss, a polyphase migmatite, spanning over almost a billion years from 3500 Ma to 2500 Ma negates a stratigraphic status for this complex, so that the decisive argument for separating the older and younger supracrustal groups loses its basis. Correlatable sequence of superposed folding in all the supracrustal rocks, the Peninsular Gneiss and the banded granulites, indicate that the gneiss ‘basement’ deformed in a ductile manner along with the cover rocks. An angular unconformity between the Sargur Group and the Dharwar Super-group, suggested from some areas in recent years, has been shown to be untenable on the basis of detailed studies, A number of small enclaves distributed throughout the gneissic terrane, with an earlier deformational, metamorphic and migmatitic history, provide the only clue to the oldest component which has now been extensively reworked.

The von Hippel-Lindau tumor suppressor gene (VHL) has a critical role in the pathogenesis of clear-cell renal cell carcinoma (RCC), as VHL mutations have been found in both von Hippel-Lindau disease-associated and sporadic RCCs. Recent studies suggest that vascular endothelial growth factor (VEGF) mRNA is upregulated in RCC- and von Hippel-Lindau disease-associated tumors. We have therefore assessed the effect of the VHL gene product on VEGF expression. VEGF promoter-luciferase constructs were transiently cotransfected with a wild-type VHL (wt-VHL) vector in several cell lines, including 293 embryonic kidney and RCC cell lines. wt-VHL protein inhibited VEGF promoter activity in a dose-dependent manner up to 5- to 10-fold. Deletion analysis defined a 144-bp region of the VEGF promoter necessary for VHL repression. This VHL-responsive element is GC rich and specifically binds the transcription factor Sp1 in crude nuclear extracts. In Drosophila cells, cotransfected VHL represses Sp1-mediated activation but not basal activity of the VEGF promoter. We next demonstrated in coimmunoprecipitates that VHL and Sp1 were part of the same complex and, by using a glutathione-S-transferase-VHL fusion protein and purified Sp1, that VHL and Sp1 directly interact. Furthermore, endogenous VEGF mRNA levels were suppressed in permanent RCC cell lines expressing wt-VHL, and nuclear run-on studies indicated that VHL regulation of VEGF occurs at least partly at the transcriptional level. These observations support a new mechanism for VHL-mediated transcriptional repression via a direct inhibitory action on Sp1 and suggest that loss of Sp1 inhibition may be important in the pathogenesis of von Hippel-Lindau disease and RCC.

A case of midfacial swelling in a middle aged woman proved to be caused by a fungus Conidiobolus coronatushas been reported. It is a very rare condition and the knowledge of this fungus affecting the rhinofacial region in human started since 1965 only. These cases pose diagnostic problem. The treatment with the combination of ketoconazole and the saturated solution of potassium iodide was effective for this fungal infection.

There is emerging evidence indicating that smooth muscle contraction and Ca2+ influx through voltage-dependent L-type Ca2+ channels are regulated by tyrosine kinases; however, the specific kinases involved are largely unknown. In rabbit colonic muscularis mucosae cells, tyrosine-phosphorylated proteins of approximately 60 and 125 kDa were observed in immunoblots using an anti-phosphotyrosine antibody and were identified as c-Src and focal adhesion kinase (FAK) by immunoblotting with specific antibodies. FAK co-immunoprecipitated with c-Src, and the phosphorylation of the c-Src.FAK complex was markedly enhanced by platelet-derived growth factor (PDGF) BB. The presence of activated c-Src in unstimulated cells was identified in cell lysates by immunoblotting with an antibody recognizing the autophosphorylated site (P416Y). In whole-cell patch-clamp studies, intracellular dialysis of a Src substrate peptide and anti-c-Src and anti-FAK antibodies suppressed Ca2+ currents by 60, 62, and 43%, respectively. In contrast, intracellular dialysis of an anti-mouse IgG or anti-Kv1.5 antibody did not inhibit Ca2+ currents. Co-dialysis of anti-c-Src and anti-FAK antibodies inhibited Ca2+ currents (63%) equivalent to dialysis with the anti-c-Src antibody alone. PDGF-BB enhanced Ca2+ currents by 43%, which was abolished by the anti-c-Src and anti-FAK antibodies. Neither the MEK inhibitor PD 098059 nor an anti-Ras antibody inhibited basal Ca2+ currents or PDGF-stimulated Ca2+ currents. The alpha1C subunit of the L-type Ca2+ channel co-immunoprecipitated with anti-c-Src and anti-phosphotyrosine antibodies, indicating direct association of c-Src kinase with the Ca2+ channel. These data suggest that c-Src and FAK, but not the Ras/mitogen-activated protein kinase cascade, modulate basal Ca2+ channel activity and mediate the PDGF-induced enhancement of L-type Ca2+ currents in differentiated smooth muscle cells.

Experiments involving fusion between the Staphylococcus aureus plasmid pI258-encoded mer operon and the reporter gene beta-lactamase, mutational analysis, and trans-complementation studies have shown that the merR gene of pI258, which shows DNA sequence similarity with known merR genes from other bacteria, regulates the expression of the mer operon in vivo. The merR gene product is a trans-acting protein that activates mer operon transcription in the presence of the inducers Hg2+ and Cd2+. A glutathione-S-transferase-MerR fusion protein specifically bound and protected a 27-nucleotide operator sequence from DNase I digestion. This operator sequence is highly homologous with mer operator sequences of other known systems.

Ribosomal RNA genes were isolated from the germinated conidial and mycelial cells of N. crassa by repeated cycles of 3H-DNA: rRNA reactions followed by hydroxyapatite chromatography. Specificity of multiple copies of those rDNAs with respect to N. crassa cell types was studied. The fraction of N. crassa germinated conidial in vitro labelled 3H-DNA recovered in the presence of rRNA isolated from the same cell type was about 2.2%, when compared with approximately 1.2% rDNAs obtained in mycelial cells. These isolated rDNAs reacted specifically to 26S and 17S rRNAs of eukaryotic (N. crassa) organisms and did not react with 4S tRNAs. rRNA:rDNA reassociation kinetics studies indicate that 90% of the rRNA genes were homogeneous and not identical with the other 10% rRNA genes isolated from N. crassa mycelia. These studies suggest that the possible heterogeneity of rDNA sequences of N. crassa cannot be attributed to inclusion of any tDNA sequences as has been shown in the heterogeneity of rDNA sequences of the bacterium Escherichia coli. The heterogeneity of multiple copies of N. crassa rDNAs could be due to differences in internal or external spacer regions of N. crassa rRNA genes.

Utilizing one-particle one-hole variations of ATDHF states by invoking commutators obtained from generators of complete set of coordinates and of momenta, the ATDHF equations were shown in an earlier work to yield the valley condition. In principle, variations of ATDHF states should also be exploited by using anticommutators involving the said generators. It is demonstrated here that owing to the canonicity condition relating the generators of coordinates and of momenta, use of anticommutators gives rise to exactly the same valley condition on the ATDHF path.