986 resultados para historical novel


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XVIII IUFRO World Congress, Ljubljana 1986.

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Fast excitatory transmission between neurons in the central nervous system is mainly mediated by L-glutamate acting on ligand gated (ionotropic) receptors. These are further categorized according to their pharmacological properties to AMPA (2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid), NMDA (N-Methyl-D-aspartic acid) and kainate (KAR) subclasses. In the rat and the mouse hippocampus, development of glutamatergic transmission is most dynamic during the first postnatal weeks. This coincides with the declining developmental expression of the GluK1 subunit-containing KARs. However, the function of KARs during early development of the brain is poorly understood. The present study reveals novel types of tonically active KARs (hereafter referred to as tKARs) which play a central role in functional development of the hippocampal CA3-CA1 network. The study shows for the first time how concomitant pre- and postsynaptic KAR function contributes to development of CA3-CA1 circuitry by regulating transmitter release and interneuron excitability. Moreover, the tKAR-dependent regulation of transmitter release provides a novel mechanism for silencing and unsilencing early synapses and thus shaping the early synaptic connectivity. The role of GluK1-containing KARs was studied in area CA3 of the neonatal hippocampus. The data demonstrate that presynaptic KARs in excitatory synapses to both pyramidal cells and interneurons are tonically activated by ambient glutamate and that they regulate glutamate release differentially, depending on target cell type. At synapses to pyramidal cells these tKARs inhibit glutamate release in a G-protein dependent manner but in contrast, at synapses to interneurons, tKARs facilitate glutamate release. On the network level these mechanisms act together upregulating activity of GABAergic microcircuits and promoting endogenous hippocampal network oscillations. By virtue of this, tKARs are likely to have an instrumental role in the functional development of the hippocampal circuitry. The next step was to investigate the role of GluK1 -containing receptors in the regulation of interneuron excitability. The spontaneous firing of interneurons in the CA3 stratum lucidum is markedly decreased during development. The shift involves tKARs that inhibit medium-duration afterhyperpolarization (mAHP) in these neurons during the first postnatal week. This promotes burst spiking of interneurons and thereby increases GABAergic activity in the network synergistically with the tKAR-mediated facilitation of their excitatory drive. During development the amplitude of evoked medium afterhyperpolarizing current (ImAHP) is dramatically increased due to decoupling tKAR activation and ImAHP modulation. These changes take place at the same time when the endogeneous network oscillations disappear. These tKAR-driven mechanisms in the CA3 area regulate both GABAergic and glutamatergic transmission and thus gate the feedforward excitatory drive to the area CA1. Here presynaptic tKARs to CA1 pyramidal cells suppress glutamate release and enable strong facilitation in response to high-frequency input. Therefore, CA1 synapses are finely tuned to high-frequency transmission; an activity pattern that is common in neonatal CA3-CA1 circuitry both in vivo and in vitro. The tKAR-regulated release probability acts as a novel presynaptic silencing mechanism that can be unsilenced in response to Hebbian activity. The present results shed new light on the mechanisms modulating the early network activity that paves the way for oscillations lying behind cognitive tasks such as learning and memory. Kainate receptor antagonists are already being developed for therapeutic use for instance against pain and migraine. Because of these modulatory actions, tKARs also represent an attractive candidate for therapeutic treatment of developmentally related complications such as learning disabilities.

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In the present study, an attempt was made to study the acute and sub-acute toxicity profile of G3-COOH Poly (propyl ether imine) PETIM] dendrimer and its use as a carrier for sustained delivery of model drug ketoprofen. Drug-dendrimer complex was prepared and characterized by FTIR, solubility and in vitro drug release study. PETIM dendrimer was found to have significantly less toxicity in A541 cells compared to Poly amido amine (PAMAM) dendrimer. Further, acute and 28 days sub-acute toxicity measurement in mice showed no mortality, hematological, biochemical or histopathological changes up to 80 mg/kg dose of PETIM dendrimer. The results of study demonstrated that G3-COOH PETIM dendrimer can be used as a safe and efficient vehicle for sustained drug delivery. (C) 2010 Elsevier Masson SAS. All rights reserved.

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We propose a new self-assembly based strategy for the design of novel lanthanide based luminescent materials. In this approach a europium hydrogel is prepared and sensitization is achieved by doping the gel with pyrene in a non-coordinated fashion.

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Germline mutations in many of the genes that are involved in homologous recombination (HR)-mediated DNA double-strand break repair (DSBR) are associated with various human genetic disorders and cancer. RAD51 and RAD51 paralogs are important for HR and in the maintenance of genome stability. Despite the identification of five RAD51 paralogs over a decade ago, the molecular mechanism(s) by which RAD51 paralogs regulate HR and genome maintenance remains obscure. In addition to the known roles of RAD51C in early and late stages of HR, it also contributes to activation of the checkpoint kinase CHK2. One recent study identifies biallelic mutation in RAD51C leading to Fanconi anemia-like disorder. Whereas a second study reports monoallelic mutation in RAD51C associated with increased risk of breast and ovarian cancer. These reports show RAD51C is a cancer susceptibility gene. In this review, we focus on describing the functions of RAD51C in HR, DNA damage signaling and as a tumor suppressor with an emphasis on the new roles of RAD51C unveiled by these reports.

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An inverse problem for the wave equation is a mathematical formulation of the problem to convert measurements of sound waves to information about the wave speed governing the propagation of the waves. This doctoral thesis extends the theory on the inverse problems for the wave equation in cases with partial measurement data and also considers detection of discontinuous interfaces in the wave speed. A possible application of the theory is obstetric sonography in which ultrasound measurements are transformed into an image of the fetus in its mother's uterus. The wave speed inside the body can not be directly observed but sound waves can be produced outside the body and their echoes from the body can be recorded. The present work contains five research articles. In the first and the fifth articles we show that it is possible to determine the wave speed uniquely by using far apart sound sources and receivers. This extends a previously known result which requires the sound waves to be produced and recorded in the same place. Our result is motivated by a possible application to reflection seismology which seeks to create an image of the Earth s crust from recording of echoes stimulated for example by explosions. For this purpose, the receivers can not typically lie near the powerful sound sources. In the second article we present a sound source that allows us to recover many essential features of the wave speed from the echo produced by the source. Moreover, these features are known to determine the wave speed under certain geometric assumptions. Previously known results permitted the same features to be recovered only by sequential measurement of echoes produced by multiple different sources. The reduced number of measurements could increase the number possible applications of acoustic probing. In the third and fourth articles we develop an acoustic probing method to locate discontinuous interfaces in the wave speed. These interfaces typically correspond to interfaces between different materials and their locations are of interest in many applications. There are many previous approaches to this problem but none of them exploits sound sources varying freely in time. Our use of more variable sources could allow more robust implementation of the probing.

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A novel gas-phase kinetic scheme for ammonium perchlorate (AP) deflagration involving 22 reactions among 18 species is developed. The kinetic scheme is based on a study of the effect of initial conditions on the solution of the differential equations of adiabatic constant-pressure combustion kinetics. The existence of condensed-phase reaction products providesalternate pathways for the consumption of NH3 and HCIOl produced by gas-phase dissociation of AP. Theoretically obtained temperature-time profiles of the novel scheme do not change when the conventional reaction pathways are included, indicatingthat the novel scheme is a substantially faster rate process. The new scheme does not involve the species CIO, which has long been considered a critical component of the AP gas phase and which is included in the conventional reaction pathways.The new scheme develops faster overall reaction rates, steeper temperature-time profiles, and in a deflagration model will result in higher heat-transfer rates from gas phase to the condensed phase.

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Before the spread of extensive settled cultivation, the Indian subcontinent would have been inhabited by territorial hunter–gatherers and shifting cultivators with cultural traditions of prudent resource use. The disruption of closed material cycles by export of agricultural produce to centres of non-agricultural population would have weakened these traditions. Indeed, the fire-based sacrificial ritual and extensive agricultural settlements might have catalysed the destruction of forests and wildlife and the suppression of tribal peoples during the agricultural colonization of the Gangetic plains. Buddhism, Jainism and later the Hindu sects may have been responses to the need for a reassertion of ecological prudence once the more fertile lands were brought under cultivation. British rule radically changed the focus of the country's resource use pattern from production of a variety of biological resources for local consumption to the production of a few commodities largely for export. The resulting ecological squeeze was accompanied by disastrous famines and epidemics between the 1860s and the 1920s. The counterflows to tracts of intensive agriculture have reduced such disasters since independence. However, these are quite inadequate to balance the state-subsidized outflows of resources from rural hinterlands. These imbalances have triggered serious environmental degradation and tremendous overcrowding of the niche of agricultural labour and marginal cultivator all over the country.

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Stereospecific synthesis of 4-formylcarane (2) has been achieved through hydroboration-carbonylation of DELTA-3-carene. Both the reactions are optimised using sodium borohydride. The method is utilised for the synthesis of sandatrile (3), a novel perfumery chemical.

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Norbornadiene and 1,2-bismethoxycarbonylcyclobutadiene furnish a novel heptacyclic system 3(whose X-ray crystal structure has been determined)and an annulated pterodactylane derivative 4 in a single step.

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X-ray analysis of the ternary complex [Cu(5′-UMP)(im)2(H2O)]·4H2O, where 5′-UMP uridine-5′-monophosphate and IM = imidazole, reveals a novel metal binding mode of pyrimidine nucleotide through the ribose group.

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The presently developed two-stage process involves diping the prefired porous disks of n-BaTiO3 in nonaqueous solutions containing Al-buty rate, Ti-isopropoxide, and tetraethyl silicate and subsequent sintering. This leads to uniform distribution of the grain-boundary layer (GBL) modifiers (Al2O3+ TiO2+ SiO2) and better control of the grain size as well as the positive temperature coefficient of resistivity characteristics. The technique is particularly suited for GBL modifiers in low concentrations (< 1%).