gebhart/patrepeval huggingface dataset:
A Forward Genetics Screen in Mice Identifies Recessive Deafness Traits and Reveals That Pejvakin Is Essential for Outer Hair Cell Function (2007)

Deafness is the most common form of sensory impairment in the human population and is frequently caused by recessive mutations. To obtain animal models for recessive forms of deafness and to identify genes that control the development and function of the auditory sense organs, we performed a forward genetics screen in mice. We identified 13 mouse lines with defects in auditory function and six lines with auditory and vestibular defects. We mapped several of the affected genetic loci and identified point mutations in four genes. Interestingly, all identified genes are expressed in mechanosensory hair cells and required for their function. One mutation maps to the pejvakin gene, which encodes a new member of the gasdermin protein family. Previous studies have described two missense mutations in the human pejvakin gene that cause nonsyndromic recessive deafness (DFNB59) by affecting the function of auditory neurons. In contrast, the pejvakin allele described here introduces a premature stop codon, causes outer hair cell defects, and leads to progressive hearing loss. We also identified a novel allele of the human pejvakin gene in an Iranian pedigree that is afflicted with progressive hearing loss. Our findings suggest that the mechanisms of pathogenesis associated with pejvakin mutations are more diverse than previously appreciated. More generally, our findings demonstrate that recessive screens in mice are powerful tools for identifying genes that control the development and function of mechanosensory hair cells and cause deafness in humans, as well as generating animal models for disease.
Possible approach for the simultaneous measurement of temperature and strain via first and second order diffraction from Bragg grating sensors (1995)

Bragg Grating Sensors (BGS) have generated great interest in recent years because of their potential use in a wide range of applications. BGS form an integral part of the optical fibre structure, being written intracore whilst the fibre is manufactured, and provide absolute wavelength encoding of information that is independent of overall system light levels, but dependent upon strain and temperature effects acting upon the sensor. However, a single measurement of the Bragg wavelength shift cannot distinguish between the effects of temperature and strain; such an ability is of primary importance if fibre optic based sensors are to realise their considerable potential in real-world applications needing, for example, a temperature insensitive or compensated strain gauge. &lt;br/&gt;&lt;br/&gt;Several discriminating techniques have been demonstrated in recent years; these include use of a second grating element encapsulated in a different material and placed in-line with the first grating and most recently the use of two superimposed fibre grating sensors However, both schemes require two gratings, whilst the latter method requires the overwriting of gratings, which may prove very difficult to achieve if writing occurs during fibre manufacture. Here we propose an alternative technique that uses the second order diffraction from a single, conventionally written BGS when illuminated with a source at approximately half the primary reflecting wavelength. We also present the results of preliminary experimental investigations&lt;br/&gt;&lt;br/&gt;
Capillary zone electrophoresis-mass spectrometry using an electrospray ionization interface (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCapillary zone electrophoresis-mass spectrometry using an electrospray ionization interfaceRichard D. Smith, Jose A. Olivares, Nhung T. Nguyen, and Harold R. UdsethCite this: Anal. Chem. 1988, 60, 5, 436–441Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/ac00156a013https://doi.org/10.1021/ac00156a013research-articleACS PublicationsRequest reuse permissionsArticle Views1418Altmetric-Citations322LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Non‐genomic mechanism of 17 beta‐oestradiol‐induced inhibition of contraction in mammalian vascular smooth muscle. (1997)

17 beta-Oestradiol (E2) at 0.1-10 microM directly inhibited various tonic and phasic smooth muscle contractions. The mechanism(s) of oestrogen-induced inhibition of contraction was studied using intact and permeabilized strips and isolated single cells of smooth muscle. 2. In endothelium-denuded vascular smooth muscle, E2 attenuated high K(+)-induced force development and myosin light chain phosphorylation, and produced rapid and reversible relaxation. There were no significant differences in these inhibitory effects between tissue types (femoral artery vs. portal vein), species (rat vs. rabbit) or sexes. 3. The inhibitory potencies of several steroidal and non-steroidal oestrogen analogues were examined and their effects were for the most part stereo-specific. However, two steroids with negligible affinities for the nuclear oestrogen receptor also strongly inhibited high K(+)-induced contraction. 4. Genomic modulators including a protein synthesis inhibitor, an RNA synthesis inhibitor, and oestrogen receptor antagonists did not affect the inhibitory actions of E2. Inhibitors of cyclic nucleotide-dependent protein kinases did not reduce the E2 effect. 5. Ca2+ release from intracellular stores by agonists and by inositol 1,4,5-trisphosphate (IP3) does not appear to be modulated by E2. Neither pretreatment with ryanodine nor with thapsigargin affected the E2-induced inhibition of high K(+)-induced contraction. 6. E2 had no effect on either normal or GTP gamma S-increased Ca2+ sensitivity of the regulatory and contractile apparatus. 7. E2 and its analogues rapidly inhibited voltage-dependent L-type Ca2+ channel currents in isolated smooth muscle cells. Repetitive stimulation was not required for E2-induced inhibition of the currents. 8. This study strongly suggests that at pharmacological concentrations oestrogen primarily reduces Ca2+ influx through inhibition of L-type Ca2+ channels in a non-genomic manner and decreases myosin light chain phosphorylation and contraction of smooth muscle.
Introduction (2003)

This book is the fruit of the collaboration between the French Institute of Pondicherry and the Madras Institute of Development Studies (MIDS) in Chennai. The papers of this book have been written by the participants of the Indo-French round-table on Water Management in South-India and in Sri Lanka held on the 31st of October 2001 in Pondicherry. Water Management: a main stake of the new millenium The water resources and their uses are one of the main stakes of the environmental and social eq...
Bacterial Infection Probes and Imaging Strategies in Clinical Nuclear Medicine and Preclinical Molecular Imaging (2013)

At present, a limited number of strategies exist for diagnostic imaging of patients with bacterial infection. While radiolabeled probes and white blood cells provide robust solutions to detect bacteria in humans, they also give false positives in cases of sterile inflammation. With the onset of bacterial drug resistance, and a clinical trend toward reducing the prescription of antibiotics, the need for highly specific infection detection protocols has been renewed. The preclinical research community has recently utilized new optical imaging strategies, alongside traditional radioimaging research, to develop novel infection probes with translational potential. Here we review the current clinical methods for imaging bacteria in humans, and discuss the efforts within the preclinical community to validate new strategies. The review of preclinical infection imaging probes is limited to those probes that could be feasibly adapted for use in humans with currently available clinical modalities.
Ischemic Neuronal Damage (2008)

Knowledge of the molecular mechanisms that underlie neuron death following stroke is important to allow the development of effective neuroprotective strategies. Since studies in human stroke are extremely limited due to the inability of collecting post mortem tissue at time points after the onset of stroke where neuronal death occurs, brain ischemia research focuses on information derived from animal models of ischemic injury. The two principal models for human stroke are induced in rodents either by global or focal ischemia. In both cases, blood flow disruptions limit the delivery of oxygen and glucose to neurons causing ATP reduction and energy depletion, initiating excitotoxic mechanisms that are deleterious for neurons. These include activation of glutamate receptors and release of excess glutamate in the extracellular space inducing neuron depolarisation and dramatic increase of intracellular calcium that in turn activates multiple intracellular death pathways. The notion that excitotoxicity leads only to neuron necrosis has been abandoned, as ultrastructural and biochemical analysis have shown signs of apoptotic and autophagic cell death in ischemic neurons and this has been further confirmed in neurons subjected to in vitro ischemia models. Both in vitro and in vivo studies, targeting a single death mechanism either by the inhibition of death-inducing molecules or the overexpression of antiapoptotic components in neurons, have shown tremendous neuroprotective potential. Despite their effectiveness in preclinical studies, a large number of neuroprotectants have failed in clinical trials for stroke suggesting that we still lack essential knowledge on the triggers and mediators of ischemic neuron death. In this review evidence will be presented on how ischemic injury occurs, what death mechanisms are activated and how these can be manipulated to induce neuroprotection.
Sites of Binding of Copper(II) Ion by Peptide (1–24) of Bovine Serum Albumin (1968)

Abstract 1. The amino-terminal peptide (1–24) of bovine serum albumin was subjected to carboxymethylation by 0.2 m bromoacetate at pH 6.8 in the presence of 0, 1, and 2 eq of copper(II) ion. The treatment with bromoacetate in the absence of copper(II) caused almost quantitative carboxymethylation of the imidazole groups of the 3 histidyl residues at positions 3, 9, and 18 in the sequences. In addition, the terminal α-amino group was apparently modified. Spectral measurements on the copper-containing complexes showed little or no effect on the copper chelation by the alkylation treatment. 2. Binding of 1 eq of copper(II) protects quantitatively the terminal α-amino group and histidyl residue 3, and appears to reduce somewhat the reactivity of histidyl residue 18. 3. Binding of 2 eq of copper(II) also protects the components of the preferred terminal site, but, in addition, both histidyl residues 9 and 18 are largely, and about equally, protected from alkylation. The binding of the 2nd eq therefore appears to involve both histidyl residues, in keeping with spectral and titration results. An intramolecular chelate structure or intermolecular chelates involving dimers or higher polymers are suggested. 4. The tetrapeptide l-aspartyl-l-threonyl-l-histidyl-l-lysine, which corresponds to the first 4 residues of peptide (1–24), was shown by titration, absorbance, and circular dichroism measurements to form an equimolar complex with copper(II) that has substantially the properties of the complex of peptide (1–24) containing 1 eq of copper(II) ion. Similar measurements on the equimolar complex of bovine serum albumin fill out a continuity that is especially evident from measurements of circular dichroism.
Trend Prediction Method for Aircraft Electrical Device Contact Resistance (2012)

A method of information granule computation is employed to predict the contact resistance for a kind of aircraft electrical relays. The aim is to reduce the dimensional computation complexity and provide practical model for the evaluation process of reliability analysis and fault diagnosis. At first, numerical data sample is split into consecutive sequences by equal window length, and then the sequences are taken to construct information granules, following that, the information granules are combined together to form new time series with reduced dimensionality. Secondly, the fuzzy c-mean clustering method is used as a technique to extract the features of the data points within each information granule. The clustered information granule is defined on the basis of fuzzy linguistic terms to provide parameters for fuzzy inference system, and the fourth order information granular predictive model is constructed in the paper. The predictive model creates the relationship between past four states and future state on the basis of rule base that is produced from fuzzy c-mean clustering. Finally, the predictive model is exploited by introducing experiment data and defining different window length. The trend prediction results are shown and validated with some discussions are presented. The predicative model can reduce the dimension effectively, it is also practical and simple compared with other methods such as neural networks computation and regressive analysis, especially in the case of trend predication application that has highly dimensional measurement data.
Guided-mode resonance biosensors employing phase detection (2004)

Example biosensors utilizing variations in guided-mode resonance phase are presented. It is shown that these phase changes can be appreciable so as to permit practical detection of ultra-thin biomolecular layers.
The Plasma and Cytoplasmic Forms of Human Gelsolin Differ in Disulfide Structure (1996)

Gelsolin is a widely distributed actin binding protein that regulates actin filament length. It exists in both an intracellular and an extracellular form that is derived from a single gene by alternative splicing. Both forms contain the six homologous domains that are responsible for function. Little is known regarding differences between the forms. We have used a combination of cysteine-specific modification with 4-vinylpyridine, HPLC peptide mapping methods, and mass spectrometry to analyze the disulfide structures of human plasma and cytoplasmic gelsolin. Of the five Cys residues in the human gelsolin sequence, all were present in the free thiol form in human cytoplasmic gelsolin, while only three of them were free thiols in the human plasma form. Cys residues 188 and 201 in domain 2 of plasma gelsolin were disulfide linked. Recombinant human plasma gelsolin that had been expressed intracellularly in Escherichia coli and as a secreted protein from Cos green monkey cells was also investigated. The E. coli product lacked the disulfide but could be converted to the plasma-like structure with mild oxidation while the mammalian product formed the correct disulfide prior to isolation. Structural differences were also detected by limited proteolysis with plasmin. The differences in proteolytic susceptibility were also due to perturbations in domain 2. These studies demonstrate that the intracellular and extracellular gelsolins are structurally distinct and suggest that at least some of the preparations of recombinant gelsolin that are being used to study structure/function may be improperly folded. The experiments also demonstrate a general method for the location of disulfide bonds in proteins.
Individual subunits of bacterial luciferase are molten globules and interact with molecular chaperones. (1993)

We have studied the assembly of a large heterodimeric protein, bacterial luciferase, by mixing purified subunits expressed separately in bacteria. The individual subunits alpha and beta contain much (66% and 50%, respectively) of the alpha-helix content of the native heterodimer as measured by circular dichroism, yet the alpha subunit lacks observable tertiary structure as measured by NMR. These results are consistent with the alpha subunit existing in a molten globule or collapsed form prior to assembly. The molecular chaperone GroEL binds reversibly to both subunits prior to assembly. Since these observations were obtained under physiological conditions, we propose that the molten globule exists as a stable form during folding or assembly in the cell. Either the molten globule form of the subunits is an authentic folding intermediate or it is in rapid equilibrium with one. GroEL may function by facilitating assembly through stabilization of these incompletely folded subunits.
Structure−Activity Relationship Studies on a Series of Novel, Substituted 1-Benzyl-5-phenyltetrazole P2X7Antagonists (2006)

1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution on the tetrazole was examined. Compounds were evaluated for activity to inhibit calcium flux in both human and rat recombinant P2X(7) cell lines using fluorometric imaging plate reader technology. Analogues were also assayed for their ability to inhibit IL-1beta release and to inhibit P2X(7)-mediated pore formation in human THP-1 cells. Compound 15d was advanced to efficacy studies in a model of neuropathic pain where significant reversal of mechanical allodynia was observed at doses that did not affect motor coordination.
Serine 133-Phosphorylated CREB Induces Transcription via a Cooperative Mechanism That May Confer Specificity to Neurotrophin Signals (1995)

A mechanism has been characterized by which the transcription factor CREB regulates neurotrophin-induced gene expression. Whereas CREB can mediate calcium- or cyclic AMP-induced c-fos transcription independently of other promoter-bound transcription factors, CREB mediates NGF induction of c-fos transcription via a novel mechanism that appears to require a cooperative interaction with another transcription factor, the serum response factor. A similar transcriptional mechanism may explain how neurotrophins and growth factors induce distinct subsets of delayed response genes. Neurotrophins induce the phosphorylation of CREB at a key regulatory site, Serine 133, with prolonged kinetics that are distinct from the transient kinetics of CREB phosphorylation elicited by growth factors. These results indicate that CREB is a versatile transcription factor that activates transcription via distinct mechanisms in a stimulus-specific manner. In addition, by selectively activating delayed response genes, CREB may confer specificity to neurotrophin signals that promote the survival and differentiation of neurons.
A Surface Functional Monomer-Directing Strategy for Highly Dense Imprinting of TNT at Surface of Silica Nanoparticles (2007)

This paper reports a surface functional monomer-directing strategy for the highly dense imprinting of 2,4,6-trinitrotoluene (TNT) molecules at the surface of silica nanoparticles. It has been demonstrated that the vinyl functional monomer layer of the silica surface can not only direct the selective occurrence of imprinting polymerization at the surface of silica through the copolymerization of vinyl end groups with functional monomers, but also drive TNT templates into the formed polymer shells through the charge-transfer complexing interactions between TNT and the functional monomer layer. The two basic processes lead to the formation of uniform core-shell TNT-imprinted nanoparticles with a controllable shell thickness and a high density of effective recognition sites. The high capacity and fast kinetics to uptake TNT molecules show that the density of effective imprinted sites in the nanoshells is nearly 5 times that of traditional imprinted particles. A critical value of shell thickness for the maximum rebinding capacity was determined by testing the evolution of rebinding capacity with shell thickness, which provides new insights into the effectiveness of molecular imprinting and the form of imprinted materials. These results reported here not only can find many applications in molecularly imprinting techniques but also can form the basis of a new strategy for preparing various polymer-coating layers on silica support.
Changing the Course of Alzheimers Disease: Emerging Disease Modifying Therapies (2006)

Drugs that prevent the onset, delay the progression, or eliminate the symptoms of Alzheimers disease are urgently needed. Current neurotransmitter-based treatments are widely used and provide modest symptom relief. The amyloid hypothesis in which the pathological processing of amyloid precursor protein (APP) produces the toxic 42-amino acid peptide (i.e., Aβ42) and initiates a cascade of amyloid accumulation, neurodegeneration, plaque formation, and dementia, is the predominant mechanistic theory of Alzheimers disease. Drug development programs focus on Aβ42, the enzymes involved in its generation (i.e., γ-secretase, β-secretase), APP, Aβ aggregation, and plaque formation as targets for therapeutic intervention. Disease modifying drugs being studied include anti-amyloid immunotherapy (active and passive immunization), γ-secretase inhibitors (LY450139), β-secretase inhibitors, selective A β42 lowering agents (Flurizan ), inhibitors of amyloid aggregation (Alzhemed™), and others. Preclinical studies and clinical trials suggest that drugs with anti-amyloid properties produce cognitive benefit. However, tolerability and adverse events are important factors to consider when developing treatments for the elderly. Disease modifying drugs that specifically target the amyloid cascade and do not interact with other biological pathways are expected to possess a lower rate of unintended adverse events. Discovery of safe and effective disease modifying therapies will usher in a new age of Alzheimers disease treatment.
Neural network optimization forE.colipromoter prediction (1991)

Methods for optimizing the prediction of Escherichia coli RNA polymerase promoter sequences by neural networks are presented. A neural network was trained on a set of 80 known promoter sequences combined with different numbers of random sequences. The conserved -10 region and -35 region of the promoter sequences and a combination of these regions were used in three independent training sets. The prediction accuracy of the resulting weight matrix was tested against a separate set of 30 known promoter sequences and 1500 random sequences. The effects of the network's topology, the extent of training, the number of random sequences in the training set and the effects of different data representations were examined and optimized. Accuracies of 100% on the promoter test set and 98.4% on the random test set were achieved with the optimal parameters.