gebhart/patrepeval huggingface dataset:
Recent Advances in the Medicinal Chemistry of Sodium Channel Blockers and their Therapeutic Potential (2009)

The voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability. Abnormal activity of sodium channels is related to several pathological processes, including cardiac arrhythmias, epilepsy, chronic pain, neurodegenerative diseases and spasticity. In view of this, VGSCs are considered important therapeutic targets for the treatment of these disorders. To date, nine VGSC isoforms have been identified and have a distinct pattern of expression within the human body. In addition, VGSCs also have distinct electrophysiological profiles with differing activation and inactivation states. As such, there is a concerted effort to develop not only isoform selective antagonists, but also antagonists that exhibit state selectivity, particularly to the inactivated state of the channel. This review will provide a brief historical prospective and will primarily focus on recent advances in the development of isoform specific and state selective sodium channel antagonists and the medicinal chemistry involved, surveying the emerging therapeutic fields.
The immunoglobulin fold family: sequence analysis and 3D structure comparisons (1999)

Fifty-two 3D structures of Ig-like domains covering the immunoglobulin fold family (IgFF) were compared and classified according to the conservation of their secondary structures. Members of the IgFF are distantly related proteins or evolutionarily unrelated proteins with a similar fold, the Ig fold. In this paper, a multiple structural alignment of the conserved common core is described and the correlation between corresponding sequences is discussed. While the members of the IgFF exhibit wide heterogeneity in terms of tissue and species distribution or functional implications, the 3D structures of these domains are far more conserved than their sequences. We define topologically equivalent residues in the Ig-like domains, describe the hydrophobic common cores and discuss the presence of additional strands. The disulfide bridges, not necessary for the stability of the Ig fold, may have an effect on the compactness of the domains. Based upon sequence and structure analysis, we propose the introduction of two new subtypes (C3 and C4) to the previous classifications, in addition to a new global structural classification. The very low mean sequence identity between subgroups of the IgFF suggests the occurrence of both divergent and convergent evolutionary processes, explaining the wide diversity of the superfamily. Finally, this review suggest that hydrophobic residues constituting the common hydrophobic cores are important clues to explain how highly divergent sequences can adopt a similar fold.
Imaging nanoparticle flow using magneto-motive optical Doppler tomography (2007)

We introduce a novel approach for imaging solutions of superparamagnetic iron oxide (SPIO) nanoparticles using magneto-motive optical Doppler tomography (MM-ODT). MM-ODT combines an externally applied temporally oscillating high-strength magnetic field with ODT to detect nanoparticles flowing through a microfluidic channel. A solenoid with a cone-shaped ferrite core extensively increased the magnetic field strength (B(max) = 1 T, [Formula: see text]) at the tip of the core and also focused the magnetic field in microfluidic channels containing nanoparticle solutions. Nanoparticle contrast was demonstrated in a microfluidic channel filled with an SPIO solution by imaging the Doppler frequency shift which was observed independently of the nanoparticle flow rate and direction. Results suggest that MM-ODT may be applied to image Doppler shift of SPIO nanoparticles in microfluidic flows with high contrast.
Trifluoromethyl Ethers and –Thioethers as Tools for Medicinal Chemistry and Drug Discovery (2014)

The ever-growing number of fluorinated compounds in medicinal and agrochemical applications has led to a remarkable positive emulation in research. The last few years have been the witness of several advances in the search of more effective and user-friendlier methods for the introduction of fluorine as substituent or of fluorinated groups on various structures. In particular, the synthesis of trifluoromethyl ethers and thioethers is receiving increasing attention due to the peculiar properties of the OCF3 and SCF3 groups. This review will cover the different methods for the preparation of trifluoromethyl ethers and thioethers, and will emphasize on the most recent developments, including the use of catalytic methods or of methodologies for trifluoromethylation or trifluoromethanesulfanylation.
Lymphocyte activation. 3. Binding sites for phytomitogens on lymphocyte subpopulations. (1972)

The presence of binding sites for concanavalin A, phytohaemagglutinin and lentil mitogen on the surface of mouse B and T lymphocytes has been investigated in relation to the previously described mitogenic selectivity of these stimulants for T cells. Purified T or B or mixed T/B suspensions of cells have been analysed both for proportions of cells with affinity for phytomitogens and for the relative density of binding sites. In addition, the specificity of mitogens for simple saccharides has been investigated in relation to binding of the former to T and B cells. Microscopic agglutination and immunofluorescent studies show that virtually 100% of T and B lymphocytes have binding sites for the three phytomitogens. Quantitative absorption experiments have demonstrated that there is virtually no difference in the relative average density of binding sites on T and B cells. Immunofluorescent studies with Con-A suggested that binding sites are uniformly present over the entire cell surface. However, when lymphocytes are metabolically active an interesting altered localization of bound Con-A molecules to one pole of the cell takes place. It is suggested that binding sites for the various phytomitogens are qualitatively and topographically distinct on the cell surface but that with respect to any one mitogen T and B cells have qualitatively and quantitatively similar binding sites. The relevance of these observations to lymphocyte activation is considered.
Are HIV positive patients resistant to statin therapy? (2007)

This study found that rosuvastatin is effective at improving potentially atherogenic lipid parameters in HIV-positive patients. The lipid changes we observed were of a smaller magnitude compared to non-HIV subjects. Our results are further supported by a small, pilot trial examining rosuvastatin effectiveness in HIV who reported similar median changes from baseline of -21.7% (TC), -22.4% (LDL-C), -30.1% (TG) with the exception of a 28.5% median increase in HDL. In light of the results revealed by this pilot study, clinicians may want to consider a possible resistance to statin therapy when treating patients with HIV metabolic syndrome.
Hot-carrier effect in ultra-thin-film (UTF) fully-depleted SOI MOSFETs (2002)

A systematic study was carried out on the hot-carrier (HC) effect in UTF FD SOI MOSFETs. It clarifies experimentally that even for very thin-film devices, the HC-induced damage is locally confined to the gate-oxide and only minor interface trap generation is caused on the BOX under front-channel stress. The BOX HC charging contributes less than 5% of the overall current degradation.
Multi-robot Simultaneous Localization and Mapping using Particle Filters (2006)

This paper describes an on-line algorithm for multi-robot simultaneous localization and mapping (SLAM). The starting point is the single-robot Rao-Blackwellized particle filter described by Hähnel et al., and three key generalizations are made. First, the particle filter is extended to handle multi-robot SLAM problems in which the initial pose of the robots is known (such as occurs when all robots start from the same location). Second, an approximation is introduced to solve the more general problem in which the initial pose of robots is not known a priori (such as occurs when the robots start from widely separated locations). In this latter case, it is assumed that pairs of robots will eventually encounter one another, thereby determining their relative pose. This relative attitude is used to initialize the filter, and subsequent observations from both robots are combined into a common map. Third and finally, a method is introduced to integrate observations collected prior to the first robot encounter, using the notion of a virtual robot travelling backwards in time. This novel approach allows one to integrate all data from all robots into a single common map.
Effects of null mutations and overexpression of capping protein on morphogenesis, actin distribution and polarized secretion in yeast. (1992)

CAP1, the gene encoding the alpha subunit of Saccharomyces cerevisiae capping protein, was cloned using a probe prepared by PCR with primers based on the amino acid sequence of purified alpha subunit peptides. The sequence is similar to that of capping protein alpha subunits of other species but not to that of the S. cerevisiae capping protein beta subunit or any other protein. Null mutants of capping protein, prepared by deletion of the coding region of CAP1 and CAP2 separately or together, are viable and have a similar phenotype. Deletion of the gene for one subunit leads to a loss of protein for the other subunit. The null mutant has a severe deficit of actin cables and an increased number of actin spots in the mother. Cells are round and relatively large. These features are heterogeneous within a population of cells and vary with genetic background. Overexpression of CAP1 and CAP2 also causes loss of actin cables and cell enlargement, as well as the additional traits of aberrant morphogenesis and cell wall thickening. Capping protein null strains and overexpression strains exhibited normal polarized secretion during bud growth as demonstrated by labeling with fluoresceinated Con A. Projection formation and chitin deposition in response to mating pheromone, mating efficiency, and bud site selection were also normal in capping protein null strains. In addition, bulk secretion of invertase was unimpaired. These data indicate that actin cables are not required for polarized secretion in S. cerevisiae.
Cloning and expression of the human S100 beta gene. (1990)

S100 protein is a low molecular weight, EF-hand, Ca2(+)-binding protein widely distributed and conserved in the central nervous system of vertebrates. The gene coding for the beta subunit of human S100 protein (S100 beta) has been recently mapped to chromosome 21. In order to study the expression of this gene in normal and abnormal brain development, we have isolated and characterized overlapping genomic clones spanning the region coding for human S100 beta and its flanking sequences. The intron-exon organization of the human S100 beta gene is similar to that of the genes coding for several other members of the S100 protein subfamily of EF-hand proteins. The human S100 beta gene is composed of 3 exons, the first of which specifies the 5'-untranslated region, while the second and third each encode a single EF-hand, Ca2(+)-binding domain. The promoter region contains several potential regulatory transcription elements including the cAMP-responsive elements CRE and AP-2. A novel sequence motif, the S100 protein element, situated in close proximity to the TATA box of the genes of several members of the S100 protein subfamily, has been identified. In addition, multiple repeats with similar nucleotide sequence and location to the recently reported beta globin direct repeat elements have been also found in the human S100 beta promoter. A full length (17.3 kilobases) copy of the human S100 beta gene was constructed and transfected into rat glioma C6 cells. Stable transfectants were shown to express correctly initiated transcripts of the human S100 beta gene, indicating that the cloned sequences contain functional regulatory transcription elements.
Molecular Complex Formation between Riboflavin and Salicylate in an Aqueous Medium (2003)

Abstract Evidence for an intermolecular interaction of riboflavin and sodium salicylate in an aqueous medium was obtained from the presence of isosbestic points in the absorption spectra and an isoemissive point in the emission spectra. The equilibrium constant was estimated from absorption and emission studies, and also from the solubility of riboflavin in an aqueous solution of sodium salicylate, and was found to be in the range of 10–14 mol dm−3. Lifetime measurements indicate a predominantly static mechanism of quenching. The Stern–Volmer constant for the quenching of riboflavin by sodium salicylate was significantly reduced upon the addition of urea. An MD simulation study on the system revealed a stacked conformation, which is probably due to a hydrophobic interaction of the two components.
Face recognition with temporal invariance: A 3D aging model (2008)

The variation caused by aging has not received adequate attention compared with pose, lighting, and expression variations. Aging is a complex process that affects both the 3D shape of the face and its texture (e.g., wrinkles). While the facial age modeling has been widely studied in computer graphics community, only a few studies have been reported in computer vision literature on age-invariant face recognition. We propose an automatic aging simulation technique that can assist any existing face recognition engine for aging-invariant face recognition. We learn the aging patterns of shape and the corresponding texture in 3D domain by adapting a 3D morphable model to the 2D aging database (public domain FG-NET). At recognition time, each probe and all gallery images are modified to compensate for the age-induced variation using an intermediate 3D model deformation and a texture modification, prior to matching. The proposed approach is evaluated on a set of age-separated probe and gallery data using a state-of-the-art commercial face recognition engine, FaceVACS. Use of 3D aging model improves the rank-1 matching accuracy on FG-NET database from 28.0% to 37.8%, on average.
A Heuristic Relaxation Method for Nonlinear Mapping in Cluster Analysis (1973)

A relaxation method mapping high-dimensional sample points to low-dimensional sample points is discussed. This method tries to preserve the local interdistance of sample points. Some special heuristics have been introduced to handle the difficulty arising from a large amount of data. Experimental results with handwritten character data and Iris data show that the method runs fast, converges rapidly, and requires a small amount of memory space.
Buspirone in the Treatment of Alcoholic Patients (1989)

Buspirone is a unique anxiolytic drug with established efficacy in the treatment of anxiety. In animals, buspirone has been shown to alter drinking preference from alcohol to water. The following study was conducted to evaluate the behavioral effects of buspirone in patients meeting the Diagnostic and Statistical Manual of Mental Disorders (3rd ed.; DSM-III) criteria of alcohol abuse. These patients were motivated to reduce or stop drinking, though none were abstinent at baseline. Buspirone was compared with placebo in a double-blind, 8-week trial in 50 outpatients with mild to moderate alcohol abuse. Patients were assessed at baseline and at end point using the following psychometric and alcohol behavior measures: Drinking Behavior Interview (DBI), Alcohol Craving Scale, the Hamilton Anxiety (HAM-A) Rating Scale, the Hamilton Depression (HAM-D) Rating Scale, and the Physician Questionnaire. Dosage was initiated at 5 mg buspirone 3 times a day (15 mg/day), with a flexible regimen to a maximum of 30 mg/day. The mean daily dose was 20.5 mg buspirone, which is comparable to the anxiolytic dose. Efficacy measures were available for 45 patients (24 buspirone, 21 placebo). The treatment discontinuation rate was markedly lower (p = 0.002) on buspirone; 12 placebo patients and 2 buspirone patients discontinued due to lack of effect (p = 0.001). No patients discontinued due to adverse effect. Buspirone reduced alcohol craving by 40% (p = 0.001), in association with reduced HAM-A and HAM-D scores (p = 0.006) and improved the physician's assessment of global psychopathology. Buspirone treatment was also associated with a 57% decrease in DBI scores; statistical comparison of the DBI data with placebo was precluded by the high discontinuation rate in the placebo group. While these results should be interpreted with caution due to the limited sample size and high placebo discontinuation rate, the findings suggest that further evaluation of buspirone in the management of alcoholism, especially abstinent alcoholics, is warranted.
Partial Mapping of Ten Genes of the Human Interferon- α Family (1981)

HulFN-alpha genes form a family of not less than 9-10 distinct members, at least three of which are arranged in tandem. In one case, two variants, believed to be alleles of the same gene, could be identified by sequence analysis. The three gene sequenced so far are devoid in introns.
Scintillator Design Via Codoping (2016)

Scintillation materials that lack intrinsic luminescence centers must be doped with optically active ions in order to provide luminescent centers that radiatively de-excite as the final step of the scintillation process. Codoping, on the other hand, can be defined as the incorporation of additional specific impurity species usually for the purpose of modifying the scintillation properties, mechanical properties, or the crystal growth behavior. In recent years codoping has become an increasingly popular approach for engineering scintillators with optimal performance for targeted applications. This report reviews several successful examples and its effect on specific properties.
An Interactive Graphical Approach to Feature Modeling Using Halfspaces and Geometric Constraints (1990)

Abstract Feature modeling enables the specification of a model with standardized high-level shape aspects that have a functional meaning for design or manufacturing. In this paper an interactive graphical approach to feature-based modeling is presented. The user can represent features as new CSG primitives, specified as a Boolean combination of halfspaces. Constraints between halfspaces specify the geometric characteristics of a feature and control feature validity. Once a new feature is defined and stored in a library, it can be used in other objects and positioned, oriented and dimensioned by direct manipulation with a graphics cursor. Constraints between features prevent feature interference and specify spatial relations between features.
Atmospheric Pressure Molecular Imaging by Infrared MALDI Mass Spectrometry (2006)

An atmospheric pressure (AP) MALDI imaging interface was developed for an orthogonal acceleration time-of-flight mass spectrometer and utilized to analyze peptides, carbohydrates, and other small biomolecules using infrared laser excitation. In molecular imaging experiments, the spatial distribution of mock peptide patterns was recovered with a detection limit of approximately 1 fmol/pixel from a variety of MALDI matrixes. With the use of oversampling for the image acquisition, a spatial resolution of 40 microm, 5 times smaller than the laser spot size, was achieved. This approach, however, required that the analyte was largely removed at the point of analysis before the next point was interrogated. Native water in plant tissue was demonstrated to be an efficient natural matrix for AP infrared laser desorption ionization. In soft fruit tissues from bananas, grapes, and strawberries, potassiated ions of the most abundant metabolites, small carbohydrates, and their clusters produced the strongest peaks in the spectra. Molecular imaging of a strawberry skin sample revealed the distribution of the sucrose, glucose/fructose, and citric acid species around the embedded seeds. Infrared AP MALDI mass spectrometric imaging without the addition of an artificial matrix enables the in vivo investigation of small biomolecules and biological processes (e.g., metabolomics) in their natural environment.
Implosion of solid liner for compression of field reversed configuration (2001)

The design and first successful demonstration of an imploding solid liner with height to diameter ratio, radial convergence, and uniformity suitable for compressing a field reversed configuration is discussed. Radiographs indicated a very symmetric implosion with no instability growth, with /spl sim/13x radial compression of the inner liner surface prior to impacting a central measurement unit. The implosion kinetic energy was 1.5 megajoules, 34% of the capacitor stored energy of 4.4 megajoules.
Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic organisation, and evaluation as a candidate for paroxysmal dystonia (2001)

Acid-sensing ion channels (ASICs) are protongated Na(+) channels. They have been implicated with synaptic transmission, pain perception as well as mechanoperception. ASIC4 is the most recent member of this gene family. It shows expression throughout the central nervous system with strongest expression in pituitary gland. ASIC4 is inactive by itself and its function is unknown. Mutations in ion channel subunits, which are homologues of ASICs lead to neurodegeneration in Caenorhabditis elegans. It has, therefore, been speculated that similar mutations in ASICs may be responsible for neurodegeneration in humans. Here, we show that ASIC4 maps to the long arm of chromosome 2 in close proximity to the locus for paroxysmal dystonic choreoathetosis (PDC), a movement disorder with unknown cause. Ion channel genes have been shown to cause several other paroxysmal neurologic disorders and are important candidate genes for PDC. We established the genomic organisation of the ASIC4 gene and screened a PDC pedigree for mutations in the coding region. Although we identified three polymorphisms in the Cterminal part of the ASIC4 protein, these were not present in each affected subject in the PDC kindred we analysed. Therefore, although the ASIC4 gene is physically mapped to the PDC locus, our data indicates that ASIC4 gene mutation is not the cause of PDC. It remains to be established if mutations in ASIC4 or other ASIC subunits may cause neurological disorders.