gebhart/patrepeval huggingface dataset:
Fragment Informatics and Computational Fragment‐Based Drug Design: An Overview and Update (2012)

Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research.
2 Yeast RNA Polymerase Subunits and Genes (1992)

OVERVIEW Yeast RNA polymerases A(I), B(II), and C(III) are organized around a common core of subunits related to the bacterial core enzyme (β′ βα 2 ) and share a set of five small subunits (ABC27, ABC23, ABC14.5, ABC10α, and ABC10β). All these subunits are essential for growth. In addition, each enzyme contains a variable number of enzyme-specific subunits, some of which are not strictly required for growth. Most subunit genes have been cloned, sequenced, and mutagenized to produce null alleles and, for several of them, conditional mutants. A functional map of RNA polymerase active site, taken in a broad sense, has begun to emerge from a combined genetic and biochemical analysis of the large subunits. GENERAL PROPERTIES OF YEAST NUCLEAR RNA POLYMERASES The budding yeast Saccharomyces cerevisiae , with its biochemically and genetically well-characterized transcription apparatus, is currently the most suitable experimental model for a comprehensive study of eukaryotic RNA polymerases (see Sentenac 1985; Gabrielsen and Sentenac 1991 and references therein; Young 1991; Thuriaux and Sentenac 1992). Yeast RNA polymerases are typically eukaryotic in their subunit complexity, and there is a fair degree of functional equivalence between the transcription machinery of yeasts and of metazoan eukaryotes (see, e.g., Struhl 1989; Sawadogo and Sentenac 1990; and other chapters in this volume). We assume, therefore, that what is learned of the yeast enzymes may largely be extrapolated to other eukaryotes. Several chapters of this volume cover important structural and functional features of the RNA polymerases of higher eukaryotes and of associated general transcription factors (Corden...
Vaccines against<i>Campylobacter jejuni</i> (1997)

Campylobacter jejuni is one of the most common causes of diarrhea worldwide. The gastrointestinal manifestations of Campylobacter infection range from watery diarrhea to severe dysentery. Campylobacter infection has also been linked to the postinfectious sequelae of reactive arthritis and Guillain-Barré syndrome. Evidence from epidemiologic and volunteer studies suggests that development of a vaccine to prevent gastrointestinal disease and limit colonization is possible. Efforts to develop live attenuated or subunit vaccines are limited by the finite knowledge of Campylobacter pathogenesis and lack of a conserved protective antigen, respectively. An oral killed, whole-cell vaccine has been shown to be safe and effective in animal models and is currently being tested in phase I volunteer studies.
Adenovirus-Like Particles Associated with a Disease of Cultured White Sturgeon, <i>Acipenser transmontanus</i> (1985)

Juvenile white sturgeon, Acipenser transmontanus, suffering from a chronic mortality had enlarged nuclei particularly in the epithelium of the straight intestine and spiral valve. These nuclei were often five times larger than those of uninfected cells and contained numerous virus particles with an average diameter of 74 nm. Although nuclear changes induced by the virus are similar to those described for certain members of the Herpesviridae, the virion morphology and absence of an envelope were, however, more characteristic of the Adenoviridae. Attempts to isolate the virus using established cell lines from selected freshwater fish and two lines recently developed from white sturgeon were unsuccessful. Nuclear enlargement indicating virus infection was, however, observed in juvenile sturgeon receiving intraperitoneal injections of homogenates of viscera from infected fish.
Mesenchymal Stem Cells from the Wharton’s Jelly of the Human Umbilical Cord: Biological Properties and Therapeutic Potential (2019)

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine.
Targeted Disruption of Peptide Transporter<i>Pept1</i>Gene in Mice Significantly Reduces Dipeptide Absorption in Intestine (2008)

PEPT1 is a high-capacity, low-affinity peptide transporter that mediates the uptake of di- and tripeptides in the intestine and kidney. PEPT1 also has significance in its ability to transport therapeutic agents and because of its potential as a target for anti-inflammatory therapies. To further understand the relevance of specific peptide transporters in intestinal physiology, pharmacology and pathophysiology, we have generated Pept1 null mice by targeted gene disruption. The Pept1 gene was disrupted by insertion of a lacZ reporter gene under the control of the endogenous Pept1 promoter. Phenotypic profiling of wild-type and Pept1 null mice was then performed, along with in vitro intestinal uptake, in situ intestinal perfusion and in vivo pharmacokinetic studies of glycylsarcosine (GlySar). Pept1 null mice lacked expression of PEPT1 protein in the intestine and kidney, tissues in which this peptide transporter is normally expressed. Pept1-deficient mice were found to be viable, fertile, grew to normal size and weight, and were without any obvious abnormalities. Nevertheless, Pept1 deletion dramatically reduced the intestinal uptake and effective permeability of the model dipeptide GlySar (i.e., by at least 80%), and its oral absorption following gastric gavage (i.e., by about 50%). In contrast, the plasma profiles of GlySar were almost superimposable between wild-type and Pept1 null animals after intravenous dosing. These novel findings provide strong evidence that PEPT1 has a major role in the in vivo oral absorption of dipeptides.
Quantifying the effect of posture on intracranial physiology in humans by MRI flow studies (2005)

The effect of posture on intracranial physiology can be quantified by MRI because posture-related changes in ICC and ICP strongly affect the dynamics of cerebral blood and CSF flows. This study provides important insight into the coupling that exists between arterial, venous, and CSF flow dynamics, and how it is affected by posture.
Multiresolution representation and visualization of volume data (1997)

A system to represent and visualize scalar volume data at multiple resolution is presented. The system is built on a multiresolution model based on tetrahedral meshes with scattered vertices that can be obtained from any initial dataset. The model is built off-line through data simplification techniques, and stored in a compact data structure that supports fast on-line access. The system supports interactive visualization of a representation at an arbitrary level of resolution through isosurface and projective methods. The user can interactively adapt the quality of visualization to requirements of a specific application task and to the performance of a specific hardware platform. Representations at different resolutions can be used together to further enhance interaction and performance through progressive and multiresolution rendering.
Reserve Readings and Student Grades: Analysis of a Case Study. (1987)

Etude dans la bibliotheque universitaire de Virginie (Etats-Unis) sur l'utilisation des documents de reserve ― livres ou photocopies qui constituent un support de cours et ont une periode de pret tres courte ― par les etudiants en fonction de leur niveau universitaire
THE GROWTH HORMONE RELEASING HORMONE (GHRH) RESPONSE TO A MIXED MEAL IS BLUNTED IN YOUNG ADULTS WITH INSULIN‐DEPENDENT DIABETES MELLITUS WHEREAS THE SOMATOSTATIN RESPONSE IS NORMAL (1990)

Following a standard mixed meal, plasma concentrations of growth hormone releasing hormone (GHRH), somatostatin (SMS) and growth hormone (GH) were measured every 30 min for 300 min in six young adults with type I insulin-dependent diabetes mellitus (IDDM) and five normal controls. Mean blood glucose concentrations were higher and mean free insulin levels lower in the diabetics compared with controls both in fasting specimens and at all times following the mixed meal. Basal concentrations (mean +/- SEM) of GHRH were similar in diabetic (12.7 +/- 1.8 pg/ml) and control subjects (11.8 +/- 1.1 pg/ml). Following ingestion of the mixed meal, a rise in GHRH was observed in the control subjects maximal between 30 and 240 min (P less than 0.025) but the response was blunted in the diabetics. Mean GHRH concentrations were greater in the controls than in the diabetic subjects at all stages during the test, the maximum difference being noted at 120 mins (P less than 0.04). Basal SMS concentrations and those observed after the mixed meal were similar in diabetic and control subjects. These results indicate that glucose and insulin may play a role in the regulation of GHRH release following a mixed meal but circulating levels of GHRH and SMS are unlikely to be relevant to the abnormal regulation of GH in IDDM.
Non-alcoholic fatty liver disease may develop in individuals with normal body mass index. (2012)

Approximately 1 of 8 NAFLD patients coming to the tertiary liver center has normal BMI. These patients do not necessarily have insulin resistance associated metabolic disorders, but they have higher levels of ALT/AST than the overweight or obese NAFLD patients.
New frontiers in membrane technology and chromatographic separations: biotechnology and genetic engineering applications (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew frontiers in membrane technology and chromatographic separations: biotechnology and genetic engineering applicationsDoris C. WarrenCite this: Anal. Chem. 1984, 56, 14, 1528A–1544APublication Date (Print):December 1, 1984Publication History Published online22 September 2008Published inissue 1 December 1984https://doi.org/10.1021/ac00278a001RIGHTS & PERMISSIONSArticle Views177Altmetric-Citations6LEARN 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 InReddit PDF (17 MB) Get e-Alerts Get e-Alerts
An optical system with potential for remote health monitoring of subsea machinery (2009)

A prototype fibre-optic sensing system is described with potential to remotely monitor the condition of three-phase variable frequency subsea motors and electric submersible pumps. An indication that the integrity of a powerful electric motor may be compromised can be gained by spectral analysis of the stator drive current, the phases of the currents, the measurement of vibration at specific locations on the motor and the temperature of the bearings. The optical interrogation system is based on an imbalanced Mach–Zehnder fibre interferometer, illuminated with a broadband source with fibre Bragg gratings (FBGs) used as the basic transducers for the current and vibration measurements. Signals were recovered at a distance of 7 km, for the 'in house' current sensor at an effective ac current of 500 A at frequencies from 10 to 1000 Hz with a S/N ratio of 45 dB, together with the relative phases between the currents. These signals were generated with a simulated high power three-phase electric motor. A commercial accelerometer was incorporated into the system which demonstrated a sensitivity of 1 mg Hz−1/2 also from 10 to 1000 Hz. As the interrogation system can only be used to detect dynamic signals, a second interrogation for quasi-static temperature measurements is required; although this was not deployed, possible applications other than bearing temperature measurement are considered.
Co-registration of hyperspectral bands (2007)

A hyperspectral consists of a great number of spectral images. Although these spectral images are obtained simultaneously, due to a number of optical effects the hyperspectral bands are not co-registered. This has been found to be particularly prominent in images of regions near the absorption bands of atmospheric gases. We have developed a method using subpixel image registration that enables us to identify the spatial misregistration between spectral bands and correct it. We use one band as a reference band and match all other spectral images to this band. We use the average row and column disparity to correct the spatial misregistration. Other than the spatial correction that we obtain we also obtain a mapping of the atmospheric gas absorption features. This is done by plotting the average disparities as a function of wavelength. Local peaks in this plot are clear evidence of absorption features of the atmospheric gases. Our method is robust to the low snr in the atmospheric absorption images with low transmission. The correction, results in a hyperspectral cube with all the bands spatially aligned. The algorithm has been applied to the following hyperspectral imagers : AISA Hawk, AISA Eagle, AVIRIS and HYPERION.
Attenuated poliovirus strain as a live vector: expression of regions of rotavirus outer capsid protein VP7 by using recombinant Sabin 3 viruses (1994)

The ability to express heterologous antigens from attenuated poliovirus strains suggests the potential for use as live vectored vaccines. Full- or partial-length sequences of the gene encoding rotavirus major outer capsid protein VP7 were cloned into the open reading frame of a full-length cDNA copy of poliovirus Sabin type 3. They were inserted either at the 5' end or immediately after the capsid protein coding region, at the junction between precursors P1 and P2. A protease cleavage site for 3C protease was introduced 3' to the foreign sequences to enable proteolytic processing of the antigen from the poliovirus polyprotein. Infectious viruses were generated from several of the DNA constructs, and the presence of the foreign gene sequences was confirmed by reverse transcription of the viral RNA and PCR amplification. Viruses with inserts of about 300 bases maintained the foreign sequences during passage in Vero cells. Viruses carrying larger sequences were unstable, and deletions were generated within the foreign sequences. Expression of the VP7 polypeptides was demonstrated by immunoprecipitation with specific antiserum of labeled proteins from cells infected with Sabin 3 recombinant viruses. Comparative studies of RNA synthesis showed similar kinetics for Sabin 3 and the Sabin 3/VP7 recombinants. One-step growth curves showed that production of recombinant viruses was slower than that of Sabin 3 and that the final titers were 1 to 1.5 logs lower. Accumulation of VP7-containing precursors in infected cells suggests that slow cleavage at the engineered 3C protease site may be a limiting step in the growth of these recombinant Sabin polioviruses and may influence the permissible size of foreign sequence to be inserted.
The reactions of inter- and intra-chain disulphide bonds in proteins with sulphite (1962)

Disulphide bonds react with sulphite according to the equation:
New amorphous alloys as micromaterials and the processing technologies (2002)

Microformability of new amorphous alloys in the supercooled liquid state and microforming techniques for the materials are shown. In the supercooled liquid state, the materials reveal perfect Newtonian viscous flow characteristics and furthermore exhibit an excellent property of microformability on a submicron scale. Microforming techniques are shown as follows; microextrusion with micro-dies made of photochemically machinable glass and made of laser-micromachined polyimide, submicron imprinting with silicon die fabricated by EB lithography and etching, microforging of microgear of 10 /spl mu/m in module with microdie fabricated by UV-LIGA process. As a result, the materials are expected to become some of the most useful materials for fabricating MEMS.
Importin-4 Regulates Gene Delivery by Enhancing Nuclear Retention and Chromatin Deposition by Polyplexes (2015)

For successful gene delivery, plasmid DNA must be able to access the nucleus in order to be transcribed. Numerous studies have shown that gene delivery occurs more readily in dividing cells, which is attributed to increased nuclear access when the nuclear envelope disassembles during mitosis; however, nonviral carriers continue to have low transfection efficiencies and require large quantities of DNA per cell to achieve reasonable gene transfer, even in dividing cells. Therefore, we hypothesized that using histone-derived nuclear localization sequences (NLS)s to target polyplexes might enhance nuclear delivery by facilitating interactions with histone effectors that mediate nuclear partitioning and retention during mitosis. We discovered a novel interaction between polyplexes linked to histone 3 (H3) N-terminal tail peptides and the histone nuclear import protein importin-4, as evidenced by strong spatial colocalization as well as significantly decreased transfection when importin-4 expression was reduced. A fraction of the histone-targeted polyplexes was also found to colocalize with the retrotranslocon of the endoplasmic reticulum, Sec61. Super resolution microscopy demonstrated a high level of polyplex binding to chromatin postmitosis, and there also was a significant decrease in the amount of chromatin binding following importin-4 knockdown. These results provide evidence that natural histone effectors mediate both nuclear entry and deposition on chromatin by histone-targeted polyplexes, and a translocation event from the endoplasmic reticulum into the cytosol may occur before mitosis to enable the polyplexes to interact with these essential cytoplasmic proteins.
Travelling‐Wave (Surge) Phenomena (2007)

This chapter contains sections titled: Theory of Travelling-wave Phenomena along Transmission Lines (Distributed-constants Circuit) Approximation of Distributed-constants Circuit and Accuracy of Concentrated-constants Circuit Behaviour of Travelling Wave at a Transition Point Behaviour of Travelling Waves at a Lightning-strike Point Travelling-wave Phenomena of Three-phase Transmission Line Line-to-ground and Line-to-line Travelling Waves The Reflection Lattice and Transient Behaviour Modes Supplement 1: General Solution Equation 18.10 for Differential Equation 18.9 Supplement 2: Derivation of Equation 18.19 from Equation 18.18
An Evaluation of Criteria for Dynamic Gridding during Reservoir Simulation of Water Flooding and Solvent Injection (2011)

Abstract Some hydrocarbon recovery processes are characterized by the existence of sharp saturation and/or concentration fronts. Examples of such processes are VAPEX, in situ combustion, or water flooding of heavy oil reservoirs in presence of viscous fingering. In order to simulate correctly what happens around the fronts, small grid sizes need to be used. If however the whole reservoir is gridded very finely, computational time becomes prohibitive. In order to circumvent this problem, dynamic gridding, also callled, automatic mesh refinement may be used. During the computation, the computational grid is adapted to the dynamics of the flow. This requires the use of an estimator in order to decide where to refine or to coarsen the grid. In this work we studied dynamic gridding for a water flooding problem. We implemented this problem using the mixed hybrid finite element method in 2-D on a triangular grid. The resulting code was validated by comparison to a commercial reservoir simulator. From literature, we adapted an a posteriori estimator that had been derived for incompressible flow, and we used this to refine our grid on each time step. We show that the grid refinement criterion captures relatively well the sharp saturation front. Heterogeneities are also well captured. The code is able to reproduce some tendencies of viscous fingering, although more time is required to avoid definitely the numerical disperion and dynamic gridding influence. This work is a preamble for a second work considering simulation of the VAPEX process using dynamic gridding. For this we decided to switch to the finite volume method, for which a second code was developed which is shortly mentionned in the perspectives. We think that dynamic gridding may be a solution that will allow the simulation of processes such as VAPEX and in situ combustion at reservoir scale, using effective grid refinement in the region of the front.