gebhart/patrepeval huggingface dataset:
The Involvement of the Tetrodotoxin-Resistant Sodium Channel Nav1.8 (PN3/SNS) in a Rat Model of Visceral Pain (2001)

The present study investigated the effect of inhibiting the expression of Na(v)1.8 (PN3/SNS) sodium channels by an antisense oligodeoxynucleotide (ODN) on bladder nociceptive responses induced by intravesical acetic acid infusion in rats. Animals were injected intrathecally with either Na(v)1.8 antisense or mismatch ODN. Control cystometrograms under urethane anesthesia during intravesical saline infusion exhibited intercontraction intervals (ICIs) that were significantly longer in antisense-treated rats than in mismatch ODN-treated rats. Intravesical infusion of 0.1% acetic acid induced bladder hyperactivity as reflected by a 68% reduction in ICIs in mismatch ODN-treated rats but did not significantly reduce ICIs in antisense-treated rats. The number of Fos-positive cells after acetic acid administration were significantly reduced in the L6 spinal cord from antisense-treated animals, compared with mismatch ODN-treated animals. In addition, Na(v)1.8 immunoreactivity was reduced in L6 dorsal root ganglion neurons in the antisense-treated rat. In patch-clamp recordings, the conductance density of TTX-resistant sodium currents in dissociated bladder afferent neurons that were labeled by axonal transport of a fluorescent dye, Fast Blue, injected into the bladder wall was also smaller in antisense-treated rats than in mismatch ODN-treated rats, whereas no changes were observed in TTX-sensitive currents. These results indicate that the Na(v)1.8 TTX-resistant sodium channels are involved in the activation of afferent nerves after chemical irritation of the bladder. These channels represent a new target for the treatment of inflammatory pain from visceral organs such as the urinary bladder.
A mobile four‐electrode array and its application to the electrical survey of planetary grounds at shallow depths (1991)

This paper deals with a mobile array for mapping the electric properties of planetary surfaces, with a resolution of the order of a few meters in all dimensions. The principle of the measuring technique is first recapitulated; the prototype model of this novel instrument is then described. The array was operated at a frequency of 128 kHz over a site with apparent resistivities in the range 20–100 Ω m and the experimental results are found to be in excellent agreement with those derived from another independent technique. It is demonstrated, from measurements collected on a second site with resistivities of the order of several kilo‐ohm meters, that this new technique also yields information about the dielectric constant of the ground. This method is not only applicable to geological surveys on Earth but also appears particularly attractive for the exploration of the surface of other planets by means of landers, penetrators, or unmanned rovers.
Structure-based design of mutant Methanococcus jannaschii tyrosyl-tRNA synthetase for incorporation of O -methyl- l -tyrosine (2002)

Although incorporation of amino acid analogs provides a powerful means of producing new protein structures with interesting functions, many amino acid analogs cannot be incorporated easily by using the wild-type aminoacyl-tRNA synthetase (aaRS). To be able to incorporate specific amino acid analogs site-specifically, it is useful to build a mutant aaRS that preferentially activates the analog compared with the natural amino acids. Experimental combinatorial studies to find such mutant aaRSs have been successful but can easily become costly and time-consuming. In this article, we describe the clash opportunity progressive (COP) computational method for designing a mutant aaRS to preferentially take up the analog compared with the natural amino acids. To illustrate this COP procedure, we apply it to the design of mutant Methanococcus jannaschii tyrosyl-tRNA synthetase (M.jann-TyrRS). Because the three-dimensional structure for M.jann-TyrRS was not available, we used the STRUCTFAST homology modeling procedure plus molecular dynamics with continuum solvent forces to predict the structure of wild-type M.jann-TyrRS. We validate this structure by predicting the binding site for tyrosine and calculating the binding energies of the 20 natural amino acids, which shows that tyrosine binds the strongest. With the COP design algorithm we then designed a mutant tyrosyl tRNA synthetase to activate O-methyl-l-tyrosine preferentially compared with l-tyrosine. This mutant [Y32Q, D158A] is similar to the mutant designed with combinatorial experiments, [Y32Q, D158A, E107T, L162P], by Wang et al. [Wang, L., Brock, A., Herberich, B. & Schultz, P. G. (2001) Science 292, 498-500]. We predict that the new one will have much greater activity while retaining significant discrimination between O-methyl-l-tyrosine and tyrosine.
Enhanced stereoselective hydrolysis of toxic organophosphates by directly evolved variants of mammalian serum paraoxonase (2006)

We addressed the ability of various organophosphorus (OP) hydrolases to catalytically scavenge toxic OP nerve agents. Mammalian paraoxonase (PON1) was found to be more active than Pseudomonas diminuta OP hydrolase (OPH) and squid O,O-di-isopropyl fluorophosphatase (DFPase) in detoxifying cyclosarin (O-cyclohexyl methylphosphonofluoridate) and soman (O-pinacolyl methylphosphonofluoridate). Subsequently, nine directly evolved PON1 variants, selected for increased hydrolytic rates with a fluorogenic diethylphosphate ester, were tested for detoxification of cyclosarin, soman, O-isopropyl-O-(p-nitrophenyl) methyl phosphonate (IMP-pNP), DFP, and chlorpyrifos-oxon (ChPo). Detoxification rates were determined by temporal acetylcholinesterase inhibition by residual nonhydrolyzed OP. As stereoisomers of cyclosarin and soman differ significantly in their acetylcholinesterase-inhibiting potency, we actually measured the hydrolysis of the more toxic stereoisomers. Cyclosarin detoxification was approximately 10-fold faster with PON1 mutants V346A and L69V. V346A also exhibited fourfold and sevenfold faster hydrolysis of DFP and ChPo, respectively, compared with wild-type, and ninefold higher activity towards soman. L69V exhibited 100-fold faster hydrolysis of DFP than the wild-type. The active-site mutant H115W exhibited 270-380-fold enhancement toward hydrolysis of the P-S bond in parathiol, a phosphorothiolate analog of parathion. This study identifies three key positions in PON1 that affect OP hydrolysis, Leu69, Val346 and His115, and several amino-acid replacements that significantly enhance the hydrolysis of toxic OPs. GC/pulsed flame photometer detector analysis, compared with assay of residual acetylcholinesterase inhibition, displayed stereoselective hydrolysis of cyclosarin, soman, and IMP-pNP, indicating that PON1 is less active toward the more toxic optical isomers.
Nucleoside Triphosphates and their Analogs (2010)

Used extensively in cellular and molecular biology research and cytogenetic applications, nucleotide analogs are currently available for the treatment of various diseases. Nucleoside Triphosphate and Their Analogs: Chemistry, Biotechnology, and Biological Applications features the contributions of 18 scientists from both academia and industry in th
Templating Nanoporous Polymers with Ordered Block Copolymers (2007)

In the midst of this era of nanotechnology and shrinking device size, block copolymers have evolved from their use in traditional application areas (e.g., adhesives, additives, and elastomers) to enable the development of materials for new emerging and more advanced technologies. This review discusses the use of block copolymers to generate nanoporous polymers that can be used either directly, in applications such as membrane filtration, or subsequently as a template for the formation of other nanostructured materials. The work within describes published research from the beginning of 2005 to the present discussing nanoporous materials in the context of: (i) nanolithography and new alignment technologies, (ii) monoliths, (iii) new fabrication techniques, and (iv) membranes. A summary and perspective on the current direction of the stimulating area of block copolymer derived nanoporous materials concludes the review.
Nonpharmacologic stroke prevention in atrial fibrillation (2005)

Atrial fibrillation is associated with significant mortality and morbidity. The burden of morbidity in atrial fibrillation is mostly due to stroke, one of the major causes of death and the leading cause of long-term disability. Although highly effective in prevention of thromboembolic stroke, several factors limit utilization of chronic oral anticoagulation therapy. Eradication of atrial fibrillation and restoration of effective atrial contraction by surgical methods, or recently, by percutaneous catheter ablation methods, are two attractive approaches for stroke prophylaxis. Surgical exclusion of the left atrial appendage has generated considerable interest in the past decades and it is now performed routinely during mitral valve surgery in many centers. Recently, minimally invasive and percutaneous methods for the exclusion of left atrial appendage have been introduced. Currently, these approaches are being evaluated in ongoing trials. This review will discuss the current status of nonpharmacologic methods in the prevention of stroke in atrial fibrillation.
B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt's lymphomas. (1982)

Abstract Two new cell surface antigens expressed on B lymphoblastoid cell lines (B-LCL) were defined with cytotoxic mouse monoclonal antibodies. One marker, BB-1 (for B lymphoblast antigen-1), was detected on human and nonhuman primate B-LCL, Epstein-Barr virus (EBV)-activated B cell blasts, most Burkitt's lymphomas, and Ia+ B lymphoblast-like myelomas. Polyclonal B cell activators such as pokeweed mitogen (PWM) and lipopolysaccharide (LPS) also induced the expression of BB-1 on immunoglobulin (Ig)-positive cells. In contrast, BB-1 could not be detected on normal lymphoid tissues by complement-dependent cytotoxicity and immunofluorescence (IF) assays or by analysis with a fluorescence-activated cell sorter (FACS). T cell blasts, T cell leukemias, and pre-B cell or erythroblastic leukemia cell lines were also BB-1 negative. Of particular interest was the finding that BB-1 was expressed on the Jijoye lymphoma but only marginally on a subline of Jijoye, P3HR-1, that lacks receptors for EBV and produces a defective virus incapable of transforming lymphocytes. A second lymphoblast antigen (LB-1) unlike BB-1, was present on both T and B cell blasts and virus-transformed T- and B-LCL but not on normal lymphoid tissues.
The synthesis of 11,11‐dideuterolinoleic acid (1971)

Abstract The synthesis of 11,11‐dideuterolinoleic acid is described. The procedure employed resulted in a product of high isotopic purity. The NMR and mass spectral analyses of the product and intermediates confirm the position and extent of deuterium incorporation.
Recombinant Domain III of Perlecan Promotes Cell Attachment through Its RGDS Sequence (1995)

Perlecan has been previously been shown to support attachment of a wide variety of cells through interactions of its core protein with the cell surface. The core protein domains involved in cell adhesion are, however, unknown. The laminin-like domain III of murine perlecan contains an RGDS sequence and is a likely candidate for supporting integrin-mediated cell attachment. We made a cDNA construct corresponding to domain III and containing an in frame signal peptide at the 5' end as well as in frame a stop codon at the 3' end by using cDNA clones to perlecan. The construct was inserted into the pRC/CMV vector and transfected into HT1080 cells, and the secreted recombinant domain III, a 130-kDa protein, was purified from the medium. The size of proteolytic fragments produced by digestion with V8 protease as well as analysis of the rotary shadowed image of the recombinant protein indicated it was produced in a native conformation. Recombinant domain III coated on tissue culture dishes, supports adhesion of an epithelial-like mouse mammary tumor cell line MMT 060562 in a dose-dependent manner. This interaction was inhibited specifically by the RGDS synthetic peptide and intact perlecan, but not laminin. This domain III RGD-dependent cell attachment activity indicates a role for perlecan in integrin-mediated signaling.
Crystal structure of inactivated Thermotoga maritima invertase in complex with the trisaccharide substrate raffinose (2006)

Thermotoga maritima invertase (beta-fructosidase), a member of the glycoside hydrolase family GH-32, readily releases beta-D-fructose from sucrose, raffinose and fructan polymers such as inulin. These carbohydrates represent major carbon and energy sources for prokaryotes and eukaryotes. The invertase cleaves beta-fructopyranosidic linkages by a double-displacement mechanism, which involves a nucleophilic aspartate and a catalytic glutamic acid acting as a general acid/base. The three-dimensional structure of invertase shows a bimodular enzyme with a five bladed beta-propeller catalytic domain linked to a beta-sandwich of unknown function. In the present study we report the crystal structure of the inactivated invertase in interaction with the natural substrate molecule alpha-D-galactopyranosyl-(1,6)-alpha-D-glucopyranosyl-beta-D-fructofuranoside (raffinose) at 1.87 A (1 A=0.1 nm) resolution. The structural analysis of the complex reveals the presence of three binding-subsites, which explains why T. maritima invertase exhibits a higher affinity for raffinose than sucrose, but a lower catalytic efficiency with raffinose as substrate than with sucrose.
Epitaxial growth and lithium ion conductivity of lithium-oxide garnet for an all solid-state battery electrolyte (2013)

Epitaxial thin films of Al-doped Li7La3Zr2O12 (LLZO) with a cubic garnet-type structure were successfully synthesized using pulsed laser deposition to investigate the lithium ion conduction in grains. Two orientations of the films were obtained depending on the Gd3Ga5O12 (GGG) substrate orientation, LLZO(001)/GGG(001) and LLZO(111)/GGG(111). The ionic conductivities in the grains of the (001) and (111) films were 2.5 × 10(-6) and 1.0 × 10(-5) S cm(-1) at 298 K, respectively, which were lower than those of polycrystalline LLZO of over 10(-4) S cm(-1). X-ray reflectometry and inductively coupled plasma mass spectrometry revealed a large amount of Al(3+) of over 0.6 moles substituted for Li(+). These results indicate that the Al(3+) substitution in the LLZO lattice decreases the number of movable lithium ions and blocks the three-dimensional lithium migration pathway. The lattice mismatch between the film and the substrate induced the lattice distortion of the LLZO, resulting in different conductivities between the (001) and (111) films. The epitaxial-film model system directly clarified a substantial impact of the Al substitution and the lattice distortion on the lithium ion conductivity in the LLZO.
Glycoprotein C of Herpes Simplex Virus Type 1 Prevents Complement-Mediated Cell Lysis and Virus Neutralization (1990)

Glycoprotein gCl of herpes simplex virus type 1 (HSV-l) binds complement component C3b. To determine if gCl modifies the interaction of complement with virus-infected cells or cell-free virus, ns-l, a mutant HSV-l strain that does not express gCl at the cell surface and does not bind C3b, was compared with its parental strain, NS. Cells infected with the gCl mutant were more susceptible to cytolysis mediated by antibody and complement or complement alone. The gCl or gDl genes were expressed in mammalian cells under the control ofan inducible promoter. Cells induced to express gCl resisted complement cytolysis, while cells expressing gDl did not. gCl modified cytolysis of virus-infected or -transfected cells by blocking alternative complement pathway activation. gCl also modified complement-dependent virus neutralization, which was mediated by inhibiting the classical complement pathway. These results indicate a protective role for gCl on the virion and at the cell surface.
Biologic and synthetic skin substitutes: An overview (2010)

ABSTRACT The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing.
Disposition and metabolism of the angiogenic moderator O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470) in human hepatocytes and tissue microsomes. (1995)

The biotransformation of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM 1470), a potent in vitro inhibitor of angiogenesis, was investigated in primary cultured human hepatocytes and microsomal fractions of various human tissues. Exposure of human hepatocytes to 5 microM [3H]TNP-470 led to a rapid metabolism of unchanged drug to six metabolic derivatives within 30 min. The predominant extracellular metabolites were M-II and M-IV, attaining a maximum level of 3.23 +/- 0.34 and 0.88 +/- 0.10 microM, respectively. M-II leveled off, while M-IV rapidly declined to 0.06 +/- 0.05 microM by 3 h. TNP-470 was undetectable after 60 min. M-V and M-VI slowly reached maximal concentrations of 0.26 +/- 0.12 and 0.32 +/- 0.16 microM, respectively. M-I only reached a concentration of 0.18 +/- 0.07 microM at 60 min and leveled at 0.13 +/- 0.06 microM for the remaining time of the experiment. The intracellular profile was different, with M-III and M-V representing the major metabolites detected. Studies using human liver microsomes demonstrated that M-IV formation was associated with an esterase-like enzymatic cleavage of TNP-470 and that this metabolite was then further metabolized by microsomal epoxide hydrolase to M-II, as evidenced by inhibition of this metabolic step by cyclohexene oxide, a microsomal epoxide hydrolase inhibitor. Extrahepatic metabolism of TNP-470 was also demonstrated using different sites of human intestinal, stomach, and kidney microsomes, with metabolite M-IV as the principal derivative detected in these tissues. Hepatic microsomal samples from seven different donors demonstrated large interindividual variations in the formation of both M-II and M-IV. In summary, this study demonstrates a rapid and extensive metabolism of TNP-470 in human tissues. The data emphasize the need to evaluate the in vivo formation and extent of TNP-470 metabolites to adequately assess the pharmacodynamic effects of this novel anticancer drug with a novel mechanism of action.
The ORCHESTRA Collaborative Data Sharing System (2008)

Sharing structured data today requires standardizing upon a single schema, then mapping and cleaning all of the data. This results in a single queriable mediated data instance. However, for settings in which structured data is being collaboratively authored by a large community, e.g., in the sciences, there is often a lack of consensus about how it should be represented, what is correct, and which sources are authoritative. Moreover, such data is seldom static: it is frequently updated, cleaned, and annotated. The ORCHESTRA collaborative data sharing system develops a new architecture and consistency model for such settings, based on the needs of data sharing in the life sciences. In this paper we describe the basic architecture and implementation of the ORCHESTRA system, and summarize some of the open challenges that arise in this setting.
3D bulk measurements of the force distribution in a compressed emulsion system (2002)

In particulate materials, such as emulsions and granular media, a "jammed" system results if particles are packed together so that all particles are touching their neighbours, provided the density is sufficiently high. This paper studies through experiment, theory and simulation, the forces that particles exert upon one another in such a jammed state. Confocal microscopy of a compressed polydisperse emulsion provides a direct 3D measurement of the dispersed phase morphology within the bulk of the sample. This allows the determination of the probability distribution of interdroplet forces, P(f) where f is the magnitude of the force, from local droplet deformations. In parallel, the simplest form of the Boltzmann equation for the probability of force distributions predicts P(f) to be of the form e(-f/p), where p is proportional to the mean force f for large forces. This result is in good agreement with experimental and simulated data.
Reaction of calcium phosphate cements with different amounts of tetracalcium phosphate and dicalcium phosphate anhydrous (1999)

Calcium phosphate cements (CPCs) with different amounts of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) (TTCP/DCPA molar ratio from 0.25 to 2.00) were prepared to further understand the setting reaction and the factors that could influence the properties of CPCs. Quantitative X-ray diffraction patterns, Fourier transform IR spectra, and diametral tensile strength of the set mass were measured along with pH measurements of the CPC suspension. Calcium-deficient hydroxyapatite (d-HAP) with a calcium to phosphate molar ratio of approximately 1.5 was formed initially in the CPC setting consisting of an equimolar mixture of TTCP and DCPA. This gradually transformed into stoichiometric HA (s-HA) with increasing incubation time. The s-HA was formed in the initial stage when the CPC contained an excess amount of TTCP. In contrast, maturation to s-HAP was slow when the CPC contained excess amounts of DCPA. The highest mechanical strength of set CPC was associated with an equimolar mixture of TTCP and DCPA, and the mechanical strength decreased as the TTCP/DCPA molar ratio deviated from 1.00. We concluded, therefore, that the setting reaction and the nature of the resulting set mass are dependent on the molar ratios of TTCP and DCPA.
Competition, cooperation, and optimization in Multi-Hop CSMA networks (2011)

The purpose of this paper is to present a new method for the study of competition and cooperation relationships among nodes in a network with a CSMA (Carrier Sense Multiple Access) protocol implemented with an exponential backoff process. Self-organized behavior is proposed. We propose a "Channel Utilization Model" with a new derived variable "channel access rate" which applies for all traffic loads. These models are applied with different optimization methods.
The rendering equation (1986)

We present an integral equation which generalizes a variety of known rendering algorithms. In the course of discussing a monte carlo solution we also present a new form of variance reduction, called Hierarchical sampling and give a number of elaborations shows that it may be an efficient new technique for a wide variety of monte carlo procedures. The resulting rendering algorithm extends the range of optical phenomena which can be effectively simulated.