gebhart/patrepeval huggingface dataset:
Seeking Ligands for Lonely Orphan Receptors (1999)

Ligands for about half of the nuclear receptor superfamily, many members of which are involved in crucial metabolic pathways, have been identified so far. Those receptors, for which the ligands are not known, are called orphan nuclear receptors. Finding the ligands for these receptors is a big challenge for pharmaceutical companies. In his Perspective, [Gustafsson][1] discusses the new discovery (as reported by [ Parks et al .][2] and [ Makishima et al .][3] in this issue) that the ligands for the farnesoid X receptor, FXR, are bile acids, important regulators of cholesterol homeostasis. Intriguingly, when bound to FXR, bile acids are able to regulate their own synthesis from cholesterol by suppressing production of a crucial biosynthetic enzyme.

 [1]: http://www.sciencemag.org/cgi/content/full/284/5418/1285
 [2]: http://www.sciencemag.org/cgi/content/short/284/5418/1365
 [3]: http://www.sciencemag.org/cgi/content/short/284/5418/1362
Targeted CTLA-4 Engagement Induces CD4+CD25+CTLA-4high T Regulatory Cells with Target (Allo)antigen Specificity (2004)

CTLA-4 (CD152) is actively involved in down-regulating T cell activation and maintaining lymphocyte homeostasis. Our earlier studies showed that targeted engagement of CTLA-4 can down-modulate T cell response and suppress allo- and autoimmune responses. In this study, we report that targeted CTLA-4 engagement can induce immune tolerance to a specific target through selective induction of an Ag-specific CD4(+)CD25(+)CTLA-4(high) regulatory T cell (Treg cell) population. Allogeneic cells coated with anti-CTLA-4 Ab induced immune hyporesponsiveness through suppression of proinflammatory cytokines IFN-gamma and IL-2, and up-regulation of the regulatory cytokines IL-10, TGF-beta1, and IL-4, presumably through the engagement of CTLA-4 on activated T cells. Although rechallenge with alloantigen failed to break the unresponsiveness, a transient recovery from tolerance was observed in the presence of high concentrations of exogenous IL-2, saturating concentrations of neutralizing anti-TGF-beta1 and anti-IL-10 Abs, and blocking anti-CTLA-4 Ab, and upon depletion of CD4(+)CD25(+) Treg cells. The CD4(+)CD25(+)CTLA-4(high) Treg cells from tolerant mice suppressed the effector function of CD25(-) T cells from Ag-primed mice. Adoptive transfer of these Treg cells into Ag-primed mice resulted in a significantly reduced alloantigen-specific response. Further characterization demonstrated that the Treg cells with memory phenotype (CD62L(-)) were more potent in suppressing the alloantigen-specific T cell response. These results strongly support that the targeted engagement of CTLA-4 has therapeutic potential for the prevention of transplant rejection.
Hypothermia Improves Outcome From Traumatic Brain Injury (2005)

Hypothermia for patients with severe traumatic brain injury (TBI) remains controversial despite a strong biological rationale and reasonable evidence from the literature. The "negative" Clifton study seems to have reduced enthusiasm for hypothermia, however the aim of this review is to analyse the evidence from all randomised controlled trials (RCT) and meta-analyses on this topic to determine whether there is adequate support for the view that hypothermia does improve outcome from TBI. The biological rationale for hypothermia is supported by animal and human mechanistic studies of TBI and human clinical studies of brain injury caused by out-of-hospital cardiac arrest. Several small single-centre RCT's have demonstrated that hypothermia leads to both improved survival and improved favourable neurological outcome in TBI. The Clifton study, which was larger and multi-centre, found hypothermia had no major benefits in TBI, although this study can be criticised for several issues of trial methodology (trial design and application of the intervention) and group comparison. Several meta-analyses have given slightly discordant results, but the two most recent meta-analyses agree that hypothermia improves favourable neurological outcome and probably survival. Subsequent to these meta-analyses, a RCT was published which has confirmed that hypothermia is beneficial in a large group of TBI patients. When the published evidence is considered in total, even if hypothermia can't be justified in all TBI patients, if it is applied optimally in the most appropriate patients, hypothermia certainly improves outcome from TBI. If hypothermia is correctly applied (early, long and cool enough) in the optimal group of TBI patients (young with elevated ICP), there seems to be no doubt that hypothermia is effective in improving both survival and favourable neurological outcome from TBI.
Recombinant carbohydrate variant of human choriogonadotropin beta-subunit (hCG beta) descarboxyl terminus (115-145). Expression and characterization of carboxyl-terminal deletion mutant of hCG beta in the baculovirus system. (1991)

A recombinant analog of human choriogonadotropin beta-subunit descarboxyl-terminal peptide (115-145 residues, delhCG beta) was obtained by the expression of corresponding beta cDNA in the baculovirus expression system. The efficiency of expression and secretion was high. The recombinant delhCG beta was purified by immunoaffinity using a specific monoclonal antibody against hCG beta and reverse phase high performance liquid chromatography. The hCG beta analog lacked the carboxyl-terminal 31-residue peptide as well as the four O-linked carbohydrates. Also, the N-linked "complex" type carbohydrates in the deletion mutant were modified to the high mannose type. The apparent molecular weights of delhCG beta in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions were found to be 19,000 and 27,500 respectively. delhCG beta on hydrolysis with endo N-acetylglucosaminidase F or H yielded a 17,500 protein band whereas treatment with N-glycanase gave a protein band with a molecular weight of 16,000. The carbohydrate analysis of delhCG beta, calculated on the basis of 4 residues of N-acetylglucosamine, showed 3 or 4 fucose, 0.6 N-acetylgalactosamine, and 11.4 mannose residues, indicating the high mannose type structures of the two N-linked carbohydrate chains. Despite the carbohydrate modification of the N-linked carbohydrates and the carboxyl-terminal deletion, the delhCG beta had about 87% of the immunological activity of the native hCG beta, indicating no significant conformational alteration induced by the mutation. The delhCG beta combined readily with native hCG alpha, and the reconstituted hCG alpha del beta required 0.031 pmol to achieve 50% inhibition of binding of the tracer with rat lutropin/choriogonadotropin receptor compared with 0.039 pmol by native hCG. Like native hCG, hCG alpha del beta also had most comparable ability to stimulate cAMP accumulation and progesterone production in rat Leydig cells. Thus it is clear from the data that the carboxyl-terminal deletion and thereby the deletion of four O-linked carbohydrates had no effect on its in vitro immunological and biological properties.
Evidence for conformational changes in Escherichia coli porphobilinogen deaminase during stepwise pyrrole chain elongation monitored by increased reactivity of cysteine-134 to alkylation by N-ethylmaleimide (1995)

Porphobilinogen deaminase from Escherichia coli becomes progressively more susceptible to inactivation by the thiophilic reagent N-ethylmaleimide (NEM) as the catalytic cycle proceeds through the enzyme-intermediate complexes ES, ES2, ES3, and ES4. Site-directed mutagenesis of potentially reactive cysteines has been used to identify cysteine-134 as the key residue that becomes modified by the reagent and leads to inactivation. Since cysteine-134 is buried at the interface between domains 2 and 3 of the E. coli deaminase molecule, the observations suggest that a stepwise conformational change occurs between these domains during each stage of tetrapyrrole assembly. Interestingly, mutation of the invariant active-site cysteine-242 to serine leads to an enzyme with up to a third of the catalytic activity found in the wild-type enzyme. Electrospray mass spectrometry indicates that serine can substitute for cysteine as the dipyrromethane cofactor attachment site.
The development of road information extraction from remote sensing images (2008)

The automatic extraction of roads from high spatial resolution remote sensing images is the hotspot and difficulty in remote sensing research, and has attracted extensive attention. Road extraction from remote sensing images is a leading direction of remote sensing image processing and widely demanded in transportation, mapping, urban planning and other fields. In this paper, the actuality of road extraction is investigated. The road extraction process is divided into five phases, which are pre-processing, low-level processing, mid-level processing, high-level processing and the application of extraction results. The methods used in each phase are analyzed. Low-level processing is considered to be the key and foundation of road extraction. Based on the representative method in low-level processing, mathematical morphology, this paper presents an approach for automatic road extraction and tests the method on remote sensing image. The experimental result shows the efficiency of the presented approach.
A Traffic-Based Method of Detecting Dead Internet Key Exchange (IKE) Peers (2004)

This document describes the method detecting a dead Internet Key Exchange (IKE) peer that is presently in use by a number of vendors. The method, called Dead Peer Detection (DPD) uses IPSec traffic patterns to minimize the number of IKE messages that are needed to confirm liveness. DPD, like other keepalive mechanisms, is needed to determine when to perform IKE peer failover, and to reclaim lost resources.
Glycotripod Amphiphiles for Solubilization and Stabilization of a Membrane‐Protein Superassembly: Importance of Branching in the Hydrophilic Portion (2008)

Intrinsic membrane proteins must usually be extracted from the native membrane with the aid of synthetic amphiphiles and then stabilized in a soluble form before detailed structural and functional characterization is possible. We describe new amphiphiles with unusual architectures that are useful for extraction and stabilization of photosynthetic protein superassemblies from bacterial membranes. Our results suggest that incorporating branch points in both the hydrophilic and lipophilic portions can lead to favorable amphiphile behavior.
Human Embryonic and Rat Adult Stem Cells with Primitive Endoderm-Like Phenotype Can Be Fated to Definitive Endoderm, and Finally Hepatocyte-Like Cells (2010)

Stem cell-derived hepatocytes may be an alternative cell source to treat liver diseases or to be used for pharmacological purposes. We developed a protocol that mimics mammalian liver development, to differentiate cells with pluripotent characteristics to hepatocyte-like cells. The protocol supports the stepwise differentiation of human embryonic stem cells (ESC) to cells with characteristics of primitive streak (PS)/mesendoderm (ME)/definitive endoderm (DE), hepatoblasts, and finally cells with phenotypic and functional characteristics of hepatocytes. Remarkably, the same protocol can also differentiate rat multipotent adult progenitor cells (rMAPCs) to hepatocyte-like cells, even though rMAPC are isolated clonally from cultured rat bone marrow (BM) and have characteristics of primitive endoderm cells. A fraction of rMAPCs can be fated to cells expressing genes consistent with a PS/ME/DE phenotype, preceding the acquisition of phenotypic and functional characteristics of hepatocytes. Although the hepatocyte-like progeny derived from both cell types is mixed, between 10-20% of cells are developmentally consistent with late fetal hepatocytes that have attained synthetic, storage and detoxifying functions near those of adult hepatocytes. This differentiation protocol will be useful for generating hepatocyte-like cells from rodent and human stem cells, and to gain insight into the early stages of liver development.
Neural network models in EMG diagnosis (1995)

In previous years, several computer-aided quantitative motor unit action potential (MUAP) techniques were reported. It is now possible to add to these techniques the capability of automated medical diagnosis so that all data can be processed in an integrated environment. In this study, the parametric pattern recognition (PPR) algorithm that facilitates automatic MUAP feature extraction and Artificial Neural Network (ANN) models are combined for providing an integrated system for the diagnosis of neuromuscular disorders. Two paradigms of learning for training ANN models were investigated, supervised, and unsupervised. For supervised learning, the back-propagation algorithm and for unsupervised learning, the Kohonen's self-organizing feature maps algorithm were used. The diagnostic yield for models trained with both procedures was similar and on the order of 80%. However, back propagation models required considerably more computational effort compared to the Kohonen's self-organizing feature map models. Poorer diagnostic performance was obtained when the K-means nearest neighbor clustering algorithm was applied on the same set of data.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Adsorption of Hydroxy-Al Polycations and Destabilization of Illite and Montmorillonite Suspensions (1990)

Abstract Water-infiltration characteristics of soil can be improved by preventing clay dispersion. The present study determined the adsorption properties of hydroxy-Al polycations (Al-p) and their relation to the destabilization of clay suspensions. Al-p was synthesized and fractionated into nominal molecular weights between 10 4 and 5 × 10 4 . The reactions of Al-p with Na-illite and Na-montmorillonite indicated a very strong affinity of Al-p to the clay surfaces. The maximum adsorptions of Al-p by Na-illite and Na-montmorillonite were found to be 0.37 and 1.7 mmole Al/g, and very close to the cation-exchange capacity of the two clays, suggesting that the adsorption was chiefly controlled by the mechanism of charge screening. Adsorption of Al-p increased the points of zero charge (PZCs) and the apparent points of zero salt effect (PZSEs) of illite and montmorillonite. PZSEs for both clays were 4.7 at their maximum Al-p adsorption, and PZCs ranged from 5.3 to 6.4, depending on solution ionic strength and the individual clay minerals. The differences in PZCs were probably due to outer-sphere complex formation between Al-p-treated illite and montmorillonite and the swamping electrolyte. Critical flocculation concentrations (CFCs) of Al-p for Na-illite and Na-montmorillonite were at 0.28 and 1.0 mmole Al/g, whereas zero electrophoretic mobilities were at about 0.36 and 1.67 mmole Al/g Al-p additions. Excessive addition of Al-p reversed this surface charge of clay colloids and restabilized the illite but not montmorillonite suspensions. This difference was probably due to the stronger and more extensive interparticle bridging of montmorillonite particles by Al-p than those of illite. The CFCs for the two clays were also found to be dependent on sodium adsorption ratio (SAR), pH, and ionic strength. Increases in SAR and pH significantly increased the CFC, whereas an increase in ionic strength decreased the CFC.
Chain mechanism for initiation of hydrocarbon oxidation reactions in a low-temperature plasma (1998)

A self-consistent model is used for a numerical study of the kinetics of plasma-chemical reactions initiated in a low-temperature gas-discharge plasma in an atmospheric-pressure CH4O2 mixture. An analysis is made of a chain mechanism for the formation of radicals in ion-molecular processes involving water and oxygen molecules, which can appreciably reduce the energy consumption needed to form the oxidation products. It is shown that under the conditions of a non-self-sustained, electron-beam-initiated, atmospheric-pressure discharge the energy consumption needed to produce methanol molecules may, at a few eV, be between four and fives times lower than that in a self-sustained discharge.
Frac-Fluid Recycling and Water Conservation: A Case History (2009)

Summary Shallow-gas fracturing is very prevalent in western Canada. Several thousand wells are typically drilled and completed in the shallow- gas fields every year. All these wells are typically hydraulically fractured. Before 1999, after testing for microtoxicity, the flowback fluid was allowed to be land farmed in southeastern Alberta. In that year, the Alberta Energy and Utilities Board began more stringent enforcement of Guide 58, which required that flowback fluid be disposed in a disposal well. At that time, one operator typically had a project of 300 to 400 wells with an average of 5 fracs per day during spring/sum- mer. When the fluid could no longer be land farmed, attempts were made to recycle the flowback fluid. The chemistry of the surfactant-gel fluid was insensitive to the water quality, which made the recycling concept successful. Several cost advantages were achieved, which will be detailed in the paper. These included freshwater costs, transportation costs, disposal costs, and chemical costs. An additional advantage that was realized involved a 50% reduction in the freshwater requirements for a project—a significant additional benefit because several years of drought conditions have caused water shortages in the area. This paper will detail the chemistry of the fracturing gel, its field application, the optimized recycling operation, and the details on cost advantages achieved, as well as future direction for further reduction in freshwater usage on a project basis.
Augmentation of the Lipopolysaccharide-Neutralizing Activities of Human Cathelicidin CAP18/LL-37-Derived Antimicrobial Peptides by Replacement with Hydrophobic and Cationic Amino Acid Residues (2002)

Mammalian myeloid and epithelial cells express various peptide antibiotics (such as defensins and cathelicidins) that contribute to the innate host defense against invading microorganisms. Among these peptides, human cathelicidin CAP18/LL-37 (L(1) to S(37)) possesses not only potent antibacterial activity against gram-positive and gram-negative bacteria but also the ability to bind to gram-negative lipopolysaccharide (LPS) and neutralize its biological activities. In this study, to develop peptide derivatives with improved LPS-neutralizing activities, we utilized an 18-mer peptide (K(15) to V(32)) of LL-37 as a template and evaluated the activities of modified peptides by using the CD14(+) murine macrophage cell line RAW 264.7 and the murine endotoxin shock model. By replacement of E(16) and K(25) with two L residues, the hydrophobicity of the peptide (18-mer LL) was increased, and by further replacement of Q(22), D(26), and N(30) with three K residues, the cationicity of the peptide (18-mer LLKKK) was enhanced. Among peptide derivatives, 18-mer LLKKK displayed the most powerful LPS-neutralizing activity: it was most potent at binding to LPS, inhibiting the interaction between LPS and LPS-binding protein, and attaching to the CD14 molecule, thereby suppressing the binding of LPS to CD14(+) cells and attenuating production of tumor necrosis factor alpha (TNF-alpha) by these cells. Furthermore, in the murine endotoxin shock model, 18-mer LLKKK most effectively suppressed LPS-induced TNF-alpha production and protected mice from lethal endotoxin shock. Together, these observations indicate that the LPS-neutralizing activities of the amphipathic human CAP18/LL-37-derived 18-mer peptide can be augmented by modifying its hydrophobicity and cationicity, and that 18-mer LLKKK is the most potent of the peptide derivatives, with therapeutic potential for gram-negative bacterial endotoxin shock.
Formylglycinamide ribonucleotide synthetase from Escherichia coli: cloning, sequencing, overproduction, isolation, and characterization (1989)

The purL gene of Escherichia coli encoding the enzyme formylglycinamidine ribonucleotide (FGAM) synthetase which catalyzes the conversion of formylglycinamide ribonucleotide (FGAR), glutamine, and MgATP to FGAM, glutamate, ADP, and Pi has been cloned and sequenced. The mature protein, as deduced by the structural gene sequence, contains 1628 amino acids and has a calculated Mr of 141,418. Comparison of the purL control region to other pur loci control regions reveals a common region of dyad symmetry which may be the binding site for the "putative" repressor protein. Construction of an overproducing strain permitted purification of the protein to homogeneity. N-Terminal sequence analysis and comparison of glutamine binding domain sequences (Ebbole & Zalkin, 1987) confirm the amino acid sequence deduced from the gene sequence. The purified protein exhibits glutaminase activity of 0.02% the normal turnover, and NH3 can replace glutamine as a nitrogen donor with a Km = 1 M and a turnover of 3 min-1 (2% glutamine turnover). The enzyme forms an isolable (1:1) complex with glutamine: t1/2 is 22 min at 4 degrees C. This isolated complex is not chemically competent to complete turnover when FGAR and ATP are added, demonstrating that ammonia and glutamine are not covalently bound as a thiohemiaminal available to complete the chemical conversion to FGAM. hydroxylamine trapping experiments indicate that glutamine is bound covalently to the enzyme as a thiol ester. Initial velocity and dead-end inhibition kinetic studies on FGAM synthetase are most consistent with a sequential mechanism in which glutamine binds followed by rapid equilibrium binding of MgATP and then FGAR. Incubation of [18O]FGAR with enzyme, ATP, and glutamine results in quantitative transfer of the 18O to Pi.
An implantable neuro-stimulator device for a retinal prosthesis (2003)

In retina pigmentosa and macular degeneration, the photoreceptor cells of the retina (rods and cones) fail to respond to light. However, the discovery that direct electrical stimulation of retinal neurons can create visual sensation in patients inspires an electronic prosthesis which bypasses the defective photoreceptors. A prosthetic system is conceptually illustrated. A prototype implantable power and data receiver and neural stimulator, 4.6/spl times/4.7 mm/sup 2/ in 1.2 /spl mu/m CMOS, can drive a 10/spl times/10 array of retinal electrodes at real-time visual rates. The prototype serves two major goals. The first is to demonstrate the wireless transfer of power and data required for an implantable prosthesis. The second is to serve as a flexible stimulus waveform generator.