gebhart/patrepeval huggingface dataset:
UV-Induced Gelation on Nanometer Scale Using Liposome Reactor (2002)

A protocol for preparation of polymer hydrogel spherical particles on a nanometer scale (nanogels) was developed. The protocol includes encapsulation of hydrogel-forming components into liposomes, UV-induced polymerization within the liposomes, solubilization of the lipid bilayer by detergent, removal of the phospholipid, detergent molecules, and their micelles by dialysis, and drying nanogels by evaporation in a temperature gradient. Dynamic light scattering technique was employed to characterize the size distribution of poly(acrylamide), poly(N-isopropylacrylamide), and poly(N-isopropylacrylamide-co-1-vinylimidazole) hydrogel particles. Hydrophobic chains of N-octadecylacrylamide were immobilized onto the surface of the poly(N-isopropylacrylamide-co-1-vinylimidazole) hydrogel particles to use them as anchors for attaching the nanogels onto the lipid bilayers. The diameter of the nanogels prepared varied between 30 and 300 nm. The solvent, temperature, and pH sensitivities of the liposomes, nanogels, and their mixtures were studied. It was found that the phospholipid bilayer always coats the surface of both unanchored and anchored hydrogel particles upon mixing. Aggregation of the lipid bilayer-coated nanogels (lipobeads) was observed when the gel particles collapsed. The mechanism of aggregation differs for the lipobeads containing unanchored cores and those containing anchored hydrogel cores. The hydrogel−liposome structures of a nanometer size are of potential importance for applications such as biomimetic sensory systems, controlled release devices, and multivalent receptors.
The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department (2012)

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department.
3D QSAR and Molecular Docking Studies of Benzimidazole Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors (2007)

The urgent need for novel HCV antiviral agents has provided an impetus for understanding the structural requisites of NS5B polymerase inhibitors at the molecular level. Toward this objective, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of 67 HCV NS5B polymerase inhibitors were performed using two methods. First, ligand-based 3D QSAR studies were performed based on the lowest energy conformations employing the atom fit alignment method. Second, receptor-based 3D QSAR models were derived from the predicted binding conformations obtained by docking all NS5B inhibitors at the allosteric binding site of NS5B (PDB ID: 2dxs). Results generated from the ligand-based model were found superior (r2cv values of 0.630 for CoMFA and 0.668 for CoMSIA) to those obtained by the receptor-based model (r2cv values of 0.536 and 0.561 for CoMFA and CoMSIA, respectively). The predictive ability of the models was validated using a structurally diversified test set of 22 compounds that had not been included in a preliminary training set of 45 compounds. The predictive r2 values for the ligand-based CoMFA and CoMSIA models were 0.734 and 0.800, respectively, while the corresponding predictive r2 values for the receptor-based CoMFA and CoMSIA models were 0.538 and 0.639, respectively. The greater potency of the tryptophan derivatives over that of the tyrosine derivatives was interpreted based on CoMFA steric and electrostatic contour maps. The CoMSIA results revealed that for a NS5B inhibitor to have appreciable inhibitory activity it requires hydrogen bond donor and acceptor groups at the 5-position of the indole ring and an R substituent at the chiral carbon, respectively. Interpretation of the CoMFA and CoMSIA contour maps in context of the topology of the allosteric binding site of NS5B provided insight into NS5B-inhibitor interactions. Taken together, the present 3D QSAR models were found to accurately predict the HCV NS5B polymerase inhibitory activity of structurally diverse test set compounds and to yield reliable clues for further optimization of the benzimidazole derivatives in the data set.
Separation of antibody helper and antibody suppressor human T cells by using soybean agglutinin. (1980)

Soybean agglutinin (SBA) binds specifically to mouse B cells and has been used in the past to separate mouse B and T spleen cells by differential agglutination of the B cells. In the present study it was found that a major T-cell subpopulation of human peripheral blood mononuclear cells is agglutinated by SBA along with the B cells and monocytes. Tests of such cell surface markers as Fc receptors for IgG and IgM, as well as functional assays of antibody production by B cells, revealed that the SBA-agglutinated cell fraction contains the antibody helper T cells whereas the unagglutinated fraction is enriched with antibody suppressor T cells. Similar observations were made in tests of the proliferative response to mumps antigen. A recently prepared monoclonal antibody, anti-Leu 2a, which recognized the same thymus-dependent antigen previously defined by a heterologous anti-human T cell serum (alpha TH2), was found to define by indirect immunofluorescence a subpopulation of SBA- cells of intermediate staining intensity which was not detectable in the SBA+ population.
The Impact of COVID-19 On Critical Cardiac Care and What is to Come Postpandemic (2020)

The UK's health service has shown immense resilience in the face of COVID-19, adapting practices and going above
Hydralazine rescues PC12 cells from acrolein‐mediated death (2006)

Acrolein, a major lipid peroxidation product, has been associated with both CNS trauma and neurodegenerative diseases. Because of its long half-life, acrolein is a potent endogenous toxin capable of killing healthy cells during the secondary injury process. Traditionally, attempts to intervene in the process of progressive cell death after the primary injury have included scavenging reactive oxygen species (so-called free radicals). The animal data supporting such an approach have generally been positive, but all human clinical trials attempting a similar outcome in human CNS injury have failed. New drugs that might reduce toxicity by scavenging the products of lipid peroxidation present a promising, and little investigated, therapeutic approach. Hydralazine, a well-known treatment for hypertension, has been reported to react with acrolein, forming hydrazone in cell-free systems. In the companion paper, we have established an acrolein-mediated cell injury model using PC12 cells in vitro. Here we test the hypothesis that the formation of hydrazone adducts with acrolein is able to reduce acrolein toxicity and spare a significant percentage of the population of PC12 cells from death. Concentrations of approximately 1 mM of this aldehyde scavenger can rescue over 80% of the population of PC12 cells. This study provides a basis for a new pharmacological treatment to reduce the effects of secondary injury in the damaged and/or diseased nervous system. In particular, we describe the need for new drugs that possess aldehyde scavenging properties but do not interfere with the regulation of blood pressure.
Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis (2001)

Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell-mediated autoimmunity. V(alpha)14 natural killer T (NKT) cells are a subset of T lymphocytes that recognize glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I-like protein CD1d. Here, we show that activation of V(alpha)14 NKT cells by the glycosphingolipid alpha-galactosylceramide (alpha-GalCer) protects susceptible mice against EAE. beta-GalCer, which binds CD1d but is not recognized by NKT cells, failed to protect mice against EAE. Furthermore, alpha-GalCer was unable to protect CD1d knockout (KO) mice against EAE, indicating the requirement for an intact CD1d antigen presentation pathway. Protection of disease conferred by alpha-GalCer correlated with its ability to suppress myelin antigen-specific Th1 responses and/or to promote myelin antigen-specific Th2 cell responses. alpha-GalCer was unable to protect IL-4 KO and IL-10 KO mice against EAE, indicating a critical role for both of these cytokines. Because recognition of alpha-GalCer by NKT cells is phylogenetically conserved, our findings have identified NKT cells as novel target cells for treatment of inflammatory diseases of the central nervous system.
The study of single-chip integrated microfluidic system (2002)

A novel single-chip integrated microfluidic system is presented. After 3D structures are formed with deep cavities and stiff mechanical membrane as sealing layer in single-chip, additional standard IC processes are applied to achieve single-chip integrated microfluidic systems, including micropumps, valves, channels, cavities and some different sensors. We have applied different principles, bimetallic and electrostatic driving, to the driving and control of the micropumps and microvalves. The final micropump driving membrane is 1 mm/spl times/1 mm/spl times/2 /spl mu/m and the valve membrane is 6 mm/spl times/0.6 mm/spl times/2 /spl mu/m. Preliminary experiments show that the on/off flow ratio of the integrated micropump is 180. The results of the sensitivity and the temperature coefficient of the sensors are also reported.
Shaly Sand Analysis using Density-Neutron Porosities from a Cased-hole Pulsed Neutron System (1999)

Abstract A density-based porosity derived from the attenuation of gamma rays created by inelastic scattering of fast neutrons has been developed1,2,3 for the Computalog PND-S pulsed neutron system. The utility of this cased-hole, density-based porosity is demonstrated in reservoir analysis of sand-shale sequences in western Canada, Texas gulf coast, and Montana. Applications (in combination with the cased-hole neutron porosity) include providing porosities where hole conditions make open-hole logging unviable, and in old wells where no modern porosity logs exist or the data is of questionable quality. Low porosity can be differentiated from gas-filled porosity with the use of this measurement in cased-hole prospecting. In shaly sand analyses, the addition of this novel density measurement to the neutron porosity and SIGMA facilitates a more comprehensive description of the reservoir. LRHO, the pulsed neutron density parameter, and RATIO, the near-to-far thermal ratio, are shown as overlays to identify gas zones. The pulsed neutron density porosity IPHI, which is used in the log analysis examples, is generated by specifically characterizing LRHO for a well or field. A prototypical borehole compensated (BHC) algorithm, that generates neutron (AIPN) and density (AIPD) porosities characterized for specific casing sizes and lithologies, is also used in the log analysis examples. The measurement theory of the PN density is reviewed as it pertains to understanding the log examples. The correlation with open-hole porosities is demonstrated in several of the log examples. Through application to some typical reservoir description and optimization problems, the log examples show the utility of these measurements in cased-hole reservoir analysis.
Correlation between the Airway Branching Patterns and the Heterogeneous Distribution of the Lesions in Bleomycin-Injured Mouse Lung: A 3-D Morphometric Study. (2001)

The possible roles of airway branching patterns on the pathogenesis of lung diseases, especially on the heterogeneous distribution of the lesions, were examined through three-dimensional (3-D) morphometric analysis of a mouse lung injury, induced by bleomycin. On serial sections of a mouse lung damaged by subcutaneous injection of bleomycin, we performed a computer-assisted reconstruction of the lung for visualizing the relation of airways with the distribution of the lesions, and defined the features of bronchial routes to each lesion by four parameters: LTB; the distance from the hilum, Ng; generation numbers, RD(min); irregularity of airway branching, and thetaTB; the grade of airway recurrence. Among these four parameters, only thetaTB was found to correlate with the severity of lesions (p < 0.05 by an ANOVA test), which was proved by a posthoc test (p < 0.0001). These results showing the acini supplied by recurrent branches are more prone to be damaged than those by non-recurrent branches suggest that branching patterns may underlie the heterogeneous distribution of lesions in diffuse interstitial lung diseases.
Imaging of Thalamocortical Dysrhythmia in Neuropsychiatry (2011)

Abnormal brain activity dynamics, in the sense of a thalamocortical dysrhythmia (TCD), has been proposed as the underlying mechanism for a subset of disorders that bridge the traditional delineations of neurology and neuropsychiatry. In order to test this proposal from a psychiatric perspective, a study using magnetoencephalography (MEG) was implemented in subjects with schizophrenic spectrum disorder (n = 14), obsessive-compulsive disorder (n = 10), or depressive disorder (n = 5) and in control individuals (n = 18). Detailed CNS electrophysiological analysis of these patients, using MEG, revealed the presence of abnormal theta range spectral power with typical TCD characteristics, in all cases. The use of independent component analysis and minimum-norm-based methods localized such TCD to ventromedial prefrontal and temporal cortices. The observed mode of oscillation was spectrally equivalent but spatially distinct from that of TCD observed in other related disorders, including Parkinson's disease, central tinnitus, neuropathic pain, and autism. The present results indicate that the functional basis for much of these pathologies may relate most fundamentally to the category of calcium channelopathies and serve as a model for the cellular substrate for low-frequency oscillations present in these psychiatric disorders, providing a basis for therapeutic strategies.
Inhibition of growth factor-dependent inositol phosphate Ca2+ signaling by antitumor ether lipid analogues. (1990)

Cytotoxic ether lipid analogues have been studied for their ability to inhibit growth factor-dependent [Ca2+]i signaling in Swiss 3T3 fibroblasts. 1-Octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) inhibited 45Ca2+ uptake and inositol(1,4,5)trisphosphate-induced 45Ca2+ release in saponin permeabilized cells with concentration producing 50% inhibition values of 55 and 360 microM, respectively. When cells were exposed to ET-18-OCH3 for 18 h before permeabilization there was selective inhibition of inositol(1,4,5)trisphosphate-induced 45Ca2+ release with a concentration producing 50% inhibition value of 20 microM, but no effect on 45Ca2+ uptake, or on 45Ca2+ release by arachidonic acid. The concentration of ET-18-OCH3 with continuous exposure to inhibit cell growth 50% was 19 microM. The ether lipid analogues 1-hexadecylthio-2-ethyl-rac-glycero-3- phosphocholine and 1-S-octadecyl-2-O-methylthiopropyl-3-N,N-dimethyl-gamma-hydroxy pro pyl ammonium iodide had effects similar to those of ET-18-OCH3 but the noncytotoxic analogue 1-alkyl-2-hydroxy-sn-glycero-3- phosphocholine was without effect. Exposure of cells to 10 microM ET-18-OCH3 produced 81% inhibition of platelet-derived growth factor-stimulated inositol phosphate formation and 66% inhibition of fluoroaluminate anion-stimulated inositol phosphate formation. Addition of ET-18-OCH3 to cells in medium with 10% fetal calf serum gave a transient increase in [Ca2+]i without causing an increase in resting [Ca2+]i, while the addition of ET-18-OCH3 to cells in medium without serum gave a sustained increase in resting [Ca2+]i. Cells exposed to 5 microM ET-18-OCH3 for 18 h showed no increase in resting [Ca2+]i but there was 95% inhibition of the [Ca2+]i response to platelet-derived growth factor, 63% inhibition of the response to bradykinin, and 55% inhibition of the response to vasopressin. The block by ether lipid analogues of inositol phosphate-mediated [Ca2+]i signaling suggests a mechanism for preventing the action of growth factors that could contribute to the inhibition of cell proliferation by the agents.
Involvement of p38 kinase in hydroxyurea-induced differentiation of K562 cells. (2001)

Hydroxyurea is a differentiation-inducing agent of human erythroleukemia K562 cells. However, the cellular mechanisms by which hydroxyurea exerts its effects on tumor cells, leading to the inhibition of cell growth and the induction of differentiation markers, are largely unknown. This study examined the role of different mitogen-activated protein kinase signal transduction pathways in hydroxyurea-induced erythroid differentiation of K562 cells. Using a panel of anti-extracellular signal-related kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 phosphospecific antibodies, we demonstrated that phosphorylation of ERK and JNK is decreased after the treatment of cells with hydroxyurea, whereas phosphorylation of p38 is increased. Moreover, inhibition of ERK activity by PD98059 induced erythroid differentiation, and it acted synergistically with hydroxyurea on hemoglobin synthesis, whereas inhibition of p38 activity by SB203580 inhibited induction of hemoglobin production by hydroxyurea. These findings suggest that the activation of p38 kinase may play important roles in the signal transduction mechanisms of hydroxyurea leading to erythroid differentiation.
Loss of Imprinting in Disease Progression in Chronic Myelogenous Leukemia (1998)

Abstract The pathophysiologic role of the Philadelphia chromosome translocation in chronic myelogenous leukemia (CML) has been known for nearly 20 years. However, the most significant morbidity and mortality in CML are caused by progression to blast crisis, about which comparatively little is known at the molecular level. Genomic imprinting is a chromosomal modification leading to parental-origin–specific gene expression in somatic cells. Recently, we and others have described loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to biallelic rather than monoallelic expression in a wide variety of solid tumors. We have now examined the imprinting status of IGF2 in samples from CML patients in stable phase, accelerated phase, and blast crisis. Five of six stable-phase patients showed normal imprinting, but LOI was found in all six cases of advanced disease (three accelerated phase, three blast crisis), which was statistically highly significant (P &lt; .01). Thus, LOI represents a novel type of genetic alteration in CML that appears to be specifically associated with disease progression.
Diastereoselective Synthesis of Hydantoin- and Isoxazoline-Substituted Dispirocyclobutanoids (2000)

Synthetic strategies for constructing novel achiral cyclobutanoid isoxazolidinoimidazolidinedione heterocycles, with a generalized structure of II, have been developed via 1,3-dipolar cycloaddition and carbanilide cyclization transformations from methylenecyclobutane 13. The exo methylene cyclobutane system has made the realization of some diasteroselectivity possible, such that the H-bond (Boc-NH) directed product (i.e., 14) was obtained with 3:1 selectivity relative to the non-H-bond directed product (i.e., 15).
GeminiII: a second generation layout validation program (2003)

Gemini is a program that is widely used to compare circuit layout against a specification. Extensions to Gemini that make it faster, enable it to isolate errors better, and extend its domain of application, are described. These improvements have been achieved by changes to the labeling algorithm, extensions to the local matching algorithm, better handling of symmetrical circuits, and the accommodation of series-connected transistors. GeminiII's algorithm is separated into global labeling and local matching phases. GeminiII dynamically switches between the two, depending on the amount of local structure contained in the circuit, taking advantage of the speed of the local matching algorithm when possible and relying on the power of the more general algorithm when the simple algorithm fails.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
State Estimation for Autonomous Flight in Cluttered Environments (2007)

Safe, autonomous operation in complex, cluttered environments is a critical challenge facing autonomous mobile systems. The research described in this paper was motivated by a particularly difficult example of autonomous mobility: flightofasmallunmannedaerialvehiclethroughaforest.Thefocuswasonenablingthethreecriticaltasks that comprise flight: 1) maintaining controlled flight while avoiding collisions (aviate); 2) flying from a known start location to a known goal location (navigate); and 3) providing information about the environment—a map—to a humanoperatororotherrobotsin the team(communicate).Presentedhere isasolution tothe problem ofestimating vehicle state (its position, orientation, and velocity) as well as the positions of obstacles or landmarks in the environment using only inertial measurements and bearings to landmarks. This is a highly nonlinear estimation problem, and standard estimation techniques such as the extended Kalman filter are prone to divergence in this application. In this paper asigma-point Kalman filter is implemented, resulting in anestimator which is ableto cope with the significant nonlinearities in the system equations and uncertainty in state estimates while remaining tractable for real-time operation. In addition, the issues of data association and landmark initialization are addressed. Estimator performance is examined through Monte Carlo simulations in two dimensions for scenarios involving unmanned aerial vehicle flight in cluttered environments. Simulations show that convergent, consistent estimates of vehicle state and obstacle positions can be obtained and that the estimates can be used by a trajectory planner to generate a path through a cluttered environment.