gebhart/patrepeval huggingface dataset:
Exploration of requirements for peptide binding to HLA DRB1*0101 and DRB1*0401. (1994)

The individual amino acid contacts responsible for peptide binding to DRB1*0101 and/or DRB1*0401 were defined using a quantitative binding assay. The differential contribution of each amino acid in two well studied T cell determinants, HA307-319 and RMBP 90-102, was delineated by comparing the IC50 values of analogues of varying length. This analysis confirmed the importance of a hydrophobic amino acid located near the amino-terminus for binding to both alleles and revealed that the contribution of the carboxyl-terminal amino acids differed between DRB1*0101 and DRB1*0401. Taking advantage of previous experiments demonstrating that all of the residues could be replaced with alanine, with the exception of the key hydrophobic amino acid, simplified analogues composed of polyalanines were used to prove 1) optimal binding depended on the position of the hydrophobic side chain relative to the amino- and carboxyl-termini; 2) aromatic amino acids were superior to aliphatic side chains at this position; and 3) a significant amount of free energy of binding arises from hydrogen bonding between the class II binding site and the amide bonds of the ligand. The role of each carbonyl and amide nitrogen was measured by assaying analogues containing reduced peptide bonds or N-methyl amino acids. Serine, but not glycine, could be used as a framework amino acid for peptide ligands, indicating that the beneficial aspects of these simplified structures was the combination of retaining the correct orientation of the peptide bonds, the restriction of the conformational freedom by limiting the possible phi/psi angles of the peptide, and avoidance of deleterious side-chain contacts. Collectively, these data were consistent with the peptide binding in a nonrepeating conformation with the vast majority of the free energy of binding arising from hydrogen bonds with the peptide backbone and a single, key hydrophobic side chain interacting in a conserved pocket in both DRB1*0101 and DRB1*0401.
Orders for New York (1989)

This novel, based on a true sequence of events in 1942, concerns a German submarine that came inshore at Long Island, New York disgorging Nazi spies into the city. Betrayed by their leader, six went to their deaths in the electric chair in Washington DC penitentiary within six weeks of landing.
Modern Perspectives in the Psychiatry of the Neuroses. Edited by John G. Howells New York: Brunner Mazel Inc. 1989. 400 pp. US$52.95. (1991)

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Nuclear Shape, Mechanics, and Mechanotransduction (2008)

In eukaryotic cells, the nucleus contains the genome and is the site of transcriptional regulation. The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell and from force generation within the cell. Here, we discuss the effect of intra- and extracellular forces on nuclear shape and structure and how these force-induced changes could be implicated in nuclear mechanotransduction, ie, force-induced changes in cell signaling and gene transcription. We review mechanical studies of the nucleus and nuclear structural proteins, such as lamins. Dramatic changes in nuclear shape, organization, and stiffness are seen in cells where lamin proteins are mutated or absent, as in genetically engineered mice, RNA interference studies, or human disease. We examine the different mechanical pathways from the force-responsive cytoskeleton to the nucleus. We also highlight studies that link changes in nuclear shape with cell function during developmental, physiological, and pathological modifications. Together, these studies suggest that the nucleus itself may play an important role in the response of the cell to force.
Purification and Characterization of the Primary Acrosomal Autoantigen of Guinea Pig Epididymal Spermatozoa1 (1988)

Previous studies showed that sperm auto- and alloantigens participate in guinea pig (GP) fertilization. In an effort to determine how alloantibodies to GP sperm acrosomal contents (AC) inhibit fertilization, we identified acrosomal auto- and alloantigens using Western blots. The predominant autoantigens migrated with Mr = 25,000, Mr = 51,000, and Mr = 55,000 under nonreducing conditions. The primary (Mr = 25,000) acrosomal autoantigen, AA1, was purified to homogeneity from AC by gel filtration, cation-exchange chromatography, chromatofocusing, and a final gel filtration. We also purified AA1 from an acidic glycerol extract of spermatozoa by gel filtration, chromatofocusing, and high-performance liquid chromatography on hydroxylapatite. AA1 is a protein and shares at least one antigenic determinant with a 51,000 Mr acrosomal component. AA1 is acrosome-specific, as determined by immunoabsorption and by indirect immunofluorescence on testicular cells. By quantitative enzyme-linked immunosorbent assay, AA1 comprises 6.4% of acrosomal protein in GP spermatozoa. On the basis of its physiochemical properties and localization, we conclude that AA1 is a unique sperm autoantigen. Surprisingly, several antibody preparations, including allo- and heteroantibodies with high anti-AA1 titers, did not inhibit fertilization in vitro. Thus, the mechanism by which alloantibodies to AC inhibit GP fertilization in vitro is not by binding to AA1.
Clues to the mechanism underlying dopamine cell death in Parkinson's disease. (1989)

The primary pathological change in Parkinson's disease is the destruction of dopamine containing cells in the zona compacta of substantia nigra. The cause of nigral cell death and the underlying mechanism remains elusive. However, the discovery of the selective nigral neurotoxin MPTP and its ability to inhibit mitochondrial energy metabolism via its metabolite MPP+ and to generate superoxide radicals suggests processes by which nigral cell death might occur. Recent postmortem evidence in brain tissue from patients dying with Parkinson's disease also suggests the occurrence of some on-going toxic mechanism. This may be a free radical process stimulated by an excess of iron within substantia nigra coupled to a generalised decrease in brain ferritin content. These data suggest altered iron handling occurs in Parkinson's disease which may lead to the generation of toxic oxygen species such as superoxide radicals. There is also evidence for an inhibition of mitochondrial function in the substantia nigra in patients with Parkinson's disease. So there may be a close association between the actions of the synthetic neurotoxin MPTP and the underlying cause of idiopathic Parkinson's disease.
Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening (2015)

Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency, and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn't affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses, and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications.
New Fundamentals in Hemostasis (2013)

Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and vascular repair. After wounding, the hemostatic system engages a plethora of vascular and extravascular receptors that act in concert with blood components to seal off the damage inflicted to the vasculature and the surrounding tissue. The first important component that contributes to hemostasis is the coagulation system, while the second important component starts with platelet activation, which not only contributes to the hemostatic plug, but also accelerates the coagulation system. Eventually, coagulation and platelet activation are switched off by blood-borne inhibitors and proteolytic feedback loops. This review summarizes new concepts of activation of proteases that regulate coagulation and anticoagulation, to give rise to transient thrombin generation and fibrin clot formation. It further speculates on the (patho)physiological roles of intra- and extravascular receptors that operate in response to these proteases. Furthermore, this review provides a new framework for understanding how signaling and adhesive interactions between endothelial cells, leukocytes, and platelets can regulate thrombus formation and modulate the coagulation process. Now that the key molecular players of coagulation and platelet activation have become clear, and their complex interactions with the vessel wall have been mapped out, we can also better speculate on the causes of thrombosis-related angiopathies.
Biologically active two-dimensional crystals of aquaporin CHIP. (1994)

Plasma membranes of several mammalian tissues are highly permeable to water due to the presence of CHIP, the 28-kDa channel-forming integral protein which is the archetypal member of the aquaporin family of water channel proteins. To define its native structure, purified red cell CHIP protein was reconstituted into lipid bilayers at a high protein-to-lipid ratio, and the resulting 3-microns diameter membrane vesicles were examined by high resolution electron microscopy. The reconstituted membranes contained highly ordered two-dimensional crystalline lattices of p422(1) symmetry in which each CHIP tetramer contained a central depression extending from the outer and inner surfaces of the membrane into the transbilayer domain of the molecule. The reconstituted membranes also exhibited extremely high osmotic water permeability, Pf = 0.472 cm/s, corresponding to the sum of activities of all incorporated CHIP molecules. These studies report the first two-dimensional crystallization of a biologically active water channel and provide direct evidence of the structure responsible for its pore-like behavior.
Second-order statistical properties of nonlinearly distorted phase-shift keyed (PSK) signals (2003)

In wireless communication systems operation of the amplifiers near saturation is often required for efficiency reasons, resulting in a nonlinearly distorted signal at the amplifier output. A popular model for the corresponding baseband equivalent nonlinear channel is a truncated Volterra series. By exploiting the bandpass nature of the channel and the statistical properties of phase-shift keyed signals, we show that the different terms in the Volterra series are white and uncorrelated with each other. This result is useful when considering blind equalization approaches for this class of systems.
Computer modeling of substrate binding to lipases from Rhizomucor miehei, Humicola lanuginosa, and Candida rugosa (1994)

The substrate-binding sites of the triacyl glyceride lipases from Rhizomucor miehei, Humicola lanuginosa, and Candida rugosa were studied by means of computer modeling methods. The space around the active site was mapped by different probes. These calculations suggested 2 separate regions within the binding site. One region showed high affinity for aliphatic groups, whereas the other region was hydrophilic. The aliphatic site should be a binding cavity for fatty acid chains. Water molecules are required for the hydrolysis of the acyl enzyme, but are probably not readily accessible in the hydrophobic interface, in which lipases are acting. Therefore, the hydrophilic site should be important for the hydrolytic activity of the enzyme. Lipases from R. miehei and H. lanuginosa are excellent catalysts for enantioselective resolutions of many secondary alcohols. We used molecular mechanics and dynamics calculations of enzyme-substrate transition-state complexes, which provided information about molecular interactions important for the enantioselectivities of these reactions.
Effects of Tumbling Trauma, Scalding and Hemorrhage on Rat Tissue Non-Protein Sulfhydryl. (1954)

1. Significant decreases in concentration of non-protein -SH were noted in rat liver following tumbling trauma, and in rat liver and kidney following severe scalding. 2. In analyses confined to the liver, a significant decrease in liver non-protein -SH was noted following severe hemorrhage. No appreciable change was noted in either liver protein -SH or extractable liver protein. 3. Blood non-protein -SH concentrations were practically identical for control and tumbled rats. Scalded rats exhibited a moderate increase in concentration of blood non-protein -SH, paralleling the hemoconcentration.
Peak Reduction of Multi-Carrier Systems by Controlled Spectral Outgrowth (2006)

One of the major drawbacks with multi-carrier (MC) modulations is the large peak-to-average power ratio (PAPR) of the transmitted signal which significantly reduces the power amplifier efficiency and the system performance. Several PAPR reducing methods which do not decrease the system performance have been proposed. In this paper, we present a new low complexity PAPR reduction technique based on the controlled spectral outgrowth (CSO) of the nearby subcarriers which neither requires the transmission of additional information nor reduces the system performance and is independent of the mapping scheme. The proposed method can be easily combined with most of the methods in the literature to provide a further peak reduction in any MC or MC spread spectrum (MC-SS) system. An analog PAPR reduction about 2.5 dB at 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-4</sup> symbol clip probability and a power increase about 0.12 dB are obtained for a 256-subcarrier of OFDM transmission
tris(2-Carboxyethyl)phosphine (TCEP) for the Reduction of Sulfoxides, Sulfonylchlorides,N-Oxides, and Azides (2003)

Click to increase image sizeClick to decrease image size Acknowledgments The authors thank Kimberley Thompson and Pierre Lavallée for useful advice.
Enhancement of seed oil content by expression of glycerol-3-phosphate acyltransferase genes (2000)

Arabidopsis thaliana was transformed with a plastidial safflower glycerol-3-phosphate acyltransferase (GPAT) and an Escherichia coli GPAT. The genes were used directly and in modified forms with, as applicable, the plastidial targeting sequence removed, and with an endoplasmic reticulum targeting sequence added. Seeds of plants transformed using only the vector were indistinguishable in oil content from wild-type control plants. All other gene constructs increased seed oil content. The unmodified safflower gene (spgpat) produced oil increases ranging from 10 to 21%. On average, the greatest increase (+22%) was observed in seeds of transformants carrying the spgpat with the targeting peptide removed. The E. coli plsB gene increased seed oil content by an average of 15%.
Neurophysiological mechanisms underlying face processing within and beyond the temporal cortical visual areas (1992)

The ways in which information about faces is represented and stored in the temporal lobe visual areas of primates, as shown by recordings from single neurons in macaques, are considered. Some neurons that respond primarily to faces are found in the cortex in the anterior part of the superior temporal sulcus (in which neurons are especially likely to be tuned to facial expression and to face movement involved in gesture), and in the TE areas more ventrally forming the inferior temporal gyrus (in which neurons are more likely to have responses related to the identity of faces). Quantitative studies of the responses of the neurons that respond differently to the faces of different individuals show that information about the identity of the individual is represented by the responses of a population of neurons, that is, ensemble encoding rather than 'grandmother cell' encoding is used. It is argued that this type of tuning is a delicate compromise between very fine tuning, which has the advantage of low interference in neuronal network operations but the disadvantage of losing the useful properties (such as generalization, completion and graceful degradation) of storage in neuronal networks, and broad tuning, which has the advantage of allowing these properties of neuronal networks to be realized but the disadvantage of leading to interference between the different memories stored in an associative network. There is evidence that the responses of some of these neurons are altered by experience so that new stimuli become incorporated in the network. It is shown that the representation that is built in temporal cortical areas shows considerable invariance for size, contrast, spatial frequency and translation. Thus the representation is in a form which is particularly useful for storage and as an output from the visual system. It is also shown that one of the representations that is built is object based, which is suitable for recognition and as an input to associative memory, and that another is viewer centred, which is appropriate for conveying information about gesture. Ways are considered in which such cortical representations might be built by competitive self-organization aided by back projections in the multi-stage cortical processing hierarchy which has convergence from stage to stage.
Identification of a family of Fc receptor homologs with preferential B cell expression (2001)

Investigation of human genome sequences with a consensus sequence derived from receptors for the Fc region of Igs (FcR) led to the identification of a subfamily of five Ig superfamily members that we term the Fc receptor homologs (FcRHs). The closely linked FcRH genes are located in a chromosome 1q21 region in the midst of previously recognized FcR genes. This report focuses on the FcRH1, FcRH2, and FcRH3 members of this gene family. Their cDNAs encode type I transmembrane glycoproteins with 3-6 Ig-like extracellular domains and cytoplasmic domains containing consensus immunoreceptor tyrosine-based activating and/or inhibitory signaling motifs. The five FcRH genes are structurally related, and their protein products share 28-60% extracellular identity with each other. They also share 15-31% identity with their closest FcR relatives. The FcRH genes are expressed primarily, although not exclusively, by mature B lineage cells. Their conserved structural features, patterns of cellular expression, and the inhibitory and activating signaling potential of their transmembrane protein products suggest that the members of this FcRH multigene family may serve important regulatory roles in normal and neoplastic B cell development.
Combining Different Hydrogen-Bonding Motifs To Self-Assemble Interwoven Superstructures (1998)

Two recognition motifs are better than one for the noncovalent synthesis of elaborate supramolecular architectures. We have created a range of multiply encircled supermolecules and interwoven arrays such as those on the right, principally using a combination of two different recognition motifs, the threading of dibenzylammonium cations (black bars) through the cavities of macrocyclic polyethers (open quadrilaterals) to form pseudorotaxanes, and carboxyl dimerization (gray).
A test battery of bacterial toxicity assays and comparison with LD50 values (1989)

Abstract The toxicity of some mycotoxins, lactones and dicarboxylic anhydrides, insecticides, herbicides, and fungicides can be detected by means of bacterial assays. In addition, the order of magnitude of the toxicity can also be evaluated. Fifty‐eight chemicals as well as extracts of peanuts, apple juices, and grains have been investigated in a test battery of three different kinds of assays. In cup plate diffusion assays a minimal amount of approximately 0. 1 mg/mL of mycotoxin may be detected by means of growth inhibition assays with Bacillus thuringiensis on one hand, and pigment synthesis inhibition assays with mutants of Serratia marcescens on the other hand. Swarming inhibition assays with the motile strains Azospirillum brasilense and Proteus mirabilis show the same sensitivity. Comparisons of our test battery with other bioassays, as well as with mammalian toxicity tests (LD 50 values), reveal correlations between these kinds of assays in regard to the test substances.
Outcome predictors and quality of life of severe burn patients admitted to intensive care unit (2010)

In severe burn patients, Baux index, severity of illness on admission to the ICU, complications, and time of first burn wound excision were the major contributors to hospital mortality. Quality of life was influenced by consequences of injury both in psychological and physical health.
GDKV-Induced Antiphospholipid Antibodies Enhance Thrombosis and Activate Endothelial Cells In Vivo and In Vitro (1999)

Antiphospholipid (aPL) Abs are associated with thrombosis, pregnancy loss, and thrombocytopenia in patients with systemic lupus erythematosus or primary antiphospholipid syndrome (APS). beta2-Glycoprotein I (beta2GPI), a phospholipid-binding serum protein, is involved in aPL binding to phospholipids. aPL can be generated in mice by immunization with beta2GPI, and these Abs are thrombogenic and cause pregnancy loss in mice. The objective of this study is to determine whether aPL induced by immunization with the phospholipid-binding site of beta2GPI are thrombogenic and whether they activate endothelial cells (EC) in vivo and in vitro. Murine monoclonal aPL were generated from spleen cells of a mouse immunized with GDKV, a synthetic 15-aa peptide spanning Gly274-Cys288 in the fifth domain of human beta2GPI, which represents the phospholipid-binding site of beta2GPI. The Abs generated had aPL and anti-beta2GPI activities. The effect of these Abs on thrombus formation and on EC activation in vivo was determined using a mouse model of thrombosis and microcirculation that enables examination of the adhesion of leukocyte to EC as an indication of EC activation as well as adhesion molecule expression using in vitro ELISA analysis. Mice injected with this monoclonal aPL showed a significant increase in leukocyte sticking and also produced larger thrombi that persisted longer. Exposure to GDKV-induced aPL for 4 h significantly increased surface Ag expression of E-selectin, ICAM-1, and VCAM-1. These data indicate that aPL induced by immunization with the phospholipid binding site of beta2GPI are thrombogenic and activate endothelial cells.