gebhart/patrepeval huggingface dataset:
Structural Requirements for Binding of Anandamide-Type Compounds to the Brain Cannabinoid Receptor (1997)

In order to establish the structural requirements for binding to the brain cannabinoid receptor (CB1), we have synthesized numerous fatty acid amides, ethanolamides, and some related simple derivatives and have determined their Ki values. A few alpha-methyl- or alpha, alpha-dimethylarachidonoylalkylamides were also examined. In the 20:4, n-6 series, the unsubstituted amide is inactive; N-monoalkylation, at least up to a branched pentyl group, leads to significant binding. N,N-Dialkylation, with or without hydroxylation on one of the alkyl groups, leads to elimination of activity. Hydroxylation of the N-monoalkyl group at the omega carbon atom retains activity. In the 20x, n-6 series, x has to be either 3 or 4; the presence of only two double bonds leads to inactivation. In the n-3 series, the limited data reported suggest that the derived ethanolamides are either inactive or less active than comparable compounds in the n-6 series. Alkylation or dialkylation of the alpha carbon adjacent to the carbonyl group retains the level of binding in the case of anandamide (compounds 48, 49); however, alpha-monomethylation or alpha,alpha-dimethylation of N-propyl derivatives (50-53) potentiates binding and leads to the most active compounds seen in the present work (Ki values of 6.9 +/- 0.7 to 8.4 +/- 1.1 nM). We have confirmed that the presence of a chiral center on the N-alkyl substituent may lead to enantiomers which differ in their levels of binding (compounds 54, 57 and 55, 56).
Role of KATP channels in protection against neuronal excitatory insults (2007)

ATP-sensitive K(+) (K(ATP)) channels that are gated by intracellular ATP/ADP concentrations are a unique subtype of potassium channels and play an essential role in coupling intracellular metabolic events to electrical activity. Opening of K(ATP) channels during energy deficits in the CNS induces efflux of potassium ions and in turn hyperpolarizes neurons. Thus, activation of K(ATP) channels is thought to be able to counteract excitatory insults and protect against neuronal death. In this review, we bring together recent studies about what kinds of molecules are needed to build and regulate arrays of K(ATP) channel functions in the CNS neurons. We propose a model to explain how K(ATP) channel activation regulates glutamate release from the pre-synaptic terminals and how this regulation protects against ischemic neuronal injury and epilepsy.
P.50: Design of a Novel Hybrid Light Guide Plate for Viewing Angle Switchable Backlight Module (2013)

Abstract We introduce a viewing angle switchable backlight module, which consists of a hybrid light guide plate and dual‐light sources on the same layer. Comparing with the conventional backlight module, the on‐axis luminance of the narrow viewing angle improved 4.9‐times and the half‐luminance angle decreased 11 degrees in the horizontal direction. When using the wide viewing angle mode, the on‐axis luminance improved 2‐times and the half‐luminance angle improved 56 degrees in the horizontal direction.
Growth Hormone Mitigates against Lethal Irradiation and Enhances Hematologic and Immune Recovery in Mice and Nonhuman Primates (2010)

Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 microg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure.
Hybrid antibodies with dual specificity for the delivery of ricin to immunoglobulin-bearing target cells. (1981)

Hybrid antibodies possessing one binding site for the toxic lectin ricin and a companion site directed against human immunoglobulin were constructed in vitro. This bifunctional reagent specifically attached to human lymphocyte surface immunoglobulin determinants and, thus situated, could simultaneously capture ricin molecules or its toxic A chain. Attachment of these components to the cell was revealed by specific fluorescein-labeled antibodies. Once concentrated at the target cell membrane, hybrid-bound toxin was subsequently released to function via its normal mechanism of biological action. It gained access to ribosomes, its intracellular target, and curtailed protein synthesis. Toxicity was not augmented for immunoglobulin-negative cells to which hybrid could not bind and free human immunoglobulin G could competitively block the enhanced effects observed for immunoglobulin-bearing cell lines. These results indicate that hybrid antibodies may be utilized to carry active agents within close proximity to the membrane of a specified cell type and thereby selectively enhance their effect.
Nrf2 is required to maintain the self-renewal of glioma stem cells (2013)

Nrf2 is required to maintain the self-renewal of GSCs, and its down-regulation can attenuate the self-renewal of GSCs significantly.
Novel algorithmic countermeasures for Differential Power Analysis attacks on smart cards (2010)

Differential Power Analysis (DPA) attacks extract the secret key of cryptographic algorithm, by analyzing the power dissipation of the smart card during the execution of the computation. Cryptosystems such as DES, the AES and public-key cryptosystems are easily perceptive to the DPA attacks. Several techniques can be used to prevent differential power analysis attacks. One method is to design algorithms that have a constant execution path, and use operations that have little variation in their power usage. In this paper we are proposing algorithmic countermeasures for differential power analysis attacks on smart cards. The proposed countermeasure is to induce a new smart card system that is not cryptosystem. The new technique, namely stegnosystem, relies on using stegnography instead of cryptography. The user has to provide her password which is compared to the password hidden in the smart card memory. The hidden password is retrieved by deciphering the stegnography key stored in the smart card. DPA attacks can measure power dissipation that leaks during deciphering the stegnography key, thus gain knowledge of the location where the password is hidden but it can't gain any information of the actual password without the actual possession of the smart card.
Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion (2009)

This study reveals the de novo generation of fatty acid nitration products in vivo and reveals the anti-inflammatory and potential therapeutic actions of OA-NO(2) in myocardial I/R injury.
Dispensable role of the human immunodeficiency virus type 2 Vpx protein in viral replication (1991)

Human immunodeficiency virus type 2 (HIV-2) is similar in genetic organization to HIV-1 but contains a unique gene (vpx) that encodes a 16-kDa protein. A replication-competent molecular clone of HIV-2 (HIV-2sbl/isy) that infects human primary cells in vitro and rhesus monkeys was used to generate three mutations in the vpx gene. In the first mutant, the vpx open reading frame was truncated at amino acid 20; the second mutant was tailored to eliminate the proline-rich carboxyl terminus of the protein; and the third mutant was obtained by addition of four amino acids (KDEL) to the carboxyl terminus of the protein to provide a retention signal in the endoplasmic reticulum. The viral infection kinetics of the three mutant viruses and isogeneic HIV-2sbl/isy in the SupT1 cell line were similar. Slight impairment in the early phases of viral replication was observed during infection of primary human peripheral blood mononuclear cells with the vpx mutant viruses. All of the vpx mutant viruses readily infected macrophages, indicating that vpx expression is dispensable for HIV-2 infection and replication in human macrophages.
Bioavailability of Oral Melatonin in Humans (1984)

We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (ka) of 1.72 h-1 (half-life = 0.40 h) and an elimination constant (ke1) of 0.87 h-1 (half-life = 0.80 h). Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60-150 min after its administration, remaining stable for approximately 1.5 h. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. This regimen extended the duration of elevated serum melatonin levels to 4-6 h. Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormone's administration, after which urinary levels tended to be higher than those predicted from serum levels. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonin's administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.
Modeling the lifetime costs of rheumatoid arthritis. (1999)

These data suggest that interventions such as autologous bone marrow transplantation, which has recently been estimated to cost roughly $60,000, may be cost saving if they eliminate the downstream incremental costs of RA.
Low temperature Si layer splitting (2002)

Wafer bonding opens up new design possibilities for the fabrication of various single crystalline semiconductor on insulator (SOI) materials. SOI has been realized by layer splitting ("smart-cut"). However, except in the cases where only a small difference in the thermal expansion coefficients between the Si and the substrates is present, other SOI material combinations usually suffer from excessive thermal stresses due to thermal mismatch between the Si and the dissimilar substrates during annealing before layer splitting. For SOQ (Si on Quartz), at room temperature the thermal expansion coefficient of Si is 2.56/spl times/10/sup -6///spl deg/C while that of synthetic quartz is only 0.5/spl times/10/sup -6///spl deg/C. A bonded 4" standard Si/quartz pair (both of /spl sim/525 /spl mu/m in thickness), will typically crack at /spl sim/180/spl deg/C. Since the splitting temperature in the smart-cut process exceeds 500/spl deg/C, the Si wafer in the Si/quartz pair has to be thinned down sufficiently (<150 /spl mu/m) to avoid cracking of the bonded pair during the Si layer splitting. However, a main advantage offered by the smart cut method is lost, namely that extensive lapping and etching to remove most of the substrate is avoided and the substrate from which the Si layer is transferred can be reused. In order to preserve these advantages a smarter-cut approach which employes a low temperature Si layer splitting technology is described.
Prostate Specific Antigen Recurrence After Definitive Therapy (2007)

Prostate specific antigen-only recurrence is the most common form of advanced prostate cancer. Optimal salvage treatments and timing of these treatments remain controversial.
The Effects of Varying Safety Conditions on the External Costs of Driving (1994)

In the past two decades, many studies have evaluated the effects of automobile or road safety conditions on driver behavior. The focus of most of these investigations has been the 'offsetting behavior' (or 'risk compensation') hypothesis, which predicts that drivers offset exogenous improvements in safety conditions by driving less safely. Generally, these studies have attempted to measure the degree to which this offsetting response might (or might not) negate the effect of mandated safety improvements in automobiles. Although the empirical evidence is not uniform, most analyses suggest that the net effect of the regulations on overall highway safety is positive, but less than predicted by traffic safety engineers (whose estimates do not allow for the behavioral modifications by drivers). Also, empirical evidence indicates that non-beneficiaries of automobile safety regulations, such as pedestrians, motor­ cyclists, and bicyclists are at greater risk. This paper extends the discussion of compensating behavior by evaluating the effects of such behavior on accident costs. In particular, I evaluate how exogenous changes in the safety level of the driving environment (road conditions, weather, etc.) affect the relative losses suffered by the party at fault and other involved parties. In so doing, the analysis augments previous studies by evaluating the influence of offsetting driver behavior on the distribution of accident costs among victims. The estimates presented here lend support to the hypothesis that improvements in the safety level of driving conditions reduce internal more than external accident costs.
Leptin Receptor Long-form Splice-variant Protein Expression in Neuron Cell Bodies of the Brain and Co-localization with Neuropeptide Y mRNA in the Arcuate Nucleus (1999)

Reduced leptin (Ob protein) signaling is proposed to be a stimulus for the activation of neuropeptide Y (NPY) gene activity and increased expression of mRNA for the long form of the leptin receptor (Ob-Rb) in the hypothalamic arcuate nucleus. To determine if Ob-Rb protein is expressed in arcuate nucleus NPY neurons, we developed an affinity-purified polyclonal antibody against amino acids 956-1102 of human Ob-Rb. This antibody specifically recognizes the cytoplasmic tail of Ob-Rb and does not react with shorter leptin-receptor variants. Western immunoblots of Ob-Rb-transfected COS cells showed a single 150-kD band, and immunofluorescence revealed intense perinuclear staining in the cytoplasm. A 150-kD band was also present in Western immunoblots of hypothalamus. Immunocytochemical staining of brain slices revealed immunoreactive Ob-Rb protein concentrated in many neuronal cell bodies in the same regions of the forebrain that also express Ob-Rb mRNA. In the hypothalamus, Ob-Rb-positive cell bodies were abundant in the arcuate nucleus and ventromedial nucleus, with lesser numbers in the dorsomedial nucleus and paraventricular nucleus. Immunostaining was also detected in cell bodies of pyramidal cell neurons of the pyriform cortex and cerebral cortex, in neurons of the thalamus, and on the surface of ependymal cells lining the third ventricle. The choroid plexus, which expresses the short Ob-Ra form, was negative. Combined immunocytochemistry for Ob-Rb protein and fluorescence in situ hybridization for NPY mRNA identified arcuate nucleus neurons containing both NPY mRNA and Ob-Rb protein. The present finding of Ob-Rb protein in neurons that express NPY mRNA supports the hypothesis that arcuate nucleus NPY neurons are direct targets of leptin and play an important role in regulation of food intake and body weight.
Influence of Habit Modifiers on Particle Shape in a Crystallization Process [Translated]<sup>†</sup> (2006)

For crystallization in solution, the method of changing particle shape by adding the impurities called habit modifiers has been attracted attention as a fabrication process of functional particles. The method is complicated due to many controlling parameters, such as supersaturation, concentration, kinds of impurities, etc. It needs to clarify the mechanism of crystal growth for the control of crystal shape. Therefore, the influence of impurities on crystal growth has been examined by experiments and simulations. In the experiment, the technique by differential scanning calorimeter (DSC) was used for measuring the properties of clusters with changing the habit modifiers. In adding habit modifiers, the number of clusters increased. The formation of clusters was investigated by molecular dynamics (MD) simulation. This simulation result agreed with the experiment result and then the formation of clusters which assembled remarkably around impurities was demonstrated by simulation.† This report was originally printed in J. Soc. Powder Technology, Japan, 41, 431-439(2004) before being translated into English by KONA Editorial Committee with the permission of the editorial committee of the Soc. Powder Technology, Japan.
4‘-O-[2-(2-Fluoromalonyl)]-l-tyrosine:  A Phosphotyrosyl Mimic for the Preparation of Signal Transduction Inhibitory Peptides (1996)

Development of phosphotyrosyl (pTyr) mimetics which are stable to protein-tyrosine phosphatases (PTPs), yet can retain biological potency when incorporated into peptides, is an active area of drug development. Since a majority of pTyr mimetics derive their "phosphofunctionality" from phosphorus-containing moieties, such as phosphonates, evolution of new inhibitors and modes of prodrug derivatization have been restricted to chemistries appropriate for phosphorus-containing moieties. A new, nonphosphorus-containing pTyr mimetic has recently been reported, L-O-(2-malonyl)tyrosine (OMT,5), which can be incorporated into peptides that exhibit good PTP and Src homology 2 (SH2) domain inhibitory potency. For phosphonate-based pTyr mimetics such as phosphonomethyl phenylalanine (Pmp,2) introduction of fluorines alpha to the phosphorus has provided higher affinity pTyr mimetics. This strategy has now been applied to OMT, and herein is reported 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine (FOMT,6) a new fluorine-containing nonphosphorus pTyr mimetic. Incorporation of FOMT into appropriate peptides results in good inhibition of both PTP and SH2 domains. In an assay measuring the inhibition of PTP 1B-mediated dephosphorylation of phosphorylated insulin receptor, the peptide Ac-D-A-D-E-X-L-amide exhibited a 10-fold enhancement in inhibitory potency for X = FOMT (19) (IC(50) = 10 microM) relative to the unfluorinated peptide, X = OMT (18) (IC(50) = 10 microM. Molecular modeling indicated that this increased affinity may be attributable to new hydrogen-bonding interactions between the fluorine and the enzyme catalytic site, and not due to lowering of pKa values. In a competition binding assay using the p85 PI 3-kinase C-terminal SH2 domain GST fusion construct, the inhibitory peptide, Ac-D-X-V-P-M-L-amide, showed no enhancement of inhibitory potency for X = FOMT (22) (IC(50) = 18 microM) relative to the unfluorinated peptide, X = OMT (21) (IC(50) = 14 microM). The use of FOMT would therefore appear to have particular potential for the development of PTP inhibitors.
Multiple genetically modified GTKO/hCD46/HLA‐E/hβ2−mg porcine hearts are protected from complement activation and natural killer cell infiltration during ex vivo perfusion with human blood (2018)

GTKO, hCD46, and HLA-E expression in porcine hearts reduced complement deposition, complement dependent injury, and myocardial NK cell infiltration during perfusion with human blood. This tested combination of genetic modifications may minimize damage from acute human-anti-pig rejection reactions and improve myocardial function after xenotransplantation.
Highly efficient phase locking and extracavity coherent combination of two diode-pumped Nd:YAG laser beams (1996)

Intracavity phase locking and extracavity combination of the two emitted beams generated by a Nd:YAG laser longitudinally pumped by two fiber-coupled diode lasers are investigated. Phase locking is performed by a diffractive component located inside a confocal Fabry-Perot resonator. The coherent addition of the two synchronized beams in a single TEM(00) wave is made by a birefringent interferometer, with 96.8% energy yield. 610-mW output power was obtained in a single-lobed beam profile with 30.5% optical-to-optical conversion efficiency in the continuous-wave regime.
Analysis of the mouse proteome. (I) Brain proteins: Separation by two-dimensional electrophoresis and identification by mass spectrometry and genetic variation (1999)

The total protein of the mouse brain was fractionated into three fractions, supernatant, pellet extract and rest pellet suspension, by a procedure that avoids any loss of groups or classes of proteins. The supernatant proteins were resolved to a maximum by large-gel two-dimensional electrophoresis. Two-dimensional patterns from ten individual mice of the commonly used inbred strain C57BL/6 (species: Mus musculus) were prepared. The master pattern was subjected to densitometry, computer-assisted image analysis and treatment with our spot detection program. The resulting two-dimensional pattern, a standard pattern for mouse brain supernatant proteins, was divided into 40 squares, calibrated, and specified by providing each spot with a number. The complete pattern and each of the 40 squares are shown in our homepage (http://www.charite.de/ humangenetik). The standard pattern comprises 8767 protein spots. To identify the proteins known so far in the brain fraction investigated, a first set of 200 spots was analyzed by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) after in-gel digestion. By screening protein databases 115 spots were identified; by extending the analysis to selected, genetically variant protein spots, 166 spots (including some spot series) were identified in total. This number was increased to 331 by adding protein spots identified indirectly by a genetic approach. By comparing the two-dimensional patterns from C57BL/6 mice with those of another mouse species (Mus spretus), more than 1000 genetically variant spots were detected. The genetic analysis allowed us to recognize spot families, i.e., protein spots that represent the same protein but that are post-translationally modified. If some members of the family were identified, the whole family was considered as being identified. Spot families were investigated in more detail, and interpreted as the result of protein modification or degradation. Genetic analysis led to the interesting finding that the size of spot families, i.e., the extent of modification or degradation of a protein, can be genetically determined. The investigation presented is a first step towards a systematic analysis of the proteome of the mouse. Proteome analysis was shown to become more efficient, and, at the same time, linked to the genome, by combining protein analytical and genetic methods.