gebhart/patrepeval huggingface dataset:
Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism (2014)

In accordance with the prominent role of orexins in the maintenance of wakefulness via activation of orexin-1 (OX1R) and orexin-2 (OX2R) receptors, various dual OX1/2R antagonists have been shown to promote sleep in animals and humans. While selective blockade of OX2R seems to be sufficient to initiate and prolong sleep, the beneficial effect of additional inhibition of OX1R remains controversial. The relative contribution of OX1R and OX2R to the sleep effects induced by a dual OX1/2R antagonist was further investigated in the rat, and specifically on rapid eye movement (REM) sleep since a deficiency of the orexin system is associated with narcolepsy/cataplexy based on clinical and pre-clinical data. As expected, the dual OX1/2R antagonist SB-649868 was effective in promoting non-REM (NREM) and REM sleep following oral dosing (10 and 30 mg/kg) at the onset of the dark phase. However, a disruption of REM sleep was evidenced by a more pronounced reduction in the onset of REM as compared to NREM sleep, a marked enhancement of the REM/total sleep ratio, and the occurrence of a few episodes of direct wake to REM sleep transitions (REM intrusion). When administered subcutaneously, the OX2R antagonist JNJ-10397049 (10 mg/kg) increased NREM duration whereas the OX1R antagonist GSK-1059865 (10 mg/kg) did not alter sleep. REM sleep was not affected either by OX2R or OX1R blockade alone, but administration of the OX1R antagonist in combination with the OX2R antagonist induced a significant reduction in REM sleep latency and an increase in REM sleep duration at the expense of the time spent in NREM sleep. These results indicate that additional blockade of OX1R to OX2R antagonism elicits a dysregulation of REM sleep by shifting the balance in favor of REM sleep at the expense of NREM sleep that may increase the risk of adverse events. Translation of this hypothesis remains to be tested in the clinic.
A class of optimal broadband phased array geometries designed for easy construction (2002)

Very regular phased array geometries, with a high degree of periodicity, will have so-called grating lobes in their directivity pattern, when they are applied above a certain frequency. In connection with source location applications these grating lobes will introduce false spurious sources in the measured source maps. The grating lobes can be suppressed by removing the periodicities, typically by the use of random geometries. Large random arrays are, however, much more difficult to build and handle than more regular arrays. Both the support structure and the cabling are more complicated. The present paper describes a set of designs, which maintain to a very high degree the low sidelobe level of the random arrays, but which have a certain regularity that allows a much simpler support structure and cabling. The design procedure is outlined and the achieved performance is compared with that of comparable regular arrays.
A novel cleavage product of human complement component C3 with structural and functional properties of cobra venom factor. (1988)

The generation of two cleavage products of human C3, termed C3o and C3p, by incubation with a C3-cleaving protease isolated from cobra venom (Naja naja siamensis) is described. The venom protease removes the C3p fragment (Mr approximately 33,000) from the C3dg region of the C3 alpha-chain. The major cleavage fragment C3o (Mr approximately 140,000) contains the unaltered beta-chain of C3 and two alpha-chain-derived polypeptides of Mr approximately 29,000 and Mr approximately 38,000, respectively. Amino-terminal amino acids sequence analysis of C3p and the three chains of C3o allowed the identification of the exact location of the two alpha-chain-derived fragments of C3o and the three cleavage sites of the venom protease. The chain structure of C3o resembles those of C3c and cobra venom factor. In contrast to C3c but like cobra venom factor (and C3b), C3o was found to support the activation of the serine protease Factor B by cleavage in the presence of Factor D and Mg2+ into Bb and Ba, generating an enzymatically active complex that is able to cleave a fluorogenic peptide substrate for C3 convertases. Since the only stretch of amino acid residues of C3o not present in C3c is the carboxyl terminus of the Mr approximately 29,000 chain of C3o, it is suggested that this region is important for the interaction with Factor B and convertase formation.
NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry (2011)

Dynamic microtubules are important to maintain neuronal morphology and function, but whether neuronal activity affects the organization of dynamic microtubules is unknown. Here, we show that a protocol to induce NMDA-dependent long-term depression (LTD) rapidly attenuates microtubule dynamics in primary rat hippocampal neurons, removing the microtubule-binding protein EB3 from the growing microtubule plus-ends in dendrites. This effect requires the entry of calcium and is mediated by activation of NR2B-containing NMDA-type glutamate receptor. The rapid NMDA effect is followed by a second, more prolonged response, during which EB3 accumulates along MAP2-positive microtubule bundles in the dendritic shaft. MAP2 is both required and sufficient for this activity-dependent redistribution of EB3. Importantly, NMDA receptor activation suppresses microtubule entry in dendritic spines, whereas overexpression of EB3-GFP prevents NMDA-induced spine shrinkage. These results suggest that short-lasting and long-lasting changes in dendritic microtubule dynamics are important determinants for NMDA-induced LTD.
Transcriptional analysis of human survivin gene expression (1999)

The preservation of tissue and organ homoeostasis depends on the regulated expression of genes controlling apoptosis (programmed cell death). In this study, we have investigated the basal transcriptional requirements of the survivin gene, an IAP (inhibitor of apoptosis) prominently up-regulated in cancer. Analysis of the 5′ flanking region of the human survivin gene revealed the presence of a TATA-less promoter containing a canonical CpG island of ∼ 250 nt, three cell cycle dependent elements, one cell cycle homology region and numerous Sp1 sites. PCR-based analysis of human genomic DNA, digested with methylation-sensitive and -insensitive restriction enzymes, indicated that the CpG island was unmethylated in both normal and neoplastic tissues. Primer extension and S1 nuclease mapping of the human survivin gene identified two main transcription start sites at position -72 and within -57/-61 from the initiating ATG. Transfection of cervical carcinoma HeLa cells with truncated or nested survivin promoter-luciferase constructs revealed the presence of both enhancer and repressor sequences and identified a minimal promoter region within the proximal -230 nt of the human survivin gene. Unbiased mutagenesis analysis of the human survivin promoter revealed that targeting the Sp1 sequences at position -171 and -151 abolished basal transcriptional activity by ∼ 63-82%. Electrophoretic mobility-shift assay with DNA oligonucleotides confirmed formation of a DNA-protein complex between the survivin Sp1 sequences and HeLa cell extracts in a reaction abolished by mutagenesis of the survivin Sp1 sites. These findings identify the basal transcriptional requirements of survivin gene expression.
Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy (2014)

Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed "chemical antibodies." In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy.
Parol Modification and the Statute of Frauds: Fitting the Pieces Together under the Uniform Commercial Code (1999)

This comment explores, respectively, the history and purpose of the statute of frauds, the requirement of the Code's statute of frauds, the distinctions between sections 2-209(2) and 2-209(3), the faults in the majority application of section 2-209(3), the proposed application of section 2-209(3), and the benefits of the submitted application of section 2-209.
Molecular Cloning of Feline Interferon cDNA by Direct Expression (1992)

A cDNA sequence coding for feline interferon has been cloned for the first time by screening a cDNA library constructed using Okayama-Berg vector and mRNA derived from the feline cells (LSA-I) induced by TPA (12-o-tetradecanoylphorbor 13-acetate) for the ability of transient expression to produce feline interferon in COS1 monkey cells. The amino acid sequence, deduced from the nucleotide sequence by comparing it with the sequences of other mammalian IFNs, consists of 171 amino acids with 6 cysteins and an N-glycosylation site at the amino acid position 79, and has about 60% homology to human IFN alpha 1. The interferon was partially purified through Blue Sepharose, and its molecular weight was estimated to be 2.4 x 10(4). The antiviral activity was acid stable, and glycosylation was suggested.
Topical antioxidant application augments the effects of intense pulsed light therapy (2009)

The addition of polyphenolic antioxidants to an IPL regimen improved the clinical, biochemical, and histological changes seen following IPL treatment alone. These data support the use of multimodal therapy to create synergy and to optimize clinical outcomes in nonablative facial skin rejuvenation.
Generation of therapeutic immunoconjugates via Residue-Specific Conjugation Technology (RESPECT) utilizing a native cysteine in the light chain framework ofOryctolagus cuniculus (2017)

The conjugation of toxins, dyes, peptides, or proteins to monoclonal antibodies is often performed via free thiol groups generated by either partial reduction methods or engineering free cysteine residues into the antibody sequence. Antibodies from the rabbit Oryctolagus cuniculus have an additional intrachain disulfide bond, whereby the light chain variable kappa domain is bridged to the constant kappa region between cysteine residues at positions 80 and 171, respectively. Chimerization of rabbit antibodies with human constant domains allows for the generation of a free thiol group at the light chain position 80 (C80) that can be used for site-specific conjugation. An efficient process for the purification and simultaneous removal of cysteinylation at the C80 site was developed. The unpaired C80 was shown to be efficiently conjugated using several different maleimido-based ligands. REsidue SPEcific Conjugation Technology (RESPECT) antibody-drug conjugates prepared using rabbit-human chimeric anti-human mesothelin rabbit antibodies and maleimido-PEG<sub>2</sub>-auristatin conjugated to C80 were shown to be highly potent and specific in vitro and effective in vivo in reduction of tumor growth in a highly aggressive mesothelin-expressing xenograft tumor model.
GENETIC ORGANIZATION IN CAENORHABDITIS ELEGANS: FINE-STRUCTURE ANALYSIS OF THE unc-22 GENE (1979)

Fine-structure analysis of the unc-22 gene of Caenorhabditis elegans has revealed a number of sites that are separable by recombination. Eight new ethyl methanesulfonate-induced recessive mutations of the unc-22 gene have been isolated. Using these new alleles, as well as e66, a number of separable sites have been identified and positioned relative to one another. The map distances obtained are found to be comparable to those associated with intragenic recombination in Drosophila melanogaster, indicating that genetic fine-structure analysis is feasible in Caenorhabditis elegans. Evidence of possible gene conversion is presented. A preliminary estimate of the unc-22 gene size is 2.4 x 10(-2) map units.
Review article: novel therapeutic options for chronic hepatitis C (2008)

Many novel promising antihepatitis C virus agents are being developed, offering hope for future therapies that may target multiple points of the viral life cycle and/or host immune response. Newer approaches should ideally provide safe, effective and more tolerable therapy to all chronic hepatitis C virus patients.
Animal models of tremor (1999)

Animal models of tremor have been widely used in experimental neurology, because they are an indispensable requirement for understanding the pathophysiology of human tremor disorders and the development of new therapeutic agents. This review focuses on three approaches to produce tremor in animals (application of tremorgenic drugs, experimental central nervous system lesions, study of genetic mutants) and their use in simulating tremor syndromes of humans. Whereas harmaline induces a postural/kinetic tremor in animals that shares some features with human essential tremor/enhanced physiological tremor, MPTP tremor is the best model available for rest tremor in people. The tremor following experimental lesion of the ventromedial tegmentum in primates closely resembles Holmes tremor in humans, whereas cerebellar intention tremor is mimicked by cooling of the lateral cerebellar nuclei. The "campus syndrome," discovered in a breed of Pietrain pigs, might be a useful model of human orthostatic tremor. However, no animal model has yet been generated that exactly recreates all features of any of the known tremor disorders in humans. Problems encountered when comparing tremor in animals and humans include differing tremor frequencies and the uncertainty, if specific transmitter abnormalities/central nervous system lesions seen in animal tremor models are characteristic for their human counterparts. The search for adequate tremor models continues.
Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. (1985)

Endotoxin producing bacteria cause disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in man is still unclear. Impairment of the fibrinolytic system has been suggested as a contributing mechanism. A single injection of Escherichia coli lipopolysaccharide in rabbits resulted in a marked and prolonged increase of the levels of a fast-acting inhibitor of plasminogen activator (PA-inhibitor) in plasma (from 3.9 +/- 0.7 to 41 +/- 13.2 U/ml after 3 h). Gel filtration studies indicated that inhibition of human tissue-type plasminogen activator (t-PA) by rabbit plasma is accompanied by a change in the elution profile of the activator compatible with the formation of an enzyme-inhibitor complex with an apparent molecular weight of 100,000. Injection of human t-PA (1,500 IU/kg body wt) in endotoxin treated animals resulted in very fast inhibition of t-PA and formation of a similar complex. The half-life of circulating PA-inhibitor activity in rabbits was about 7 min as estimated by donor receiver plasma transfusion experiments. Stimulation of cultured human endothelial cells with endotoxin resulted in enhanced rate of accumulation of PA-inhibitor activity in the culture medium (two- to sevenfold increase). In five patients with septicemia, markedly increased levels of PA-inhibitor (14.3 +/- 15.5 U/ml) as compared with control subjects (1.3 +/- 0.7 U/ml) were observed in plasma. A very strong correlation (r = 0.98) was found between inhibition of t-PA and of urokinase in all conditions, suggesting that this fast-acting inhibitor reacts with both plasminogen activators. These data suggest that the appearance of this fast-acting PA-inhibitor is very sensitive to endotoxin stimulation. The marked increase in the level of PA-inhibitor in blood may contribute to the pathogenesis of DIC in septicemia.
Genetics of endometriosis. (2005)

The data obtained by such studies will allow to expand our knowledge on the pathogenesis of the disease and, more importantly, to develop individualized therapies and prevention strategies to apply at high-risk populations.
Inflammatory Mediators are Altered in the Acute Phase of Posttraumatic Complex Regional Pain Syndrome (2006)

Elevated IL-8 and sTNFR I/II levels indicate an association between CRPS I and an inflammatory process. Normal WBC, CRP, and IL-6 give evidence for localized inflammation. The hypothesis of neurogenic-induced inflammation mediated by neuropeptides is supported by elevated substance P levels.
A combination of HbA1c, fasting glucose and BMI is effective in screening for individuals at risk of future type 2 diabetes: OGTT is not needed (2006)

The combination of HbA1c, FPG and BMI are effective in screening for individuals at risk of future clinical diagnosis of type 2 diabetes. OGTT or FHD is not necessary.
A quantitative assessment of thread-level speculation techniques (2002)

Speculative thread-level parallelism has been recently proposed as an alternative source of parallelism that can boost the performance for applications where independent threads are hard to find. Several schemes to exploit thread level parallelism have been proposed and significant performance gains have been reported. However, the sources of the performance gains are poorly understood as well as the impact of some design choices. In this work, the advantages of different thread speculation techniques are analyzed as are the impact of some critical issues including the value predictor, the branch predictor, the thread initialization overhead and the connectivity among thread units.
GNA Trinucleotide Loop Sequences Producing Extraordinarily Stable DNA Minihairpins (1997)

d(GCGAAAGC) and d(GCGAAGC) fragments form extraordinarily stable DNA minihairpins containing only two G-C base pairs and a GAAA or GAA loop, respectively, with a Tm of 76 degrees C. These sequences are frequently found in some important regions such as replication origins and promoter regions for transcription. We examined all 64 possible DNA fragments, d(GCNNNGC), in which the triloop region of the d(GCGAAGC) minihairpin was randomized and found that only four fragments, d(GCGNAGC) (N = A, G, C, or T), formed extraordinarily stable minihairpins as shown by their gel mobility and resistance to a single-stranded DNA-specific exonuclease. Structural and thermodynamic analyses suggest that the extraordinary stability is caused by a unique structural property of the trinucleotide sequences corresponding to the GNA loop.
N-Alkylidenesulfinamides (1999)

Abstract This review covers the preparation and reactions of racemic and chiral N-alkylidene-sulfinamides or sulfinimines, based on a CA search. Racemic sulfinimines have been prepared by imine formation of sulfinamides with ketones (only ketones containing electron-withdrawing groups react), oxidation of N-akylidenesulfenamides, and rearrangement of N-chlorosulfoximines. The chiral compounds have been prepared by addition of organomagnesium or organolithium reagents or of diisobutylaluminium hydride to nitriles, followed by l-menthyl (S)-p-toluenesulfinate, displacement reactions of lithium hexamethyldisilazide with l-menthyl (S)-p-toluenesulfinate, followed by CsF and aldehydes, asymmetric oxidation of N-alkylidenesulfenamides, and reactions of l-menthyl imidic esters with p-toluenesulfinyl chloride. Thermal fragmentations, nucleophilic addition reactions (attack at imino carbon) of N-alkylidenesulfinamides with various nucleophiles, and 1,3-dipolar cycloadditions illustrate the versatility of this functional group in organic synthesis.
Fruit flies with additional expression of the elongation factor EF-1 alpha live longer. (1989)

In Drosophila melanogaster, the decrease in protein synthesis that accompanies aging is preceded by a decrease in elongation factor EF-1 alpha protein and mRNA. Here we show that Drosophila transformed with a P-element vector containing an EF-1 alpha gene under control of hsp70 regulatory sequences have a longer life-span than control flies.
Primary Cilia in Normal and Pathological Tissues (1995)

The medical literature in pathology contains a surprising number of anecdotal reports of primary cilia, with authors often expressing some incredulity at finding such organelles. In this update of an earlier review, I will argue that primary cilia should by now be regarded as regular cell organelles, not some form of atypical response to unusual circumstances. In all situations in which their presence is essential, they unquestionably act as sensory transducers. Detection by electron microscopy has been the most reliable means until recently, but is time-consuming and slow for any systematic investigation or experimental approach. Immunostaining with an antibody direct against detyrosinated tubulin is rapidly changing the situation, and we can now detect their presence, frequency, disposition and overall characteristics relatively quickly, allowing better statistical analysis and correlations in abnormal physiological and pathological conditions. To be useful and meaningful, comparative studies need a reliable database of information about primary cilia under 'normal' circumstances. It is hoped that such work will in itself give much further insight into the general significance of these organelles, especially combined with the more experimental approaches that can now be adopted in the study of their development and function, which looks increasingly promising with the new technological improvements.
Single longitudinal mode operation of two-section GaInAsP/InP lasers under pulsed excitation (1983)

Experimental and analytical results show single longitudinal mode operation of groove-coupled two-section GaInAsP/InP lasers during the initial turn-on transient. Optical outputs remain single mode (spurious down ≥10 dB) for temperature ranges <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sim \pm3\deg</tex> C. Laser thresholds and internal current densities are comparable to conventional devices without grooves. Analytical results characterizing the grooves, the below threshold coupled-resonator mode selection, and the complete dynamical buildup of laser energy are summarized. Waveguide scattering theory forms the basis for much of the analysis.
Glycopeptide antibiotics: A mechanism-based screen employing a bacterial cell wall receptor mimetic. (1986)

The evolution of a highly targeted screening program for the discovery of antibiotics of the glycopeptide (vancomycin) class is described. A holistic approach was utilized which optimized not just screening techniques but also the selection of candidate producer cultures and their growth under conditions which enhanced production of target compounds. Two screen techniques were utilized; differential inhibition of a vancomycin-resistant strain and its susceptible parent, and a specific antagonism screen using the reversal of glycopeptide activity by a tripeptide analog of the glycopeptide receptor, diacetyl-L-lysyl-D-alanyl-D-alanine. The latter screen was 2- to 32-fold more sensitive to known glycopeptides than the former, and was absolutely specific, yielding no false positive responses. The use of the tripeptide antagonism assay, combined with optimized culture selection and growth conditions yielded novel glycopeptide antibiotics at a rate of 1 per 320 cultures screened. With a holistic approach to screening and properly optimized techniques, large numbers of cultures do not need to be examined in order to discover novel antibiotics.