gebhart/patrepeval huggingface dataset:
N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of dextromethorphan in rats (1993)

The present study examined whether the antitussive agent dextromethorphan, which is an antagonist at the N-methyl-D-aspartate (NMDA) receptor, depresses spinal reflexes in rats. Injection of both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and of dextromethorphan dose-dependently reduced the magnitude of the polysynaptic flexor reflex without affecting the monosynaptic H-reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of dextromethorphan on the flexor reflex was prevented by co-administration with NMDA but not with the non-NMDA agonist alpha-amino-3-hydroxy-5-terthyl-4-isoxazole-propionic acid. These data suggest that dextromethorphan exerts a muscle relaxant action via the NMDA receptor.
Robust Endpoint Detection for Speech Recognition Based on Discriminative Feature Extraction (2006)

Accurate endpoint detection is important for improving the speech recognition capability. This paper proposes a novel endpoint detection method which combines energy-based and likelihood ratio-based voice activity detection (VAD) criteria, where the likelihood ratio is calculated with speech/non-speech Gaussian mixture models (GMMs). Moreover, the proposed method introduces the discriminative feature extraction technique (DFE) in order to improve the speech/non-speech classification. The DFE is used in the training of parameters required for calculating the likelihood ratio. Experimental results have shown that the proposed endpointer achieves good performance compared to an energy-based endpointer in terms of start-of-speech (SOS) and end-of-speech (EOS) detections. Due to the improvement of the endpointer, the performance of automatic speech recognition (ASR) has also been improved.
A hypothesis on the pathophysiological mechanisms that underlie levodopa‐ or dopamine agonist‐induced dyskinesia in Parkinson's disease: Implications for future strategies in treatment (1990)

Long-term treatment of human Parkinson's disease with levodopa or dopamine agonists is often complicated by the appearance of abnormal involuntary movements (dyskinesias) that are extremely difficult to control. Little is known of the cause, pathophysiological mechanisms, or possible strategies for amelioration of this manifestation of dyskinesia. A hypothesis is set forth on the neural mechanisms that mediate levodopa- or dopamine agonist-induced dyskinesia (in particular chorea) as a side effect of the treatment of parkinsonism. Evidence is drawn from both clinical observations and experimental studies in a spectrum of movement disorders ranging from ballism through chorea to parkinsonism. It is proposed that (a) All forms of chorea, whatever their origin, share a common underlying neural mechanism. (b) Disordered activity of the subthalamic nucleus is central to the generation of choreic movements. In levodopa- or dopamine agonist-induced dyskinesia, (c) The site of action of dopaminergic agents in causing chorea is the putamen. (d) The specific pathophysiological state conducive to the appearance of chorea is brought about by the long-term exposure of the dopamine-depleted (parkinsonian) putamen to exogenous dopaminergic agents. (e) Long-term exposure to dopaminergic agents causes (either directly or indirectly) preferential inhibition of the subpopulation of putaminal neurones that project specifically to the lateral segment of the globus pallidus. This causes disinhibition of lateral pallidal neurones, which become overactive and physiologically inhibit the subthalamic nucleus. (f) The hypothesis suggests a number of possible strategies that might be useful for the alleviation of levodopa-induced dyskinesia.
Acoustic Sensor for Voice with Embedded Physiology (1999)

Abstract : The Army Research Laboratory (ARL) is developing sensor technology to monitor the soldier's voice and physiology by using enhanced acoustic sensors. The physiological sensor consists of liquid or gel contained within a small, conformable, rubber bladder or pad that also includes a hydrophone. This enables the collection of high signal-to-noise ratio cardiac, respiratory, voice, and other physiological data. The pad also minimizes interference from ambient noise because it couples poorly with airborne noise. It is low cost and comfortable to wear for extended periods. When the sensor pad is in contact with a patient's thorax, neck, or temple region, sounds can be immediately and continuously monitored. This can aid in the remote assessment, diagnosis, and treatment of cardiac and respiratory functions, as well as provide human stress and performance indicators such as heart and breath rates, voice stress, and gross motor indicators. The neck sensor picks up the wearer's voice well, with fidelity sufficient to be used as a hands-free voice activation mechanism using speech recognition software, or for voice communications. The pulse is also detectable from the carotid artery, and excellent breath sounds are present as well. This attachment area is often unobstructed by other equipment or clothing, and is easy to attach quickly to a subject.
Silver(I)-Promoted Conversion of Thioamides to Amidines: Divergent Synthesis of a Key Series of Vancomycin Aglycon Residue 4 Amidines That Clarify Binding Behavior to Model Ligands (2012)

Development of a general Ag(I)-promoted reaction for the conversion of thioamides to amidines is disclosed. This reaction was employed to prepare a key series of vancomycin aglycon residue 4 substituted amidines that were used to clarify their interaction with model ligands of peptidoglycan precursors and explore their resulting impact on antimicrobial properties.
Roles of eIF2Î± kinases in the pathogenesis of Alzheimerâ€™s disease (2014)

Cell signaling in response to an array of diverse stress stimuli converges on the phosphorylation of eukaryotic initiation factor-2α (eIF2α). Evidence is accumulating that persistent eIF2α phosphorylation at Ser51 through prolonged overactivation of regulatory kinases occurs in neurodegenerative diseases such as Alzheimer's disease (AD), leading to shutdown of general translation and translational activation of a subset of mRNAs. Recent advances in the development of gene-based strategies and bioavailable inhibitors, which specifically target one of the eIF2α kinases, have enabled us to investigate pathogenic roles of dysregulated eIF2α phosphorylation pathways. This review provides an overview of animal model studies in this field, focusing particularly on molecular mechanisms by which the dysregulation of eIF2α kinases may account for synaptic and memory deficits associated with AD. A growing body of evidence suggests that correcting aberrant eIF2α kinase activities may serve as disease-modifying therapeutic interventions to treat AD and related cognitive disorders.
Software for DNA sequencing by hybridization (1997)

Sequencing by hybridization (SBH) is a promising alternative approach to DNA sequencing and mutation detection. Analysis of the resolving power of SBH involves rather difficult combinatorial and probabilistic problems, and sometimes computer simulation is the only way to estimate the parameters and limitations of SBH experiments. This paper describes a software package, DNA-SPECTRUM, which allows one to analyze the resolving power and parameters of SBH. We also introduce the technique for visualizing multiple SBH reconstructions and describe applications of DNA-SPECTRUM to estimate various SBH parameters. DNA-SPECTRUM is available at http://www-hto.usc.edu/software/sbh/index. html.
Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines (2008)

The various alternative in vivo and in vitro growth conditions of tumorigenic EOC cell lines appeared to modestly influence the global chromosome 3 transcriptome supporting the notion that the in vitro cell line models are a viable option for testing gene candidates.
Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A (2003)

Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases.
Nuclear Actin Regulates Dynamic Subcellular Localization and Activity of the SRF Cofactor MAL (2007)

Actin, which is best known as a cytoskeletal component, also participates in the control of gene expression. We report a function of nuclear actin in the regulation of MAL, a coactivator of the transcription factor serum response factor (SRF). MAL, which binds monomeric actin, is cytoplasmic in many cells but accumulates in the nucleus upon serum-induced actin polymerization. MAL rapidly shuttles between cytoplasm and nucleus in unstimulated cells. Serum stimulation effectively blocks MAL nuclear export, which requires MAL-actin interaction. Nuclear MAL binds SRF target genes but remains inactive unless actin binding is disrupted. Fluorescence resonance energy transfer analysis demonstrates that the MAL-actin interaction responds to extracellular signals. Serum-induced signaling is thus communicated to nuclear actin to control a transcriptional regulator.
Covalent Modification of Carbon Surfaces by Aryl Radicals Generated from the Electrochemical Reduction of Diazonium Salts (1997)

Electrochemical reduction of a wide variety of aromatic diazonium salts on carbon electrodes (glassy carbon, highly oriented pyrolytic graphite) leads to the covalent attachment of the corresponding aromatic radicals. The films thus deposited on glassy carbon surfaces require mechanical abrasion to be removed. Cyclic voltammetry, X-ray photoelectron spectroscopy, polarization modulation IR reflection absorption spectroscopy, Auger spectroscopy, and Rutherford backscattering spectroscopy allow the characterization of the overlayer and an estimate of the surface coverage. The latter can be controlled through diazonium concentration and electrolysis duration. The mechanism of derivatization is discussed on the basis of the kinetic data obtained from cyclic voltammetry and preparative electrolysis. This versatile method of surface modification may find applications in the field of carbon−epoxy composites as attested by the successful binding of grafted p-aminophenyl groups with epichlorhydrin.
Simultaneous Nitrogen Doping and Reduction of Graphene Oxide (2009)

We developed a simple chemical method to obtain bulk quantities of N-doped, reduced graphene oxide (GO) sheets through thermal annealing of GO in ammonia. X-ray photoelectron spectroscopy (XPS) study of GO sheets annealed at various reaction temperatures reveals that N-doping occurs at a temperature as low as 300 degrees C, while the highest doping level of approximately 5% N is achieved at 500 degrees C. N-doping is accompanied by the reduction of GO with decreases in oxygen levels from approximately 28% in as-made GO down to approximately 2% in 1100 degrees C NH(3) reacted GO. XPS analysis of the N binding configurations of doped GO finds pyridinic N in the doped samples, with increased quaternary N (N that replaced the carbon atoms in the graphene plane) in GO annealed at higher temperatures (> or = 900 degrees C). Oxygen groups in GO were found responsible for reactions with NH(3) and C-N bond formation. Prereduced GO with fewer oxygen groups by thermal annealing in H(2) exhibits greatly reduced reactivity with NH(3) and a lower N-doping level. Electrical measurements of individual GO sheet devices demonstrate that GO annealed in NH(3) exhibits higher conductivity than those annealed in H(2), suggesting more effective reduction of GO by annealing in NH(3) than in H(2), consistent with XPS data. The N-doped reduced GO shows clearly n-type electron doping behavior with the Dirac point (DP) at negative gate voltages in three terminal devices. Our method could lead to the synthesis of bulk amounts of N-doped, reduced GO sheets useful for various practical applications.
Synthesis, Physicochemical Characterization, and Biological Activities of New Carnosine Derivatives Stable in Human Serum As Potential Neuroprotective Agents (2010)

The synthesis and the physicochemical and biological characterization of a series of carnosine amides bearing on the amido group alkyl substituents endowed with different lipophilicity are described. All synthesized products display carnosine-like properties differentiating from the lead for their high serum stability. They are able to complex Cu(2+) ions at physiological pH with the same stoichiometry as carnosine. The newly synthesized compounds display highly significant copper ion sequestering ability and are capable of protecting LDL from oxidation catalyzed by Cu(2+) ions, the most active compounds being the most hydrophilic ones. All the synthesized amides show quite potent carnosine-like HNE quenching activity; in particular, 7d, the member of the series selected for this kind of study, is able to cross the blood-brain barrier (BBB) and to protect primary mouse hippocampal neurons against HNE-induced death. These products can be considered metabolically stable analogues of carnosine and are worthy of additional investigation as potential neuroprotective agents.
C-KLAM: Constrained keyframe-based localization and mapping (2014)

In this paper, we present C-KLAM, a Maximum A Posteriori (MAP) estimator-based keyframe approach for SLAM. Instead of discarding information from non-keyframes for reducing the computational complexity, the proposed C-KLAM presents a novel, elegant, and computationally-efficient technique for incorporating most of this information in a consistent manner, resulting in improved estimation accuracy. To achieve this, C-KLAM projects both proprioceptive and exteroceptive information from the non-keyframes to the keyframes, using marginalization, while maintaining the sparse structure of the associated information matrix, resulting in fast and efficient solutions. The performance of C-KLAM has been tested in experiments, using visual and inertial measurements, to demonstrate that it achieves performance comparable to that of the computationally-intensive batch MAP-based 3D SLAM, that uses all available measurement information.
Heuristic approach to particle detection on virgin and patterned silicon wafers (1995)

Detection of particles deposited on both smooth and patterned silicon surfaces is examined in terms of maximizing the signal-to-background ratio. Components of the signal and background are examined separately. To understand the origin of the collected signal, laser light scattering of individual polystyrene spheres deposited on a polished silicon surface is studied. It is shown that for sphere sizes of 1 to 20 μm, scattering is an interference phenomenon of light from two sources: one is the reflection of the laser light on the particle, the second is the reflection on the silicon surface after two refractions. The effect of illumination under different angles is estimated and compared with experiment on spheres as small as 100 nm in diameter. The background scatter produced by patterned wafers is also examined. Techniques for its reduction, such as optimization of the azimuthal illumination angle, and in the case of high-density dynamic random access memory (DRAM) wafers, by Fourier filtering, are presented. In regard to the latter, the effects of a selective filtering of this diffraction pattern are examined vis-à-vis the resultant perturbation of the relatively weak transforms of the actual particulates. It was found that even some of the most rudimentary of spatial filters can be used to achieve noteworthy improvements in detection sensitivity. Achievements are reported of up to 5x improvement in SNR for intradie measurements and up to 10-fold improvement in total particle count.
THE UPTAKE AND DIGESTION OF IODINATED HUMAN SERUM ALBUMIN BY MACROPHAGES IN VITRO (1967)

Mouse peritoneal macrophages take up I*-HSA from their medium during in vitro cultivation. Conditions which promote I*-HSA uptake are the same as those which stimulate formation of pinocytic vesicles. Autoradiography of cells pulsed with (125)I-HSA showed that intracellular isotope is localized in perinuclear granules, or secondary lysosomes. Following a pulse of (125)I-HSA, intracellular radioactivity decreases and the amount of TCA-soluble isotope in the medium increases correspondingly. About 50% of the intracellular isotope is lost in 5 hr. The release of isotope from pulsed cells is not inhibited by parafluorophenylalanine, 2,4-dinitrophenol or by a reduction of the serum concentration of the medium. However, the processing of ingested (125)I-HSA is reversibly inhibited by reduced temperature. The TCA-soluble radioactive material excreted by pulsed macrophages was identified as monoiodotyrosine.
Targeted Disruption of Soluble Epoxide Hydrolase Reveals a Role in Blood Pressure Regulation (2000)

Renal microsomal cytochrome P-450 monooxygenase-dependent metabolism of arachidonic acid generates a series of regioisomeric epoxyeicosatrienoic acids that can be further metabolized by soluble epoxide hydrolase to the corresponding dihydroxyeicosatrienoic acids. Evidence exists that these metabolites affect renal function and, in particular, blood pressure regulation. To examine this possibility, blood pressure and renal arachidonic acid metabolism were examined in mice with a targeted disruption of the soluble epoxide hydrolase gene. Systolic blood pressure of male soluble epoxide hydrolase-null mice was lower compared with wild-type mice in both the absence and presence of dietary salt loading. Both female soluble epoxide hydrolase-null and wild-type female mice also had significantly lower systolic blood pressure than male wild-type mice. Renal formation of epoxyeicosatrienoic and dihydroxyeicosatrienoic acids was markedly lower for soluble epoxide hydrolase-null versus wild-type mice of both sexes. Although disruption of soluble epoxide hydrolase in female mice had minimal effects on blood pressure, deletion of this gene feminized male mice by lowering systolic blood pressure and altering arachidonic acid metabolism. These data provide the first direct evidence for a role for soluble epoxide hydrolase in blood pressure regulation and identify this enzyme as a novel and attractive target for therapeutic intervention in hypertension.
BIOSYNTHETIC PROTEIN TRANSPORT AND SORTING BY THE ENDOPLASMIC RETICULUM AND GOLGI (1987)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Inhibition of human complement by a C3-binding peptide isolated from a phage-displayed random peptide library (1996)

We have screened a phage-displayed random peptide library for binding to C3b, the proteolytically activated form of complement component C3, and have identified a novel peptide that suppresses complement activation. This phage-displayed peptide bound to C3, C3b, and C3c, but not to C3d, indicating that it binds to the C3c region of C3. A synthetic 27-amino acid peptide corresponding to the phage-displayed peptide also bound to C3 and C3 fragments and inhibited both the classical and alternative pathways of complement activation. The inhibition of complement activation was reversible. Studies with overlapping peptides indicated that the functional activity was located in the cyclic 13-amino acid N-terminal region (ICVVQDWGHHRCT) of the parent peptide. Reduction and alkylation of this 13-residue synthetic peptide destroyed its inhibitory activity. Analysis of the mechanism of inhibition revealed that the peptide inhibited C3 cleavage in normal human serum as well as when the alternative pathway was reconstituted with purified complement components, and the observed inhibition was not due to sterically hindered access to the C3a/C3b cleavage site. Further, the peptide did not inhibit the cleavage of factor B, indicating that it did not affect the interaction of CA with factor B or the formation of C3b,Bb. The peptide also had no effect on the binding of properdin to C3, demonstrating that the observed inhibition of C3 cleavage in normal human serum was not due in part to its effect on the properdin-stabilized C3 convertase, C3b,Bb,P. These results indicate that the peptide we have identified interacts with C3 to inhibit its activation.
The Molecular Biology of RU486. Is There a Role for Antiprogestins in the Treatment of Breast Cancer?* (1992)

ENDOCRINE therapy used either prophylactically or therapeutically for the treatment of locally advanced or metastatic breast cancers offers many advantages to patients whose tumors contain functional estrogen and progesterone receptors (ER and PR). The range of treatments defined as endocrine include surgical ablation of endocrine glands, administration of pharmacological doses of steroid hormones, chemical blockade of steroid hormone biosynthesis, and inhibition of endogenous steroid hormone action at the tumor with synthetic antagonists. The last of these approaches is the most widely used, making the antiestrogen tamoxifen the preferred first-line therapeutic agent for treatment of hormone-dependent metastatic breast cancer. The wide-spread use of tamoxifen reflects its efficacy and low toxicity, and the fact that it makes good physiological sense to block the local proliferative effects of estrogens directly at the breast. But are estrogens the only hormones with a proliferative impact on the breast and on breast cancers? This review focuses on evidence that progesterone also has proliferative actions in the breast; on the role of synthetic progestins in breast cancer treatment; on the molecular biology of progesterone antagonists; and on the preliminary data showing that progesterone antagonists may be powerful new tools for the management of metastatic breast cancer, because they block the local effects of endogenous progesterone on breast cell proliferation. The reader is also referred to the excellent general review on progestin regulation of cell proliferation by Clarke and Sutherland (1). The structures of the agonists and antagonists discussed in this review are shown in Fig. 1.