gebhart/patrepeval huggingface dataset:
Lysines 128 and 132 Enable Lipopolysaccharide Binding to MD-2, Leading to Toll-like Receptor-4 Aggregation and Signal Transduction (2003)

Three cell-surface proteins have been recognized as components of the mammalian signaling receptor for bacterial lipopolysaccharide (LPS): CD14, Toll-like receptor-4 (TLR4), and MD-2. Biochemical and visual studies shown here demonstrate that the role of CD14 in signal transduction is to enhance LPS binding to MD-2, although its expression is not essential for cellular activation. These studies clarify how MD-2 functions: we found that MD-2 enables TLR4 binding to LPS and allows the formation of stable receptor complexes. MD-2 must be bound to TLR4 on the cell surface before binding can occur. Consequently, TLR4 clusters into receptosomes (many of which are massive) that recruit intracellular toll/IL-1/resistance domain-containing adapter proteins within minutes, thus initiating signal transduction. TLR4 activation correlates with the ability of MD-2 to bind LPS, as MD-2 mutants that still bind TLR4, but are impaired in the ability to bind LPS, conferred a greatly blunted LPS response. These findings help clarify the earliest events of TLR4 triggering by LPS and identify MD-2 as an attractive target for pharmacological intervention in endotoxin-mediated diseases.
Neuropharmacology of Phencyclidine: Basic Mechanisms and Therapeutic Potential (1990)

Neuropharmacology of Phencyclidine: Basic Mechanisms and Therapeutic Potential, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/pharmtox/30/1/annurev.pa.30.040190.003423-1.gif
Coagulation and sepsis (2012)

Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands *See also p. 2704. The author has not disclosed any potential conflicts of interest.
Synaptic Reorganization in Scaled Networks of Controlled Size (2007)

Neurons in plastic regions of the brain undergo fundamental changes in the number of cells connecting to them as a result of development, plasticity and disease. Across these same time periods, functional changes in cellular and synaptic physiology are known to occur and are often characterized as developmental features of these periods. However, it remains possible that many such changes are direct consequences of the modified degree of partnering, and that neurons intrinsically scale their physiological parameters with network size. To systematically vary a recurrent network's number of neurons while measuring its synaptic properties, we used microfabricated extracellular matrix adhesive islands created with soft lithography to culture neuronal clusters of precise sizes, and assessed their intrinsic connectivity using intracellular recordings and confocal microscopy. Both large and small clusters supported constant densities of excitatory and inhibitory neurons. However, neurons that were provided with more potential partners (larger clusters) formed more connections per cell via an expanded dendritic surface than cocultured smaller clusters. Electrophysiologically, firing rate was preserved across clusters even as size and synapse number increased, due in part to synapses in larger networks having reduced unitary strengths, and sparser paired connectivity. Larger networks also featured a particular increase in the number of excitatory connections onto inhibitory dendrites. We suggest that these specific homeostatic mechanisms, which match the number, strength, and architecture of connections to the number of total available cellular partners in the network, could account for several known phenomena implicated in the formation, organization and degeneration of neuronal circuits.
Calcitonin in Phantom Limb Pain (1999)

PLP is a challenging disorder that is often difficult to treat. Like all other types of pain, PLP is a tremendous source of morbidity and should be treated aggressively. Though evidence is very limited, one or two doses of intravenous salmon calcitonin 200 IU may be an effective treatment. The minor adverse effects reported in the literature would seem to indicate the relative safety of this regimen; however, clinicians should be aware of the rare but severe hypersensitivity reactions that can occur with salmon calcitonin. Intranasal calcitonin appears to be similar in efficacy to the parenteral formulation, at least in pain associated with vertebral crush fractures. Long-term studies using intranasal calcitonin for relief of PLP are warranted given the ease of administration of this dosage form.
[CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study for postmenopausal women with advanced or recurrent breast cancer (no. 1)--investigation of recommended clinical dose CGS20267 Study Group]. (2002)

To determine the recommended clinical dose of CGS20267 (Letrozole), we conducted a randomized comparative study as a late phase II study (first part) in postmenopausal women with advanced or recurrent breast cancer. Forty-one patients were randomly assigned to receive 0.5 mg or 1.0 mg once daily. There were no statistically significant differences in background between the two groups. Although there was no significant difference in the objective response rates between the two groups, the rate was higher at 1.0 mg (44.4%) than at 0.5 mg (38.1%). We also combined these data with the results of an early phase II study. The objective response rates (CR + PR) were 31.4% at 0.5 mg and 42.2% at 1.0 mg, and response rates consisting of CR, PR, and NC for longer than 6 months were significantly higher at a dose of 1.0 mg (68.9%) than 0.5 mg (41.2%). Side effects included drug-related adverse events in 36.8% at 0.5 mg and in 31.6% at 1.0 mg. All of the events were grade 2 or lower, indicating a favorable tolerability of CGS20267. These results demonstrated that CGS20267 1.0 mg once daily is more effective than 0.5 mg, and has comparable safety, in the treatment of postmenopausal women with advanced or recurrent breast cancer. We conclude the recommended clinical dose of CGS20267 should be 1.0 mg once daily.
Fanconi's anemia: the preanemic phase. (1979)

Anticipation of Franconi's anemia prior to the development of overt marrow aplasia may prevent some morbidity and mortality from infectious and hemorrhagic complications. A presumptive diagnosis was made in a firstborn child and radial anomalies, small size, elevated fetal hemoglobin, intermittent excessive chromosome breakage and elevated T-antigen expression in fibroblasts infected with Simian virus 40. Serial studies may help identify infants and young children at risk to develop this type of constitutional marrow hypoplasia.
Arsenite and cadmium(II) as probes of glucocorticoid receptor structure and function. (1990)

Low concentrations of arsenite, but not arsenate, and Cd2+ blocked steroid binding to the glucocorticoid receptors of HTC cells. Inhibition by arsenite was faster and occurred at lower concentrations than for Cd2+. Half-maximal inhibition of [3H]dexamethasone binding was seen after a 30-min preincubation with approximately 7 microM arsenite. The effect of arsenite and of Cd2+ appears to be mediated by a reaction with vicinal dithiols of the receptor as shown by (a) the reversal of arsenite inhibition by much lower concentrations of dithiothreitol (approximately 0.1 mM) than of beta-mercaptoethanol (approximately 10 mM); (b) the ability of both arsenite and Cd2+ to block [3H]dexamethasone 21-mesylate labeling of receptors but not of other thiol-containing proteins; and (c) the known selectivity of arsenite and of Cd2+ for reactions with vicinal dithiols. Arsenite forms a tight complex with these vicinal dithiols since the removal of loosely associated arsenite by gel exclusion chromatography did not reverse the inhibition of steroid binding. The effect of other ions on steroid binding was also examined. Half-maximal inhibition of binding occurred with approximately 5 microM selenite, whereas up to 300 microM Zn2+ was without effect. Much higher concentrations of arsenite were required for effects on unactivated and activated complexes. Arsenite slowly induced a loss of unactivated complexes but rapidly inhibited a portion of the DNA binding of activated complexes. Any effect on activation occurred at arsenite concentrations equal to or higher than those that inhibited DNA binding. In contrast, Cd2+ concentrations similar to those that block steroid binding caused a biphasic loss of unactivated complexes and a marginal loss of activated complexes. This is the first report of effects of arsenite on glucocorticoid receptors. These results confirm directly our earlier hypothesis that steroid binding to rat glucocorticoid receptors involves a vicinal dithiol (Miller, N. R., and Simons, S. S., Jr. (1988) J. Biol. Chem. 263, 15217-15225) and show that arsenite is a potent new reagent for probing receptor structure and function.
Quantitative Hydrogeological Study of an Unconfined Aquifer by GPR along Tuul River in Ulaanbaatar (2007)

To assess the potential of ground penetrating radar (GPR) for detecting and monitoring groundwater movement and for estimating the hydraulic properties of an aquifer, we conducted GPR surveys at a water
Proposal of unique PV system for large-scale photovoltaic power generation system (2003)

In order to make a PV power generation system survive as an economically viable option against other renewable energy sources, drastic reduction of energy cost is inevitable. The authors have been working on the development of a unique PV system to reduce total system cost including solar panel, power conversion unit and installation work. In the proposed concept, AC photovoltaic device and adhesive mounting method were introduced for the dedicated use in power station. By introducing this concept, it is feasible that the system cost will be reduced to 1/3 compared to the conventional system. The authors believe that the concept is suitable for very large-scale PV systems in desert areas.
Fatty Acids and Retinopathy (2011)

Neovascularization is a pathogenic event common to retinopathy of prematurity and age-related macular degeneration. A recent study uncovers a mechanism that mediates a nutritional effect on this process in mice.
Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility (1998)

We hypothesized that selective control of ventricular contractility might be mediated by postganglionic parasympathetic neurons in the cranial medial ventricular (CMV) ganglion plexus located in a fat pad at the base of the aorta. Sinus rate, atrioventricular (AV) conduction (ventricular rate during atrial pacing), and left ventricular contractile force (LV dP/dt during right ventricular pacing) were measured in eight chloralose-anesthetized dogs both before and during bilateral cervical vagus stimulation (20-30 V, 0.5 ms pulses, 15-20 Hz). Seven of these dogs were tested under beta-adrenergic blockade (propranolol, 0.8 mg kg(-1) i.v.). Control responses included sinus node bradycardia or arrest during spontaneous rhythm, high grade AV block or complete heart block, and a 30% decrease in contractility from 2118 +/- 186 to 1526 +/- 187 mm Hg s(-1) (P < 0.05). Next, the ganglionic blocker trimethaphan (0.3-1.0 ml of a 50 microg ml(-1) solution) was injected into the CMV fat pad. Then vagal stimulation was repeated, which now produced a relatively small 5% (N.S., P > 0.05) decrease in contractility but still elicited the same degree of sinus bradycardia and AV block (N = 8, P < 0.05). Five dogs were re-tested 3 h after trimethaphan fat pad injection, at which time blockade of vagally-induced negative inotropy was partially reversed, as vagal stimulation decreased LV dP/dt by 19%. The same dose of trimethaphan given either locally into other fat pads (PVFP or IVC-ILA) or systemically (i.v.) had no effect on vagally-induced negative inotropy. Thus, parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation. Blockade of the CMV fat pad had no effect on vagally-mediated slowing of sinus rate or AV conduction.
The DEEP2 Redshift Survey (2000)

The DEIMOS spectrograph is nearing completion in the UC Lick shops and will be delivered to the Keck Observatory in 2001. Once it is operational, a team of astronomers will initiate DEEP2, a major redshift survey of galaxies that will consume approximately 120 nights at the Keck Observatory over a three year period. Our goal is to gather high-quality spectra of ~60,000 galaxies with Z&gt;0.7 in order to study the properties and large scale clustering of galaxies at $Z \approx 1$. The survey will be done at high spectral resolution, R=λ/Δλ~3500, allowing us to work between the bright OH sky emission lines and to infer linewidths for many of the target galaxies. The linewidth data will facilitate the execution of the classical redshift-volume cosmological test, which can provide a precision measurement of the equation of state of the Universe.
Expression of CXCR4 Predicts Poor Prognosis in Patients with Malignant Melanoma (2005)

This article provides the first evidence that CXCR4 expression could be an independent and powerful prognostic marker in primary cutaneous malignant melanomas.
Multiplexed Screening of Neutral Mass-Tagged RNA Targets against Ligand Libraries with Electrospray Ionization FTICR MS:  A Paradigm for High-Throughput Affinity Screening (1999)

We demonstrate that binding of mixtures of aminoglycosides can be measured simultaneously against multiple RNA targets of identical length and similar (or identical) molecular weight. Addition of a neutral mass tag to one of the RNA targets shifts the detected peaks to a higher mass/charge ratio, where complexes with small molecules can be identified unambiguously. An appropriately placed neutral mass tag does not alter RNA--ligand binding. The utility of this strategy is demonstrated with model RNAs corresponding to the decoding region of the prokaryotic and eukaryotic rRNAs and a mixture of five aminoglycosides. Complexes are observed between the aminoglycoside library and the prokaryotic rRNA model, while no aminoglycoside was observed to bind to the mass-tagged eukaryotic rRNA model. The differential binding data is consistent with the eukaryotic A-site rRNA having a different conformation compared with the prokaryotic A-site that prevents entry and binding of neomycin-class aminoglycosides. Mass spectrometric analysis of neutral mass-tagged macromolecular targets represents a new high-throughput screening paradigm in which the interaction of multiple targets against a collection of small molecules can be evaluated in parallel.
Characterization of the requirements for localization of phytochrome B to nuclear bodies (2003)

Phytochromes are red- and far-red-sensing photoreceptors that detect the quantity, quality, and duration of light throughout the entire life cycle of plants. Phytochromes accumulate in the cytoplasm in the dark. As one of the earliest responses after light illumination, phytochromes localize to the nucleus where they become associated with discrete nuclear bodies (NBs). Here, we describe the steady-state dynamics of Arabidopsis phytochrome B (phyB) localization in response to different light conditions and define four phyB subnuclear localization patterns: diffuse nuclear localization, small and numerous NBs only, both small and large NBs, and large NBs only. We show that phyB nuclear import is not sufficient for phyB NB formation. Rather, phyB accumulation in NBs is mainly determined by the percentage of the total amount of phyB protein that is in the active phyB conformer, with large NBs always correlating with strong phyB responses. A genetic screen to identify determinants required for subnuclear localization of phyB resulted in several phyB mutants, mutants deficient in phytochrome chromophore biosynthesis, and mutations in at least one previously uninvestigated locus. This study lays the groundwork for future investigations to identify the molecular mechanisms of light-regulated partitioning of plant photoreceptors to discrete subnuclear domains.
Multi-turn Dialogue Response Generation in an Adversarial Learning Framework (2019)

We propose an adversarial learning approach for generating multi-turn dialogue responses. Our proposed framework, hredGAN, is based on conditional generative adversarial networks (GANs). The GAN's generator is a modified hierarchical recurrent encoder-decoder network (HRED) and the discriminator is a word-level bidirectional RNN that shares context and word embeddings with the generator. During inference, noise samples conditioned on the dialogue history are used to perturb the generator's latent space to generate several possible responses. The final response is the one ranked best by the discriminator. The hredGAN shows improved performance over existing methods: (1) it generalizes better than networks trained using only the log-likelihood criterion, and (2) it generates longer, more informative and more diverse responses with high utterance and topic relevance even with limited training data. This improvement is demonstrated on the Movie triples and Ubuntu dialogue datasets using both automatic and human evaluations.
CCD correlators for auditory models (2002)

Surface-channel charge-coupled devices (CCDs) provide a mechanism for analog signal delay that can be built using an ordinary double-poly CMOS digital process, such as offered by Orbit through MOSIS. This technique has been applied to implement the correlation processing needed in auditory models of the sort proposed by J.C.R. Licklider (1951) for monaural pitch perception and sound separation. The resulting chips take analog audio in and produce analog video out (moving pictures of the correlogram representation of the sound) in real time. These chips present a variety of interesting analog and digital design challenges, which are addressed here. The first working experimental chips show real-time correlograms with 84 cochlea taps and 70 CCD delay stages per tap. There remains at least one unanticipated and as yet not understood problem with these circuits, resulting in a serious skew in the displayed correlation levels. Several circuit improvements are planned for the next generation of experimental chips.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis of Polymer Brushes on Silicate Substrates via Reversible Addition Fragmentation Chain Transfer Technique (2002)

Reversible addition fragmentation chain transfer (RAFT) has been used to synthesize polymer brushes. Styrene, methyl methacrylate, and N,N-dimethylacrylamide brushes were prepared under RAFT conditions using silicate surfaces that were modified with surface-immobilized azo initiators. Films with controlled thicknesses were produced. RAFT was also used to synthesize PS-b-PDMA and PDMA-b-PMMA block copolymer brushes that displayed reversible surface properties upon treatment with block-selective solvents.
Targeting Apoptosis Pathways in Cancer Therapy (2005)

Apoptosis, or programmed cell death, is a mechanism by which cells undergo death to control cell proliferation or in response to DNA damage. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy. These novel agents include those targeting the extrinsic pathway such as tumor necrosis factor-related apoptosis-inducing ligand receptor 1, and those targeting the intrinsic Bcl-2 family pathway such as antisense bcl-2 oligonucleotides. Many pathways and proteins control the apoptosis machinery. Examples include p53, the nuclear factor kappa B, the phosphatidylinositol 3 kinase pathway, and the ubiquitin/proteosome pathway. These can be targeted by specific modulators such as bortezomib, and mammalian target of rapamycin inhibitors such as CCI-779 and RAD 001. Because these pathways may be preferentially altered in tumor cells, there is potential for a selective effect in tumors sparing normal tissue. This article reviews the current understanding of the apoptotic pathways, including the extrinsic (cytoplasmic) and intrinsic (mitochondrial) pathways, and the agents being developed to target these pathways.
Complex Fluids: Probing Mechanical Properties of Biological Systems with Optical Tweezers (2010)

The mechanical properties of cells are crucial for cell sensing and reaction to mechanical environments. This review describes the basic principles of optical tweezers and their use as force sensors for studying the mechanical properties of biological systems. It covers experiments of four groups of biological systems arranged by increasing complexity: (a) packaging DNA into viral capsids by bacteriophage portal motors and the dynamical stiffness of DNA upon protein binding, (b) actin-coated giant vesicles and the myosin-II embedded actin polymer network, (c) suspension cells, and (d) adhesion cells. These examples demonstrate how optical tweezers have been used to improve the understanding of the mechanical properties of biological systems at subcellular and molecular levels.
Identification of volatile metabolites from five fungal species cultivated on two media (1995)

Five fungal species, Aspergillus versicolor, Penicillium commune, Cladosporium cladosporioides, Paecilomyces variotii, and Phialophora fastigiata, were cultivated on two media, malt extract agar and dichloran glycerol agar. Culture flasks provided with inlet and outlet tubes were used and purified, and humidified air was constantly led through the flasks. Air samples from the cultures were sorbed on Tenax GR and analyzed by thermal desorption-gas chromatography. The produced volatile metabolites were analyzed by mass spectrometry. Various hydrocarbons, alcohols, ketones, ethers, esters, sulfur-containing compounds, and terpenes were identified. The most commonly produced substances were 2-methyl-1-propanol, 2-methyl-1-butanol, 3-methyl-1-butanol, 3-methylfuran, and dimethyl disulfide. The production was highly dependent on both medium and species.
Analytical accuracy and user-friendliness of the Afinion point-of-care CRP test (2013)

Letter to the editor
Smallest dead volume microvalves for integrated chemical analyzing systems (2002)

Normally open, normally closed, and three-way microvalves were developed. These microvalves had a simple structure and small dead volume on the order of tens of nl. Each microvalve was driven by a stack-type piezo-actuator and the controllable flow range is from 1 mu l/min to tens of mu l/min. These valves are useful for constructing integrated chemical analyzing systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>