gebhart/patrepeval huggingface dataset:
New Structural and Functional Aspects of the Type I Interferon-Receptor Interaction Revealed by Comprehensive Mutational Analysis of the Binding Interface (2000)

Type I interferons bind to two cell surface receptors, ifnar1 and ifnar2, as the first step in the activation of several signal transduction pathways that elicit an anti-viral state and an anti-proliferative response. Here, we quantitatively mapped the complete binding region of ifnar2 on interferon (IFN)alpha2 by 35 individual mutations to alanine and isosteric residues. Of the six "hot-spot" residues identified (Leu-30, Arg-33, Arg-144, Ala-145, Met-148, and Arg-149), four are located on the E-helix, which is located at the center of the binding site flanked by residues on the A-helix and the AB-loop. The contribution of residues of the D-helix, which have been previously implicated in binding, proved to be marginal for the interaction with the extracellular domain of ifnar2. Interestingly, the ifnar2 binding site overlaps the largest continuous hydrophobic patch on IFNalpha2. Thus, hydrophobic interactions seem to play a significant role stabilizing this interaction, with the charged residues contributing toward the rapid association of the complex. Relating the anti-viral and anti-proliferative activity of the various interferon mutants with their affinity toward ifnar2 results in linear function over the whole range of affinities investigated, suggesting that ifnar2 binding is the rate-determining step in cellular activation. Dose-time analysis of the anti-viral response revealed that shortening the incubation time of low-level activation cannot be compensated by higher IFN doses. Considering the strict dependence of the cellular response on affinity, these results suggest that for maintaining transcription of IFN-responsive genes over a longer time period, low but continuous signaling through the IFN receptor is essential.
Narrow channel 2-D MESFET for low power electronics (1995)

A 2-D MESFET utilizing sidewall Schottky contacts on either side of a very narrow 2-d electron gas channel is described. Record transconductance of 295 and 130 mS/mm have been achieved at room temperature in 1.0 and 0.5 micron wide devices, respectively. We also present accurate 2-D MESFET current-voltage and capacitance-voltage models. These models have been implemented into AIM-Spice which was used to simulate DCFL inverter and ring oscillator circuits. The ring oscillator simulations predict a power-delay product of less than 0.1 fJ/gate at room temperature, suggesting that the 2-D MESFET may be useful for ultra low power electronics applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Update on the clinical development of cangrelor (2010)

Antiplatelet drugs represent the cornerstone of treatment for cardiovascular atherothrombotic disease. Dual oral antiplatelet therapy with aspirin and oral ADP-receptor antagonists, such as clopidogrel, has been the standard choice for prevention of ischemic events in patients with acute coronary syndrome and in those undergoing percutaneous coronary intervention. However, due to the limitations of clopidogrel, such as interindividual-response variability, drug-drug interactions, slow onset of action and irreversible inhibitory effects, novel antiplatelet agents are under clinical development. Cangrelor is a reversible, potent, competitive inhibitor of the ADP P2Y(12) receptor that is administered intravenously and rapidly achieves near complete inhibition of ADP-induced platelet aggregation. These pharmacological properties make cangrelor a promising drug for clinical use. However, recent large-scale Phase III clinical investigations failed to show significant clinical benefit on the primary end point with cangrelor. This article provides an overview of the current status of knowledge on cangrelor, focusing on its pharmacologic properties and clinical development.
Comparison of Platelet‐Rich Plasma, Bovine Porous Bone Mineral, and Guided Tissue Regeneration Versus Platelet‐Rich Plasma and Bovine Porous Bone Mineral in the Treatment of Intrabony Defects: A Reentry Study (2002)

The results of this study show that both combinations of PRP/BPBM/GTR and PRP/BPBM are effective in the treatment of intrabony defects present in patients with advanced chronic periodontitis. The results also suggest that GTR adds no clinical benefit to PRP/BPBM. Further studies are necessary to assess the individual role played by PRP and BPBM in the clinical outcome achieved with their combination.
Controllable Preparation of Nanoparticles by Drops and Plugs Flow in a Microchannel Device (2008)

Well controlled two-liquid-phase flows in a T-junction microchannel device have been realized. The system of H2SO4 and BaCl2, respectively, in two phases to form BaSO4 nanoparticles was used as a probe to characterize the microscale two-phase flow and transport conditions of a system with interphase mass transfer and chemical reaction. Nanoparticles with narrow size and good dispersibility were produced through drops or plugs flow in the microdevice. As a novel work, the influence of mass transfer and chemical reaction on interfacial tension and flow patterns was discussed based on the experiments. At the same time, the effect of the two-phase flow patterns on the nanoparticle size was also discussed. It was found that the increase of the amount of mass transfer and chemical reaction could change the flow patterns from plugs flow to drops flow. The drop diameter or plug length could be changed in a wide range. Accordingly, a new parameter of mu(0)u(c)/gamma(0)/Q(d) was defined to distinguish the flow patterns. The prepared nanoparticles ranged in size from 10 to 40 nm. Apparently, the particle size decreased with the increase of the drop diameter or plug length. Reasons were discussed based on the mass transfer direction and speed in drops and plugs flow patterns.
Biochemical and Pharmacologic Heterogeneity in Low Molecular Weight Heparins. Impact on the Therapeutic Profile (2004)

Ever since the introduction of low molecular weight heparins (LMWHs) for clinical use, one of the major questions raised relates to product interchangeability and the differences between each of the individual LMWH preparations. Although differences between various commercially available products have been described in terms of molecular weight profile and biologic properties, very limited information on the direct comparison of individual products in a defined clinical setting is available at this time. European Pharmacopeia (EP) and the World Health Organization (WHO) have developed guidelines to characterize these agents in terms of molecular weight and biologic profiles. On a gravimetric basis, these potency assignments differ for anti-Xa and anti-IIa activities in terms of U potency per mg. The relative distribution of various molecular weight components has also been reported to vary. The oligosaccharide composition, microstructural differences in terms of specific sugars and the presence of unique structural features and the interaction with endogenous mediators such as antithrombin (AT) and heparin cofactor II (HC II) also differ. At equivalent anti-Xa levels, the amount of the anti-IIa activity and anticoagulant activity differs. Since the bioavailability and relative pharmacokinetics of the anti-Xa and anti-IIa effects are different, the specific pharmacodynamic effects of these drugs also differ. A large preclinical data base is now available on the differences between various LMWHs. However, only limited clinical data is available in the current literature. To date, the LMWHs have been primarily used for the management of post-surgical DVT. Only smaller dosages (30-40 mg or 2,500 to 4,000 anti-Xa U total dose) have been used. In these studies, because of the low dose and subcutaneous route of administration, the differences in clinical effects are rather small. Since LMWHs are now developed for therapeutic use, where relatively higher doses are used, these pharmacokinetic/pharmacodynamic differences will become more apparent. The reported differences in the clinical efficacy of LMWHs in such indications as unstable angina may be due to their pharmacologic properties and molecular composition. There are also major differences in the non-anticoagulant actions of these agents such as their ability to interact with growth factors and antithrombotic effects. Based on the available literature, it can be concluded that each product exhibits individuality.
2-Hydroxycyclohexanecarboxyl Coenzyme A Dehydrogenase, an Enzyme Characteristic of the Anaerobic Benzoate Degradation Pathway Used by Rhodopseudomonas palustris (2000)

A gene, badH, whose predicted product is a member of the short-chain dehydrogenase/reductase family of enzymes, was recently discovered during studies of anaerobic benzoate degradation by the photoheterotrophic bacterium Rhodopseudomonas palustris. Purified histidine-tagged BadH protein catalyzed the oxidation of 2-hydroxycyclohexanecarboxyl coenzyme A (2-hydroxychc-CoA) to 2-ketocyclohexanecarboxyl-CoA. These compounds are proposed intermediates of a series of three reactions that are shared by the pathways of cyclohexanecarboxylate and benzoate degradation used by R. palustris. The 2-hydroxychc-CoA dehydrogenase activity encoded by badH was dependent on the presence of NAD(+); no activity was detected with NADP(+) as a cofactor. The dehydrogenase activity was not sensitive to oxygen. The enzyme has apparent K(m) values of 10 and 200 microM for 2-hydroxychc-CoA and NAD(+), respectively. Western blot analysis with antisera raised against purified His-BadH identified a 27-kDa protein that was present in benzoate- and cyclohexanecarboxylate-grown but not in succinate-grown R. palustris cell extracts. The active form of the enzyme is a homotetramer. badH was determined to be the first gene in an operon, termed the cyclohexanecarboxylate degradation operon, containing genes required for both benzoate and cyclohexanecarboxylate degradation. A nonpolar R. palustris badH mutant was unable to grow on benzoate or cyclohexanecarboxylate but had wild-type growth rates on succinate. Cells blocked in expression of the entire cyclohexanecarboxylate degradation operon excreted cyclohex-1-ene-1-carboxylate into the growth medium when given benzoate. This confirms that cyclohex-1-ene-1-carboxyl-CoA is an intermediate of anaerobic benzoate degradation by R. palustris. This compound had previously been shown not to be formed by Thauera aromatica, a denitrifying bacterium that degrades benzoate by a pathway that is slightly different from the R. palustris pathway. 2-Hydroxychc-CoA dehydrogenase does not participate in anaerobic benzoate degradation by T. aromatica and thus may serve as a useful indicator of an R. palustris-type benzoate degradation pathway.
Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens (1994)

Protein phosphatase 2A consists of three subunits, the catalytic subunit (C) and two regulatory subunits (A and B). The A subunit has a rod-like shape and consists of 15 nonidentical repeats. It binds the catalytic subunit through repeats 11 to 15 at the C terminus and the tumor antigens encoded by small DNA tumor viruses through overlapping but distinct regions at N-terminal repeats 2 to 8. A model of the A subunit was developed on the basis of the fact that uncharged or hydrophobic amino acids are conserved at eight defined positions within each repeat. Helical wheel projections suggested that each repeat can be arranged as two interacting amphipathic helixes connected by a short loop. Mutational analysis of the A subunit revealed that the proposed loops are important for binding of tumor antigens, the B subunit, and the C subunit. Native gel analysis of mutant A subunits synthesized in vitro demonstrated that the binding region for the B subunit, previously thought to include repeats 2 to 8, covers repeats 1 to 10 and that the B and C subunits cooperate in binding to the A subunit.
Enabling Components for Future High-Speed Coherent Communication Systems (2011)

Next-generation high-speed coherent optical communication systems targeting beyond 100-Gb/s per channel, have opened opportunities for innovations in component and subsystem areas that this tutorial will attempt to address, covering photonics, electronics and signal processing technologies.
Magnetic Resonance Angiography Detection of Abnormal Carotid Artery Plaque in Patients With Cryptogenic Stroke (2015)

Our findings suggest that a proportion of strokes classified as cryptogenic may be mechanistically related to complicated, nonhemodynamically significant cervical carotid artery plaque that can easily be detected by routine magnetic resonance imaging/magnetic resonance angiography acute stroke protocols.
Novel statistical approaches to text classification, machine translation and computer-assisted translation (2008)

This thesis presents diverse contributions in the fields of text classification, machine translation and computer-assisted translation under the statistical framework.
Multiwaveguide implantable probe for light delivery to sets of distributed brain targets (2010)

Optical fibers are commonly inserted into living tissues such as the brain in order to deliver light to deep targets for neuroscientific and neuroengineering applications such as optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins. However, an optical fiber is limited to delivering light to a single target within the three-dimensional structure of the brain. We here demonstrate a multiwaveguide probe capable of independently delivering light to multiple targets along the probe axis, thus enabling versatile optical control of sets of distributed brain targets. The 1.45-cm-long probe is microfabricated in the form of a 360-μm-wide array of 12 parallel silicon oxynitride (SiON) multimode waveguides clad with SiO(2) and coated with aluminum; probes of custom dimensions are easily created as well. The waveguide array accepts light from a set of sources at the input end and guides the light down each waveguide to an aluminum corner mirror that efficiently deflects light away from the probe axis. Light losses at each stage are small (input coupling loss, 0.4 ± 0.3 dB; bend loss, negligible; propagation loss, 3.1 ± 1 dB/cm using the outscattering method and 3.2 ± 0.4 dB/cm using the cutback method; corner mirror loss, 1.5 ± 0.4 dB); a waveguide coupled, for example, to a 5 mW source will deliver over 1.5 mW to a target at a depth of 1 cm.
Matrix assisted laser desorption/ionization-time of flight-mass spectrometry analysis of proteins detected by anti-phosphotyrosine antibody on two-dimensional-gels of fibrolast cell lysates after tumor necrosis factor-α stimulation (2000)

We describe efficient methods for using functional proteomics analysis to study signal transduction pathways in murine fibroblast L929 cells following stimulation with tumor necrosis factor (TNF)-alpha. After stimulation with TNF-alpha, cellular proteins of L929 cells were extracted with a lysis buffer containing 0.3% sodium dodecyl sulfate (SDS) for 10-30 min time intervals, and were separated by two-dimensional (2-D) electrophoresis followed by immunoblot analysis with anti-phosphotyrosine antibody and alkaline phosphatase-anti IgG antibody conjugate. To improve detection sensitivity by immunoblot analysis we used a chemifluorescent substrate for alkaline phosphatase. One hundred protein spots were detected in the TNF-alpha stimulated L929 cell extract by immunoblot analysis. The use of chemifluorescence allowed us to quantitate immunoblotted spots with fluoroscanner so that we were able to detect time-dependent changes of a number of immunoblotted spots. Protein spots on a silver-stained 2-D gel corresponding to those detected by immunoblot analysis were subjected to in-gel trypsin digestion- matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)-mass spectrometry analysis, respectively. Twenty-one proteins detected by immunoblot analysis were identified by MS-Fit database search analysis. Among them, the proteins that show time-dependent changes in staining intensity include vimentin, tubulin beta-chain, eukaryotic translation initiation factor 1A, chromatin assembly factor 1 (P48 subunit), probable protein disulfide isomerase P5, and several other proteins. Vimentin and tubulin beta-chain have been reported to be phosphorylated at tyrosine residues and involved in the signal transduction pathway induced by TNF-alpha. However, the other proteins have no previously known function in the signal transduction pathway. Thus, the methods used in this study seem to be suitable for the identification of time-dependent changes in many proteins that are involved in signal transduction. Usefulness of the method for comprehensive analysis of the proteins involved in signal transduction pathway and the limitations of the method are discussed.
Neutrophil Elastase Degrades Cystic Fibrosis Transmembrane Conductance Regulator via Calpains and Disables Channel Function In Vitro and In Vivo (2012)

These data provide a new mechanism and show for the first time a link between NE-calpains activation and CFTR loss of function in bacterial lung infections relevant to CF and to other chronic inflammatory lung conditions.
PqsD Is Responsible for the Synthesis of 2,4-Dihydroxyquinoline, an Extracellular Metabolite Produced by Pseudomonas aeruginosa (2008)

2,4-Dihydroxyquinoline (DHQ) is an abundant extracellular metabolite of the opportunistic pathogen Pseudomonas aeruginosa that is secreted into growth medium in stationary phase to concentrations comparable with those of the Pseudomonas quinolone signal. Using a combination of biochemical and genetic approaches, we show that PqsD, a condensing enzyme in the pqs operon that is essential for Pseudomonas quinolone signal synthesis, accounts for DHQ formation in vivo. First, the anthraniloyl moiety is transferred to the active-site Cys of PqsD to form an anthraniloyl-PqsD intermediate, which then condenses with either malonyl-CoA or malonyl-acyl carrier protein to produce 3-(2-aminophenyl)-3-oxopropanoyl-CoA. This short-lived intermediate undergoes an intramolecular rearrangement to form DHQ. DHQ was produced by Escherichia coli coexpressing PqsA and PqsD, illustrating that these two proteins are the only factors necessary for DHQ synthesis. Thus, PqsD is responsible for the production of DHQ in P. aeruginosa.
A wavelength-division multiplexed passive optical network with cost-shared components (1994)

We demonstrate a passive optical network (PON), based on a wavelength-division multiplexing router, with modulators (instead of lasers) at the subscriber terminals. A single, cost-shared, tunable laser is time-division multiplexed to provide bidirectional switched WDM services for N subscribers with independent formats and bit-rates for each. Simultaneous support of telephony and compressed digital video are presented in which RF subcarrier multiplexing is used to provide service segregation and resolve upstream packet contention.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hypoxia: A Link between Fibrogenesis, Angiogenesis, and Carcinogenesis in Liver Disease (2010)

Liver injury causes vascular disorganization and local tissue hypoxia starting early in disease course. In this context, hypoxia acts not only as an aggravating factor of cell damage and inflammation, but also as an inhibitor of liver regeneration, a major stimulus of angiogenesis and fibrogenesis, and a promoter of liver carcinogenesis. Many of the effects of hypoxia are mediated by hypoxia-inducible factor-1alpha (HIF-1alpha), an oxygen-sensitive transcription factor. Compared to cells in the periportal area, intralobular hepatic stellate cells (HSCs) are more responsive to hypoxia and like other pericytes play a key role in angiogenesis through interactions with endothelial cells VIA platelet-derived growth factor (PGDF) and vascular endothelial growth factor (VEGF) signaling, at the leading edge of fibrotic septa. Although required for successful liver repair, angiogenesis in cirrhosis may be inefficient because of the immaturity and permeability of VEGF-induced neo-vessels, and thereby may fail to correct liver hypoxia. The multiple receptor tyrosine kinase inhibitors, acting on VEGF and PDGF receptors, initially designed for cancer treatment, show in addition to therapeutic efficacy in patients with hepatocellular carcinoma, beneficial effects on many aspects of the progression of liver diseases, including, fibrosis, inflammation and portal hypertension.
3-Phosphoglycerate dehydrogenase, a key enzyme for l-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain. (2001)

l-Serine is synthesized from glycolytic intermediate 3-phosphoglycerate and is an indispensable precursor for the synthesis of proteins, membrane lipids, nucleotides, and neuroactive amino acids d-serine and glycine. We have recently shown that l-serine and its interconvertible glycine act as Bergmann glia-derived trophic factors for cerebellar Purkinje cells. To investigate whether such a metabolic neuron-glial relationship is fundamental to the developing and adult brain, we examined by in situ hybridization and immunohistochemistry the cellular expression of 3-phosphoglycerate dehydrogenase (3PGDH), the initial step enzyme for de novo l-serine biosynthesis in animal cells. At early stages when the neural wall consists exclusively of the ventricular zone, neuroepithelial stem cells expressed 3PGDH strongly and homogeneously. Thereafter, 3PGDH expression was downregulated and eventually disappeared in neuronal populations, whereas its high expression was transmitted to the radial glia and later to astrocytes in the gray and white matters. In addition, 3PGDH was highly expressed throughout development in the olfactory ensheathing glia, a specialized supporting cell that thoroughly ensheathes olfactory nerves. These results establish a fundamental link of the radial glia/astrocyte lineage and olfactory ensheathing glia to l-serine biosynthesis in the brain. We discuss this finding in the context of the hypothesis that 3PGDH expression in these glia cells contributes to energy metabolism in differentiating and differentiated neurons and other glia cells, which are known to be vulnerable to energy loss.