gebhart/patrepeval huggingface dataset:
Small Molecules Showing Significant Protection of Mice against Botulinum Neurotoxin Serotype A (2010)

Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism that could afflict large, unprotected populations if the toxin were employed in an act of bioterrorism. Current post-exposure therapy is limited to symptomatic treatment or passive immunization that is effective for treating infant botulism at a cost of US $45,300 per treatment regimen. Antibodies can neutralize the extracellular but not the intracellular BoNTA. Moreover, antibody production, storage, and administration in a mass casualty scenario pose logistical challenges. Alternatively, small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are sought to antagonize the extracellular or intracellular toxin. While several such molecules reportedly demonstrated efficacy in protecting cells against BoNTA, there is scant information to show that small molecules can significantly protect mammals against BoNTA. Herein we report the development of effective small-molecules BoNTAe inhibitors with promising in vivo pharmacokinetics. One such molecule has an in vivo half-life of 6.5 hours and is devoid of obvious sign of toxicity. Pre-treatment with this molecule at 2 mg/kg protected 100% and 70% of treated mice against BoNTA at 5 times of its median-lethal dose during the periods of 2 and 4 half-lives of the inhibitor, respectively. In contrast, 40% and 0% of untreated mice survived during the respective periods. Similar levels of protection were also observed with two other small molecules. These results demonstrate that small molecules can significantly protect mice against BoNTA and support the pursuit of small-molecule antagonists as a cost-effective alternative or as an adjunct to passive immunity for treating botulism.
Recombinant variant of <i>Fasciola hepatica</i> fatty acid binding protein impairs the NF-κB activation in response to toll-like receptors agonists (2016)

Abstract In recent years, it has been demonstrated that a strong Th2 immune response is able to suppress the inflammatory type or Th1 response; this Th1 response is linked to septic shock and some autoimmune diseases. Fasciola hepatica promotes a Th2 response during chronic infections, hence the production of anti-inflammatory cytokines. Our research group published that fatty acid binding protein (FABP) purified in native form (Fh12) from F. hepatica adult worm impairs the inflammatory cytokines storm typically induced by exposure to Lipopolysaccharides (LPS). Our work aimed to determine whether a recombinant variant of FABP could have a similar effect. We optimized the expression in E. Coli of an isoform of FABP named Fh15 and performed western blot analysis to confirm an immunological similarity between Fh12 and Fh15. Human monocytes THP1-CD14 cells were treated with Fh15, then stimulated separately with specific activation ligands for TLR 2, 4, 5 and 8 in order to determine the capacity to inhibit the NF-κB activation; we used Quanti-Blue medium to quantify the inhibition. Our results showed that both proteins are immunologically similar. Also, Fh15 was able to block the NF-κB activation induced by specific TLR ligands up to 95%, showing similar capacity as Fh12. The use of bacterial expression lead us to conclude that the glycosylation sites described for Fh12 are not required for the effect. We can anticipate that Fh15 has the potential to exhibit an inflammatory cytokines suppression effect. Fh15 impairs the NF-κB activation induced by different TLR-ligands suggesting a broad spectrum of action. We are working to elucidate the mechanisms for this effect and examine the potential of Fh12 and Fh15 as anti-inflammatory molecules in animal models.
Compilation of weighted finite-state transducers from decision trees (1996)

We report on a method for compiling decision trees into weighted finite-state transducers. The key assumptions are that the tree predictions specify how to rewrite symbols from an input string, and the decision at each tree node is stateable in terms of regular expressions on the input string. Each leaf node can then be treated as a separate rule where the left and right contexts are constructable from the decisions made traversing the tree from the root to the leaf. These rules are compiled into transducers using the weighted rewite-rule rule-compilation algorithm described in (Mohri and Sproat, 1996).
Prothymosin alpha in human blood. (1987)

The major cross-reacting peptide in human plasma detected with a radioimmunoassay (RIA) for thymosin alpha 1 was identified as prothymosin alpha, based on its elution properties in gel-filtration chromatography and its amino acid composition after purification by HPLC. A small quantity (less than 10%) of the total cross-reacting material was recovered in fractions corresponding to lower molecular weight thymosin alpha 1-like peptides. The total quantity of cross-reacting material detected in human blood, expressed as thymosin alpha 1 equivalents, was 11-14 pmol/ml (approximately 90% was recovered in the leukocyte fraction, approximately 10% was in the plasma fraction, and 1-2% was in the erythrocyte fraction). The peptide present in leukocytes was also identified as prothymosin alpha. After correction for the 5-times lower molar reactivity of prothymosin alpha in the thymosin alpha 1 RIA employed in these experiments, we estimate that the content of prothymosin alpha in human blood is 55-70 pmol/ml (0.6-0.8 microgram/ml). The relatively small quantities recovered in the erythrocyte and plasma fractions may be attributed to contamination of the former by leukocytes or to leakage from leukocytes into the plasma.
Graphene-Nickel composite films on flexible PCB for temperature monitoring (2017)

This paper presents a novel method to fabricate temperature sensor arrays by screen printing Graphene - Nickel (Ni) nanocomposite film on flexible printed circuit board (PCB). Screen printing is a cost effective fabrication technique to get uniform thickness film on a substrate. The fabricated temperature sensor array, each having sensing thickness of around 50 μm is studied for the temperature response. The synthesized RGO nanosheets and RGO-Ni nanocomposite were characterized by XRD and FE-SEM for structural and compositional analysis. Temperature variation is measured in terms of change in resistance. It is observed that resistance decreases with the increase in temperature showing NTC (Negative Temperature Coefficient) behavior. The calculated response of the sensor in terms of sensitivity is around 2.455 Ω / K and temperature coefficient of resistance (TCR) is around - 2.635 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> Ω / Ω / K. Our approach shows a very simple fabrication process for making mass production of sensors on PCB that can be easily integrated with electronic devices and as a wearable body temperature sensor.
InP tunnel junctions for InP/InGaAs tandem solar cells (1995)

We report, for the first time, an epitaxially grown InP p(+)/n(++) tunnel junction. A diode with peak current densities up to 1600 Al/sq cm and maximum specific resistivities (Vp/lp - peak voltage to peak current ratio) in the range of 10(exp -4)Om sq cm is obtained. This peak current density is comparable to the highest results previously reported for lattice matched In(0.53)Ga(0.47)As tunnel junctions. Both results were obtained using chemical beam epitaxy (CBE). In this paper we discuss the electrical characteristics of these tunnel diodes and how the growth conditions influence them.
A persistent-mode 0.5 T solid-nitrogen-cooled MgB<sub>2</sub>magnet for MRI (2016)

This paper presents construction details and test results of a persistent-mode 0.5-T MgB<sub>2</sub> magnet developed at the Francis Bitter Magnet Lab, MIT. The magnet, of 276-mm inner diameter and 290-mm outer diameter, consisted of a stack of 8 solenoidal coils with a total height of 460 mm. Each coil was wound with monofilament MgB<sub>2</sub> wire, equipped with a persistent-current switch and terminated with a superconducting joint, forming an individual superconducting loop. Resistive solder joints connected the 8 coils in series. The magnet, after being integrated into a testing system, immersed in solid nitrogen, was operated in a temperature range of 10-13 K. A two-stage cryocooler was deployed to cool a radiation shield and the cold mass that included mainly ~60 kg of solid nitrogen and the magnet. The solid nitrogen was capable of providing a uniform and stable cryogenic environment to the magnet. The magnet sustained a 0.47-T magnetic field at its center persistently in a range of 10-13 K. The current in each coil was inversely calculated from the measured field profile to determine the performance of each coil in persistent-mode operation. Persistent-current switches were successfully operated in solid nitrogen for ramping the magnet. They were also designed to absorb magnetic energy in a protection mechanism; its effectiveness was evaluated in an induced quench.
A low-power inverted ladder D/a converter (2006)

Interpolating, dual resistor ladder digital-to-analog converters (DACs) typically use the fine, least significant bit (LSB) ladder floating upon the static most significant bit (MSB) ladder. The usage of the LSB ladder incurs a penalty in dynamic performance due to the added output resistance and switch matrix parasitic capacitance. Current biasing of the LSB ladder addresses this issue by employing active circuitry. We propose an inverted ladder DAC, where an MSB ladder slides upon two static LSB ladders. While using no active components this scheme achieves lower output resistance and parasitic capacitance for a given power budget. We present a 0.35-mum, 3.3-V implementation consuming 22-muA current with output resistance of 40 kOmega and effective parasitic capacitance of 650 fF
Signal processing, glycosylation, and secretion of mutant hemagglutinins of a human influenza virus by Saccharomyces cerevisiae. (1987)

We investigated the nature of signal recognition, transport, and secretion of mutant hemagglutinins (HAs) of a human influenza virus by the yeast Saccharomyces cerevisiae. The cDNA sequences encoding variant forms of influenza HA were expressed in S. cerevisiae. The HA polypeptides (HA500 and HA325) that were synthesized with their N-terminal signal peptides were correctly targeted to the membrane compartment where they were glycosylated. In contrast, the HA polypeptides (HA484 and HA308) lacking the signal peptide were expressed in the cytoplasm and did not undergo any glycosidic modification, demonstrating the importance of the heterologous signal sequence in the early steps of translocation in S. cerevisiae. The analysis of the N-terminal amino acid sequence of HA500 and HA325 polypeptides demonstrated the correct cleavage of the signal peptide, indicating the structural compatibility of a heterologous signal peptide for efficient recognition and processing by the yeast translocation machinery. The membrane-sequestered and glycosylated HA polypeptides were relatively stable in S. cerevisiae compared with the signal-minus, nonglycosylated HA molecules. Although both the anchor-minus HA (HA500) and HA1 (HA325) polypeptides were targeted efficiently to the membrane, their glycosylation and transport patterns were shown to be different. During pulse-chase, the HA500 remained cell-associated with no detectable secretion into the extracellular medium, whereas the HA325 secreted into the medium. Furthermore, only the cell-associated and secreted forms of HA325 and not HA500 appeared to have undergone hyperglycosylation with the extensive addition of high-molecular-weight outer-chain mannans. Possible reasons for the observed phenotypic behavior of these two mutant HAs are discussed.
Soluble CD80 restores T cell activation and overcomes tumor cell Programmed Death Ligand-1-mediated suppression (P2041) (2013)

Abstract Many tumor cells escape anti-tumor immunity through their expression of Programmed Death Ligand 1 (PDL1 or B7-H1), which interacts with T cell-expressed PD1 and results in T cell apoptosis. We previously reported that transfection of human tumor cells with a membrane-bound form of the costimulatory molecule CD80 prevented PD1 binding and restored T cell activation. We now report that membrane-bound CD80 similarly reduces PDL1-PD1-mediated suppression by mouse tumor cells, and that a fusion protein consisting of the extracellular domains of CD80 fused to an Fc domain of IgG1 overcomes PDL1-mediated suppression by human tumor cells. T cell activation experiments assessing costimulation indicate that the soluble CD80 fusion protein mediates its effects by binding to PDL1 and inhibiting PDL1-PD1 interactions. Comparison of the CD80 fusion protein to antibodies specific for PD1 or PDL1 demonstrate that soluble CD80 treatment is more effective in restoring T cell activation than treatment with mAb to either PD1 or PDL1. These studies identify soluble CD80 as an alternative and potentially more efficacious therapeutic agent for overcoming PDL1-induced immune suppression and facilitating tumor-specific immunity.
Nonlinear Reference Phases in Synthetic Optical Holography (2014)

The recent development of synthetic optical holography has provided an opportunity to generate arbitrary reference waves in digital holography, which may not have linear phase. As an interesting case, we consider a reference whose phase varies sinusoidally in space. The hologram is inverted by combining at least two windowed Fourier terms from the intensity image. The fact that the reference can be generated by an oscillating reference mirror with limited travel range in open loop simplifies the requirements for synthetic holography.
Estimation of borehole fluid slowness using sonic array waveforms (2009)

Mud slowness is an important parameter controlling wave propagation in a fluid‐filled borehole. However, there is no direct measurement of this quantity in the hole at sonic frequencies. The most common approach to measure fluid slowness consists of performing slowness measurements at the surface using mud sample or using empirical laws linking mud slowness as a function of mud density and type. However, these measurements at the surface does not reproduce real well conditions introducing erroneous mud slowness estimate, while empirical equations tend to provide reasonable results but can yield wrong estimates if assumptions are not valid or uncertainties in some parameters are too large. An alternative approach consists in analyzing dispersive modes contained in recorded data and from this study deriving an estimate of the mud slowness. The drawback of this non automatic method is that it relies heavily on the skill of the person that analyzes the dispersion plots. To overcome these limitations, a probabilistic approach combining the high frequency monopole data and outputs from the monopole radial profiling has been developed to get an estimate of the mud slowness. In addition, this algorithm provides an automatic procedure based on the Scholte wave slowness to automatically set the parameters (center and standard deviation) of the a‐priori probability distribution function of the mud slowness. This point is usually critical while using Bayesian approach. Robustness and efficiency of this algorithm will be illustrated on real field data.
Site Selective C-H Functionalization of Mitragyna Alkaloids Reveals a Molecular Switch for Tuning Opioid Receptor Signaling Efficacy (2020)

Mitragynine is the most abundant alkaloid component of the psychoactive plant material “kratom”, which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We developed a new synthetic method for selective functionalization of the unexplored C11 position of the mitragynine scaffold (C6 position in indole numbering) via the use of an indole-ethylene glycol adduct and subsequent iridium-catalyzed borylation. We discovered that C11 represents a key locant for fine-tuning opioid receptor signaling efficacy. In the 7-hydroxymitragynine (7OH) series, the high efficacy parent compound was transformed to an equipotent low efficacy agonist by introducing a fluorine substituent in this position (11-F-7OH), as demonstrated in vitro at both mouse and human mu opioid receptors (mMOR/hMOR) and in vivo in mouse analgesia tests after systemic administration. Low efficacy opioid agonists are of high interest as candidates for generating safer opioid medications with mitigated adverse effects.
Surfactant Templating Effects on the Encapsulation of Iron Oxide Nanoparticles within Silica Microspheres (2007)

Hollow silica microspheres encapsulating ferromagnetic iron oxide nanoparticles were synthesized by a surfactant-aided aerosol process and subsequent treatment. The cationic surfactant cetyltrimethyl ammonium bromide (CTAB) played an essential role in directing the structure of the composite. Translation from mesoporous silica particles to hollow particles was a consequence of increased loading of ferric species in the precursor solution and the competitive partitioning of CTAB between silicate and ferric colloids. The hypothesis was that CTAB preferentially adsorbed onto more positively charged ferric colloids under acidic conditions. At a critical Fe/Si ratio, most of the CTAB was adsorbed onto ferric colloids and coagulated the colloids to form larger clusters. During the aerosol process, a silica shell was first formed due to the preferred silicate condensation on the gas-liquid interface of the aerosol droplet. Subsequent drying concentrated the ferric clusters inside the silica shell and resulted in a silica shell/ferric core particle. Thermal treatment of the core shell particle led to encapsulation of a single iron oxide nanoparticle inside each silica hollow microsphere.
Lessons Learned in over 100 Zebra Mussel Control Applications at Industrial Facilities (1998)

Abstract Since their introduction into US waterways, Zebra Mussels (Dreissena polymorphae) have spread rapidly throughout the Great Lakes and Mississippi regions. These mussels have continued to colonize the intake pipes of industrial water supplies and water distribution systems throughout the affected areas. Their colonization has compromised plant safety and production efficiency, and steadily increased costs to water users. The design of each industrial plant water distribution system is unique. A comprehensive zebra mussel control strategy using the best available options must be considered in each specific situation. This paper discusses the successful use of one strategy (a quaternary ammonia-based molluscicide) in the battle against zebra mussels. The commercial life cycle of an industrial molluscicide began with initial toxicity screening in the laboratory. The evaluation continued at plant sites through field trials and applications. Lessons learned from these experiences helped direct our efforts toward the development of a second generation program.
New Design Limits Plot for Overview of Load-Resistance Relationship in Wellbore Tubular Design (2018)

Abstract In the tubular design of oil and gas wells, visualization of the loads and design limits (resistance over design factor) in a single 2D plot can help provide well designers a safety-factor overview of a particular string section. This plot is called a design limits plot (DLP). This paper illustrates the theoretical foundation and construction procedure of a new DLP, which is believed to more accurately represent safety factors. The new DLP was built by plotting differential pressure, ΔP, vs. equivalent axial load Feq (= Fa + min(pi, po)×AS, where Fa is the axial force, AS is the cross-sectional area, and pi and po are the internal and external pressures, respectively), for both envelopes (design limits) and load points. Temperature-deration effects were applied to load points instead of envelopes so that the safety factor could be neatly represented by the relative load-point location with respect to the room-temperature envelopes. For comparison, the triaxial yield envelope was plotted together with API envelopes (axial, burst, and collapse). A field example is presented that demonstrates the application of the new DLP for wellbore tubular design. It is shown that, for load cases in which counter-load pressures (which are defined as pi for collapse loads and po for burst loads) are high, the new DLP represents the safety factors more accurately and comprehensively. Using the equivalent axial load instead of the axial force in the new DLP allows for better consistency with both the von Mises triaxial yield criterion and the API 5C3 2015 addendum. The new DLP not only represents a more accurate overview of safety factors, but also facilitates direct reading of pipe burst/collapse ratings.
Polarization and modal analysis of a large-area, polarization-maintaining higher-order-modes fiber via a Bragg grating (2019)

We report a method for the characterization of the higher-order modes in polarization-maintaining multimode optical fibers using a Bragg grating. We evaluate a 400 µm diameter, polarization-maintaining higher-order-modes fiber by inscribing a Bragg grating, resonant at the wavelength <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"> <mml:mi>λ</mml:mi> <mml:mo>∼</mml:mo> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mn>1067</mml:mn> </mml:mrow> <mml:mspace width="thickmathspace"/> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi mathvariant="normal">n</mml:mi> <mml:mi mathvariant="normal">m</mml:mi> </mml:mrow> </mml:math> . By comparing the reflection spectra of the light polarized along the slow and the fast axes of the fiber and using the derived mathematical relations, we estimate the birefringence and the polarization-extinction ratio of the various higher-order modes in the fiber. This represents a simple and attractive approach for a detailed investigation of the multimode polarization-maintaining fibers that are emerging as an invaluable tool for advanced manufacturing, defense, bio-imaging, and telecommunications systems.
Tantalum-Based Ceramics for Refractory Composites (2006)

A family of tantalum-based ceramics has been invented as ingredients of high-temperature composite insulating tiles. These materials are suitable for coating and/or permeating the outer layers of rigid porous (foam-like or fibrous) ceramic substrates to (1) render the resulting composite ceramic tiles impervious to hot gases and (2) enable the tiles to survive high heat fluxes at temperatures that can exceed 3,000 F ( 1,600 C).
Timeline index (2013)

Managing temporal data is becoming increasingly important for many applications. Several database systems already support the time dimension, but provide only few temporal operators, which also often exhibit poor performance characteristics. On the academic side, a large number of algorithms and data structures have been proposed, but they often address a subset of these temporal operators only. In this paper, we develop the Timeline Index as a novel, unified data structure that efficiently supports temporal operators such as temporal aggregation, time travel, and temporal joins. As the Timeline Index is independent of the physical order of the data, it provides flexibility in physical design; e.g., it supports any kind of compression scheme, which is crucial for main memory column stores. Our experiments show that the Timeline Index has predictable performance and beats state-of-the-art approaches significantly, sometimes by orders of magnitude.