gebhart/patrepeval huggingface dataset:
Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig<sup>TM</sup>) molecule that specifically and potently neutralizes both IL-1α and IL-1β (2015)

Interleukin-1 (IL-1) cytokines such as IL-1α, IL-1β, and IL-1Ra contribute to immune regulation and inflammatory processes by exerting a wide range of cellular responses, including expression of cytokines and chemokines, matrix metalloproteinases, and nitric oxide synthetase. IL-1α and IL-1β bind to IL-1R1 complexed to the IL-1 receptor accessory protein and induce similar physiological effects. Preclinical and clinical studies provide significant evidence for the role of IL-1 in the pathogenesis of osteoarthritis (OA), including cartilage degradation, bone sclerosis, and synovial proliferation. Here, we describe the generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig) of the IgG1/k subtype that specifically and potently neutralizes IL-1α and IL-1β. In ABT-981, the IL-1β variable domain resides in the outer domain of the DVD-Ig, whereas the IL-1α variable domain is located in the inner position. ABT-981 specifically binds to IL-1α and IL-1β, and is physically capable of binding 2 human IL-1α and 2 human IL-1β molecules simultaneously. Single-dose intravenous and subcutaneous pharmacokinetics studies indicate that ABT-981 has a half-life of 8.0 to 10.4 d in cynomolgus monkey and 10.0 to 20.3 d in rodents. ABT-981 exhibits suitable drug-like-properties including affinity, potency, specificity, half-life, and stability for evaluation in human clinical trials. ABT-981 offers an exciting new approach for the treatment of OA, potentially addressing both disease modification and symptom relief as a disease-modifying OA drug.
An Energy-Efficient In-Memory BNN Architecture With Time-Domain Analog and Digital Mixed-Signal Processing (2019)

Neural networks (NN) have been widely used in various applications. However, the high computational complexity and energy consumption of NNs impede their deployment on embedded and mobile platforms, where computational resources and energy are limited. Most of the existing accelerators are based on traditional Von Neumann(VN) architecture, which separates computing from storage, and the massive data movement between the processor and off-chip memory causes great power consumption. In-memory computing (IMC) architecture integrates computing and storage together to eliminate explicit memory access, reducing energy-hungry data transmission. On the other hand, binary neural network (BNN) restricts the weight and activation value to either -1 or +1, converting a large number of multiplications into simple bit-wise XNOR logical operations, and significantly reduces the complexity of computation and amount of memory access. We propose an energy efficient in-memory BNN architecture that performs matrix-vector multiplication (M×V) of FC layers. The bit-wise XNOR operation is realized on the bit line of SRAM, making the data fetching is part of the computation. The accumulation and binarization are performed in time domain with analog and digital mixed-signal processing, which can be blended with SRAM to minimize the data transmission overhead. In the operating condition of TT 0.5V 25 ć 50MHZ, the energy efficiency is 96.249 TOPS/W, surpassing the conventional digital implementation with similar performance by 2.09×.
An Isolate of Human Immunodeficiency Virus Type 1 Originally Classified as Subtype I Represents a Complex Mosaic Comprising Three Different Group M Subtypes (A, G, and I) (1998)

Full-length reference clones and sequences are currently available for eight human immunodeficiency virus type 1 (HIV-1) group M subtypes (A through H), but none have been reported for subtypes I and J, which have only been identified in a few individuals. Phylogenetic information for subtype I, in particular, is limited since only about 400 bp of env gene sequences have been determined for just two epidemiologically linked viruses infecting a couple who were heterosexual intravenous drug users from Cyprus. To characterize subtype I in greater detail, we employed long-range PCR to clone a full-length provirus (94CY032.3) from an isolate obtained from one of the individuals originally reported to be infected with this subtype. Phylogenetic analysis of C2-V3 env gene sequences confirmed that 94CY032.3 was closely related to sequences previously classified as subtype I. However, analysis of the remainder of its genome revealed various regions in which 94CY032.3 was significantly clustered with either subtype A or subtype G. Only sequences located in vpr and nef, as well as the middle portions of pol and env, formed independent lineages roughly equidistant from all other known subtypes. Since these latter regions most likely have a common origin, we classify them all as subtype I. These results thus indicate that the originally reported prototypic subtype I isolate 94CY032 represents a triple recombinant (A/G/I) with at least 11 points of recombination crossover. We also screened HIV-1 recombinants with regions of uncertain subtype assignment for the presence of subtype I sequences. This analysis revealed that two of the earliest mosaics from Africa, Z321B (A/G/?) and MAL (A/D/?), contain short segments of sequence which clustered closely with the subtype I domains of 94CY032.3. Since Z321 was isolated in 1976, subtype I as well as subtypes A and G must have existed in Central Africa prior to that date. The discovery of subtype I in HIV-1 hybrids from widely distant geographic locations also suggests a more widespread distribution of this virus subtype, or at least segments of it, than previously recognized.
Automated Content Scoring of Spoken Responses in an Assessment for Teachers of English (2013)

This paper presents and evaluates approaches to automatically score the content correctness of spoken responses in a new language test for teachers of English as a foreign language who are non-native speakers of English. Most ex-isting tests of English spoken proficiency elic-it responses that are either very constrained (e.g., reading a passage aloud) or are of a pre-dominantly spontaneous nature (e.g., stating an opinion on an issue). However, the assess-ment discussed in this paper focuses on essen-tial speaking skills that English teachers need in order to be effective communicators in their classrooms and elicits mostly responses that fall in between these extremes and are moder-ately predictable. In order to automatically score the content accuracy of these spoken re-sponses, we propose three categories of robust features, inspired from flexible text matching, n-grams, as well as string edit distance met-rics. The experimental results indicate that even based on speech recognizer output, most of the feature correlations with human expert rater scores are in the range of r = 0.4 to r = 0.5, and further, that a scoring model for pre-dicting human rater proficiency scores that in-cludes our content features can significantly outperform a baseline without these features (r = 0.56 vs. r = 0.33). 1
High-yield novel leech hyaluronidase to expedite the preparation of specific hyaluronan oligomers (2014)

Hyaluronidases (HAases), particularly leech HAases, have attracted intense attention due to their broad applications in medical treatments and great potential for the enzymatic production of hyaluronan oligosaccharides. However, little is known about this third interesting family of HAases. Here, we applied the random amplification of cDNA ends polymerase chain reaction (RACE-PCR) approach to identify the first leech HAase-encoding gene. By combining protein engineering and high-density culture, we achieved high-level production (8.42 × 10(5) U ml(-1)) in the yeast Pichia pastoris secretory expression system. Compared with the commercial bovine testicular HAase, the recombinant leech HAase exhibited superior enzymatic properties. Furthermore, analysis of the hydrolytic process suggested that this novel enzyme adopts a nonprocessive endolytic mode, yielding a narrow-spectrum of specific HA oligosaccharides with different incubation times. Large-scale production of this novel leech HAase will not only greatly promote medical applications but also facilitate the enzymatic production of specific HA oligosaccharides.
Uncoupling of Pyrin-only Protein 2 (POP2)-mediated Dual Regulation of NF-κB and the Inflammasome (2011)

Activation of transcription factor NF-κB and inflammasome-directed caspase-1 cleavage of IL-1β are key processes in the inflammatory response to pathogen or host-derived signals. Pyrin-only proteins (POPs) are restricted to Old World monkeys, apes, and humans and have previously been shown to impair inflammasome assembly and/or NF-κB p65 transcriptional activity in transfected epithelial cells. However, the biological role of POP2 and the molecular basis for its observed functions are not well understood. In this report we demonstrate that POP2 regulates TNFα and IL-1β responses in human monocytic THP-1 cells and in stable transfectants of mouse J774A.1 macrophages. Deletion analysis of POP2 revealed that the first α-helix (residues 1-19) is necessary and sufficient for both inflammasome and NF-κB inhibitory functions. Further, key acidic residues Glu(6), Asp(8), and Glu(16), believed critical for Pyrin/Pyrin domain interaction, are important for inflammasome inhibition. Moreover, these mutations did not reduce the effect of POP2 upon NF-κB, indicating that the inflammasome and NF-κB inhibitory properties of POP2 can be uncoupled mechanistically. Collectively, these data demonstrate that POP2 acts as a regulator of inflammatory signals and exerts its two known functions through distinct modalities employed by its first α-helix.
Switched tracking control of a human limb during asynchronous neuromuscular electrical stimulation (2015)

Neuromuscular electrical stimulation (NMES) is a method commonly used for rehabilitation whereby an applied electrical stimulus induces muscle contractions. NMES can also evoke functional movements; however, a fundamental limitation is the early onset of fatigue. Asynchronous stimulation is a method that can reduce fatigue by utilizing multiple stimulation channels to segregate and switch between different sets of motor units. However, one limitation is that switching introduces discontinuities since each set of motor units responds differently to stimulation. Therefore, there is a need to design a controller which considers the switching dynamics and differing muscle response. In preliminary work, a control law was developed for asynchronous stimulation. However, the previous control design required there to be a finite window of time where the control voltage is transitioned from one channel to another. Since a transition period is undesirable in practice (as it will lead to increased fatigue), a switched systems analysis is used in the present work to design a controller that allows for instantaneous switching. The developed controller yields semiglobal exponential tracking of a desired angular trajectory for a person's knee-shank complex. The result of the work is promising for the implementation of asynchronous stimulation for closed-loop rehabilitative procedures and in assistive devices as an approach to limit NMES-induced fatigue while tracking a desired trajectory.
Reducing solid particle erosion damage in large steam turbines (1985)

L'erosion des tuyeres et des auges de turbines a vapeur causee par les particules solides coute cher (diminution du fonctionnement de l'appareil, reparations et remplacement des pieces erodees). Pour pallier a ces inconvenients, General Electric a mis sur pied un ensemble de recherches pour: a) comprendre les mecanismes de l'erosion au moyen de simulations numeriques des trajectoires et vitesses des particules; b) evaluer les revetements anti-corrosion des auges et des tuyeres; c) realiser les ameliorations possibles passant par l'installation de nouveaux revetements et d'une malification du trajet de la vapeur en tenant compte des etudes de a) et b)
Effects of Foam Microbubbles on Electrical Resistivity and Capillary Pressure of Partially Saturated Porous Media (2020)

Laboratory measurements of capillary pressure (<i>P<sub>c</sub></i>) and the electrical resistivity index (<i>RI</i>) of reservoir rocks are used to calibrate well logging tools and to determine reservoir fluid distribution. Significant studies on the methods and factors affecting these measurements in rocks containing oil, gas, and water are adequately reported in the literature. However, with the advent of chemical enhanced oil recovery (EOR) methods, surfactants are mixed with injection fluids to generate foam to enhance the gas injection process. Foam is a complex and non-Newtonian fluid whose behavior in porous media is different from conventional reservoir fluids. As a result, the effect of foam on <i>P<sub>c</sub></i> and the reliability of using known rock models such as the Archie equation to fit experimental resistivity data in rocks containing foam are yet to be ascertained. In this study, we investigated the effect of foam on the behavior of both <i>P<sub>c</sub></i> and <i>RI</i> curves in sandstone and carbonate rocks using both porous plate and two-pole resistivity methods at ambient temperature. Our results consistently showed that for a given water saturation (<i>S<sub>w</sub></i>), the <i>RI</i> of a rock increases in the presence of foam than without foam. We found that, below a critical <i>S<sub>w</sub></i>, the resistivity of a rock containing foam continues to rise rapidly. We argue, based on knowledge of foam behavior in porous media, that this critical <i>S<sub>w</sub></i> represents the regime where the foam texture begins to become finer, and it is dependent on the properties of the rock and the foam. Nonetheless, the Archie model fits the experimental data of the rocks but with resulting saturation exponents that are higher than conventional gas-water rock systems. The degree of variation in the saturation exponents between the two fluid systems also depends on the rock and fluid properties. A theory is presented to explain this phenomenon. We also found that foam affects the saturation exponent in a similar way as oil-wet rocks in the sense that they decrease the cross-sectional area of water available in the pores for current flow. Foam appears to have competing and opposite effects caused by the presence of clay, micropores, and conducting minerals, which tend to lower the saturation exponent at low <i>S<sub>w</sub></i>. Finally, the <i>P<sub>c</sub></i> curve is consistently lower in foam than without foam for the same <i>S<sub>w</sub></i>.
Identical <i>APC</i> exon 15 mutations result in a variable phenotype in familial adenomatous polyposis (1993)

Germ-line mutations in the adenomatous polyposis coli (APC) gene result in familial adenomatous polyposis coli (APC), an inherited syndrome that predisposes affected individuals to early onset of colorectal cancer. Somatic APC mutations also have been detected in sporadic colon tumors. We have used single strand conformational polymorphism (SSCP) analysis to scan a region of the APC gene that frequently is mutated in both APC and sporadic colorectal cancer. Four truncating mutations were found between codons 1060 and 1327 in 17 of 68 unrelated APC individuals. Fourteen of these persons carried either of two previously described five-nucleotide deletions which represent about 20% of APC mutations in these pedigrees. Patients with mutations in this region of exon 15 develop a classic APC colonic phenotype with multiple, diffuse adenomas developing by the second or third decade. However, the density of adenomas and the extracolonic disease manifestations associated with this syndrome are variable among individuals with identical APC mutations.
Three-dimensional digital topological characterization of cancellous bone architecture (2000)

Cancellous bone consists of a network of bony struts and plates that provide mechanical strength to much of the skeleton at minimum weight. It has been shown that loss in bone mass is accompanied by architectural changes that relate to both scale and topology of the network. In this paper, the concept of three-dimensional (3D) digital topology is presented for characterizing the local topology of each bone voxel after skeletonization of the binary bone images. This method allows us to identify each voxel as belonging to a surface, curve, or junction structure in the trabecular bone network. The method has been quantitatively validated on synthetic images demonstrating its relative immunity to partial volume blurring and noise. Parameters introduced to characterize network topology include surface-to-curve ratio and erosion index. Finally, the technique is shown to quantify the architecture of human trabecular bone in magnetic resonance micro-images acquired from cadavers and in vivo.© 2000 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 11, 81–90, 2000
CORC Technical Report TR-2002-03 Robust portfolio selection problems (2002)

In this paper we show how to formulate and solve robust portfolio selection problems. The objectiveoftheserobustformulationsistosystematicallycombatthesensitivityoftheoptimal portfolio to statistical and modeling errors in the estimates of the relevant market parameters. We introduce \uncertainty for the market parameters and show that the robust portfolio selection problems corresponding to these uncertainty structures can be reformulated as second-order cone programs and, therefore, the computational efiort required to solve them iscomparabletothatrequiredforsolvingconvexquadraticprograms. Moreover,weshowthat these uncertainty structures correspond to confldence regions associated with the statistical procedures employed to estimate the market parameters. Finally, we demonstrate a simple recipe for e‐ciently computing robust portfolios given raw market data and a desired level of confldence.
Treating transgenic Alzheimer mice with a β-secretase inhibitor, what have we learned? (2011)

β-Secretase is an attractive target of amyloid-reduction therapy for Alzheimer's disease. Currently, no efficacy data is available from clinical trials of β-secretase inhibitors. Treating young transgenic Tg2576 mice with a brain-penetrating β-secretase inhibitor reduced brain amyloid-β by about 50% and rescued the age-related cognitive decline. Implications from these model studies on the design of clinical trials are discussed herein.
Potent and Orally Bioavailable 8-Bicyclo[2.2.2]octylxanthines as Adenosine A<sub>1</sub> Receptor Antagonists (2006)

In the search for a selective adenosine A1 receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4-substituted 8-cyclohexyl and 8-bicyclo[2.2.2]octylxanthines were investigated. The binding affinities of a variety of cyclohexyl and bicyclo[2.2.2]octylxanthines for the rat and human adenosine A1, A2A, A2B, and A3 receptors are presented. Bicyclo[2.2.2]octylxanthine 16 exhibited good pharmaceutical properties and in vivo activity in a rat diuresis model (ED50=0.3 mg/kg po). Optimization of the bridgehead substituent led to propionic acid 29 (BG9928), which retained high potency (hA1, Ki=7 nM) and selectivity for the adenosine A1 receptor (915-fold versus adenosine A2A receptor; 12-fold versus adenosine A2B receptor) with improved oral efficacy in the rat diuresis model (ED50=0.01 mg/kg) as well as high oral bioavailability in rat, dog, and cynomolgus monkey.
Driving Safety and Real-Time Glucose Monitoring in Insulin-Dependent Diabetes (2019)

Our goal is to address the need for driver-state detection using wearable and in-vehicle sensor measurements of driver physiology and health. To address this goal, we deployed in-vehicle systems, wearable sensors, and procedures capable of quantifying real-world driving behavior and performance in at-risk drivers with insulin-dependent type 1 diabetes mellitus (DM). We applied these methodologies over 4 weeks of continuous observation to quantify differences in real-world driver behavior profiles associated with physiologic changes in drivers with DM (N=19) and without DM (N=14). Results showed that DM driver behavior changed as a function of glycemic state, particularly hypoglycemia. DM drivers often drive during at-risk physiologic states, possibly due to unawareness of impairment, which in turn may relate to blunted physiologic responses (measurable heart rate) to hypoglycemia after repeated episodes of hypoglycemia. We found that this DM driver cohort has an elevated risk of crashes and citations, which our results suggest is linked to the DM driver's own momentary physiology. Overall, our findings demonstrate a clear link between at-risk driver physiology and real-world driving. By discovering key relationships between naturalistic driving and parameters of contemporaneous physiologic changes, like glucose control, this study directly advances the goal of driver-state detection through wearable physiologic sensors as well as efforts to develop "gold standard" metrics of driver safety and an individualized approach to driver health and wellness.
Incorporation of crosslinking agents into poly(vinyl phosphonic acid) as a route to glass–polyalkenoate cements of improved compressive strength (1993)

A method for incorporating potential crosslinking agents into poly(vinyl phosphonic acid)(PVPA) is described. Polymers with increased relative molar mass have been synthesized and used to fabricate experimental PVPAbased dental cements of improved compressive strength. The presence of these crosslinking agents was found to make no significant difference to the working and setting times or overall handling characteristics of these cements.
A Novel Chromogenic Assay Equivalent to the One Stage Prothrombin Time (PT) (1979)

A chromogenic assay equivalent to the PT has been developed which, it is expected, will allow the standardization of therapeutic limits. Assays were performed by combining 0.25 ml S-2238 (2mM), 0.40 ml tissue thromboplastin, and 0.050 ml plasma in 1.40 ml TRIS buffer (pH=8.50, I=0.15). The rate of thrombin generation was obtained by automatically computing the slope of In (A405nm/min. ) vs time. The results indicated that thromboplastin does not interfere with S-2238 hydrolysis. Thrombin production (A/min.) occurs just before clotting, rises rapidly to a maximum and falls. During its rise, the thrombin concentration increases as a positive exponential, exp(bt). The exponential rate, called b, is constant from the initial appearance to the maximum thrombin concentration, b is proportional to plasma concentration and to log Factor (X, VII, V) concentration for dilutions with deficient plasma. Log 1/b correlates with log PT using dicoumarolized plasmas. Thrombin appearance is quite delayed (12 min.) in diluted, deficient plasma. Thus, the assay appears sensitive to the extrinsic system and can be used to monitor dicoumarolized plasmas. Unlike the standard PT, this assay directly measures the rate of thrombin production and could be standardized by comparing the exponential rate to specific Factor concentrations.
Characterizing spinal muscular atrophy with electrical impedance myography (2010)

Electrical impedance myography (EIM) is a non-invasive, painless technique for the evaluation of neuromuscular disease, and here we evaluate its potential application in spinal muscular atrophy (SMA). Twenty-one SMA patients and 18 healthy children underwent EIM of biceps brachii and tibialis anterior using a commercially available impedance device. Hand-held dynamometry and ultrasound assessment of subcutaneous fat thickness were also performed. All EIM parameters differed significantly between both SMA patients and normal subjects and between type 2 and type 3 SMA patients. In addition, EIM had an accuracy level as high as 93% for correctly categorizing patients as type 2 or type 3. Multiple regression analyses confirmed a strong association between EIM and dynamometry. These results confirm that EIM can accurately categorize patients with SMA. Because EIM requires no patient effort and is rapid to apply, it may serve a useful role in future SMA clinical trials.