gebhart/patrepeval huggingface dataset:
Ion Channel Blockers for the Treatment of Neuropathic Pain (2010)

Neuropathic pain, a severe chronic pain condition characterized by a complex pathophysiology, is a largely unmet medical need. Ion channels, which underlie cell excitability, are heavily implicated in the biological mechanisms that generate and sustain neuropathic pain. This review highlights the biological evidence supporting the involvement of voltage-, proton- and ligand-gated ion channels in the neuropathic pain setting. Ion channel modulators at different research or development stages are reviewed and referenced. Ion channel modulation is one of the main avenues to achieve novel, improved neuropathic pain treatments. Voltage-gated sodium and calcium channel and glutamate receptor modulators are likely to produce new, improved agents in the future. Rationally targeting subtypes of known ion channels, tackling recently discovered ion channel targets or combining drugs with different mechanism of action will be primary sources of new drugs in the longer term.
Functionalized Porous Polymer Sheets as Models of Thermoresponsive Membranes for Water Treatment. (1996)

Abstract : A novel approach to thermoresponsive polymeric membranes based on molded monolithic sheets of macroporous polymers has been demonstrated. The macroporous sheet prepared from glycidyl methacrylate ethylene dimethacrylate is functionalized either by free-radical grafting of N-isopropylacrylamide, or, better, by copolymerization of N-isopropylacrylamide onto the vinylated surface of the pores of the polymer sheet. The macroporous polymers modified with poly(N-isopropylacrylamide) were shown to be thermoresponsive. Changes in the temperature of a flow system incorporating the modified macroporous material were accompanied by significant changes in the backpressure required to effect flow. This study confirms the feasibility of thermoresponsive membranes for water purification.
BIM-based building design coordination: processes, bottlenecks, and considerations (2019)

Successful management of the building design coordination process is critical to the efficient delivery of cost-effective and quality projects. The traditional setting of design coordination, however, is inefficient and error-prone. Building information modelling (BIM) has proven valuable for increasing satisfaction with the meeting process and decreasing arguments over issues. Despite the many advantages of BIM tools, however, many design coordination issues remain undetected, design issues are poorly documented, and coordination strategies are inefficient. The objective of this study was to develop a characterization of the BIM building design coordination process, identify the bottlenecks in the current process, and provide design considerations to alleviate the bottlenecks. The bottlenecks include: outdated BIM, disconnected trades, lack of terminology, insufficient documentation, inefficient transitions across views and artifacts, unavailability of design information, information discrepancy, unfit navigation tools, and office–site disconnect. The outcomes of this research is useful for future construction projects and the software development community.
Association of the α2δ1 subunit with Cav3.2 enhances membrane expression and regulates mechanically induced ATP release in MLO-Y4 osteocytes (2011)

Voltage-sensitive calcium channels (VSCCs) mediate signaling events in bone cells in response to mechanical loading. Osteoblasts predominantly express L-type VSCCs composed of the α(1) pore-forming subunit and several auxiliary subunits. Osteocytes, in contrast, express T-type VSCCs and a relatively small amount of L-type α(1) subunits. Auxiliary VSCC subunits have several functions, including modulating gating kinetics, trafficking of the channel, and phosphorylation events. The influence of the α(2)δ auxiliary subunit on T-type VSCCs and the physiologic consequences of that association are incompletely understood and have yet to be investigated in bone. In this study we postulated that the auxiliary α(2) δ subunit of the VSCC complex modulates mechanically regulated ATP release in osteocytes via its association with the T-type Ca(v) 3.2 (α(1H) ) subunit. We demonstrated by reverse-transcriptase polymerase chain reaction, Western blotting, and immunostaining that MLO-Y4 osteocyte-like cells express the T-type Ca(v)3.2(α(1H)) subunit more abundantly than the L-type Ca(v)1.2 (α(1C)) subunit. We also demonstrated that the α(2) δ(1) subunit, previously described as an L-type auxiliary subunit, complexes with the T-type Ca(v)3.2 (α(1H)) subunit in MLO-Y4 cells. Interestingly, siRNA-mediated knockdown of α(2) δ(1) completely abrogated ATP release in response to membrane stretch in MLO-Y4 cells. Additionally, knockdown of the α(2)δ(1) subunit resulted in reduced ERK1/2 activation. Together these data demonstrate a functional VSCC complex. Immunocytochemistry following α(2)δ(1) knockdown showed decreased membrane localization of Ca(v) 3.2 (α(1H)) at the plasma membrane, suggesting that the diminished ATP release and ERK1/2 activation in response to membrane stretch resulted from a lack of Ca(v) 3.2 (α(1H)) at the cell membrane.
Challenge benchmarks for verification of real-time programs (2010)

Real-time systems, and in particular safety-critical systems, are a rich source of challenges for the program verification community as software errors can have catastrophic consequences. Unfortunately, it is nearly impossible to find representative safety-critical programs in the public domain. This has been significant impediment to research in the field, as it is very difficult to validate new ideas or techniques experimentally. This paper presents open challenges for verification of real-time systems in the context of the Real-time Specification for Java. But, our main contribution is a family of programs, called CDx, which we present as an open source benchmark for the verification community.
Temporal Resolution Phantom: A Device and Method for Measurement of a CT Scanner’s Temporal Resolution (2008)

A calibration phantom that can be used to measure the temporal resolution of a CT scanner was designed utilizing a deterministic design process. The system was first defined in terms of a set of functional requirements based on parameters of the imaging modality. It was necessary to generate multiple time-varying signals visible to the scanner, each with a pre-determined temporal frequency. Roll-off in the scanner’s ability to resolve the modulation of certain signals would be used to determine the scanner’s temporal resolution. Based on size limitations imposed by the scanning environment, the phantom utilizes multiple planetary gear assemblies, driven by a common shaft, to achieve a wide range of rotational velocities. Results obtained with an alpha prototype agreed with the theory. It was determined that further development of the phantom was necessary to increase the sensitivity of the measurement. The latest prototype phantom has been used to measure the temporal resolution of two different scanners and it was shown that temporal resolution of each is different from the gantry rotation time.
Pharos 2023: an integrated resource for the understudied human proteome (2022)

The Illuminating the Druggable Genome (IDG) project aims to improve our understanding of understudied proteins and our ability to study them in the context of disease biology by perturbing them with small molecules, biologics, or other therapeutic modalities. Two main products from the IDG effort are the Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/), which curates and aggregates information, and Pharos (https://pharos.nih.gov/), a web interface for fusers to extract and visualize data from TCRD. Since the 2021 release, TCRD/Pharos has focused on developing visualization and analysis tools that help reveal higher-level patterns in the underlying data. The current iterations of TCRD and Pharos enable users to perform enrichment calculations based on subsets of targets, diseases, or ligands and to create interactive heat maps and UpSet charts of many types of annotations. Using several examples, we show how to address disease biology and drug discovery questions through enrichment calculations and UpSet charts.
Impact of Species Diversity on the Design of RNA-Based Diagnostics for Antibiotic Resistance in Neisseria gonorrhoeae (2019)

Quantitative assessment of antibiotic-responsive RNA transcripts holds promise for a rapid point-of-care (POC) diagnostic tool for antimicrobial susceptibility testing. These assays aim to distinguish susceptible and resistant isolates by transcriptional differences upon drug exposure. However, an often-overlooked dimension of designing these tests is that the genetic diversity within a species may yield differential transcriptional regulation independent of resistance phenotype. Here, we use a phylogenetically diverse panel of <i>Neisseria gonorrhoeae</i> and transcriptome profiling coupled with reverse transcription-quantitative PCR to test this hypothesis, to identify azithromycin responsive transcripts and evaluate their potential diagnostic value, and to evaluate previously reported diagnostic markers for ciprofloxacin resistance (<i>porB</i> and <i>rpmB</i>). Transcriptome profiling confirmed evidence of genetic distance and population structure impacting transcriptional response to azithromycin. Taking this into account, we found azithromycin-responsive transcripts overrepresented in susceptible strains compared to resistant strains and selected four candidate diagnostic transcripts (<i>rpsO</i>, <i>rplN</i>, <i>omp3</i>, and NGO1079) that were the most significantly differentially regulated between phenotypes across drug exposure. RNA signatures for these markers categorically predicted resistance in 19/20 cases, with the one incorrect categorical assignment for an isolate at the threshold of reduced susceptibility. Finally, we found that <i>porB</i> and <i>rpmB</i> expression were not uniformly diagnostic of ciprofloxacin resistance in a panel of isolates with unbiased phylogenetic sampling. Overall, our results suggest that RNA signatures as a diagnostic tool are promising for future POC diagnostics; however, development and testing should consider representative genetic diversity of the target pathogen.
Recent Developments of CMOS Image Sensors (2003)

Recent developments in CMOS image sensors are reviewed. High-speed, wide-dynamic-range, and range or 3D cameras are typical examples of recent success of CMOS image sensors. The fastest CMOS image with 100 M pixels reaches 2000 frames/s. Many techniques for achieving wide dynamic range have been proposed. CMOS image sensors employing wide dynamic range pixels with logarithmic response are applied for imaging of arc-welding process. CMOS sensors for real-time range imaging based on light stripe scanning, TOF (time of flight), and stereoscopic measurement methods are developed. The image quality of CMOS image sensor is being improved by the process technology and signal processing techniques.
Molecular definition of a narrow interval at 7q22.1 associated with myelodysplasia (1996)

Chromosome 7 translocations, deletions, or monosomy are associated with myelodysplasia (MDS) and acute myeloid leukemia both in children and adults. These chromosomal anomalies represent one of the most common cytogenetic abnormalities associated with these diseases and usually herald a poor prognosis. In this study two cosmid DNA probes that mapped to 7q22.1 and were known to be separated by approximately 500 kb were identified to flank the proximal inversion breakpoint in a patient carrying a constitutional inversion (7q22.1-34) associated with MDS. A yeast artificial chromosome (YAC) clone that encompassed the two cosmids was identified and shown to span the breakpoint. Fluorescence in situ hybridization was then used to analyze six additional patients with myelodysplasia and chromosomal rearrangements of the 7q22 region (three patients had translocations and three carried deletions). The breakpoint in one of the patients was found to be contained within the same YAC clone that spanned the inversion breakpoint. Moreover, this same interval was determined to be absent in all three patients with chromosomal deletions. These results suggest that this segment of DNA on chromosome 7q22.1 may contain specific gene(s) that have a significant role in myeloid malignancies.
Ubiquitous computing and the role of geometry (2000)

M. Weiser (<http://www.ubiq.com/hypertext/weiser/UbiHome.html>) described ubiquitous computing as "invisible, everywhere computing that does not live on a personal device of any sort, but is in the woodwork everywhere". The EasyLiving project at Microsoft Research is focused on those aspects of ubiquitous computing that are relevant to smart environments, including work in distributed computing, geometric world modeling, computer vision and user interfaces. Though the need for research in distributed computing, perception and interfaces is widely recognized, the importance of an explicit geometric world model for ubiquitous computing has not been well-articulated. This article elucidates the role of geometry in ubiquitous computing, offering example scenarios that require or benefit greatly from geometric knowledge, and describing four primary benefits of a geometric model.
La naissance improbable du siège d’avion en composite (2015)

« La cabine d’un avion n’use guère de hautes technologies » se disent trois jeunes, qui décident de concevoir des sièges d’avion en composite et en titane. Ils ne savaient pas que c’était impossible, alors ils l’ont fait.
Histidine residues of zinc ligands in β-lactamase II (1978)

1. The Zn(II)-requiring beta-lactamase from Bacillus cereus 569/H/9, which has two zinc-binding sites, was examined by 270 MHz 1H n.m.r. spectroscopy. Resonances were assigned to five histidine residues. 2. Resonances attributed to three of the histidine residues in the apoenzyme shift on the addition of one equivalent of Zn(II). 3. Although these three histidine residues are free to titrate in the apoenzyme, none of them titrates over the pH range 6.0–9.0 in the mono-zinc enzyme. 4. The ability of the C-2 protons of these three histidine residues to exchange with solvent (2H2O) is markedly decreased on Zn(II) binding. 5. It is proposed that these three histidine residues act as zinc ligands at the tighter zinc-binding site. 6. Resonances attributed to a fourth histidine residue shift on addition of further zinc to the mono-zinc enzyme. It is proposed that this histidine residue acts as a Zn(II) ligand at the second zinc-binding site.
A STATIC ANALYSIS FRAMEWORK FOR LIVELOCK FREEDOM IN CSP ∗ (2012)

In a process algebra with hiding and recursion it is possible to create processes which compute internally without ever communicating with their environment. Such processes are said to diverge or livelock. In this paper we show how it is possible to conservatively classify processes as livelock-free through a static analysis of their syntax. In particular, we present a collection of rules, based on the inductive structure of terms, which guarantee livelock-freedom of the denoted process. This gives rise to an algorithm which conservatively flags processes that can potentially livelock. We illustrate our approach by applying both BDD-based and SAT-based implementations of our algorithm to a range of benchmarks, and show that our technique in general substantially outperforms the model checker FDR whilst exhibiting a low rate of inconclusive results.
Dialogue Strategy Adaptation to New Action Sets Using Multi-Dimensional Modelling (2021)

A major bottleneck for building statistical spoken dialogue systems for new domains and applications is the need for large amounts of training data. To address this problem, we adopt the multi-dimensional approach to dialogue management and evaluate its potential for transfer learning. Specifically, we exploit pre-trained task-independent policies to speed up training for an extended task-specific action set, in which the single summary action for requesting a slot is replaced by multiple slot-specific request actions. Policy optimisation and evaluation experiments using an agenda-based user simulator show that with limited training data, much better performance levels can be achieved when using the proposed multi-dimensional adaptation method. We confirm this improvement in a crowd-sourced human user evaluation of our spoken dialogue system, comparing partially trained policies. The multi-dimensional system (with adaptation on limited training data in the target scenario) outperforms the one-dimensional baseline (without adaptation on the same amount of training data) by 7% perceived success rate.
Combination Therapy With Zoledronic Acid and FES‐Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial (2019)

Abstract Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation‐ (FES‐) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES‐rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES‐rowing alone with FES‐rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV ( p = 0.05 to 0.006), the CTI ( p = 0.009), and the BR ( p = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing‐only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia ( p = 0.05). A subgroup analysis of the rowing‐only arm showed that gains in the CSI at the tibial metaphysis varied in a dose‐dependent fashion based on the total amount of exercise performed ( p = 0.009). These findings demonstrate that the osteogenic response to FES‐rowing is dose‐dependent. Combination therapy with ZA and FES‐row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
A MEMS Coriolis Mass Flow Sensing System with Combined Drive and Sense Interface (2019)

This paper describes an interface circuit for a MEMS Coriolis mass flow sensor that combines both drive and sense circuitry. The MEMS sensor consists of a suspended resonant tube, which is read-out by comb capacitors and driven into oscillation by current flowing through a drive coil in a magnet field. The interface circuit comprises a low-noise front-end that performs capacitance-to-voltage (C/V) conversion, and a drive-loop with automatic amplitude control. Drive motion can also be detected from the output of the front-end, allowing both drive and sense functions to be combined. The front-end is chopped to mitigate its 1/ f noise. When implemented with commercial off-the-shelf (COTS) components, the proposed interface draws 250 mA from a single 5-V supply. Mass flow measurements with Nitrogen gas (N <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> ) show that the sensor’s drive frequency drifts by less than 1 mHz (rms) per hour, while its zero stability is less than 2.6 mg/h during an 80s measurement.
Monitoring and multiplexing fiber Fabry-Perot interferometer sensors using a linearly tunable Er:fiber laser (2003)

A new method for the monitoring of interferometer fiber optic sensors which utilizes a frequency-scanned fiber laser is investigated. The interrogation technique is based on the principle that if the laser frequency varies linearly with time, the optical signal reflected or transmitted is intensity-modulated at a frequency proportional to the optical path difference (OPD) in the interferometer. Fourier components in the detected optical output signal then correspond to the OPDs of any interferometers which have contributed to this modulation. The position of a peak in the power spectrum of this signal is proportional to the OPD of the interferometer responsible for that peak. Fine tuning of the OPD value is determined from the phase of the corresponding Fourier component. Experimentally, an Er:fiber laser scanned over a 46 nm range centered at 1545 nm was used to monitor intrinsic fiber Fabry-Perot interferometers (FFPIs). Variations in the laser scan rate were compensated using the optical signal modulated by a reference FFPI held at constant temperature. For three multiplexed sensors arranged in series, temperature was measured from 20&deg;C to 610&deg;C with a 0.02&deg;C resolution.
Discrete-time method for robust global stabilization of induction motor (2000)

The paper considers the problem of regulation of velocity and rotor flux norm of an induction motor. The rotor flux is assumed unmeasurable, load torque and rotor resistance may be unknown and time varying, with small non-differentiable disturbances present. A simple and robust discrete-time control technique is justified theoretically and tested experimentally. It can be considered as a generalization and modification of field oriented control. In its ‘non-adaptive’ modification, it ensures global exponential stability of a closed-loop system, if at least local stabilization of the system by static control is possible, for given parameter estimates. In adaptive version it provides identification and global exponential stabilization of the system. Copyright © 2000 John Wiley & Sons, Ltd.
Continuous space language modeling techniques (2010)

This paper focuses on comparison of two continuous space language modeling techniques, namely Tied-Mixture Language modeling (TMLM) and Neural Network Based Language Modeling (NNLM). Additionally, we report on using alternative feature representations for words and histories used in TMLM. Besides bigram co-occurrence based features we consider using NNLM based input features for training TMLMs. We also describe how we improve certain steps in building TMLMs. We demonstrate that TMLMs provide significant improvements of over 16% relative and 10% relative in Character Error Rate (CER) for Mandarin speech recognition, over the trigram and NNLM models, respectively in a speech to speech translation task.