gebhart/patrepeval huggingface dataset:
Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity (2017)

Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D<sup>pol</sup>) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D<sup>pol</sup> in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show <i>in vitro</i> growth kinetics and plaque morphologies similar to those of the wild-type (WT) A<sub>24</sub> Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F<sup>HF</sup>) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I<sup>LF</sup>) and W237L<sup>LF</sup> mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates.<b>IMPORTANCE</b> Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D<sup>pol</sup> mutations that affect polymerase fidelity. Recombinant FMDVs containing substitutions at 3D<sup>pol</sup> tryptophan residue 237 were genetically stable and displayed plaque phenotypes and growth kinetics similar to those of the wild-type virus in cell culture. We further demonstrate that viruses harboring either a W237F<sup>HF</sup> substitution or W237I<sup>LF</sup> and W237L<sup>LF</sup> mutations were highly attenuated in animals. Our study shows that obtaining 3D<sup>pol</sup> fidelity variants by protein engineering based on polymerase structure and function could be exploited for the development of attenuated FMDV vaccine candidates that are safer and more stable than strains obtained by selective pressure via mutagenic nucleotides or adaptation approaches.
Characterization, modeling, and design of an electrostatic chuck with improved wafer temperature uniformity (1995)

The resulting temperature distribution of a silicon wafer held by an electrostatic chuck (ESC) in an electron-cyclotron-resonance chemical vapor deposition (ECR-CVD) reactor is characterized and modeled. The effects of the clamping voltage VESC, pressure between the ESC and wafer PHe, and the surface finish and pattern on the ESC are investigated. Heat transfer coefficients between the wafer and various ESCs are determined experimentally. A model is developed to predict the temperature distribution at the surface of the wafer, and used to explain the experimentally observed temperature variations both within wafer and between different chucks. The model is then used to aid in the design of an ESC which provides improved temperature uniformity at the wafer surface. The results of this study indicate: (a) the thermal resistances across the interface between the wafer and ESC control both the absolute wafer temperature and the wafer temperature uniformity; (b) the surface roughness of the ESC and the size of the ‘‘contact’’ regions are major design factors controlling the absolute temperature of the wafer—the temperature can be adjusted by varying the value of VESC and fine tuned by adjusting the value of PHe; (c) the nonuniform temperature distribution across the wafer surface is dictated by the surface pattern on the ESC, the variation in surface roughness, and the size of the ESC relative to the wafer; (d) wafer temperature variations from chuck to chuck are reduced by controlling the surface finish of the ESC and by ensuring that PHe is a dominant heat transfer mechanism; and (e) maximum uniformity in the temperature of the wafer is obtained when the radius of the ESC is matched as closely as possible to that of the wafer. We have shown that numerical heat transfer models can be used to optimize the geometry of the ESC to provide a uniform distribution of temperature across the surface of the wafer.
Regioisomeric Effects of Donor–Acceptor–Acceptor′ Small‐Molecule Donors on the Open Circuit Voltage of Organic Photovoltaics (2016)

Donor-acceptor-acceptor' small-molecule donors are synthesized to investigate regioisomeric effects on organic photovoltaic device performance. Cross-conjugation in 2-((7-(N-(2-ethylhexyl)-benzothieno[3,2-b]thieno[3,2-d]pyrrol-2-yl)benzo[c][1,2,5]thiadiazol-4-yl)methylene)malononitrile leads to an increased open-circuit voltage compared with its isomer 2-((7-(N-(2-ethylhexyl)-benzothieno[3,2-b]thieno[2,3-d]pyrrol-2-yl)benzo[c][1,2,5]thiadiazol-4-yl)methylene)malononitrile. A correlation is then established between molecular conjugation length and orbital energies, and hence open-circuit voltage.
Minimum-volume coil arrangements for generation of uniform magnetic fields (2002)

This paper describes an optimization method for designing electromagnetic coil arrangements that generate uniform magnetic fields. The method can accurately and efficiently determine an arrangement that minimizes the volume of the coils. An important advantage of the method is that the solutions it generates are guaranteed to be global minimums. The method may be useful for designing large superconducting magnets, since their cost depends strongly on the amount of superconducting wire required. It is also shown that the method can be applied to minimize the power consumption of resistive magnets.
A Method of Generating Full Color in a Liquid Crystal Display Using Birefringent Filters (2001)

Color generation in a typical liquid crystal device (LCD) is usually done via an array of absorptive color filters placed over the LC subpixels. These filters offer at best 33% transmission resulting in dark displays and the need for high intensity backlights. In this paper we clearly explain a new method of color generation based on a polarization interference filter (PIF) scheme called the Solc filter. The design offers high throughput and chromaticity due to its non-absorptive nature. The design is based on work done by ColorLink Inc. and is extended to show possible use in a display device.
High-latency, low-bandwidth windowing in the Jupiter collaboration system (1995)

Article High-latency, low-bandwidth windowing in the Jupiter collaboration system Share on Authors: David A. Nichols Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CA Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CAView Profile , Pavel Curtis Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CA Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CAView Profile , Michael Dixon Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CA Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CAView Profile , John Lamping Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CA Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CAView Profile Authors Info & Claims UIST '95: Proceedings of the 8th annual ACM symposium on User interface and software technologyDecember 1995 Pages 111–120https://doi.org/10.1145/215585.215706Online:01 December 1995Publication History 99citation2,591DownloadsMetricsTotal Citations99Total Downloads2,591Last 12 Months44Last 6 weeks3 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
SSH Key Management Challenges and Requirements (2019)

SSH (Secure Shell) uses public keys for authenticating servers and users. This paper summarizes progress in SSH key management so far, highlights outstanding problems, and presents requirements for a long-term solution. Proposals are solicited from the research community to address the issue. The problem is of high practical importance, as most of our critical Internet infrastructure, cloud services, and open source software development is protected using these keys.
Monoclonal Antibody to Mouse Lipopolysaccharide Receptor Protects Mice against the Lethal Effects of Endotoxin (1990)

Specific endotoxic lipopolysaccharide (LPS) binding sites on the cell membranes of murine lymphocytes and macrophages that may serve as functional receptors for LPS have recently been identified using photoactivatable cross-linking LPS derivatives. A monoclonal antibody (Mab 5D3) with specificity for this 80-kDa protein has also been generated and characterized. The capacity of MAb 5D3 to protect mice against the lethal effects of endotoxin was investigated. Pretreatment of CF1 mice with as little as 15 micrograms of MAb 5D3 provided virtually complete protection against a dose of endotoxin 10-fold greater than that required to kill all mice in an untreated control group using the galactosamine sensitization model. Significant protection was also afforded normal mice given MAb 5D3 relative to saline. Several lines of evidence suggest that MAb 5D3-mediated protection is due to the agonist properties of this antibody rather than a receptor blockade mechanism.
Handedness control of sub-millijoule mid-infrared (6&#x2013;12&#x03BC;m) vortex laser (2015)

We demonstrate the handedness control of a 6-12μm optical vortex output from an optical vortex parametric laser formed of a 1-μm vortex pumped KTiOPO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> optical parametric oscillator in combination with a ZnGeP <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> difference frequency generator.
Mutations in an Auxin Receptor Homolog AFB5 and in SGT1b Confer Resistance to Synthetic Picolinate Auxins and Not to 2,4-Dichlorophenoxyacetic Acid or Indole-3-Acetic Acid in Arabidopsis (2006)

Although a wide range of structurally diverse small molecules can act as auxins, it is unclear whether all of these compounds act via the same mechanisms that have been characterized for 2,4-dichlorophenoxyacetic acid (2,4-D) and indole-3-acetic acid (IAA). To address this question, we used a novel member of the picolinate class of synthetic auxins that is structurally distinct from 2,4-D to screen for Arabidopsis (Arabidopsis thaliana) mutants that show chemically selective auxin resistance. We identified seven alleles at two distinct genetic loci that conferred significant resistance to picolinate auxins such as picloram, yet had minimal cross-resistance to 2,4-D or IAA. Double mutants had the same level and selectivity of resistance as single mutants. The sites of the mutations were identified by positional mapping as At4g11260 and At5g49980. At5g49980 is previously uncharacterized and encodes auxin signaling F-box protein 5, one of five homologs of TIR1 in the Arabidopsis genome. TIR1 is the recognition component of the Skp1-cullin-F-box complex associated with the ubiquitin-proteasome pathway involved in auxin signaling and has recently been shown to be a receptor for IAA and 2,4-D. At4g11260 encodes the tetratricopeptide protein SGT1b that has also been associated with Skp1-cullin-F-box-mediated ubiquitination in auxin signaling and other pathways. Complementation of mutant lines with their corresponding wild-type genes restored picolinate auxin sensitivity. These results show that chemical specificity in auxin signaling can be conferred by upstream components of the auxin response pathway. They also demonstrate the utility of genetic screens using structurally diverse chemistries to uncover novel pathway components.
Chronic ankle pain and fibrosis successfully treated with a new noninvasive augmented soft tissue mobilization technique (ASTM): a case report (1998)

This clinical case report demonstrates the clinical effectiveness of a new form of soft tissue mobilization in the treatment of excessive connective tissue fibrosis (scar tissue) around an athlete's injured ankle. The scar tissue was causing the athlete to have pain with activity, pain on palpation of the ankle, decreased range of motion, and loss of function. Surgery and several months of conventional physical therapy failed to alleviate the athlete's symptoms. As a final resort, augmented soft tissue mobilization (ASTM) was administered. ASTM is an alternative nonsurgical treatment modality that is being researched at Performance Dynamics (Muncip, IN). ASTM is a process that uses ergonomically designed instruments that assist therapists in the rapid localization and effective treatment of areas exhibiting excessive soft tissue fibrosis. This is followed by a stretching and strengthening program. Upon the completion of 6 wk of ASTM therapy, the athlete had no pain and had regained full range of motion and function. This case report is an example of how a noninvasive augmented form of soft tissue mobilization (ASTM) demonstrated impressive clinical results in treating a condition caused by connective tissue fibrosis.
Properties of one-dimensional magnetophotonic crystals for use in optical isolator devices (2002)

A one-dimensional (1-D) magnetophotonic crystal (MPC) film made of a magneto-optical layer with nonmagnetic layers laminated thereon has an enhanced Faraday rotation. Theoretical studies about 1-D MPC films for use in magneto-optical (MO) applications of optical communication were carried out. The calculations revealed that required optical isolator performance (transmittance T>95% and Faraday rotation angle /spl theta//sub F/=45/spl deg/) can be fulfilled with the periodic multilayer films having only two or three magnetic layers. The structure of 1-D MPC films satisfying the optical isolator performance is very simple, which is very attractive for actual optical isolator fabrication.
The Fc Region of an Antibody Impacts the Neutralization of West Nile Viruses in Different Maturation States (2013)

Flavivirus-infected cells secrete a structurally heterogeneous population of viruses because of an inefficient virion maturation process. Flaviviruses assemble as noninfectious, immature virions composed of trimers of envelope (E) and precursor membrane (prM) protein heterodimers. Cleavage of prM is a required process during virion maturation, although this often remains incomplete for infectious virus particles. Previous work demonstrated that the efficiency of virion maturation could impact antibody neutralization through changes in the accessibility of otherwise cryptic epitopes on the virion. In this study, we show that the neutralization potency of monoclonal antibody (MAb) E33 is sensitive to the maturation state of West Nile virus (WNV), despite its recognition of an accessible epitope, the domain III lateral ridge (DIII-LR). Comprehensive epitope mapping studies with 166 E protein DIII-LR variants revealed that the functional footprint of MAb E33 on the E protein differs subtly from that of the well-characterized DIII-LR MAb E16. Remarkably, aromatic substitutions at E protein residue 306 ablated the maturation state sensitivity of E33 IgG, and the neutralization efficacy of E33 Fab fragments was not affected by changes in the virion maturation state. We propose that E33 IgG binding on mature virions orients the Fc region in a manner that impacts subsequent antibody binding to nearby sites. This Fc-mediated steric constraint is a novel mechanism by which the maturation state of a virion modulates the efficacy of the humoral immune response to flavivirus infection.
Recent Progress on the Identification of Metabotropic Glutamate 4 Receptor Ligands and Their Potential Utility as CNS Therapeutics (2011)

This Review describes recent activity in the advancement of ligands for the metabotropic glutamate 4 receptor subtype and their potential utility as central nervous system (CNS) therapeutics. Until recently, there was a paucity of compounds with suitable selectivity and druglike properties to elucidate the value of this target. The search for selective entities has led several groups to the investigation of allosteric modulators as a path to optimization of potential ligands. Recent efforts, discussed here, have afforded a variety of derivatives with improvements in potency, solubility, and pharmacokinetic properties that garner support for continued investigation and optimization.
Learning urban users' choices to improve trip recommendations (2015)

We analyze the work of urban trip planners and the relevance of trips they recommend upon user queries. We propose to improve the planner recommendations by learning from choices made by travelers who use the transportation network on the daily basis. We analyze a large collection of individual travelers' trips collected from the automated fare collection systems; we convert the trips into pair-wise preferences for traveling from a given origin to a destination at a given time point. We model passenger preferences with a number of smoothed time-dependent latent variables which are used to learn a ranking function for trips. This function can be used to re-rank the top planner's recommendations. Results of tests for cities of Nancy, France and Adelaide, Australia show a considerable increase of the recommendation relevance.
Accurately measuring human movement using articulated ICP with soft-joint constraints and a repository of articulated models (2007)

A novel approach for accurate markerless motion capture combining a precise tracking algorithm with a database of articulated models is presented. The tracking approach employs an articulated iterative closest point algorithm with soft-joint constraints for tracking body segments in visual hull sequences. The database of articulated models is derived from a combination of human shapes and anthropometric data, contains a large variety of models and closely mimics variations found in the human population. The database provides articulated models that closely match the outer appearance of the visual hulls, e.g. matches overall height and volume. This information is paired with a kinematic chain enhanced through anthropometric regression equations. Deviations in the kinematic chain from true joint center locations are compensated by the soft-joint constraints approach. As a result accurate and a more anatomical correct outcome is obtained suitable for biomechanical and clinical applications. Joint kinematics obtained using this approach closely matched joint kinematics obtained from a marker based motion capture system.
Interference mitigation with rate splitting in multi-cell wireless networks (2012)

Cell-edge users inevitably experience strong interference from adjacent cells, and consequently suffer from performance degradation. Currently, Han-Kobayashi (HK) rate splitting scheme is viewed as the best strategy to cancel the interference and improve the performance. As a special superposition coding scheme, the HK rate splitting scheme has been shown to potentially achieve the channel capacity. However, the way from theory to practice is not straightforward. Current investigations adapting the HK rate splitting scheme to practical applications only deal with the strongest interference and treat the other interferences as noise. In general, more than one strong interferer usually exists, which is targeted in this work. By applying a multi-layer rate splitting scheme for more than one strong interferer, a new ordered detection is proposed and a power allocation algorithm is derived associated with the detection order. Simulation results show that the multi-layer rate splitting scheme mitigates the interference from two different interferers and provides more than twice the gain in terms of average throughput compared with a reference scheme with a fixed frequency reuse factor of 3 in a realistic wireless network.
Comparison of new sequences for high‐resolution cartilage imaging (2003)

The high prevalence of osteoarthritis continues to demand improved accuracy in detecting cartilage injury and monitoring its response to different treatments. MRI is the most accurate noninvasive method of diagnosing cartilage lesions. However, MR imaging of cartilage is limited by scan time, signal-to-noise ratio (SNR), and image contrast. Recently, there has been renewed interest in SNR-efficient imaging sequences for imaging cartilage, including various forms of steady-state free-precession as well as driven-equilibrium imaging. This work compares several of these sequences with existing methods, both theoretically and in normal volunteers. Results show that the new steady-state methods increase SNR-efficiency by as much as 30% and improve cartilage-synovial fluid contrast by a factor of three. Additionally, these methods markedly decrease minimum scan times, while providing 3D coverage without the characteristic blurring seen in fast spin-echo images.
Detection of H. pylori in Urease Test Negative Gastric Samples by a Novel Multiplex PCR Assay (2005)

Purpose: All patients with dyspepsia, either newly or previously diagnosed, should be tested for H. pylori infection. The CLOtest assay is widely used in clinical practice to detect the urease enzyme of H. pylori in gastric mucosal biopsies and many physicians consider it as a gold standard method. However, this is not sensitive enough to diagnose H. pylori infection. We have developed a novel one-step multiplex PCR detection system that can amplify 10 DNA fragments from 5 DNA regions in the genome of H. pylori at the same time. The objective of this study was to assess the diagnostic value of this new multiplex PCR assay to detect H. pylori infection, and further evaluated the negative results from the CLOtest. Methods: This study was performed on the same urease test negative gastric specimen, which had been detected by CLOtest from 276 individuals with dyspepsia symptoms undergoing endoscopy at Evanston Northwestern Healthcare. The CLOtest was performed first and if the result was negative, the negative specimen was collected from the CLOtest gel. From this specimen, the DNA was isolated and was performed the one-step multiplex PCR. Results: Positive results were achieved in 42% (116/276) with multiplex PCR from the H. pylori negative samples tested by CLOtest. Conclusions: Our results indicate that our multiplex PCR method is a highly specific and sensitive method in the detection of H. pylori. The results of H. pylori tested by current methods should be carefully reviewed to ensure that the result is not a false-negative and to obtain the correct diagnosis it would be better that the negative samples of CLOtest were further confirmed by the multiplex PCR assay.
A Peptoid “Antibody Surrogate” That Antagonizes VEGF Receptor 2 Activity (2008)

We report a two-color, cell-based screen to identify specific receptor-binding compounds in a combinatorial library of peptoids displayed on beads. We apply this strategy to the isolation of vascular endothelial growth factor receptor 2 (VEGFR2)-binding peptoids. A dimeric derivative of one of these lead compounds is shown to be an antagonist of VEGFR2 activity both in vitro and in vivo. This methodology provides a potentially general route to synthetic molecules that bind integral membrane receptors with affinities and specificities similar to those of antibodies, but which are far smaller and easier to make and manipulate.