gebhart/patrepeval huggingface dataset:
Structure-guided design of the TIL1383I T cell receptor (2020)

Abstract T cell therapy is an exciting form of cancer immunotherapy in which T cells are engineered to target specific tumor antigens. We employed a structure-guided design approach with the goal of engineering a safer and more effective variant of the TIL1383I T cell receptor (TCR) currently under study in clinical trials for malignant melanoma. Using our unpublished structure of TIL1383I we are in process of designing a panel of TCR variants with the goal of identifying candidates that improve “focus” towards the tyrosinase antigen presented on the MHC class I molecule HLA-A2. Structural analysis of TIL1383I revealed key residues, particularly beta-chain residues E97, G101, L102, responsible for engaging the tyrosinase peptide bound to HLA-A2. The crystal structure of TIL1383I in complex with tyrosinase-HLA-A2 also highlighted its uncharacteristic binding geometry and we therefore hypothesize that this binding orientation is associated with the observed CD8 co-receptor independence of TIL1383I. Indeed, functional analysis with TIL1383I-transduced CD8-positive and CD8-negative T cells, transduced T cells expressing a truncated CD8 lacking the intracellular LCK signaling domain, and tyrosinase peptide variants presented by HLA-A2 mutants outline this co-receptor independence. Combined with our interrogation of tyrosinase peptide cross-reactivity via a peptide positional scanning library approach, structure-guided design resulted in the identification of TIL1383I variants with improved binding affinities to the tyrosinase peptide as well as an understanding of structural characteristics that may contribute to TIL1383I’s co-receptor independence.
A 30 ns 16Kx1 fully static RAM (1981)

A fully static 16K/spl times/1 random access memory (SRAM) with significantly improved speed is discussed. Design innovations using conservative 2.5 /spl mu/m transistors and state-of-the-art double level poly (DLP) scaled NMOS technology were utilized to accomplish 30 ns address and chip select access times with an active power of 550 mW and standby power of 75 mW. A cost effective DLP process was developed using `shared' contacts in the cell. These `shared' contacts utilize second level poly to provide connection between the first poly level and moat, reduced the number of contacts per cell to four. The DPL cell size is 1.6 mil/SUP 2/ (1000 /spl mu/m/SUP 2/) which yields a bar size of 158/spl times/264 mil/SUP 2/ (4.0/spl times/6.7 mm/SUP 2/). In this fully static design a novel architecture was used to power down half of the X-decoders in the active mode using the AO address buffer signals. This technique allowed the use of power saved in the X-decoder to be distributed throughout the circuit to improve overall access times. One of the other major speed improvements came from utilizing column sense amps. The use of the column sense amp improves the overall speed by more than 20 percent. A write cycle of 30 ns has been achieved with a typical write pulse width of 10 ns.
Effect of the Composition of Oxide Layers Formed by Plasma Electrolytic Oxidation on the Mechanism of Peroxide Oxidative Desulfurization (2020)

The peroxide oxidation of thiophene, thioanisole, and dibenzothiophene in the presence of Ce, Zr, Ce + Zr, W, and W + Zn oxide layers formed by plasma electrolytic oxidation on the titanium surface was studied. The composition of the resulting composites was found to affect the activity and conversion of the organosulfur substrates. It was shown by the radical inhibition method that the composites differed in the mechanism of their catalytic action.
Using Computational Fluid Dynamics to Simulate Flow Fields from various Melt Blowing Dies (2005)

This paper is an investigation of the flow fields generated by dual rectangular jets. Specifically, the jets examined are the same as the common slot dies used in the industrial melt blowing process. In this process, a molten polymer is attenuated by air discharging from dual jets. The velocity and turbulence of these flow fields determine the rate and quality of polymer fiber production. The flow field characteristics can be simulated quickly and efficiently using computational fluid dynamics (CFD). These CFD simulations require the use of an appropriate length scale to describe the flow field. This paper describes how these CFD simulations can be used to compare the flow fields generated by different jet geometries.
N-terminal VP1 Truncations Favor T = 1 Norovirus-Like Particles (2020)

Noroviruses cause immense sporadic gastroenteritis outbreaks worldwide. Emerging genotypes, which are divided based on the sequence of the major capsid protein VP1, further enhance this public threat. Self-assembling properties of the human norovirus major capsid protein VP1 are crucial for using virus-like particles (VLPs) for vaccine development. However, there is no vaccine available yet. Here, VLPs from different variants produced in insect cells were characterized in detail using a set of biophysical and structural tools. We used native mass spectrometry, gas-phase electrophoretic mobility molecular analysis, and proteomics to get clear insights into particle size, structure, and composition, as well as stability. Generally, noroviruses have been known to form mainly <i>T</i> = 3 particles. Importantly, we identified a major truncation in the capsid proteins as a likely cause for the formation of <i>T</i> = 1 particles. For vaccine development, particle production needs to be a reproducible, reliable process. Understanding the underlying processes in capsid size variation will help to produce particles of a defined capsid size presenting antigens consistent with intact virions. Next to vaccine production itself, this would be immensely beneficial for bio-/nano-technological approaches using viral particles as carriers or triggers for immunological reactions.
Highly unsaturated phosphorus compounds: Trimeric and dimeric sulfides of a α,β‐di‐<i>tert</i>‐butyl vinyl phosphaalkyne (2010)

Abstract The first examples of sulfides of a 1,3,5‐triphosphabenzene were synthesized by the sulfurization of parent 1,3,5‐triphosphabenzene 2 . Disulfide 7 was found to be remarkably thermally stable, the stability likely coming from the contribution of resonance forms 7A and 7B . In addition to two hydrolysis products of trisulfide 8 , which can be anticipated in unsaturated phosphorus chemistry, a new and not trivial bicyclic bridgehead five‐membered heterocycle 10 was isolated among the decomposition products of 8 . © 2010 Wiley Periodicals, Inc. Heteroatom Chem 22:114–118, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20664
PinPoint Multistage Fracturing Stimulation – Global Applications and Case Histories from Russia (2008)

Abstract Creating multiple zone stimulations in complex reservoirs presents unique challenges for the completion engineer. Effectively stimulating each individual pay interval using separate fracturing treatments can be costly and time consuming. Historically, efforts to stimulate multiple zones usually consisted of casing fracs with limited entry perforating and using sand plugs to separate zones, or tubing fracs with retrievable bridge plugs and packers. The challenge was to rethink the approach to this technology and develop more cost effective and efficient solutions. Those efforts have resulted in a new approach called pinpoint stimulation. New pinpoint stimulation methods have resulted in reduced cycle time for operators. This means doing multiple service operations in a single trip to the well. If performed individually, perforating, fracturing, setting isolation plugs, and cleaning out the wellbore for each interval can add days or weeks to a completion, delaying production-to-sales and increasing overall costs. Now, we perforate, fracture stimulate, and clean out with a single trip to the wellsite. Each treatment stage is customized for the intervals treated and many more intervals can be stimulated economically. Pinpoint multistage fracturing is available in 16 different processes for many types of well completions. In this paper, we present different techniques for a wide variety of applications and provide actual treatment data and results including recent case histories from Russia.
3D shape measurements of fast moving rough surfaces by two tilted interference fringe systems (2013)

Shape measurement of moving, especially rotating objects is an important task in the field of process control. The Laser Doppler Distance Sensor was invented for this purpose. It is realized by two tilted interference fringe systems and enables the simultaneous measurement of the surface velocity and profile. The distance is coded in the phase difference between the generated interference signals of two photo detectors. In order to achieve a distance uncertainty of below 1&mu;m a steep calibration function is necessary. This can be achieved by increasing the tilting angle. However, due to the speckle effect at rough surfaces, random envelopes and phase jumps occur disturbing the phase difference estimation with increasing tilting angle. This problem was overcome recently by employing a receiving optics matching reducing the distance uncertainty by about one magnitude. By evaluating the Doppler frequencies of the two fringe systems the surface velocity and thereby the objects mean diameter can be calculated as well as angular misalignment of the sensor can be detected.
Predation of the Peach Aphid Myzus persicae by the mirid Predator Macrolophus pygmaeus on Sweet Peppers: Effect of Prey and Predator Density (2015)

Integrated Pest Management strategies are widely implemented in sweet peppers. Aphid biological control on sweet pepers includes curative applications of parasitoids and generalist predators, but with limited efficiency. Macrolophus pygmaeus is a zoophytophagous predator which has been reported to predate on aphids, but has traditionally been used to control other pests, including whiteflies. In this work, we evaluate the effectiveness of M. pygmaeus in controlling Myzus persicae (Homoptera: Aphididae) by testing different combinations of aphid and predator densities in cage-experiments under greenhouse conditions. The impact of the presence of an alternative factitious prey (E. kuehniella eggs) was also investigated. Macrolophus pygmaeus, at densities of four individuals/plant, caused rapid decline of newly established aphid populations. When aphid infestations were heavy, the mirid bug reduced the aphid numbers but did not fully eradicate aphid populations. The availability of a factitious prey did not influence M. pygmaeus predation on aphids. Based on our data, preventive application of M. pygmaeus, along with a supplementary food source , is recommended to control early infestations of aphids.
Water adsorption and desorption kinetics on single crystal and thin film MgO(100) surfaces (1996)

Molecular beam scattering and temperature programmed desorption are used to study the adsorption and desorption kinetics of H{sub 2}O (D{sub 2}O) on single crystal, sputtered single crystal, and thin film MgO(100) surfaces. We find that water adsorbs on all three substrates via precursor mediated adsorption kinetics with near unit sticking probability, independent of coverage or temperature below 200K, with a high temperature peak at about 235K that saturates at approximately 1 water molecule per surface metal ion, and a non-saturable low temperature peak at about 160K, corresponding to the formation of multilayer ice. The high temperature desorption feature is strongly substrate dependent, with features of first order (associative) kinetics on the well ordered substrate, and features of second order (dissociative) kinetics on the highly defective thin film and sputtered substrates.
Global Molecular Epidemiology of Respiratory Syncytial Virus from the 2017−2018 INFORM-RSV Study (2020)

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. INFORM-RSV is a multiyear clinical study designed to describe the global molecular epidemiology of RSV in children under 5 years of age by monitoring temporal and geographical evolution of current circulating RSV strains, F protein antigenic sites, and their relationships with clinical features of RSV disease. During the pilot season (2017-2018), 410 RSV G-F gene sequences were obtained from 476 RSV-positive nasal samples collected from 8 countries (United Kingdom, Spain, The Netherlands, Finland, Japan, Brazil, South Africa, and Australia). RSV B (all BA9 genotype) predominated over RSV A (all ON1 genotype) globally (69.0% versus 31.0%) and in all countries except South Africa. Geographic clustering patterns highlighted wide transmission and continued evolution with viral spread. Most RSV strains were from infants of <1 year of age (81.2%), males (56.3%), and patients hospitalized for >24 h (70.5%), with no differences in subtype distribution. Compared to 2013 reference sequences, variations at F protein antigenic sites were observed for both RSV A and B strains, with high-frequency polymorphisms at antigenic site Ø (I206M/Q209R) and site V (L172Q/S173L/K191R) in RSV B strains. The INFORM-RSV 2017-2018 pilot season establishes an important molecular baseline of RSV strain distribution and sequence variability with which to track the emergence of new strains and provide an early warning system of neutralization escape variants that may impact transmission or the effectiveness of vaccines and MAbs under development.
High-speed and high-ON/OFF ratio split-ring-resonator-based active metamaterial using varactor diodes (2016)

A split-ring-resonator-based active metamaterial was investigated for manipulating the spatial intensity profile or wavefront of transmissive waves. In this work, varactor diodes were mounted at gaps in split-ring resonators to electrically control the waves. The fabricated active SRRs exhibit an ON/OFF ratio of 15 dB and a change in the transmission phase of 40 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">o</sup> /layer by applying voltage to the varactor diodes. Measurement of intensity modulation revealed modulation speed of more than 20 MHz, in which the change in the intensity of 15 dB was the same as that for static condition.
Atomic layer deposition of anatase TiO2 coating on silica particles: growth, characterization and evaluation as photocatalysts for methyl orange degradation and hydrogen production (2012)

Atomic layer deposition is used to deposit crystalline anatase TiO2 on 500 nm silica support particles over a range of shell thicknesses. The core–shell morphology combines nanometer thickness titania with silica that is readily separable from liquid media. The composite particles are evaluated as photocatalysts for destruction of the model pollutant methyl orange and, after deposition of platinum co-catalyst, for the sacrificial generation of hydrogen from water. The catalytic activities normalized to surface area are higher than those of P25 mixed anatase/rutile titania nanoparticles.
The identification of new protein kinase inhibitors as targets in modern drug discovery. (2006)

In recent years there has been great interest in developing protein kinase inhibitors as therapeutic agents for a variety of diseases. This article provides an overview on the history, development and validity of kinases as drug targets, as well as a description of kinase research, including its limitations, challenges and successes.
Glyceollins, Soy Isoflavone Phytoalexins, Improve Oral Glucose Disposal by Stimulating Glucose Uptake (2012)

Soy glyceollins, induced during stress, have been shown to inhibit cancer cell growth in vitro and in vivo. In the present study, we used prediabetic rats to examine the glyceollins effect on blood glucose. During an oral glucose tolerance test (OGTT), the blood glucose excursion was significantly decreased in the rats treated with oral administration of either 30 or 90 mg/kg glyceollins. Plasma analysis demonstrated that glyceollins are absorbed after oral administration, and duration of exposure extends from 20 min to at least 4 h postadministration. Exposure of 3T3-L1 adipocytes to glyceollins significantly increased both insulin-stimulated and basal glucose uptake. Basal glucose uptake was increased 1.5-fold by exposure to 5 μM glyceollin in a dose-response manner. Coincubation with insulin significantly stimulated maximal glucose uptake above basal uptake levels and tended to increase glucose uptake beyond the levels of either stimulus alone. On a molecular level, polymerase chain reaction showed significantly increased levels of glucose transporter GLUT4 mRNA in 3T3-L1 adipocytes, especially when the cells were exposed to 5 μM glyceollins for 3 h in vitro. It correlated with elevated protein levels of GLUT4 detected in the 5 μM glyceollin-treated cells. Thus, the simulative effect of the glyceollins on adipocyte glucose uptake was attributed to up-regulation of glucose transporters. These findings indicate potential benefits of the glyceollins as an intervention in prediabetic conditions as well as a treatment for type 1 and type 2 diabetes by increasing both the insulin-mediated and the basal, insulin-independent, glucose uptake by adipocytes.
Guest Editorial Special Issue on LCoS Technology (2011)

The seven papers in this special issue address a selection of some of the issues concerning the liquid crystal on silicon technology, from fabrication and design to some of the applications.
Real-time collision detection and distance computation on point cloud sensor data (2013)

Most prior techniques for proximity computations are designed for synthetic models and assume exact geometric representations. However, real robots construct representations of the environment using their sensors, and the generated representations are more cluttered and less precise than synthetic models. Furthermore, this sensor data is updated at high frequency. In this paper, we present new collision- and distance-query algorithms, which can efficiently handle large amounts of point cloud sensor data received at real-time rates. We present two novel techniques to accelerate the computation of broad-phase data structures: 1) we present a progressive technique that incrementally computes a high-quality dynamic AABB tree for fast culling, and 2) we directly use an octree representation of the point cloud data as a proximity data structure. We assign a probability value to each leaf node of the tree, and the algorithm computes the nodes corresponding to high collision probability. In practice, our new approaches can be an order of magnitude faster than previous methods. We demonstrate the performance of the new methods on both synthetic data and on sensor data collected using a Kinect™ for motion planning for a mobile manipulator robot.
Tissue microarrays: applications in genomic research (2005)

The widespread application of tissue microarrays in cancer research and the clinical pathology laboratory demonstrates a versatile and portable technology. The rapid integration of tissue microarrays into biomarker discovery and validation processes reflects the forward thinking of researchers who have pioneered the high-density tissue microarray. The precise arrangement of hundreds of archival clinical tissue samples into a composite tissue microarray block is now a proven method for the efficient and standardized analysis of molecular markers. With applications in cancer research, tissue microarrays are a valuable tool in validating candidate markers discovered in highly sensitive genome-wide microarray experiments. With applications in clinical pathology, tissue microarrays are used widely in immunohistochemistry quality control and quality assurance. The timeline of a biomarker implicated in prostate neoplasia, which was identified by complementary DNA expression profiling, validated by tissue microarrays and is now used as a prognostic immunohistochemistry marker, is reviewed. The tissue microarray format provides opportunities for digital imaging acquisition, image processing and database integration. Advances in digital imaging help to alleviate previous bottlenecks in the research pipeline, permit computer image scoring and convey telepathology opportunities for remote image analysis. The tissue microarray industry now includes public and private sectors with varying degrees of research utility and offers a range of potential tissue microarray applications in basic research, prognostic oncology and drug discovery.
The Changing Landscape of Targeted Breast Cancer Therapies (2020)

Experts provide perspective on the rapidly changing landscape of targeted therapies in breast cancer treatment, and the importance of matching the right agent with the right patient.
Mapping Lipid Networks in Cancer by Integrated Proteomics and Metabolomics (2007)

Breakthroughs in the diagnosis and treatment of cancer depend on the discovery of new biomarkers and therapeutic targets for this disease. Toward this end, global molecular profiling methods hold great promise, as they provide a relatively unbiased portrait of the biochemical composition of cancer cells and can reveal unanticipated alterations in their metabolic and signaling networks. Nonetheless, the identification and functional characterization of enzymatic pathways that support cancer pathogenesis have, to date, been hindered by a lack of “systems biology” techniques that can evaluate their activity in complex biological samples. To address this problem, we have introduced functional proteomic and metabolomic technologies termed activity‐based protein profiling (ABPP) and discovery metabolite profiling (DMP), respectively. ABPP, which utilizes active site‐directed chemical probes to determine the functional state of large numbers of enzymes directly in whole proteomes, has enabled the discovery of enzyme activities that are elevated in aggressive cancer cells and tumors. DMP, which constitutes a global, untargeted method to characterize metabolic fluxes, has facilitated the discovery of natural substrates for known and novel cancer‐related enzymes. In this presentation, I will discuss our group's progress towards uniting the ABPP and DMP methods to an integrated platform for the global analysis of biochemical pathways altered in human cancer cells. Specifically, I will discuss: 1) the identification of enzyme activities and lipid metabolites that are elevated in aggressive cancer cells, and 2) the integration of these enzymes and small molecules into networks and our efforts to test the function of these biochemical pathways in cancer pathogenesis.