gebhart/patrepeval huggingface dataset:
Limiting αIIb Extension at the Genu Differentially Affects Binding of Small and Large Ligands to αIIbβ3 (2008)

Abstract Structural data of integrin αIIbβ3 have been interpreted as supporting a model in which: the receptor exists primarily in a “bent,” low affinity conformation on unactivated platelets, and activation induces an extended, high affinity conformation prior to, or following, ligand binding. Previous studies found that “clasping” the αIIb head domain to the β3 tail decreased fibrinogen binding. To study the role of αIIb extension about the genu we created and analyzed an energy-optimized model of the complete extracellular domain of αIIbβ3 and then introduced a disulfide “clamp” between the αIIb thigh and calf-1 domains by mutating αIIb R597 and Y645 to cysteine residues. Increased mobility of the clamped mutant on SDS-PAGE under nonreducing, but not reducing conditions, relative to the WT receptor supported the successful introduction of a new disulfide bond. Clamped αIIbβ3 had markedly reduced ability to bind the large soluble ligands fibrinogen [induced by mAb AP5; net normalized fluorescence intensity (NNFI) of 17 ± 2 for normal αIIbβ3 and 0.4 ± 0.2 for clamped αIIbβ3; n=3; p&amp;lt;0.001] and PAC1 [induced by mAb PT25-2; NNFIs of 17 ± 7 and 2 ± 1, respectively (n=3; p&amp;lt;0.001)]. The defect in fibrinogen and PAC-1 binding could be partially restored (~40–50%) by treating the cells with the reducing agent DTT. In contrast, the clamp had little effect on the binding of the Mr 7,500 snake venom kistrin (non-significant ~30% reduction) or αIIbβ3-mediated adhesion to immobilized fibrinogen (non-significant ~20% reduction). Remarkably, the defect in binding the large soluble ligands was rescued by co-expressing clamped αIIb with the β3- activating mutation N339S. The clamped αIIbβ3 also displayed a defect in kistrin-induced (200 nM) exposure of the mAb AP5 epitope in the PSI domain of β3 (NNFI 50 ± 11 for normal αIIbβ3 vs. 24 ± 5 for clamped αIIbβ3; p&amp;lt;0.001; n=5), and this abnormality was also reversed by DTT. By analyzing the solvent accessible areas in our model of αIIbβ3 with and without extension, we determined that extension results in a 370 Å2 reduction in buried solvent-accessible area in the PSI domain as a result of losing some of its interactions with the IEGF-2 domain. We hypothesize that clamping αIIb may, therefore, partially preserve these PSI-IEGF-2 domain interactions. Collectively, our studies support a role for αIIb extension in the binding of large, but not small ligands, and suggest that αIIb extension is less important for interactions with immobilized than soluble fibrinogen. Our data are consistent with αIIb extension resulting in increased access to the ligand binding site and/or destabilizing β3 headpiece-tailpiece interactions and thus facilitating the conformational change(s) that affect the intrinsic affinity of the binding pocket for ligand. They may also provide an explanation for the paradoxical finding that platelet binding of soluble fibrinogen requires exogenous activation, whereas platelet adhesion to immobilized fibrinogen does not.
Translation of BAFF Inhibition from Mouse to Non-human Primate and Human (2009)

The identification of BAFF as a fundamental B cell survival factor in mouse and man, its over-expression in certain autoimmune disease patient populations, and the discovery of three cognate receptors, stimulated interest in understanding the role of BAFF in the pathogenesis of autoimmunity, and designing novel therapeutics to blunt B cell participation in disease pathogenesis via blockade of this pathway. Positive clinical trial results with B cell depletion have demonstrated beyond doubt the pathogenic B cell component in human rheumatoid arthritis [1, 2]. This current chapter focuses on data obtained in mice (both normal and disease models), non-human primates and human clinical trials with several large molecule inhibitors of the BAFF B cell survival pathway. The focus is on normal, non-diseased animals as well as rheumatology diseases and disease models although implications are clear for all other diseases with a B cell pathogenic component. Three strategies for blocking BAFF/receptor interactions have been used in mice and primates, 1) blocking antibodies directed specifically against BAFF, 2) receptor/ receptor fragment- Fc fusion proteins (receptor:Fc) to act as decoys, and 3) depleting mAb directed against BR3, the BAFF receptor responsible for transducing a survival signal and which is expressed on all mature B cells. The first two strategies target B cells indirectly by depriving them of a survival signal, while the third option utilizes an additional direct approach through antibody mediated cell killing. We described the experience with each of these types of molecules first in mice, then monkeys and human. Finally, we discuss the differences observed between species regarding in vivo blockade of this pathway and potential implications for human disease therapy.
Preliminary Evaluation of Nonlinear Effects on TCA Flutter (1998)

The objective of this study is to investigate the effect of nonlinear aerodynamics, especially at high angles-of-attack with leading-edge separation, on the TCA flutter properties at transonic speeds. In order to achieve that objective, flutter simulations with Navier-Stokes CFD must be performed. To this end, time-marching Navier-Stokes solutions are computed for the TCA wing/body configuration at high angles-of-attack in transonic flight regimes. The approach is to perform non-linear flutter calculations on the TCA at two angles-of-attack, the first one being a case with attached flow (a=2.8 degrees) and the second one being a high angle-of-attack case with a wing leading edge vortex (a=12.11 degrees). Comparisons of the resulting histories and frequency damping information for both angles-of-attack will evaluate the impact of high-alpha aerodynamics on flutter.
SELF-SETTING AND INJECTABLE HYALURONIC ACID HYDROGELS WITH BIOINSPIRED PROPERTIES FOR SKELETAL TISSUE ENGINEERING (2018)

Tissue engineering is a promising approach to regenerate damaged skeletal tissues. In particular, the use of injectable hydrogels alleviates common issues of poor cell viability and engraftment. Ho...
Sustainable production of gluconic acid and glucuronic acid <i>via</i> microwave-assisted glucose oxidation over low-cost Cu-biochar catalysts (2022)

Gluconic acid and glucuronic acid are produced from biomass-derived glucose over low-cost biochar-supported Cu catalysts in a microwave-enhanced base-free system.
Rationale for the Application of RANKL Inhibition in the Treatment of Langerhans Cell Histiocytosis (2014)

RANKL is highly expressed in active LCH at the lesional level, concomitant to p65 NFκB activation. The use of RANKL inhibition as a rational therapeutic approach of the disease now needs further clinical evaluation.
Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy (2022)

These findings demonstrate that lisaftoclax is a novel, orally bioavailable BH3 mimetic BCL-2-selective inhibitor with considerable potential for the treatment of certain hematologic malignancies.
Natural resistance to cancers: a Darwinian hypothesis to explain Peto’s paradox (2012)

We conclude that assessing wildlife species in their natural ecosystems, especially through theoretical modeling, is the most promising way to understand how evolutionary processes can favor one or the other pathway. This will provide important insights into mechanisms of cancer resistance.
AffectAura (2012)

We present AffectAura, an emotional prosthetic that allows users to reflect on their emotional states over long periods of time. We designed a multimodal sensor set-up for continuous logging of audio, visual, physiological and contextual data, a classification scheme for predicting user affective state and an interface for user reflection. The system continuously predicts a user's valence, arousal and engage-ment, and correlates this with information on events, communications and data interactions. We evaluate the interface through a user study consisting of six users and over 240 hours of data, and demonstrate the utility of such a reflection tool. We show that users could reason forward and backward in time about their emotional experiences using the interface, and found this useful.
Sustainability in Network-on-Chips by Exploring Heterogeneity in Emerging Technologies (2019)

With the scaling of technology, the computing industry is experiencing a shift from multi-core to many-core architectures. However, traditional metallic-based on-chip interconnects may not scale to support many-core architectures due to high power dissipation, and increased communication latency. Attention has recently shifted to emerging technologies such as silicon-photonics and wireless interconnects to implement future on-chip communications. Although emerging technologies show promising results for power-efficient, low-latency, and scalable on-chip interconnects, the use of single technology may not be sufficient to scale future architectures. In this paper, we extend the heterogeneous architecture Optical-Wireless Network-on-Chip (OWN [1]) to Reconfigurable Optical-Wireless Network-on-Chip (R-OWN) by introducing run-time reconfigurable wireless channels. Like OWN, R-OWN is designed such that one-hop photonic interconnect is used up to 64 cores (called a cluster) and communication beyond a cluster is one-hop wireless to limit the network diameter to a maximum of three hops. The photonic bandwidth is efficiently shared using time division multiplexing (TDM) while the wireless bandwidth is shared using frequency division multiplexing (FDM). By exploiting the heterogeneity of two emerging technologies, we reduce the energy/bit, improve performance via reconfiguration, and thereby improve the sustainability of NoCs and CMPs. We propose a preliminary assessment of implementing heterogeneous technologies with the router microarchitecture. Further, we also discuss the design of horn antenna for implementing the wireless channels. Our results indicate that R-OWN improves the performance (throughput and latency) by 15 percent when compared to OWN while consuming 7 percent more energy than OWN. Further, OWN and R-OWN improve energy-efficiency by 54-61 percent when compared to WCube and CMesh architectures, respectively. It should be noted that both OWN and R-OWN require less area than state-of-the-art wired, wireless, and optical on-chip networks.
Refocusing capabilities in a miniaturized multi-channel multi-resolution imaging system using a tunable lens (2014)

Inspired by nature, many application domains might gain from combining the multi-channel design of the compound eyes of insects and the refocusing capability of the human eye in one compact configuration. Multi-channel refocusing imaging systems are nowadays only commercially available in bulky and expensive designs since classical refocusing mechanisms cannot be integrated in a miniaturized configuration. We designed a wafer-level multi-resolution two-channel imaging system with refocusing capabilities using a voltage tunable liquid lens. One channel is able to capture a wide field-of-view image (2x40&deg;) of a surrounding with a low angular resolution (0.078&deg;), whereas a detailed image of a small region of interest (2x7.57&deg;) can be obtained with the high angular resolution channel (0.0098&deg;). The latter high angular resolution channel contains the tunable lens and therefore also the refocusing capabilities. In this paper, we first discuss the working principle, tunability and optical quality of a voltage tunable liquid lens. Based on optical characterization measurements with a Mach-Zehnder interferometer, we designed a tunable lens model. The designed tunable lens model and its validation in an imaging setup show a diffraction-limited image quality. Following, we discuss the performance of the designed two-channel imaging system. Both the wide field-of-view and high angular resolution optical channels show a diffraction-limited performance, ensuring a good image quality. Moreover, we obtained an improved depth-of-field, from 0.254m until infinity, in comparison with the current state-of-the art published wafer-level multi-channel imaging systems, which show a depth-of-field from 9m until infinity.
Applications in Musculoskeletal Physical Therapy (2016)

Surface electromyography (sEMG) is typically applied in musculoskeletal physical therapy for the assessment of disturbed motor control and for monitoring change with rehabilitation. This chapter explores fundamental methods of EMG assessment as a means of evaluating neuromuscular impairment in patients with musculoskeletal disorders with a focus on two of the most common musculoskeletal complaints, namely, low back pain and neck pain. Distinct modifications of the sEMG signal can be identified during sustained voluntary or electrically elicited muscle contractions, and the analysis of myoelectric manifestations of muscle fatigue can provide important information about physiological changes evolving in the muscle. The amplitude of the surface EMG can be estimated by a scheme of demodulation, smoothing, and relinearization. An approach to monitoring the amplitude of activity of muscles with sEMG is to measure tuning curves. The chapter further reviews some of the most frequently applied analyses in musculoskeletal physical therapy research.
ChemInform Abstract: Heteronuclear NMR Pulse Sequences Applied to Biomolecules (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Neural Activity while Imitating Emotional Faces is Related to Both Lower and Higher-Level Social Cognitive Performance (2017)

Abstract Imitation and observation of actions and facial emotional expressions activates the human fronto-parietal mirror network. There is skepticism regarding the role of this low-level network in more complex high-level social behaviour. We sought to test whether neural activation during an observation/imitation task was related to both lower and higher level social cognition. We employed an established observe/imitate task of emotional faces during functional MRI in 28 healthy adults, with final analyses based on 20 individuals following extensive quality control. Partial least squares (PLS) identified patterns of relationships between spatial activation and a battery of objective out-of-scanner assessments that index lower and higher-level social cognitive performance, including the Penn emotion recognition task, reading the mind in the eyes, the awareness of social inference test (TASIT) parts 1, 2, and 3, and the relationships across domains (RAD) test. Strikingly, activity in limbic, right inferior frontal, and inferior parietal areas during imitation of emotional faces correlated with performance on emotion evaluation (TASIT1), social inference - minimal (TASIT2), social inference - enriched (TASIT3), and the RAD tests. These results show a role for this network in both lower-level and higher-level social cognitive processes which are collectively critical for social functioning in everyday life.
SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples (2021)

Abstract Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.
One-dimensional performance modelling of the ram accelerator in sub-detonative regime (2010)

A one-dimensional performance analysis code has been developed at the ”Laboratoire de Combustion et de D´etonique” to predict the thrust in the thermally choked ram accelerator propulsive mode. This research code incorporates the following equations of state: ideal gas, Boltzmann, Percus-Yevick, and Becker-Kistiakowsky-Wilson for both quasi-steady and unsteady flow situations. Experimental data from a representative ram accelerator experiment at the University&#13;\nof Washington 38-mm-bore facility were used for code validation. The predicted thrust and velocity agreed well with experimental measurements. Details about the algorithm for thrust calculations in the thermally choked ram accelerator propulsive mode under unsteady flow conditions while incorporating the influence of real gas behavior in the combustion process are presented.
Local Heat Transfer in Turbine Disk-Cavities: Part I — Rotor and Stator Cooling With Hub Injection of Coolant (1990)

Results are presented from an experimental study designed to obtain detailed radial heat transfer coefficient distributions applicable to the cooling of disk-cavity regions of gas turbines. An experimental apparatus has been designed to obtain local heat transfer data on both the rotating and stationary surfaces of a parallel geometry disk-cavity system. The method employed utilizes thin thermochromic liquid crystal coatings together with video system data acquisition and computer-assisted image analysis to extract heat transfer information. The color display of the liquid crystal coatings is detected through the analysis of standard video chromanance signals. The experimental technique used is an aerodynamically steady but thermally transient one which provides consistent disk-cavity thermal boundary conditions while yet being inexpensive and highly versatile. A single circular jet is used to introduce fluid from the stator into the disk-cavity by impingement normal to the rotor surface. The present study investigates hub injection of coolant over a wide range of parameters including disk rotational Reynolds numbers of 2 to 5 · 105, rotor/stator spacing-to-disk radius ratios of .025 to .15, and jet mass flow rates between .10 and .40 times the turbulent pumped flow rate of a free disk. The results are presented as radial distributions of local Nusselt numbers. Rotor heat transfer exhibits regions of impingement and rotational domination with a transition region between, while stator heat transfer shows flow reattachment and convection regions with evidence of an inner recirculation zone. The local effects of rotation, spacing, and mass flow rate are all displayed. The significant magnitude of stator heat transfer in many cases indicates the importance of proper stator modeling to rotor and disk-cavity heat transfer results.
Feature Disentanglement in generating three-dimensional structure from\n two-dimensional slice with sliceGAN (2021)

Deep generative models are known to be able to model arbitrary probability\ndistributions. Among these, a recent deep generative model, dubbed sliceGAN,\nproposed a new way of using the generative adversarial network (GAN) to capture\nthe micro-structural characteristics of a two-dimensional (2D) slice and\ngenerate three-dimensional (3D) volumes with similar properties. While 3D\nmicrographs are largely beneficial in simulating diverse material behavior,\nthey are often much harder to obtain than their 2D counterparts. Hence,\nsliceGAN opens up many interesting directions of research by learning the\nrepresentative distribution from 2D slices, and transferring the learned\nknowledge to generate arbitrary 3D volumes. However, one limitation of sliceGAN\nis that latent space steering is not possible. Hence, we combine sliceGAN with\nAdaIN to endow the model with the ability to disentangle the features and\ncontrol the synthesis.\n
Leveraging Uncertainty for Deep Interpretable Classification and Weakly-Supervised Segmentation of Histology Images (2022)

Trained using only image class label, deep weakly supervised methods allow image classification and ROI segmentation for interpretability. Despite their success on natural images, they face several challenges over histology data where ROI are visually similar to background making models vulnerable to high pixel-wise false positives. These methods lack mechanisms for modeling explicitly non-discriminative regions which raises false-positive rates. We propose novel regularization terms, which enable the model to seek both non-discriminative and discriminative regions, while discouraging unbalanced segmentations and using only image class label. Our method is composed of two networks: a localizer that yields segmentation mask, followed by a classifier. The training loss pushes the localizer to build a segmentation mask that holds most discrimiantive regions while simultaneously modeling background regions. Comprehensive experiments over two histology datasets showed the merits of our method in reducing false positives and accurately segmenting ROI.
Monitoring molecular dynamics using coherent electrons from high harmonic generation (2006)

We report a previously undescribed spectroscopic probe that makes use of electrons rescattered during the process of high-order harmonic generation. We excite coherent vibrations in SF(6) using impulsive stimulated Raman scattering with a short laser pulse. A second, more intense laser pulse generates high-order harmonics of the fundamental laser, at wavelengths of approximately 20-50 nm. The high-order harmonic yield is observed to oscillate, at frequencies corresponding to all of the Raman-active modes of SF(6), with an asymmetric mode most visible. The data also show evidence of relaxation dynamics after impulsive excitation of the molecule. Theoretical modeling indicates that the high harmonic yield should be modulated by both Raman and infrared-active vibrational modes. Our results indicate that high harmonic generation is a very sensitive probe of vibrational dynamics and may yield more information simultaneously than conventional ultrafast spectroscopic techniques. Because the de Broglie wavelength of the recolliding electron is on the order of interatomic distances, i.e., approximately 1.5 A, small changes in the shape of the molecule lead to large changes in the high harmonic yield. This work therefore demonstrates a previously undescribed spectroscopic technique for probing ultrafast internal dynamics in molecules and, in particular, on the chemically important ground-state potential surface.