gebhart/patrepeval huggingface dataset:
Spliceosome: Physiology and Disease Pathogenesis (2016)

Abstract Pre-mRNA splicing is an essential step for the expression of intron-containing genes, i.e., the majority of genes. Splicing is a high-fidelity process, as required for the correct expression of proteins. However, there is flexibility in the selection of competing splice sites, which gives rise to alternative splicing, a regulated process that greatly increases the diversity of the proteome. Splicing is catalyzed in a stepwise manner by the spliceosome, a macromolecular machine that consists of 5 small RNAs and more than 100 proteins. Key insights about the structure and dynamics of spliceosomal complexes have recently been obtained through cryo-electron microscopy studies. Dysregulated splicing can arise from mutations in the splice sites or regulatory elements of individual genes, from alterations in the levels of regulatory splicing factors (activators and repressors), or from mutations in splicing-factor genes. All of these scenarios can give rise to various cancers, depending on the affected gene and the cellular context. Interestingly, recurrent somatic heterozygous mutations in particular splicing factors involved in branchpoint-sequence and 3'-splice-site recognition have emerged as key drivers of certain myeloid neoplasias. This presentation will review relevant features of the spliceosome machinery, the functional implications for normal and pathological conditions, and the potential for novel therapies. Disclosures Krainer: Ionis Pharmaceuticals: Consultancy, Honoraria, Patents &amp; Royalties, Research Funding; Stoke Therapeutics: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Co-founder, Patents &amp; Royalties; Cold Spring Harbor Laboratory: Employment, Membership on an entity's Board of Directors or advisory committees, Patents &amp; Royalties; H3 Biomedicine: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.
Enhancing Biohydrogen Production from Chlorella Vulgaris FSP-E Under Mixotrophic Cultivation Conditions (2014)

In this study, three indigenous microalgae strains (Scenedesmus subspicatus GY-16, Chlorella vulgaris FSP-E, and Anistrodesmus gracilis GY-09) were evaluated for their performance on producing carbohydrates, which serve as feedstock for bioH2 production. The results show that C. vulgaris FSP-E displayed the highest growth rate (825.6 mg/L/d) and carbohydrate productivity (365.8 mg/L/d). Different sodium acetate concentrations were supplemented into the growth medium to investigate the effect of organic carbon source on biomass and carbohydrate productivity. The results show that using 2000 mg/l sodium acetate to grow C. vulgaris FSP-E resulted in the highest biomass and carbohydrate productivity of 1022.3 mg/l/d and 498.5 mg/l/d, respectively. Meanwhile, to assess the practical applicability of the proposed microalgae-based carbohydrates production system, the photobioreactor was further operated on semi-batch mode for a prolonged incubation time under the optimal conditions. The results show that the biomass and carbohydrate productivity of C. vulgaris FSP-E was stably maintained at 1173.6 and 371.4 mg/L/d, respectively. Due to the high carbohydrate content, C. vulgaris FSP-E is considered an excellent feedstock for biohydrogen fermentation. Using the acidic hydrolysate of C. vulgaris FSP-E as feedstock, the separate hydrolysis and fermentation (SHF) process could achieve high-yield hydrogen production with a maximum hydrogen yield of 2.67 g hydrogen/g microalgae biomass, which is higher than most reported values. These results indicate that using carbohydrate-rich microalgae as feedstock to produce biohydrogen is indeed feasible for practical applications.
Fifteen‐month duration of immunity for the serovar Grippotyphosa fraction of a tetravalent canine leptospirosis vaccine (2018)

Forty-four specific pathogen-free beagles, median age 65 days, received two subcutaneous doses of either a commercially available, five-way combination vaccine or the same vaccine in combination with a tetravalent <i>Leptospira</i> bacterin (Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona). They were subsequently challenged with a pathogenic strain <i>L kirschneri</i> serovar Grippotyphosa 470 days following completion of the vaccination protocol. Titres of agglutinating serum antibodies were determined at various time points before and after both vaccination and challenge, along with postchallenge reisolation of the challenge organisms from blood and urine, and evaluation of renal histopathology. Clinical signs of generalised leptospirosis were not observed in any of the dogs after challenge. In order to demonstrate efficacy, leptospirosis was defined as having at least one positive urine sample and a positive renal histopathology score; or, in the absence of renal pathology, multiple positive urine samples. Leptospiremia was not demonstrated in any of the vaccinated dogs versus 27 per cent of the controls; leptospiruria was noted in 5 per cent of the vaccinates compared with 76 per cent of controls; and renal lesions were observed in 15 per cent of the vaccinates and 65 per cent controls. Using these criteria, the vaccine was able to significantly prevent leptospirosis (P=0.0001) in the vaccinated animals. This study establishes duration of immunity of at least 15 months for the prevention of disease and renal excretion of leptospires for the <i>Leptospira</i> serovar Grippotyphosa fraction of a quadrivalent <i>Leptospira</i> vaccine.
Macromolecular Crystallography for Synthetic Abiological Molecules: Combining xMDFF and PHENIX for Structure Determination of Cyanostar Macrocycles (2015)

Crystal structure determination has long provided insight into structure and bonding of small molecules. When those same small molecules are designed to come together in multimolecular assemblies, such as in coordination cages, supramolecular architectures and organic-based frameworks, their crystallographic characteristics closely resemble biological macromolecules. This resemblance suggests that biomacromolecular refinement approaches be used for structure determination of abiological molecular complexes that arise in an aggregate state. Following this suggestion we investigated the crystal structure of a pentagonal macrocycle, cyanostar, by means of biological structure analysis methods and compared results to traditional small molecule methods. Cyanostar presents difficulties seen in supramolecular crystallography including whole molecule disorder and highly flexible solvent molecules sitting in macrocyclic and intermolecule void spaces. We used the force-field assisted refinement method, molecular dynamics flexible fitting algorithm for X-ray crystallography (xMDFF), along with tools from the macromolecular structure determination suite PHENIX. We found that a standard implementation of PHENIX, namely one without xMDFF, either fails to produce a solution by molecular replacement alone or produces an inaccurate structure when using generic geometry restraints, even at a very high diffraction data resolution of 0.84 Å. The problems disappear when taking advantage of xMDFF, which applies an optimized force field to realign molecular models during phasing by providing accurate restraints. The structure determination for this model system shows excellent agreement with the small-molecule methods. Therefore, the joint xMDFF-PHENIX refinement protocol provides a new strategy that uses macromolecule methods for structure determination of small molecules and their assemblies.
ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts (2021)

Coptidis Rhizoma is the dried rhizome from the <i>Coptis chinensis</i> Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, <i>N</i>-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC.
Integrated Computational Materials and Mechanical Modeling for Additive Manufacturing of Alloys with Graded Structure Used in Fossil Fuel Power Plants (2022)

Wire-arc additive manufacturing (WAAM) has demonstrated its unique capability of producing large-size alloy components with a significantly reduced fabrication time and enhanced geometry design freedom. In this project, the team has developed an ICME (Integrated Computational Materials Engineering) modeling framework, which supports the WAAM of the AUSC (Advanced Ultra-Supercritical) power plant components. The manufacturing design has been applied to Inconel 740H, steel P91, as well as the dissimilar alloy components between steel P91 and Inconel 740H. The ICME model framework is developed by considering two types of modeling. First, mechanistic modeling has been applied to control the printing quality and understand the sequence of the dissimilar printing of the wall structure. The following models have been included in the developed ICME framework: finite element thermal model, grain structure model, residual stress simulation, crystal plasticity model, CALPHAD-based precipitation kinetic model, phase stability prediction, thermal expansion predictive model, and heuristic creep model. Secondary, a physics-based machine learning model has also been developed based on the ICME model structure. The machine learning model development is based on the ICME model prediction with calibration of the experiments. In addition, the WAAM has been utilized as a high-throughput experimental tool rapidly generating a gradient of alloy composition to facilitate experimental database generation for process-structure-property relationships. Such a database directly supported the ICME-enhanced machine learning, which further assisted in intermediate composition block design between P91 and 740H. A high-throughput screening study of the oxidation resistance has been performed based on such high-throughput experimentation. Based on the computational design, several dissimilar alloy manufacturing with post-heat treatment have been performed with a comprehensive evaluation of mechanical performance, including hardness mapping, yield strength, creep resistance. In this project, the single component of P91 and 740H processed by WAAM after heat treatment designed by ICME has demonstrated higher performance in yield strength and creep resistance than the wrought materials. The P91 sample prepared by WAAM with ICME-designed heat treatment performs better than P92 in creep resistance. The designed graded alloy printing with intermediate block shows a promising performance that exceeds the traditional welding. Moreover, the current research indicates the high need for location-specific design analysis with uncertainty quantification, an important topic that deserves more dedicated research. The achievement of this project demonstrated the promising future of WAAM in structural alloy manufacturing for energy power plant development. Successful printing requires synergetic efforts made by manufacturing, mechanical, and materials sciences.
Analysis of subwavelength traffic grooming efficiency in optical mesh networks (2004)

While deploying the next generation of optical networks with a mesh topology, telecommunications carriers are being confronted with a choice between wavelength switches that can switch traffic at SONET STS-48 (2.5 Gbps) granularity and subwavelength grooming capable switches that can switch at STS-1 (51 Mbps) granularity. The former consumes high fragmented/unused capacity to support low capacity end-to-end circuits using high capacity STS-48 channels (given current subwavelength traffic levels) while the latter may require relatively complicated hardware design that decreases switch scalability. Two-tier network architectures combine the benefits of STS-1 and STS-48 switches by using an upper tier of STS-48 switches for routing and restoration and a lower tier of STS-1 switches for grooming efficiency. A partial two-tier architecture, where STS-1 switches are restricted to a subset of the network nodes, has been shown in to closely match the grooming benefits of a full lower STS-1 tier. We furnish a detailed upper hound analysis of how the fragmented/unused capacity in STS-48 channels (fragmentation loss) varies with the grooming capability of a network for arbitrary traffic scenarios. We show that the upper bounds derived in this paper are in agreement with results obtained using efficient routing and grooming algorithms discussed. Because the bounds obtained do not make any assumptions about traffic and are easy to compute, they are suited for incorporation into a network engineering tool for deciding strategic placement of STS-1 switches in partial two-tier networks. Our work is not biased towards any particular network architecture but aims to analyze the grooming efficiency of two-tier networks.
Long‐term ear‐EEG monitoring of sleep – A case study during shift work (2023)

The interest in sleep as a potential clinical biomarker is growing, but the standard method of sleep assessment, polysomnography, is expensive, time consuming, and requires a lot of expert assistance for both set-up and interpretation. To make sleep analysis more available both in research and in the clinic, there is a need for a reliable wearable device for sleep staging. In this case study, we test ear-electroencephalography. A wearable, where electrodes are placed in the outer ear, as a platform for longitudinal at-home recording of sleep. We explore the usability of the ear-electroencephalography in a shift work case with alternating sleep conditions. We find the ear-electroencephalography platform to be reliable both in terms of showing substantial agreement to polysomnography after long-time use (with an overall agreement, using Cohen's kappa, of 0.72) and by being unobtrusive enough to wear during night shift conditions. We find that fractions of non-rapid eye movement sleep and transition probability between sleep stages show great potential as sleep metrics when exploring quantitative differences in sleep architecture between shifting sleep conditions. This study shows that the ear-electroencephalography platform holds great potential as a reliable wearable for quantifying sleep "in the wild", pushing this technology further towards clinical adaptation.
Sugar Determines Antibody Activity (2006)

Understanding the functional consequences of the identity and sequence of the sugars attached to antibodies may be useful in designing therapies for a range of disorders.
Residual energy scan for monitoring sensor networks (2003)

It is important to have continuously updated information about network resources and application activities in a wireless sensor network after it is deployed in an unpredictable environment. Such information can help notify users of resource depletion or abnormal activities. However, constrained by the low user-to-node ratio, limited energy and bandwidth resources, it is infeasible to extract the state of each individual node. In this paper, we propose an approach to constructing abstracted scans of sensor network health by applying in-network aggregation of network state. Specifically, we design a residual energy scan which approximately depicts the remaining energy distribution within a sensor network. Simulations show that our approach has good scalability and energy-efficiency characteristics, compared to continuously extracting the residual energy level individually from each node.
HIV-1-Tat Protein Inhibits SC35-mediated Tau Exon 10 Inclusion through Up-regulation of DYRK1A Kinase (2015)

The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism involved Tat-mediated increased expression of DYRK1A and was prevented by DYRK1A silencing. In addition, we found that Tat associates with TAU RNA, further demonstrating that Tat interferes with host RNA metabolism in the absence of viral infection. Altogether, our data unravel a novel mechanism of Tat-mediated neuronal toxicity through dysregulation of the SC35-dependent alternative splicing of TAU exon 10. Furthermore, the increased immunostaining of DYRK1A in HIV+ brains without pathology points at dysregulation of DYRK1A as an early event in the neuronal complications of HIV infection.
A new patterning process concept for large-area transistor circuit fabrication without using an optical mask aligner (1994)

A new concept to produce large thin film transistor liquid crystal displays (TFT-LCD's) without using an optical mask aligner is proposed which emphasizes patterning technology. Some experimental thin film transistors (TFT's) are fabricated according to the concept and operated like conventional transistors fabricated by using an optical mask aligner. The concept includes improvement of printing technology and development of a double-layer resist method. The latter method employs a printed ink pattern and a photoresist. This prevents contamination of thin films by metal impurities which affect electrical characteristics of the TFT's. A special gravure offset printing technology is proposed, composed of a large thixotropy valued UV ink, and a fine, precision etched glass intaglio. The experimental TFT's, with a designed minimum gate length of 10 /spl mu/m, have comparable electric characteristics to those of conventional poly-Si TFT's.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Control and Validation of Automated Lane Centering and Lane Changing Maneuver (2009)

This paper describes an automated lane changing control system that has been developed at General Motors Research and Development. This system uses a single monochrome camera to recognize lane markings on the road ahead and uses multiple short range radars to detect surrounding traffic and objects. A sensing unit calculates the host vehicle’s lateral displacement and the heading angle from the center of its lane as well as the relative distance and relative speed of each object. Since the smoothness and comfort of lane change maneuvering are important measures of the control performance, the vehicle dynamic model is integrated into the desired path generation and vehicle’s controller design to reduce the vehicle lateral acceleration and the lateral offset overshoot during the lane change maneuvering. To avoid heavy computation, a simplified model predictive control algorithm is proposed. The control algorithm calculates a steering angle command at the current time step to drive the vehicle to the desired path. The control method and algorithms are implemented on a demonstration vehicle and validated at straight roads and various curve roads of up to 0.001 [1/m] curvature for different vehicle speeds up to 100 [km/hr]. The results show that lane change maneuvering is successfully completed with lateral offset error less than 20 cm.
Cooperative Quasi-Static Planar Manipulation With Multiple Robots (2010)

In this paper we address the modeling, control, and planning of planar manipulation tasks with multiple robots equipped with simple end-effectors. Each robot is able to influence the motion of an object either by exerting forces through the end-effector or by contact through a robot body. We develop a quasi-static model for the planar manipulation task that incorporates mathematical models of the object-ground contact, the object-robot contact and the compliant end-effector. This model allows us to predict object velocities for specified robot motions. We use this model to develop a simple motion planning algorithm for object manipulation that allows robots to select grasps, regrasp when necessary and manipulate an object along desired trajectories. Our experiments validate the mathematical models and demonstrate the feasibility of multirobot manipulation using the quasi-static model and the motion planning algorithm.
Unified scatter model for rough surfaces at large incident and scatter angles (2007)

A new unified surface scatter model has been developed that produces accurate results for rougher surfaces than the classical Rayleigh-Rice vector perturbation theory and for larger incident and scattered angles than the classical Beckmann-Kirchhoff theory. It is a generalization of the linear systems formulation developed by Harvey and Shack in the mid 1970s. The scattered light behavior is characterized by a two-parameter family of surface transfer functions. The rather computationally intensive process of calculating the scattered intensity from rough surfaces at large incident angles is described and shown to agree well with experimental data. Furthermore, the smooth-surface approximation to this new generalized surface scatter theory yields an improved solution to the inverse scattering problem of characterizing optical surfaces from BRDF measurements. The new obliquity factor greatly reduces the ubiquitous and annoying "hook" at the high spatial frequency end of surface PSDs predicted by the Rayleigh-Rice theory. Comparisons of this new theory and the Rayleigh-Rice theory will be made with experimental BRDF measurements provided by John Stover, author of the companion paper entitled "Limitations of Rayleigh-Rice perturbation theory for describing surface scatter".