gebhart/patrepeval huggingface dataset:
Androgen Receptor Splice Variants Dimerize to Transactivate Target Genes (2015)

Constitutively active androgen receptor splice variants (AR-V) lacking the ligand-binding domain have been implicated in the pathogenesis of castration-resistant prostate cancer and in mediating resistance to newer drugs that target the androgen axis. AR-V regulates expression of both canonical AR targets and a unique set of cancer-specific targets that are enriched for cell-cycle functions. However, little is known about how AR-V controls gene expression. Here, we report that two major AR-Vs, termed AR-V7 and AR(v567es), not only homodimerize and heterodimerize with each other but also heterodimerize with full-length androgen receptor (AR-FL) in an androgen-independent manner. We found that heterodimerization of AR-V and AR-FL was mediated by N- and C-terminal interactions and by the DNA-binding domain of each molecule, whereas AR-V homodimerization was mediated only by DNA-binding domain interactions. Notably, AR-V dimerization was required to transactivate target genes and to confer castration-resistant cell growth. Our results clarify the mechanism by which AR-Vs mediate gene regulation and provide a pivotal pathway for rational drug design to disrupt AR-V signaling as a rational strategy for the effective treatment of advanced prostate cancer.
Machine Learning for high speed channel optimization (2019)

Design of printed circuit board (PCB) stack-up requires the consideration of characteristic impedance, insertion loss and crosstalk. As there are many parameters in a PCB stack-up design, the optimization of these parameters needs to be efficient and accurate. A less optimal stack-up would lead to expensive PCB material choices in high speed designs. In this paper, an efficient global optimization method using parallel and intelligent Bayesian optimization is proposed for the stripline design.
Optimization of Airfoil Blend Limits With As-Manufactured Geometry Finite Element Models (2021)

Abstract Conventional airfoil blend repair limits are established using nominal, design intent geometry. This convention does not explicitly consider the inherent blade-to-blade structural response variation associated with geometric manufacturing deviations. In this work, we explore whether accounting for these variations leads to significant differences in blend depths and develop a novel approach to effectively predict blade-specific blend allowable. These blade-specific values maximize the part repairability according to their proximity to defined structural integrity constraints. The methodology is demonstrated on the as-manufactured geometry of an aerodynamic research rig compressor rotor. Geometric point cloud data of this rotor is used to construct as-built finite element models (FEMs) of each airfoil. The effect of two large blends on these airfoils demonstrates the opportunity of blade-specific blend limits. A new approach to determine each airfoil's blend repair capacity is developed that uses sequential least-squares quadratic programing and a parametric blended blade FEM that accounts for manufacturing geometry variations and variable blend geometry. A mesh morphing algorithm modifies a nominal geometry model to match the as-built airfoil surface and blend geometry. The numerical optimization maximizes blend depth values within the frequency, mode shape, and high cycle fatigue constraint boundaries. It is found that there are large variations in blend depth allowable between blades and competing structural integrity criteria are responsible for their limits. It is also found that, despite complex modal behavior caused by eigenvalue veering, the proposed optimization approach converges. The developed methodologies may be used in the future to extend blend limits, enable continued operations, and reduce sustainment costs.
Generic Deep Networks with Wavelet Scattering (2013)

We introduce a two-layer wavelet scattering network, which involves no learning, for object classification. This scattering transform computes a spatial wavelet transform on the first layer and a joint wavelet transform along spatial, angular and scale variables in the second layer. Image classification results are given on Caltech databases.
Fibrocyte: New participant in the pathogenesis of renal fibrosis (2008)

Progressive fibrosis is a common pathological finding in various organs, resulting in organ failure. Renal fibrosis is a progressive disease caused by diverse clinical entities. Irrespective and independent of the primary lesion, it is the severity of renal fibrosis that correlates best with the loss of renal function and the risk for progression to renal failure. A circulating population of cells (termed fibrocytes) that display leukocyte markers such as CD45 and CD34 as well as mesenchymal markers including type I collagen has been described. Fibrocytes have been reported to rapidly enter sites of tissue injury and contribute to the pathogenesis of fibrotic conditions. Fibrocytes express CCR7 and migrate in response to secondary lymphoid tissue chemokine (SLC/CCL21). We hypothesized that CCR7-positive fibrocytes contribute to renal fibrosis. To investigate this idea, renal fibrosis was induced by unilateral ureteral obstruction in mice. CD45- and type I collagen-dual positive fibrocytes infiltrated in the fibrotic kidneys and the number of infiltrated fibrocytes increased with the progression of the extent of fibrosis in an experimental murine renal fibrosis model. Most infiltrated fibrocytes in the kidneys were positive for CCR7. In addition, CCL21 protein co-localized with high endothelial venulelike vessels in fibrotic kidneys. The blockade of CCL21/CCR7 signaling reduced the number of infiltrating fibrocytes as well as the extent of renal fibrosis, which was confirmed by the reduction of the amount of hydroxyproline and the levels of renal transcripts of pro α1 chain of type I collagen and transforming growth factor-β1. These results suggest that CCR7-positive fibrocytes infiltrate into the kidney via CCL21-positive vessels, thereby, contributing to the pathogenesis of renal fibrosis. Thus, regulating the recruitment and activation of fibrocytes by modulation of CCL21/CCR7 signaling may provide a novel therapeutic approach for combatting organ fibrosis.
Causal network inference using biochemical kinetics (2014)

Supplementary data are available at Bioinformatics online.
Muscle injuries and repair: the role of prostaglandins and inflammation. (2003)

Skeletal muscle injuries are a common problem in trauma and orthopaedic surgery. Muscle injuries undergo the healing phases of degeneration, inflammation, regeneration, and fibrosis. Current and experimental therapies to improve muscle regeneration and limit muscle fibrosis include conservative and surgical principles with the adjuvant use of non-steroidal anti-inflammatory drugs (NSAIDs) and growth factor manipulation. NSAIDs appear to have a paradoxical effect on the healing of muscle injuries with early signs of improvement and subsequent late impairment in functional capacity and histology. In vitro and in vivo studies have explored the role of the cyclooxygenases and prostaglandins in the biological processes of healing muscle, including precursor cell activation, myoblast proliferation, myoblast fusion, and muscle protein synthesis. Through use of more specific cyclooxygenase inhibitors, we may be able to better understand the role of inflammation in muscle healing.
Improving head-up display with waveguides and holographic optical elements (2019)

Head-up displays offer ease-of-use and safety advantages over traditional head-down displays when implemented in aircraft and vehicles. Unfortunately, in the traditional head-up display projection method, the size of the image is limited by the size of the projection optics. In many vehicular systems, the size requirements for a large field of view head-up display exceed the space available to allocate for these projection optics. Thus, an alternative approach is needed to present a large field of view image to the user. By using holographic optical elements affixed to waveguides, it becomes possible to reduce the size of the projection system, while producing a comparatively large image. Additionally, modulating the diffraction efficiency of some of the holograms in the system presents an expanded viewing eyebox to the viewer. This presentation will discuss our work to demonstrate a magnified far-field image with an in-line two-dimensional eyebox expansion. It will explore recording geometries and configurations and will conclude by discussing challenges for future implementation.
Deep learning‐based multi‐class damage detection for autonomous post‐disaster reconnaissance (2020)

Timely assessment of damages induced to buildings due to an earthquake is critical for ensuring life safety, mitigating financial losses, and expediting the rehabilitation process as well as enhancing the structural resilience where resilience is measured by an infrastructure's capacity to restore full functionality post extreme events. Since manual inspection is expensive, time consuming and risky, low-cost unmanned aerial vehicles or robots can be leveraged as a viable alternative for quick reconnaissance. Visual data captured by the sensors mounted on the robots can be analyzed, and the damages can be detected and classified autonomously. The present study proposes the use of deep learning-based approaches to this end. Region-based convolutional neural network (Faster RCNN) is exploited to detect four different damage types, namely, surface crack, spalling (which includes façade spalling and concrete spalling), and severe damage with exposed rebars and severely buckled rebars. The performance of the proposed approach is evaluated on manually annotated image data collected from reinforced concrete buildings damaged under several past earthquakes such as Nepal (2015), Taiwan (2016), Ecuador (2016), Erzincan (1992), Duzce (1999), Bingol (2003), Peru (2007), Wenchuan (2008), and Haiti (2010). Several experiments are presented in the paper to illustrate the capabilities, as well as the limitations, of the proposed approach for earthquake reconnaissance. It was observed that Inception-ResNet-v2 significantly outperforms the other networks considered in this study. The research outcome is a stepping stone forward to facilitate the autonomous assessment of buildings where this can be potentially useful for insurance companies, government agencies, and property owners.
Early scanning and late scanning after injection of FDG are equally sensitive in the detection of Alzheimer pattern: An analysis on 3D PET Data from J-ADNI (2011)

1257 Objectives 18F-FDG-PET with 3D acquisition is used as a potential biomarker for multicenter Alzheimer’s disease (AD) neuroimaging studies, because of the high sensitivity and low radiation exposure. However, the optimal scanning time for 3D-FDG-PET to detect an AD uptake pattern has not been investigated. This study aimed to compare the sensitivity for detecting an AD pattern between early scanning (ES) and late scanning (LS). Methods The subjects were recruited as clinical AD, MCI or normal in the Japanese AD neuroimaging initiative, and imaged for 30-60 min post-injection of FDG. Three independent experts blinded to the clinical information classified the FDG uptake pattern of the 30-60 min summed images based on criteria proposed by Silverman et al. (JAMA 2001). Target ROIs were defined based on significant differences in FDG uptake between 20 patients with an AD uptake pattern and 20 subjects with a normal pattern. ES and LS images were obtained as data acquired for 30-35 and 55-60 min, respectively. A further 37 patients and 39 normal controls, served as test subjects to evaluate the diagnostic performance, using the Z scores in the target ROIs. Results FDG uptake in the bilateral frontal lobes was greater in LS than ES, while radioactivity in the venous sinus was greater in ES than LS. However, there were no significant differences between ES and LS (sensitivity: 0.97 vs. 0.97; specificity: 0.82 vs. 0.84; AUC: 0.96 vs. 0.97). Conclusions For 3D-FDG-PET scanning, it would be beneficial to use an early scanning protocol to detect AD
Light-induced blockage of cell division with a chromatin-targeted phototoxic fluorescent protein (2011)

Proteins of the GFP (green fluorescent protein) family are widely used as passive reporters for live cell imaging. In the present study we used H2B (histone H2B)-tKR (tandem KillerRed) as an active tool to affect cell division with light. We demonstrated that H2B-tKR-expressing cells behave normally in the dark, but transiently cease proliferation following green-light illumination. Complete light-induced blockage of cell division for approx. 24 h was observed in cultured mammalian cells that were either transiently or stably transfected with H2B-tKR. Illuminated cells then returned to normal division rate. XRCC1 (X-ray cross complementing factor 1) showed immediate redistribution in the illuminated nuclei of H2B-tKR-expressing cells, indicating massive light-induced damage of genomic DNA. Notably, nondisjunction of chromosomes was observed for cells that were illuminated during metaphase. In transgenic Xenopus embryos expressing H2B-tKR under the control of tissue-specific promoters, we observed clear retardation of the development of these tissues in green-light-illuminated tadpoles. We believe that H2B-tKR represents a novel optogenetic tool, which can be used to study mitosis and meiosis progression per se, as well as to investigate the roles of specific cell populations in development, regeneration and carcinogenesis in vivo.
Implementing advanced AC drive controls using auto-coding methods (2015)

This paper investigates the usability of model-based auto-code generation methods for AC drive controls applications in research and teaching labs. As an emerging software technology, auto coding methods can automatically generate the control law code from Simulink™ blocks, which offers benefits for teaching labs, rapid prototyping for research, and hardware-in-the-loop for testing. However, the use of auto-coding methods also introduces additional implementation issues and limitations, compared to conventional hand-coded on micro-controller systems. This paper demonstrates experimental implementation and evaluation of several advanced AC drive controls on a three phase inverter driven surface permanent magnet synchronous machines (SPMSM) dynamometer using auto-coding methods. Implementing issues and challenges of auto-code generation are explored including the variability of execution time, execution sequence, and undocumented time delay in analog interfaces. Improvements of the auto-coding system were achieved through multiple iterative modifications.
A reinvestigation of the bamberger‐ham phenazine. Synthesis: A limitation (1979)

Abstract The Bamberger‐Ham condensation of 4‐substituted nitrosobenzenes in concentrated sulfuric acid reported as a method of synthesis for phenazine N ‐oxides has been found to be limited to electron donating substituents. Methyl 4‐nitrosobenzoale has been found to react under these conditions to give dimethyl 2‐nitrodiphenylamine‐4, 5‐diearboxylate ( 2 ). Compounds of unknown structure previously reported to arise from acid treatment of 4‐bromo‐ and 4‐chloronilrosobenzene have been shown to be 4, 5‐dibromo‐2‐nitrosophenylamine ( 10 ) and the analogous dichloro compound. Treatment under stronger acidic conditions (oleum) converted 10 but not 2 into the corresponding phenazine N ‐oxide. Mechanistic implications are discussed.
Optimized Operation for Infrastructure-Supported Wireless Sensor Networks (2010)

Due to the energy-constrained nature of wireless sensor networks (WSNs), a variety of communication protocols which rely on cluster-based topologies to enhance network capacity or to prolong network operational lifetime have been well studied heretofore. In this paper, we instead study a comprehensive perspective that searches for an optimal operation that considers backbone node placement and communication scheduling methods, as well as network connectivity properties. Specifically, we aim to answer the following three questions: how many backbone nodes are necessary, where to position these nodes, and which backbone nodes can communicate simultaneously to maximally serve the networks. We study the scalability of our approach and its dependency on parameters such as network size and density and present simulation results.
A continuous reactor system for production of lactulose (1994)

A continuous reactor process was developed to produce lactulose from lactose. A system of two CSTRs in series with a tubular finishing reactor gave conversion to lactulose of about 76%. The reactors ran at 71-75 degrees C with a volumetric hold-up in the CSTRs of 22.7 dm3 and in the tubular reactor of 2.6 dm3. Each CSTR had a nominal residence time of 44 min. The flow rate was 0.53 dm3 min-1.
Mutations predictive of hyperactive Ras signaling correlate with inferior survival across high-risk pediatric acute leukemia (2020)

We thus propose that hyperactive Ras signaling confers inferior survival in high-risk pediatric acute leukemia and that Ras pathways should be molecularly characterized to inform clinical decision making and to identify patients for experimental clinical trials and RAS-targeted therapy.
Post-Catalytic Complexes with Emtricitabine or Stavudine and HIV-1 Reverse Transcriptase Reveal New Mechanistic Insights for Nucleotide Incorporation and Drug Resistance (2020)

Human immunodeficiency virus 1 (HIV-1) infection is a global health issue since neither a cure nor a vaccine is available. However, the highly active antiretroviral therapy (HAART) has improved the life expectancy for patients with acquired immunodeficiency syndrome (AIDS). Nucleoside reverse transcriptase inhibitors (NRTIs) are in almost all HAART and target reverse transcriptase (RT), an essential enzyme for the virus. Even though NRTIs are highly effective, they have limitations caused by RT resistance. The main mechanisms of RT resistance to NRTIs are discrimination and excision. Understanding the molecular mechanisms for discrimination and excision are essential to develop more potent and selective NRTIs. Using protein X-ray crystallography, we determined the first crystal structure of RT in its post-catalytic state in complex with emtricitabine, (-)FTC or stavudine (d4T). Our structural studies provide the framework for understanding how RT discriminates between NRTIs and natural nucleotides, and for understanding the requirement of (-)FTC to undergo a conformation change for successful incorporation by RT. The crystal structure of RT in post-catalytic complex with d4T provides a "snapshot" for considering the possible mechanism of how RT develops resistance for d4T via excision. The findings reported herein will contribute to the development of next generation NRTIs.
Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics (2019)

Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against DENV with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested that J9 and J8 followed divergent somatic hypermutation pathways, and that a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a new epitope that can be exploited for vaccine design.
Enhanced News-reading: Interactive and Visual Integration of Social Media Information (2014)

Today, everyone has the possibility to acquire additional information sources as supplement to articles from newspapers or online news. The limitations of classical newspaper articles and restrictions of additional materials on online newsportals often lead to the situation where the reader demands additional news sources and more detailed information. When using the Internet, exploiting new information sources is a trivial task. Besides professionally administered information sources, like for example large newsportals such as cnn.com, there is a growing amount of user generated content available. Services like Twitter, Facebook or Reddit allow free discussion of any subject, giving everyone the possibility to participate. In this paper, we demonstrate an approach that combines professionally generated news content with user-generated data. This approach effectively enriches the information landscape and broadens the context of a given subject. For the presented system, we focus on Reddit, one of the biggest web portals for user-generated contents. Taking the general nature of user generated content into account, we exploit meta-data and apply Natural Language Processing (NLP) methods to allow users to filter additional information, which is also supported visually.
Resveratrol Inhibits the Release of Mediators from Bone Marrow-Derived Mouse Mast cellsin vitro (2004)

Resveratrol is a natural phytoalexin occurring in grapes, vines and peanuts and possesses both antitumor and antioxidation capabilities. Its chemoprotective actions are attributed partially to its anti-inflammation effect. The present study is aimed at checking the inhibitory actions of resveratrol on the release of mediators from bone marrow-derived mouse mast cells (BMMC) in vitro. Mast cells were prepared by isolating bone marrow cells from intact mice femora and culturing them for 4 weeks in the presence of IL-3 and FCS. The release reaction was triggered by IgE or calcium ionophore (A23187). Mediated by IgE, the release of histamine and tumor necrosis factor-alpha was significantly inhibited by resveratrol at a concentration of 100 microM; IgE-mediated release of leukotrienes and prostaglandin D (2) was also strongly suppressed at concentrations of 100 and 10 microM. Also, A23187-mediated release of histamine and leukotrienes release was strongly reduced by resveratrol at concentrations of 100 and 10 microM, respectively. Resveratrol exhibited its behavior without a significant cytotoxic activity against mast cells. In conclusion, resveratrol is a potent non-selective inhibitor of mediator release from activated mast cells and deserves further investigation of its biological modulations.