gebhart/patrepeval huggingface dataset:
Therapeutic shutdown of HBV transcripts promotes reappearance of the SMC5/6 complex and silencing of the viral genome in vivo (2021)

These results reveal that therapeutics abrogating all HBV transcripts including HBx promote epigenetic suppression of the HBV minichromosome, whereas strategies protecting the human hepatocytes from reinfection are needed to maintain cccDNA silencing.
Deconvolved phase imaging for diffraction tomography (2011)

We present a new technique for coherent imaging based on digital holographic microscopy. For high-resolution tomography, the diffraction effect of the microscope objective is corrected by the system’s complex point spread function.
Biosynthetic thiolase from Zoogloea ramigera. Evidence for a mechanism involving Cys-378 as the active site base (1991)

Biosynthetic thiolase from Zoogloea ramigera was inactivated with a mechanism-based inactivator, 3-pentynoyl-S-pantetheine-11-pivalate (3-pentynoyl-SPP) where K1 = 1.25 mM and kinact = 0.26 min-1, 2,3-pentadienoyl-SPP obtained from nonenzymatic rearrangement of 3-pentynoyl-SPP where K1 = 1.54 mM and kinact = 1.9 min-1 and an affinity labeling reagent, acryl-SPP. The results obtained with the alkynoyl and allenoyl inactivators are taken as evidence that thiolase from Z. ramigera is able to catalyze proton abstraction uncoupled from carbon-carbon bond formation. The inactivator, 3-pentynoyl-SPP and the affinity labeling reagent, acryl-SPP, trap the same active site cysteine residue, Cys-378. To assess if Cys-378 is the active site residue involved in deprotonation of the second molecule of acetyl-CoA, a Gly-378 mutant enzyme was studied. In the thiolysis direction the Gly-378 mutant was more than 50,000-fold slower than wild type and over 100,000-fold slower in the condensation direction. However, the mutant enzyme was still capable of forming the acetyl-enzyme intermediate and incorporated 0.81 equivalents of 14C-label after incubation with [14C]Ac-CoA for 60 min. The reversible exchange of 32P-label from [32P]CoASH into Ac-CoA, catalyzed by the Gly-378 mutant enzyme, proceeded with a Vmax (exchange) 8,000-fold less than the wild type enzyme but at least 10-fold faster than the overall condensation reaction. These data provide evidence that Cys-378 is the active site base.
Ultra-fast model of the switched reluctance motor (2002)

This paper describes a magnetic/electric circuit model of the switched reluctance motor that is especially well adapted for rapid computation or simulation. The model is based on a set of normalised "gage curves" of flux-linkage versus rotor position at constant current, which are used for the interpolation required to recover instantaneous current from the known rotor position and flux-linkage during a dynamic simulation. The particular structure of the gage curves is key not only to the speed of calculation, but also to their ability to represent all the main nonlinearities arising from the variable geometry, the variable saturation of overlapping pole corners, and the variable bulk saturation of poles and yokes. In addition, they have sufficient differentiability to ensure that there are no discontinuities in the computed instantaneous torque or its rate of change. For high accuracy the gage curve model needs to be calibrated and it is shown how this is done with great economy of effort by a very fast finite-element procedure developed specially for the purpose. The variable coefficients of the gage-curve model are related to identifiable physical phenomena in the machine in a strongly intuitive way, and it is shown that the accuracy of the finite-element calculations combined with the speed and intuitive clarity of the gage-curve model results in a set of analytical tools that surpasses what has been available before.
Hypoxia-directed Magnetic Resonance-guided Focused Ultrasound Therapy (2018)

Compelling clinical and experimental evidence clearly indicates that tumor hypoxia remains a challenge for radiation and chemotherapy. The general consensus is that tumor hypoxia is a major cause of treatment failures. We therefore hypothesize that it would be beneficial to detect the hypoxic areas in tumors and irreversibly ablate them to reduce hypoxia related resistance. To test this hypothesis, we propose preclinical studies using a mouse tumor model and PET/MRI guidance to thermally ablate hypoxic-tissue prior to ionizing radiation. In humans, this approach may significantly shorten focused ultrasound thermal ablation treatment times since only hypoxic regions of tumors are targeted.
A Potential Role for PDGF-C in Experimental and Clinical Proliferative Vitreoretinopathy (2007)

The predominance of PDGF isoforms that activate PDGFRalpha support the ligand hypothesis as an explanation of why PDGFRalpha is more capable of inducing PVR than is PDGFRbeta. Furthermore, the profile of PDGF isoforms observed in the rabbit model accurately reflected the clinical specimens from patients with PVR. Finally, these findings implicate one of the new PDGF family members as an important contributor to experimental and clinical PVR.
Abstract 3802: Withacnistin blocks binding of STAT3 and STAT5 to growth factor and cytokine receptors and induces regression of breast tumors in vivo (2014)

Abstract The binding of STAT3 and STAT5 to growth factor and cytokine receptors such as EGFR and the IL-6 receptor gp130 is critical to their activation and ability to contribute to malignant transformation. Therefore, interfering with these biochemical processes could lead to the discovery of novel anti-cancer agents. In this manuscript, we show that the natural product, Withacnistin (Wit) blocks EGF- and IL-6-stimulated binding of STAT3 and STAT5 to EGFR and gp130. Furthermore, Wit inhibits EGF-, PDGF-, IL-6-, IFNβ- and GM-CSF-stimulation of tyrosine phosphorylation of STAT3 and STAT5 but not of EGFR or PDGFR. The inhibition of P-STAT3 and P-STAT5 occurred very rapidly, within minutes of Wit treatment and growth factor stimulation. Wit also inhibits STAT3 nuclear translocation, DNA binding, promoter transcriptional activation, and it suppresses the expression levels of STAT3 target genes such as Bcl-xL and Mcl-1. Finally, Wit induces apoptosis, inhibits anchorage-independent growth and invasion, and causes breast tumor regression in an ErbB2-driven transgenic mouse model. These data warrant further development of Wit as a novel anti-cancer drug for targeting tumors that harbor hyperactivated STAT3 and STAT5. Citation Format: Xiaolei Zhang, Michelle A. Blaskovich, Kara D. Forinash, Said M. Sebti. Withacnistin blocks binding of STAT3 and STAT5 to growth factor and cytokine receptors and induces regression of breast tumors in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3802. doi:10.1158/1538-7445.AM2014-3802
EVALUATION OF GUARDRAIL TO CONCRETE BRIDGE RAIL TRANSITIONS (2003)

In December 2001, the Design Division and Bridge Division of Texas Department of Transportation released a new standard for an approach guardfence to concrete bridge rail transition that complies with the testing requirements of National Cooperative Highway Research Program (NCHRP) Report 350 for use on high-speed roadways. Because there are no national transition designs that have been developed and tested for lower speed conditions, the same transition standard is typically applied to all roadways regardless of speed. However, the new thrie beam transition design represents a significant increase in installation cost and complexity over the previous design. Thus, it may be cost prohibitive to require use of the same design on all roadways. The purpose of this research was to develop a transition that is suitable for use on lower speed roadways and that is less expensive and complex than the current high-speed design. A low-cost transition was successfully evaluated at 45 mph impact speeds under NCHRP Report 350 Test Level 2 conditions. A second objective of the project was to evaluate the need for the curb detail that is one of the design elements of the newly adopted thrie beam transition design. Elimination of the curb would greatly enhance installation flexibility and reduce installation cost. The assessment of the curb was accomplished through full-scale crash testing.
Reducing Cycle Time and Errors in the Design and Layout of MEMS (2003)

A design methodology is presented which decreases cycle time and opportunities for error through automated execution of a consistent design procedure. The Product Design Generator (PDG) methodology is useful for existing devices with a well-established design process. Two such examples are given, the Thermomechanical In-plane Microactuator (TIM) and the micro force gauge. In both PDGs, the designer inputs a finite set of requirements which automatically updates parametric design models. The necessary analyses are then executed, and product artifacts such as a CAD file, technical document, and test procedures are generated. The application of this method reduces the opportunities for error by ten times for the TIM PDG and five times for the micro force gauge PDG. The design cycle time is reduced from hours to minutes for both devices.
Double-Sequence Frequency Synchronization for Wideband Millimeter-Wave Systems with Few-Bit ADCs (2018)

In this paper, we propose and evaluate two novel double-sequence low-resolution frequency synchronization methods in millimeter-wave (mmWave) systems. In our system model, the base station uses analog beams to send the synchronization signal with infinite-resolution digital-to-analog converters. The user equipment employs a fully digital front end to detect the synchronization signal with low-resolution analog-to-digital converters (ADCs). The key ingredient of the proposed methods is the custom designed synchronization sequence pairs, from which there exists an invertible function (a ratio metric) of the carrier frequency offset (CFO) to be estimated. We use numerical examples to show that the ratio metric is robust to the quantization distortion. Further, we analytically characterize the CFO estimation performances of our proposed designs assuming a single user. To implement our proposed methods in a multi-user scenario, we propose to optimize the double-sequence design parameters such that: (i) for each individual user, the impact of the quantization distortion on the CFO estimation accuracy is minimized, and (ii) the resulting frequency range of estimation can capture as many users' CFOs as possible. Numerical results reveal that our proposed algorithms provide a flexible means to estimate CFO in a variety of low-resolution settings.
Prediction of Chromatographic Retention and Protein Identification in Liquid Chromatography/Mass Spectrometry (2002)

Liquid chromatography coupled on- or off-line with mass spectrometry is rapidly advancing as a tool in proteomics capable of dealing with the inherent complexity in biology and complementing conventional approaches based on two-dimensional gel electrophoresis. Proteins can be identified by proteolytic digestion and peptide mass fingerprinting or by searching databases using short-sequence tags generated by tandem mass spectrometry. This paper shows that information on the chromatographic behavior of peptides can assist protein identification by peptide mass fingerprinting in liquid chromatography/mass spectrometry. This additional information is significant and already available at no extra experimental cost.
Characterization of 3D MEMS structural dynamics with a conformal multi-channel fiber optic heterodyne vibrometer (2012)

Insight into transient structural interactions, including coupled vibrations and modal non-degeneracy (mode splitting) is important to the development of current and next generation vibratory gyroscopes and MEMS resonators. Device optimization based on characterization of these effects is currently time consuming and limited by the requirement to perform spatially distributed measurements with existing single point sensors. In addition, the effects of interest and the diagnosis of their underlying causes and dependences are not readily revealed by traditional modal and finite element analyses. This paper, accordingly, discusses the design of a novel multi-channel fiber-optic heterodyne vibrometer which addresses this requirement directly. We describe a fiber-optic interferometer design which incorporates many standard fiber-optic telecommunications components, configured to support dynamic imaging of the real-time structural behavior of macro and micro vibratory resonators, including planar and 3D micro electromechanical systems (MEMS). The capabilities of the new sensor are illustrated by representative data obtained from a variety of 3D vibratory MEMS structures currently under development.
Robust Mosaicing Method with Correction of Motion Distorsions and Tissue Deformations for In Vivo Fibered Microscopy (2007)

Filed 02.08.2007, published 12.02.2009 Application number US 11/832,674 Also published as US7978932, US8218901, US20110261262
Management in the Japan Maritime Self Defense Force: the effects of Japanese values and beliefs (1997)

This thesis examines the organization and management of Japan Maritime Self-Defense Force (JMSDF) and its similarities and common features with Japanese corporate management, a common style grounded in culture and more specifically in the Japanese educational system. In nearly one hundred years organizational theory, practices, and systems were mostly transplanted from the United States and European countries. However, these systems evolved to fit the environment and culture of the Japanese people. This study investigates features and relationships among the Japanese environment, culture, educational systems, and management style. Japanese society and culture deeply effect the education system, and this system in turn socializes people in basic beliefs and values (e.g., harmony and loyalty) foundational to Japanese corporate practices (e.g., group decision making and lifetime employment). This study seeks to advance our understanding of how JMSDF participates in the same culture, is grounded in the same beliefs, and engages in similar practices as other Japanese organizations
Effects of Varying Doses of Supplemental Conjugated Linoleic Acid on Production and Energetic Variables During the Transition Period (2007)

Supplementing a high dose of dietary conjugated linoleic acid (CLA) inhibits milk fat synthesis in dairy cows immediately postpartum. During negative net energy balance (EBAL), it appears that moderate CLA-induced milk fat depression causes a positive response in milk yield; however, as milk fat depression becomes more severe, the milk yield response diminishes. Multiparous Holstein cows (n = 31) were randomly assigned to 1 of 3 treatments beginning 9 +/- 6 d before expected calving and ceased at 40 d in milk (DIM): 1) 578 g/d of a rumen-inert (RI) palm fatty acid distillate (control), 2) 600 g/d of RI-CLA for the entire trial period (CLA-1), and 3) 600 g/d of RI-CLA until 10 DIM followed by 200 g/d for the remainder of the trial (CLA-2). Each dose provided equal amounts of fatty acids by replacing and balancing each treatment with a RI palm fatty acid distillate. Doses provided a total of 522 g of fatty acids/ d and 0, 174, or 58 (depending upon DIM) g of CLA (mixed isomers)/d. To improve palatability, doses were mixed with 600 g/d of dried molasses; one-half of the supplement was fed at 0800 h, and the remainder at 1900 h. Individual milk yield, dry matter intake, and body weight were recorded daily and milk composition determined every other day. There was no overall CLA effect on either the content or yield of milk protein or lactose. Both CLA treatments decreased overall milk fat content (26.0 and 18.3%) and yield (22.5 and 17.3%) with CLA-induced milk fat depression becoming significant by d 8. The CLA-induced milk fat depression increased in magnitude with progressing DIM until reaching a plateau on d 18 for CLA-1 (43%) and on d 14 for CLA-2 (33%), although neither milk fat trans-10, cis-12 CLA content (1.8 mg/g) nor its transfer efficiency (6.3%) changed over time. Treatments had no effect on overall dry matter intake or milk yield, but there was a treatment x time interaction for milk production, as cows fed either CLA treatment had increased milk yield after the second week of lactation. Cows fed either CLA treatment had a significant improvement in overall EBAL (-5.1 vs. -1.8 Mcal/d), a decrease in nonesterified fatty acid levels (12%), and an increase in glucose levels (11%). A dietary supplement containing trans-10, cis-12 CLA markedly improves EBAL and bioenergetic variables and increases milk yield in the total mixed ration-fed transitioning dairy cow.
Selective Epitaxy as Contact Passivation Approach in Bifacial n-Type PERT Solar Cells (2017)

This works focuses on the introduction of selective epitaxy as a contact passivation approach for bifacial n-type PERT solar cells. Because of the use of a metal grid on their rear side, bifacial cells provide a higher energy yield through rear illumination but have larger recombination losses than their monofacial counterparts with point contacts. A breakdown analysis of the recombination losses in bifacial cells fabricated with a homogeneous emitter, and for which efficiency values above 22.5 % were already achieved, reveals that there is still an important contribution of the emitter J0,metal (3000-4000 fA/cm2 for 1.2 % metal contact fraction) and that the emitter J0,pass can also be further improved to increase efficiency. This works aims at reducing the recombination losses in these devices by introducing in one single step an epitaxially grown highly doped layer at the p-type regions to be contacted. The structures here fabricated up to the step just prior to metallization (including patterning of both emitter and BSF) demonstrate the potential of this approach to significantly reduce the recombination losses compared to the reference without a selective epitaxial contact passivation scheme: (a) homogeneous emitter with SiO2 passivation: J0,total=90 fA/cm2, iVoc=681 mV, (b) homogeneous emitter with Al2O3 passivation: J0,total=70 fA/cm2, iVoc=688 mV, and (c) selective emitter via selective epitaxy with SiO2 passivation: J0,total=55 fA/cm2, iVoc=695 mV. Keeping in mind that this approach also brings the possibility to independently optimize the emitter in the passivated regions to reduce Auger recombination, further gain in passivation may still be possible, which increases the potential of this structure to achieve higher efficiency values at cell level.
Li2S6‐Integrated PEO‐Based Polymer Electrolytes for All‐Solid‐State Lithium‐Metal Batteries (2021)

The integration of Li<sub>2</sub> S<sub>6</sub> within a poly(ethylene oxide) (PEO)-based polymer electrolyte is demonstrated to improve the polymer electrolyte's ionic conductivity because the strong interplay between O<sup>2-</sup> <sub>(PEO)</sub> and Li<sup>+</sup> from Li<sub>2</sub> S<sub>6</sub> reduces the crystalline volume within the PEO. The Li/electrolyte interface is stabilized by the in situ formation of an ultra-thin Li<sub>2</sub> S/Li<sub>2</sub> S<sub>2</sub> layer via the reaction between Li<sub>2</sub> S<sub>6</sub> and lithium metal, which increases the ionic transport at the interface and suppresses lithium dendrite growth. A symmetric Li/Li cell with the Li<sub>2</sub> S<sub>6</sub> -integrated composite electrolyte has excellent cyclability and a high critical current density of 0.9 mA cm<sup>-2</sup> at 40 °C. Impressive electrochemical performance is demonstrated with all-solid-state Li/LiFePO<sub>4</sub> and high-voltage Li/LiNi<sub>0.8</sub> Mn<sub>0.1</sub> Co<sub>0.1</sub> O<sub>2</sub> cells at 40 °C.
The Adaptive Proline Response in P. falciparum Is Independent of PfeIK1 and eIF2α Signaling (2019)

We have previously identified the cytoplasmic prolyl tRNA synthetase in Plasmodium falciparum as the functional target of the natural product febrifugine and its synthetic analogue halofuginone (HFG), one of the most potent antimalarials discovered to date. However, our studies also discovered that short-term treatment of asexual blood stage P. falciparum with HFG analogues causes a 20-fold increase in intracellular proline, termed the adaptive proline response (APR), which renders parasites tolerant to HFG. This novel resistance phenotype lacks an apparent genetic basis but remains stable after drug withdrawal. On the basis of our findings that HFG treatment induces eIF2α phosphorylation, a sensitive marker and mediator of cellular stress, we here investigate if eIF2α-signaling is functionally linked to the APR. In our comparative studies using a parasite line lacking PfeIK1, the Plasmodium orthologue of the eIF2α-kinase GCN2 that mediates amino acid deprivation sensing, we show that HFG activity and the APR are independent from PfeIK1 and eIF2α signaling.
Preclinical Validation of Tumor-Penetrating and Interfering Peptides against Chronic Lymphocytic Leukemia (2022)

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. The disease is characterized by the accumulation of tumoral B cells resulting from a defect of apoptosis. We have <i>in vitro</i> and <i>in vivo</i> preclinically validated a tumor-penetrating peptide (named TT1) coupled to an interfering peptide (IP) that dissociates the interaction between the serine/threonine protein phosphatase 2A (PP2A) from its physiological inhibitor, the oncoprotein SET. This TT1-IP peptide has an antitumoral effect on CLL, as shown by the increased survival of mice bearing xenograft models of CLL, compared to control mice. The peptide did not show toxicity, as indicated by the mouse body weight and the biochemical parameters, such as renal and hepatic enzymes. In addition, the peptide-induced apoptosis <i>in vitro</i> of primary tumoral B cells isolated from CLL patients but not of those isolated from healthy patients. Finally, the peptide had approximately 5 h half-life in human serum and showed pharmacokinetic parameters compatible with clinical development as a therapeutic peptide against CLL.
The Use of Biodegradable Poly(e-caprolactone) Scaffolds in a Rat Spinal Cord Injury Model (2007)

Brumblay, Hunter Geoffrey M.D.; Leveque, Jean-Christophe A. M.D.; Wong, Darice Y. M.S.; Fuller, Angela B.A; Hollister, Scott Ph.D.; La Marca, Frank M.D.
Peptides modulating conformational changes in secreted chaperones: From in silico design to preclinical proof of concept (2009)

Blocking conformational changes in biologically active proteins holds therapeutic promise. Inspired by the susceptibility of viral entry to inhibition by synthetic peptides that block the formation of helix-helix interactions in viral envelope proteins, we developed a computational approach for predicting interacting helices. Using this approach, which combines correlated mutations analysis and Fourier transform, we designed peptides that target gp96 and clusterin, 2 secreted chaperones known to shift between inactive and active conformations. In human blood mononuclear cells, the gp96-derived peptide inhibited the production of TNFalpha, IL-1beta, IL-6, and IL-8 induced by endotoxin by >80%. When injected into mice, the peptide reduced circulating levels of endotoxin-induced TNFalpha, IL-6, and IFNgamma by >50%. The clusterin-derived peptide arrested proliferation of several neoplastic cell lines, and significantly enhanced the cytostatic activity of taxol in vitro and in a xenograft model of lung cancer. Also, the predicted mode of action of the active peptides was experimentally verified. Both peptides bound to their parent proteins, and their biological activity was abolished in the presence of the peptides corresponding to the counterpart helices. These data demonstrate a previously uncharacterized method for rational design of protein antagonists.