gebhart/patrepeval huggingface dataset:
Virological Control by the CD4-Binding Site Antibody N6 in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys (2017)

Passive immunotherapy against HIV-1 will most likely require broadly neutralizing antibodies (bnAbs) with maximum breadth and potency to ensure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross-clade pseudoviruses. We evaluated the <i>in vivo</i> antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically simian-human immunodeficiency virus (SHIV)-SF162P3-infected macaques. A single dose of N6-LS suppressed plasma viral loads in 4 out of 5 animals at day 7, while the combination of both antibodies suppressed all animals. The combination of both antibodies had no additive antiviral effect compared to a single dose of PGT121, potentially reflecting the nearly 10-fold-higher potency of PGT121 against this SHIV. Viral rebound occurred in the majority of suppressed animals and was linked to declining plasma bnAb levels over time. In addition to the effect on plasma viremia, bnAb administration resulted in significantly reduced proviral DNA levels in PBMCs after 2 weeks and in lymph nodes after 10 weeks. Autologous neutralizing antibody (nAb) responses and CD8<sup>+</sup> T-cell responses were not significantly enhanced in the bnAb-treated animals compared to control animals, arguing against their contribution to the viral effects observed. These results confirm the robust antiviral activity of N6-LS <i>in vivo</i>, supporting the further clinical development of this antibody.<b>IMPORTANCE</b> Monocloncal antibodies (MAbs) are being considered for passive immunotherapy of HIV-1 infection. A critical requirement for such strategies is the identification of MAbs that recognize the diversity of variants within circulating but also reservoir viruses, and MAb combinations might be needed to achieve this goal. This study evaluates the novel bnAb N6-LS alone or in combination with the bnAb PGT121, in rhesus macaques that were chronically infected with SHIV. The results demonstrate that N6-LS potently suppressed plasma viral loads in the majority of animals but that the combination with PGT121 was not superior to PGT121 alone in delaying time to viral rebound or reducing peripheral blood mononuclear cell (PBMC) or lymph node proviral DNA levels. The occurrence of viral escape variants in an N6-LS-monotreated animal, however, argues for the need to maximize breadth and antiviral efficacy by combining bnAbs for therapeutic indications.
Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2 (2001)

FGF-2 has been implicated in the cardiac response to hypertrophic stimuli. Angiotensin II (Ang II) contributes to maintain elevated blood pressure in hypertensive individuals and exerts direct trophic effects on cardiac cells. However, the role of FGF-2 in Ang II–induced cardiac hypertrophy has not been established. Therefore, mice deficient in FGF-2 expression were studied using a model of Ang II–dependent hypertension and cardiac hypertrophy. Echocardiographic measurements show the presence of dilated cardiomyopathy in normotensive mice lacking FGF-2. Moreover, hypertensive mice without FGF-2 developed no compensatory cardiac hypertrophy. In wild-type mice, hypertrophy was associated with a stimulation of the c-Jun N-terminal kinase, the extracellular signal regulated kinase, and the p38 kinase pathways. In contrast, mitogen-activated protein kinase (MAPK) activation was markedly attenuated in FGF-2–deficient mice. In vitro, FGF-2 of fibroblast origin was demonstrated to be essential in the paracrine stimulation of MAPK activation in cardiomyocytes. Indeed, fibroblasts lacking FGF-2 expression have a defective capacity for releasing growth factors to induce hypertrophic responses in cardiomyocytes. Therefore, these results identify the cardiac fibroblast population as a primary integrator of hypertrophic stimuli in the heart, and suggest that FGF-2 is a crucial mediator of cardiac hypertrophy via autocrine/paracrine actions on cardiac cells.
Lithiation of 1,2‐Dichloroethene in Flow Microreactors: Versatile Synthesis of Alkenes and Alkynes by Precise Residence‐Time Control (2012)

It′s all about the timing: Precise control of the residence time (tRx; see picture) of reactive intermediates in flow microreactors enables the reaction pathway of lithiated 1,2-dichloroethene to be switched to produce either alkenes or alkynes. This method also allows versatile syntheses of asymmetric disubstituted dichloroalkenes and alkynes. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Designing a coprocessor for recurrent computations (2002)

We present the design of an application-specific coprocessor for algorithms that can be modeled as uniform recurrences or "uniformized" affine recurrences. The coprocessor has a regular array of processors connected to an access-unit for intermediate storage of data. The distinguishing feature of our approach is that we assume the coprocessor to be interfaced to a standard, slow (single-ported) memory with low bandwidth. Hence, good performance is achieved by effectively exploiting data locality in the applications by the compiler, and the final architecture is chosen by a tradeoff analysis driven by the mapping process. Preliminary results indicate that the coprocessor has significantly lower clock rates or higher performance than that of existing RISC processors and is cost-effective for executing loop computations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Geographic Information System Application Development for Utility Infrastructure Systems (1992)

Application of data and information to solve municipal infrastructure problems and enhance system operation is the ultimate key to a successful geographic information system (GIS) program. This paper highlights a number of application issues to be considered in developing GIS application packages used in the planning, design, operation, and management of water resource and utility infrastructure systems. Some areas that require standardization in the application of GIS are also addressed.
EGF816 Exerts Anticancer Effects in Non–Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor (2016)

Non-small cell lung cancer patients carrying oncogenic EGFR mutations initially respond to EGFR-targeted therapy, but later elicit minimal response due to dose-limiting toxicities and acquired resistance. EGF816 is a novel, irreversible mutant-selective EGFR inhibitor that specifically targets EGFR-activating mutations arising de novo and upon resistance acquisition, while sparing wild-type (WT) EGFR. EGF816 potently inhibited the most common EGFR mutations L858R, Ex19del, and T790M in vitro, which translated into strong tumor regressions in vivo in several patient-derived xenograft models. Notably, EGF816 also demonstrated antitumor activity in an exon 20 insertion mutant model. At levels above efficacious doses, EGF816 treatment led to minimal inhibition of WT EGFR and was well tolerated. In single-dose studies, EGF816 provided sustained inhibition of EGFR phosphorylation, consistent with its ability for irreversible binding. Furthermore, combined treatment with EGF816 and INC280, a cMET inhibitor, resulted in durable antitumor efficacy in a xenograft model that initially developed resistance to first-generation EGFR inhibitors via cMET activation. Thus, we report the first preclinical characterization of EGF816 and provide the groundwork for its current evaluation in phase I/II clinical trials in patients harboring EGFR mutations, including T790M.
Bone Mechanical Properties in Healthy and Diseased States (2018)

The mechanical properties of bone are fundamental to the ability of our skeletons to support movement and to provide protection to our vital organs. As such, deterioration in mechanical behavior with aging and/or diseases such as osteoporosis and diabetes can have profound consequences for individuals' quality of life. This article reviews current knowledge of the basic mechanical behavior of bone at length scales ranging from hundreds of nanometers to tens of centimeters. We present the basic tenets of bone mechanics and connect them to some of the arcs of research that have brought the field to recent advances. We also discuss cortical bone, trabecular bone, and whole bones, as well as multiple aspects of material behavior, including elasticity, yield, fracture, fatigue, and damage. We describe the roles of bone quantity (e.g., density, porosity) and bone quality (e.g., cross-linking, protein composition), along with several avenues of future research.
RE: BACTERIAL INFECTION IN PROSTATODYNIA (1998)

No AccessJournal of UrologyClinical Urology: Letters to the Editor1 Oct 1998RE: BACTERIAL INFECTION IN PROSTATODYNIA J.E. Lowentritt, K. Kawahara, L.G. Human, W.J.G. Hellstrom, and G.J. Domingue J.E. LowentrittJ.E. Lowentritt , K. KawaharaK. Kawahara , L.G. HumanL.G. Human , W.J.G. HellstromW.J.G. Hellstrom , and G.J. DomingueG.J. Domingue View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)62574-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "RE: BACTERIAL INFECTION IN PROSTATODYNIA." The Journal of Urology, 160(4), pp. 1440–1441 References 1 : On chronic prostatitis with special studies of staphylococcus epidermis. Scand. J. Urol. Nephrol.1989; 123: 2. Google Scholar 2 : Coagulase-negative staphylococcus in chronic prostatitis. J. Urol.1992; 147: 398. Link, Google Scholar 3 : Update on clinical significance of coagulase-negative staphylococci. Clin. Microbiol. Rev.1994; 7: 117. Google Scholar 4 : Prostatitis: myths and realities. Urology1998; 51: 362. Google Scholar 5 : Prostatitis. Clin. Microbiol. Rev.1998; . in press. Google Scholar © 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 160Issue 4October 1998Page: 1440-1441 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.Metrics Author Information J.E. Lowentritt More articles by this author K. Kawahara More articles by this author L.G. Human More articles by this author W.J.G. Hellstrom More articles by this author G.J. Domingue More articles by this author Expand All Advertisement PDF downloadLoading ...
Structure Modification of an Active Azo-Compound as a Route to New Antimicrobial Compounds (2017)

Some novel (phenyl-diazenyl)phenols <b>3a</b>-<b>g</b> were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by ¹H-NMR, DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC) of each compound was determined against Gram-positive and Gram-negative bacteria and <i>Candida albicans</i>. Compounds <b>3b</b> and <b>3g</b> showed the highest activity against <i>S. aureus</i> and <i>C. albicans</i>, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure-activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity.
A Mars Ascent Vehicle for potential mars sample return (2017)

This paper will cover the conceptual design of a Mars Ascent Vehicle (MAV) and efforts underway to raise the TRL at both the component and system levels. A system down select was executed resulting in a Hybrid Propulsion based Single Stage To Orbit (SSTO) MAV baseline architecture. This paper covers the Point of Departure design, as well as results of hardware developments that will be tested in several upcoming flight opportunities.
Enhancement of thermospin effect in ZGNRs via p-n co-doping on edge (2016)

Electronic and thermoelectric properties are studied for ferromagnetic zigzag graphene nanoribbons (ZGNRs) co-doped by a pair of boron and nitrogen atoms on one edge. In case of the 1st nearest neighbor co-doping, the two dopants are partly neutralized by each other and the corresponding impurity states approach to the Fermi energy symmetrically from high and low energies. As a result, the electronic properties are effectively manipulated and the conductances of different spin show opposite behaviours. Over a large range from zero temperature to higher-than-room temperature, the system shows a strong spin thermopower with a spin Seebeck coefficient much bigger than the charge one. These findings suggest that doped ZGNRs can be promising materials for spintronic and thermospintronic devices.
Processing Satellite Images on Tertiary Storage: A Study of the Impact of Tile Size on Performance (1996)

Before raw data from a satellite can be used by an Earth scientist, it must first undergo a number of processing steps including basic processing, cleansing, and geo-registration. Processing actually expands the volume of data collected by a factor of 2 or 3 and the original data is never deleted. Thus processing and storage requirements can exceed 2 terrabytes/day. Once processed data is ready for analysis, a series of algorithms (typically developed by the Earth scientists) is applied to a large number of images in a data set. The focus of this paper is how best to handle such images stored on tape using the following assumptions: (1) all images of interest to a scientist are stored on a single tape, (2) images are accessed and processed in the order that they are stored on tape, and (3) the analysis requires access to only a portion of each image and not the entire image.
Approach for end-to-end QoS mapping and handling (2005)

One of the promising configurations to support QoS-aware applications is by combining capabilities of IntServ and DiffServ architectures. However, guaranteeing end-to-end QoS over such architectures requires the deployment of several mechanisms. In particular, multiple domains may consider different QoS parameters or manage them differently. In this paper, a framework is proposed to easy the analysis of QoS mapping between Internet domains. Abstract functions are proposed to contribute to the definition of a formal system for reasoning on QoS requirements and service level agreement.
HIV-1 entry inhibitors: closing the front door (2004)

Highly active antiretroviral therapy (HAART) has led to major declines in morbidity and mortality of HIV-1-infected individuals, but the increasing prevalence of drug-resistant viral isolates, combined with the toxicity and other limitations of current treatments, make the development of new therapies a high priority. As knowledge of viral entry has expanded, this step of the viral life cycle has become a target for novel therapeutic strategies. An emerging group of antiretrovirals, known collectively as entry inhibitors, targets several distinct steps in viral entry including CD4 binding, chemokine receptor engagement and the structural changes in the viral envelope required for fusion between viral and cellular membranes. Many entry inhibitors are in various stages of clinical development, with one already licensed for use. This review will provide an overview of the mechanisms involved in the entry process, highlight promising entry blockers under development and discuss several considerations related to treatment that are unique to this class of antiretroviral drugs.
A naturally occurring point substitution in Cdc25A, and not Fv2/Stk, is associated with altered cell-cycle status of early erythroid progenitor cells (2002)

The Friend virus susceptibility gene 2 (Fv2) controls the polyclonal expansion of infected cells that occurs early during Friend erythroleukemia virus infection. Fv2 has recently been shown to encode a truncated form of the Stk receptor tyrosine kinase (Sf-Stk). This observation, coupled with earlier work, suggested that Sf-Stk drives the expansion of infected cells by forming a complex with the Friend virus envelope glycoprotein, gp55, and the erythropoietin receptor. Fv2 has also been implicated in the control of cell cycling in early erythroid progenitors (erythroid blast-forming units [BFU-Es]). Mouse strains that are homozygous for the resistant allele of Fv2 (Fv2(rr)) have few actively cycling BFU-Es. In this report, we demonstrate that the control of BFU-E cycling is encoded by a gene linked to, but distinct from, Fv2, and suggest that this gene is the dual-specific protein phosphatase Cdc25A, which regulates the G1- to S-phase transition of the cell cycle. We show that a naturally occurring allele of Cdc25A, which increases Cdc25A phosphatase activity and promotes cell-cycle progression, segregates in mouse strains that exhibit high levels of BFU-E cell cycling. In wild-type mice, this allele of Cdc25A does not overtly affect erythropoiesis; however, when this allele is combined with a mutation of the Kit receptor (Kit(WV)), the anemia of the mice is enhanced. Furthermore, overexpression of Cdc25A in bone marrow cells causes a defect in the BFU-E colony formation. These results suggest that proper regulation of the cell cycle through Cdc25A is required for normal erythropoiesis.
Formulation of Penetration Enhancers in Polymers (1988)

AbstractTwo commercial polymer matrices were prepared : the hydrophilic macromolecular polyvinyl alcohol-povidone type and the hydrophobic microseal silastic silicone type. Different blends of the penetration enhancers Azone, 2-Pyrol and M-Pyrol in glycerine were incorporated with the drug, levodopa. The in-vitro dissolution of drug from these matrices and its diffusion through a semi-permeable membrane were measured. Results show that povidone polymers released 10 times more levodopa than did silicone polymers. The penetration enhancers significantly increased the rate of release of drug.
Effects of nanostructuring and substrate symmetry on antiferromagnetic domain structure in LaFeO3thin films (2011)

The antiferromagnetic domain structure in LaFeO${}_{3}$ thin-film epilayers grown on La${}_{0.7}$Sr${}_{0.3}$MnO${}_{3}$ is imaged combining linearly polarized x-ray-absorption spectroscopy with photoemission electron microscopy. Detailed analysis of polarization-dependent domain contrast from magnetic dichroism reveals two sets of symmetrically different antiferromagnetic easy axes in the LaFeO${}_{3}$ layer along the in-plane $\ensuremath{\langle}110\ensuremath{\rangle}$ and $\ensuremath{\langle}100\ensuremath{\rangle}$ crystalline axes (pseudocubic notation), respectively. We show that extended antiferromagnetic domains can be stabilized selectively for nanowires defined in this perovskite thin-film system along either orientation of the easy axes. The results demonstrate how the equilibrium domain structure of thin-film nanoscale antiferromagnets depend on a combination of substrate symmetry, nanowire dimensions, and in-plane crystalline orientation.
Fully Printed Geranium-Inspired Encapsulated Arrays for Quantitative Odor Releasing (2019)

Olfactory is an extremely fine way of perception. However, the process of smelling is prone to various interference factors. Further development to enhance the communication desires an odor-releasing strategy, which could quantitatively offer a variety of fragrances. Here, we report a fully printing strategy to heterogeneously integrate odor-containing materials and protective coating films. Inspired from the fragrance-containing drum structure on the geranium leaf, encapsulated arrays are fully printed on the flexible or rigid substrates with more than 20 spices. Quantitative concentrations of odor molecules can be released from the encapsulated arrays after scraping the protective poly(lactic-<i>co</i>-glycolic) acid (PLGA) shells. Importantly, various odor-based arrays are printed on the same flexible substrate, which permits selective releasing and arbitrary mixing of the spices. Effective odor-releasing properties of encapsulated arrays make them promising for food security and anticounterfeiting, investigating olfactory discrimination abilities, and strengthening olfactory communication.
Accurate measurements of small charges collected on junctions from alpha particle strikes using an accelerator-produced microbeam (1995)

We describe an accelerator-based system for accurate experiments of alpha particle strikes on integrated circuits. It produces a high-flux, micron-dimensioned collimated beam in air. High speed blanking controls the arrival time and number of alphas. We accurately measure the small alpha-generated charges that collect on junctions using novel test structures and measure SRAM soft error rates. The test structure results are compared to results from our fast alpha-strike simulator.
Pedestrian Travel Pattern Discovery Using Mobile Bluetooth Sensors (2012)

The ubiquity of mobile devices, coupled with their need to communicate wirelessly, provides a wealth of data that, if properly handled, can be used to quickly enhance understanding and recognition of transport patterns. This dataset provides an opportunity to create a very low maintenance sensor infrastructure that is scalable and inexpensive. This paper presents a proof of concept experiment for a new mobile device-based framework for transportation data collection and interpretation. A novel “app-based” sensing paradigm, which turns smartphones into Bluetooth sensors, is developed, tested, and evaluated in this study for the purposes of travel data collection and analysis. Of particular interest are the spatial and temporal patterns that evolve as a result of daily human activity in very dense urban cores and campuses, where non-motorized modes dominate. The test results indicate that this new data collection framework is effective and has great potential for future pedestrian travel pattern discovery and activity data collection.
Informed Consent and SUPPORT (2013)

In the summer of 1963, the nation watched in sadness as Patrick Bouvier Kennedy, the youngest child of President John F. Kennedy and First Lady Jacqueline Bouvier Kennedy, was born prematurely and then died of lung disease 2 days later at Children's Hospital in Boston. Even now, it is common knowledge that children born prematurely are at high risk for death.So it is easy to imagine the stress when, in 2005, your new baby decides to come into the world after only 6 months of gestation, long before your pregnancy has reached term. You know that extremely premature babies . . .
ChemInform Abstract: C‐3 Hydroxyalkylation of Some Imidazo[1,2‐a]azines. (1986)

Abstract The title reaction of the N‐ heterocycles (I), (VI) and (VIII) with formaldehyde (II) yields the desired alcohols (III), (VII) and (IX), in part together with by‐products.
[Molecular basis of hereditary antithrombin defects in 10 Czech families]. (2000)

Four novel mutations in families with type I antithrombin deficiency were characterised. In one family two different genetic defects were identified to be responsible for type I and II phenotypes. Altogether our data agree with the expected heterogeneity of the AT genetic defect.