gebhart/patrepeval huggingface dataset:
Host cell species-specific effect of cyclosporine A on simian immunodeficiency virus replication (2012)

CsA treatment enhanced SIV replication in human T cells but abrogated SIV replication in macaque T cells, implying a host cell species-specific effect of CsA on SIV replication. Further analyses indicated a positive effect of CypA on SIV infection into macaque but not into human T cells. These results suggest possible contribution of CypA to the determination of SIV tropism.
Oxygenation and blood flow in tumors treated with hydralazine: Evaluation with a novel luminescence-based fiber-optic sensor (2002)

Two optical methods were used simultaneously to evaluate the effect of a vasoactive drug hydralazine on oxygenation and blood flow in SA-1 tumors in A/J mice. A novel luminescence-based optical sensor (OxyLite instrument, Oxford Optronix, UK) was used to monitor partial pressure of oxygen (pO2) in tumors. Laser Doppler flowmetry was used to assess relative blood perfusion in tumors. Measurements were performed continuously on anesthetized mice before and after i.v. injection of hydralazine at a dose of 2.5 mg/kg. Hydralazine reduced pO2 on average by 80% minutes after injection. Our results indicate that hydralazine could be used to improve the antitumor effectiveness of hypoxic cell-specific therapies. We demonstrated that both optical methods can be used successfully to detect changes in blood perfusion and oxygenation in tumors after blood flow-modifying treatments. Some aspects of pO2 measurement with the new luminescence-based method require further investigation.
Design and synthesis of novel small molecule inhibitors of MYST proteins (2017)

Epigenetics is defined as alterations to gene expression, resulting from indirect changes to DNA which occur during post-translational modification events. These changes in the phenotypical expression of a cell occur without alterations being made to the underlying genotype. One of the major epigenetic events which occur in cells is histone acetylation, with this process ultimately being governed by Histone acetyltransferase (HAT) proteins. This thesis focusses on the development of novel small molecule inhibitors of the MOZ (or MYST3) protein, a HAT protein which belongs to the MYST family of proteins. The MOZ protein has been identified to be an upstream regulator of a range of cellular pathways which govern cellular senescence and cancer formation. Furthermore this protein has also been identified to play a role in embryonic development. The project began with a HTS leading of over 243,000 compounds, leading to the identification of one compound which was deemed to be an acceptable starting point for a medicinal chemistry campaign. This initial hit was developed into a small class of analogues to begin the SAR exploration of the MOZ binding pocket. Chapter 2 discusses the development of the 2nd generation analogues. This research involved the exploration of three different streams of compounds, all of which were identified to have slightly different binding modes within the MOZ protein. The compounds explored in this chapter focused on probing the SAR surrounding the “right hand side” of the common core. In chapter 3 the SAR surrounding the “left hand side” of the common core was explored. This work included exploration and development of a range of synthetic procedures to allow for the development of a broader range of small molecule inhibitors of the MOZ protein. Chapter 4 discusses the further development of one class of compounds identified in the 2nd generation exploration, this work resulted in the development of the 3rd generation inhibitors of the MOZ protein. This class of compounds resulting in an increase in the potency of inhibitors, whilst furthering the exploration of the SAR at the “right hand side” of the common core. In chapter 5 development of replacements for the common core were investigated. Until this point of the project all small molecule inhibitors of the MOZ protein had be reliant on a specific core structure to which variations to the surrounding regions had be included. This work led to the development of a class of MOZ inhibitors which were able to rival the potency of the 2nd and 3rd generation analogues but had the added bonus of opening up a wide scope of core changes for future exploration. Overall this project resulted in the identification of a large number of highly potent classes of small molecule inhibitors of the MOZ protein. Furthermore a favourable replacement for the common core of these molecules was identified and the initial SAR for this new class of compounds was undertaken, paving the way for future exploration of inhibitors of the MOZ protein.
Electrical compensation technology for high speed signal and its feasibility study on 40-Gb/s transmission (2007)

Electrical compensation of optical fiber transmission related impairment, which is recognized as very important for high speed signal transmission, are discussed. A successful suppression of PMD-induced BER fluctuation in ultra-long distance transmission by the electrical equalizer is demonstrated as a feasibility study.
Sialidases on Mammalian Sperm Mediate Deciduous Sialylation during Capacitation (2012)

Sialic acids (Sias) mediate many biological functions, including molecular recognition during development, immune response, and fertilization. A Sia-rich glycocalyx coats the surface of sperm, allowing them to survive as allogeneic cells in the female reproductive tract despite female immunity. During capacitation, sperm lose a fraction of their Sias. We quantified shed Sia monosaccharides released from capacitated sperm and measured sperm sialidase activity. We report the presence of two sialidases (neuraminidases Neu1 and Neu3) on mammalian sperm. These are themselves shed from sperm during capacitation. Inhibiting sialidase activity interferes with sperm binding to the zona pellucida of the ovum. A survey of human sperm samples for the presence of sialidases NEU1 and NEU3 identified a lack of one or both sialidases in sperm of some male idiopathic infertility cases. The results contribute new insights into the dynamic remodeling of the sperm glycocalyx prior to fertilization.
Diurnal variations in vagal and sympathetic cardiac control (1990)

To investigate the diurnal variation in autonomic cardiac control, the magnitudes of the power spectral components of supine and standing heart rate variability were measured during controlled respiration (15 breaths/min). Examination was performed hourly between 0700 and 2300 h in eight male subjects whose activities and food intake were controlled for 24 h in the laboratory. The respiratory component (0.25 Hz) was greater in the morning than in the late afternoon (P less than 0.05) and decreased 30 min after food intake (P less than 0.01) in the supine position, but it was unaffected by the time of day or food intake while in the standing position. The Mayer wave component (0.03-0.15 Hz) did not change with the time of day, but it increased 90 min after food intake in both supine and standing positions (P less than 0.01 and P less than 0.05, respectively). These data suggest that supine vagal cardiac control during the waking period increases in the morning and decreases 30 min after food intake and that sympathetic cardiac control increases 90 min after food intake.
AKAP150‐dependent cooperative TRPV4 channel gating is central to endothelium‐dependent vasodilation and is disrupted in hypertension (678.10) (2014)

Endothelial cell (EC) dysfunction is a hallmark of hypertension. We recently discovered that local Ca 2+ influx through clusters of functionally coupled TRPV4 channels (detected optically as “TRPV4 sparklets”) drives physiological vasodilation. Here, we show that stimulation of EC muscarinic receptors activated TRPV4 sparklets exclusively at discrete sites at myoendothelial projections (MEPs)—specialized regions of ECs that contact adjacent smooth muscle cells. This activation was dependent on protein kinase C (PKC) and was absent in mice lacking the PKC‐anchoring protein AKAP150 (A‐kinase anchoring protein 150), which was localized predominantly to MEPs. Cooperative gating of TRPV4 channels within a cluster amplified Ca 2+ influx at MEPs by more than 2‐fold. This cooperativity was largely absent at non‐MEP sites and was virtually eliminated by chelation of intracellular Ca 2+ or AKAP150 knockout, suggesting AKAP150‐dependent potentiation of TRPV4 activity by Ca 2+ influx via adjacent channels. Notably, MEP‐localization of AKAP150 was disrupted in angiotensin II‐induced hypertension, leading to a complete loss of muscarinic activation of TRPV4 channels, much weaker coupling among TRPV4 channels at MEPs, and approximately an 80% reduction in carbachol‐induced vasodilation. Our results support the concept that endothelial‐dependent vasodilation of resistance arteries is enabled by MEP‐localized AKAP150, which ensures the proximity of PKC to TRPV4 channels and coupled channel gating necessary for efficient communication of the endothelium to the smooth muscle cells in arteries—a molecular configuration that is disrupted in hypertension. Grant Funding Source : Supported by HL044455, 1P01HL095488, R37DK053832, R01HL098243 to MTN
Lack of mother-to-child HIV-1 transmission is associated with elevated serum levels of 90 K immune modulatory protein (2000)

These results suggest that high 90 K protein serum levels in HIV-1-infected mothers and their new-borns are associated with lack of mother-to-child HIV-1 transmission.
Seroepidemiology of <i>Coxiella burnetii</i> in Wild White-Tailed Deer ( <i>Odocoileus virginianus</i> ) in New York, United States (2012)

Coxiella burnetii is an environmentally resistant bacterium that has been reported in wildlife populations. Frequent contact on pasture between white-tailed deer (Odocoileus virginianus) and cattle has been reported by farmers in the Northeast U.S., and transmission of C. burnetii is thought to occur between wild deer and domestic livestock such as cows, sheep, and goats. Blood samples were collected from white-tailed deer throughout New York State in 2009 and 2010 and examined for anti-C. burnetii phase II antibodies via indirect microimmunofluorescence assays. Exploratory spatial cluster analysis revealed a lack of significant clustering of C. burnetii-seropositive deer. Logistic regression analysis revealed a significant association between the C. burnetii serostatus of deer and sex, percent agriculture, shrub, and forest cover, and townships with more than 10 bovine herds. A lack of significant association was revealed between the serostatus of deer and the year of sampling, soil type, percent wetland and open water cover, total annual precipitation, and townships with more than two sheep or goat herds. Because four different land cover types were associated with a higher probability of C. burnetii seropositivity, it is likely that land cover is not a discriminating factor in C. burnetii exposure. This is probably because C. burnetii environmental contamination is widespread and not localized to certain cover types. The social behavior of male deer may contribute to the lack of spatial clustering. Bucks typically travel over greater distances, which leads to a greater variety of encountered environments and a greater chance for exposure to C. burnetii. Because increasing agricultural land cover and townships with greater than 10 bovine herds are associated with an increased probability of diagnosing a seropositive deer, it appears likely that transmission of C. burnetii between domestic livestock and white-tailed deer may occur.
CTLA-4 engagement regulates NF-κB activation in vivo (2002)

CTLA-4 engagement inhibits TCR-dependent functions and CTLA-4(-/-) mice develop a lymphoproliferative disorder leading to early lethality. In vitro, ligation of CTLA-4 reduces TCR-mediated activation of NF-kappaB, a transcription factor implicated in promoting T cell survival and cytokine production. However, whether NF-kappaB inhibition downstream of CTLA-4 is necessary for down-regulation of T cell responses is not known. We hypothesized that signaling pathways that are antagonized when CTLA-4 is engaged should be augmented when CTLA-4 is absent and found thatspontaneous NF-kappaB activity was increased in T cells from CTLA-4(-/-) mice. To determine the importance of NF-kappaB inhibition upon CTLA-4 engagement in vivo, CTLA-4(-/-) mice were interbred with mice expressing a transdominant IkappaBalpha mutant under the control of the Lck promoter. The resulting mice had reduced spontaneous NF-kappaB activity in T cells,delayed mortality, and reduced leukocytic accumulation in spleen, lymph nodes, and exocrine pancreas as compared with CTLA-4(-/-) littermates. However, impaired NF-kappaB activation in T cells did not prevent the up-regulation of activation markers on T cells or the acquisition of effector cytokine production. Thus, impaired NF-kappaB activity in T cells prevents specific aspects of the CTLA-4(-/-) phenotype, suggesting that inhibition of NF-kappaB activation is one of the key biochemical events regulated by CTLA-4 ligation in vivo.
A study on persistent scheduling for VoIP services in UMB system (2008)

In next-generation cellular systems including 3.9G and IMT-advanced systems, voice-over-IP (VoIP) services will be provided to users instead of conventional circuit switch-based voice calls. VoIP packets have peculiar characteristics that the packet length is short and packets are frequently generated. These phenomena require significant radio resources to send control channels in which resource assignment messages are conveyed ahead of VoIP packets transmission. In order to deal with this issue, persistent scheduling was proposed. There are several reports on persistent scheduling; however, sufficient study on it has not yet been conducted. This paper proposes persistent scheduling schemes that allow multiple resource usages using a threshold of queuing latency and then shows performance results based on ultra mobile broadband (UMB) system, which was standardized by the Third Generation Partnership Project 2 (3GPP2) as a 3.9G cellular system. Through computer simulations, it turns out that the proposed persistent scheduler gives improvement of 30% in terms of VoIP capacity compared to the basic persistent scheduler.
A kinetic model for silicide formation through thin-film metal-silicon reactions (1992)

A simple method, which uses numerical calculations to estimate diffusion fluxes into reactive interfaces during silicide formation processes, has been developed. Based on analysis of calculated diffusion fluxes from experiments from five different published papers, a model has been proposed to explain the unique kinetic behavior associated with thin-film metal-silicon diffusion couples. The reactive interface in a metal-silicon diffusion couple is considered to be a reaction region, and the reaction process is divided into three steps. Several physical quantities have been defined to describe each of these steps, i.e., the diffusion flux of moving reactant to the reaction region Jm, the release rate of nonmoving reactant rn, and the formation rate of the growing phase F. The relationship between these quantities has been demonstrated by means of a reaction process plot, which is also developed in this study.
Supplementary Movie 1 from &lt;i&gt;In Vivo&lt;/i&gt; Imaging of Drug-Induced Mitochondrial Outer Membrane Permeabilization at Single-Cell Resolution (2023)

&lt;p&gt;AVI file, 406KB, Time lapse image sequence of MDA-MB-231 breast cancer cells treated with ABT-263, shown in brightfield.&lt;/p&gt;
An Improved Humanized Mouse Model for Excisional Wound Healing Using Double Transgenic Mice (2017)

<b>Objective:</b> Splinting full-thickness cutaneous wounds in mice has allowed for a humanized model of wound healing. Delineating the epithelial edge and assessing time to closure of these healing wounds via macroscopic visualization have remained a challenge. <b>Approach:</b> Double transgenic mice were created by crossbreeding K14-Cre and ROSA<sup>mT/mG</sup> reporter mice. Full-thickness excisional wounds were created in K14-Cre/ROSA<sup>mT/mG</sup> mice (<i>n</i> = 5) and imaged using both normal and fluorescent light on the day of surgery, and every other postoperative day (POD) until wound healing was complete. Ten blinded observers analyzed a series of images from a single representative healing wound, taken using normal or fluorescent light, to decide the POD when healing was complete. K14-Cre/ROSA<sup>mT/mG</sup> mice (<i>n</i> = 4) were subsequently sacrificed at the four potential days of rated wound closure to accurately determine the histological point of wound closure using microscopic fluorescence imaging. <b>Results:</b> Average time to wound closure was rated significantly longer in the wound series images taken using normal light, compared with fluorescent light (mean POD 13.6 vs. 11.6, *<i>p</i> = 0.008). Fluorescence imaging of histological samples indicated that reepithelialization was complete at 12 days postwounding. <b>Innovation:</b> We describe a novel technique, using double transgenic mice K14-Cre/ROSA<sup>mT/mG</sup> and fluorescence imaging, to more accurately determine the healing time of wounds in mice upon macroscopic evaluation. <b>Conclusion:</b> The accuracy by which wound healing can be macroscopically determined <i>in vivo</i> in mouse models of wound healing is significantly enhanced using K14-Cre/ROSA<sup>mT/mG</sup> double transgenic mice and fluorescence imaging.
Traction force microscopy of engineered cardiac tissues (2018)

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.
Investigation of space-charge effects in gaseous tritium as a source of distortions of the beta spectrum observed in the Troitsk neutrino-mass experiment (2008)

Results of searches for effects of space-charge accumulation in the gaseous tritium source in the Troitsk neutrino-mass experiment are presented. The broadening and the shift of the L3 line of conversion electrons in a 83m Kr gaseous source circulating together with tritium was investigated. The attained limit on the magnitude of fluctuations of the space-charge potential makes it possible to set a limit on the negative neutrino mass squared in the Troitsk neutrino-mass experiment (−0.8 < Δ m 2 ≤ 0 eV2), a spurious effect associated with this potential. A statistically reliable shift of the position of the L3 line is discovered. This indicates that processes of of space-charge accumulation do indeed proceed in the source at a level that is significant for the future experiment Katrin.
Characterization of Structural Inhomogeneities in GaAs/AIGaAs Superlattices (1989)

Abstract Thin films containing periodic chemical or strain modulation (e.g. artificial superlattices or SL) are often characterized nondestructively by X-ray double-axis diffractometry. The satellite peaks from the modulated structure allow analysis of layer structure, elemental concentration and strain profile. This paper focuses on the effect of layer uniformity on the rocking curves of (001) GaAs/Al x Ga 1-x AsSL. Double-axis diffractometry for results from MBE samples with 800 Å SL periods and x=0.35 are compared for GaAs/AlGaAs layer thicknesses of 350/450, 400/400 and 450/350 Å. Symmetric (004) and asymmetric (315) diffraction planes are used to measure parallel and perpendicular misfit strains, layer periodicity and aluminum concentration. A modified kinematical scattering model, correcting for absorption and extinction, is used to calculate the satellite peak intensities and spacings. The relative thicknesses of GaAs and AlGaAs and the aluminum elemental concentration are optimized by matching with experimental results. The effect of nonuniform layer thickness on SL peak intensities is also investigated. The experimental results, the modified kinematical scattering calculations and dynamical theory agree closely for the 3-4 /zm thickness layers studied.
Guiding Epithelial Cell Phenotypes with Engineered Integrin-Specific Recombinant Fibronectin Fragments (2010)

The extracellular matrix (ECM) provides important cues for directing cell phenotype. Cells interact with underlying ECM through cell-surface receptors known as integrins, which bind to specific sequences on their ligands. During tissue development, repair, and regeneration of epithelial tissues, cells must interact with an interstitial fibronectin (Fn)-rich matrix, which has been shown to direct a more migratory/repair phenotype, presumably through interaction with Fn's cell binding domain comprised of both synergy Pro-His-Ser-Arg-Asn (PHSRN) and Arg-Gly-Asp (RGD) sequences. We hypothesized that the Fn synergy site is critical to the regulation of epithelial cell phenotype by directing integrin specificity. Epithelial cells were cultured on Fn fragments displaying stabilized synergy and RGD (FnIII9'10), or RGD alone (FnIII10) and cell phenotype analyzed by cytoskeleton changes, epithelial cell-cell contacts, changes in gene expression of epithelial and mesenchymal markers, and wound healing assay. Data indicate that epithelial cells engage RGD only with αv integrins and display a significant shift toward a mesenchymal phenotype due, in part, to enhanced transforming growth factor-β activation and/or signaling compared with cells on the synergy containing FnIII9'10. These studies demonstrate the importance of synergy in regulating epithelial cell phenotype relevant to tissue engineering as well as the utility of engineered integrin-specific ECM fragments in guiding cell phenotype.
Topical Interferon for Treating Condyloma Acuminata in Women (1988)

We conducted a randomized, double-blind, placebo-controlled trial of two forms of topical interferon therapy for condyloma acuminata in women. Gel containing 10(6) IU of leukocyte interferon/g, with or without nonoxynol-9, was compared with treatment with gel base alone. Eighty-nine patients applied the gel three times a day for four weeks and were studied for at least 16 w. Side effects were generally mild and limited to the site of application for all three drugs. Although a transient, statistically significant therapeutic effect was noted early in the course of treatment with both interferon gels as compared with placebo, this effect was lost by the end of the follow-up period, possibly because of a generally high response rate in patients receiving placebo. Hence, there was no overall difference in the number of patients with a partial or complete response to any of the agents by the end of therapy or by the end of the study.