gebhart/patrepeval huggingface dataset:
Differential Dependence of the D1 and D5Dopamine Receptors on the G Protein γ7 Subunit for Activation of Adenylylcyclase (2001)

The D(1) dopamine receptor, G protein gamma(7) subunit, and adenylylcyclase are selectively expressed in the striatum, suggesting their potential interaction in a common signaling pathway. To evaluate this possibility, a ribozyme strategy was used to suppress the expression of the G protein gamma(7) subunit in HEK 293 cells stably expressing the human D(1) dopamine receptor. Prior in vitro analysis revealed that the gamma(7) ribozyme possessed cleavage activity directed exclusively toward the gamma(7) RNA transcript (Wang, Q., Mullah, B., Hansen, C., Asundi, J., and Robishaw, J. D. (1997) J. Biol. Chem. 272, 26040-26048). In vivo analysis of cells transfected with the gamma(7) ribozyme showed a specific reduction in the expression of the gamma(7) protein. Coincident with the loss of the gamma(7) protein, there was a noticeable reduction in the expression of the beta(1) protein, confirming their interaction in these cells. Finally, functional analysis of ribozyme-mediated suppression of the beta(1) and gamma(7) proteins revealed a significant attenuation of SKF81297-stimulated adenylylcyclase activity in D(1) dopamine receptor-expressing cells. By contrast, ribozyme-mediated suppression of the beta(1) and gamma(7) proteins showed no reduction of SKF81297-stimulated adenylylcyclase activity in D(5) dopamine receptor-expressing cells. Taken together, these data indicate that the structurally related D(1) and D(5) dopamine receptor subtypes utilize G proteins composed of distinct betagamma subunits to stimulate adenylylcyclase in HEK 293 cells. Underscoring the physiological relevance of these findings, single cell reverse transcriptase-polymerase chain reaction analysis revealed that the D(1) dopamine receptor and the G protein gamma(7) subunit are coordinately expressed in substance P containing neurons in rat striatum, suggesting that the G protein gamma(7) subunit may be a new target for drugs to selectively alter dopaminergic signaling within the brain.
Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation (2017)

HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.
Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity (2018)

Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4-trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO<sub>2</sub> ), and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer-cell lines. Synthetic ozonides were shown to have the highest cytotoxicity on HepG2 (IC<sub>50</sub> =0.19-0.59 μm), and some of these compounds selectively targeted liver cancer (selectivity index values for compounds 13 a and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher than those of paclitaxel, artemisinin, and artesunic acid. In contrast some ozonides showed only moderate antimalarial activity against the chloroquine-sensitive 3D7 strain of P. falciparum (IC<sub>50</sub> from 2.76 to 24.2 μm; 12 b, IC<sub>50</sub> =2.76 μm; 13 a, IC<sub>50</sub> =20.14 μm; 14 a, IC<sub>50</sub> =6.32 μm). These results suggest that these derivatives have divergent mechanisms of action against cancer cells and malaria-infected cells. A cyclic voltammetry study of the peroxides was performed, but most of the compounds did not show direct correlation in oxidative capacity-activity. Our findings offer a new source of antimalarial and anticancer agents through structural modification of peroxide compounds.
A qualitative measurement survey of popular Internet-based IPTV systems (2008)

Television over the Internet (IPTV) is regarded as the killer application for next generation networks (NGN). While the ITU is currently moving toward the standardized of IPTV, several existing applications like Joost and Zattoo are currently already providing a large amount of video content to Internet users. In this paper we study some popular video content delivery mechanisms and characterize them by measurements to study the user-perceived quality of experience (QoE).
G9a selectively represses a class of late-replicating genes at the nuclear periphery (2009)

We have investigated the role of the histone methyltransferase G9a in the establishment of silent nuclear compartments. Following conditional knockout of the G9a methyltransferase in mouse ESCs, 167 genes were significantly up-regulated, and no genes were strongly down-regulated. A partially overlapping set of 119 genes were up-regulated after differentiation of G9a-depleted cells to neural precursors. Promoters of these G9a-repressed genes were AT rich and H3K9me2 enriched but H3K4me3 depleted and were not highly DNA methylated. Representative genes were found to be close to the nuclear periphery, which was significantly enriched for G9a-dependent H3K9me2. Strikingly, although 73% of total genes were early replicating, more than 71% of G9a-repressed genes were late replicating, and a strong correlation was found between H3K9me2 and late replication. However, G9a loss did not significantly affect subnuclear position or replication timing of any non-pericentric regions of the genome, nor did it affect programmed changes in replication timing that accompany differentiation. We conclude that G9a is a gatekeeper for a specific set of genes localized within the late replicating nuclear periphery.
<title>Infrared parallel-slab division-of-amplitude photopolarimeter</title> (1999)

In this paper we describe novel designs of IR versions of the parallel-slab division-of-amplitude photopolarimeter (IR-PS-DOAP) to measure the state of polarization of light as determined by the four Stokes parameters. The IR-PS-DOAP uses no movable parts or modulation and thus fast and simultaneous measurement is obtained. We present two different designs. The first employs a uniform, thin, transparent, film coating on the front surface of the parallel-slab. The second employs strips of thin, transparent, film coating on the front surface of the parallel-slab. A performance analysis comparison between the two will be presented. For wavelengths up to approximately 3.5 micrometers , SiO<SUB>2</SUB>, is totally transparent and is selected to be the slab material for the IR-PS-DOAP. For wavelengths beyond 3.5 micrometers , SiO<SUB>2</SUB> becomes absorbent and will be replaced by another transparent material like Irtran2, for example. The instrument matrix of the system is non- singular; hence the state of polarization is completely determined. The IR-PS-DOAP is compact, light-weight, rugged and based on reflective optics, so that predictive theory of instrument performance is applicable.
Correlation of low density polyethylene rheological measurements, with optical and processing properties (1977)

Abstract The processing properties of low density polyethylene melts, such as drawdown and neck‐in, and the final product properties, such as film haze and gloss, have been successfully correlated with rheological functions and the level of longchain branching. The rheological functions employed are the entrance pressure drop Δ P o and the swell ratio S o , determined at a specified shear stress using aft‐orifice with a length/ diameter ( L / D ) ratio of zero. The calculation of shear stress requires additional measurements using adie with a finite L / D e.g. 20. The rheological functions Δ P o , and S o are governed by the level of high molecular weight species and/or the level of long‐chain branching(LCB). If determined at a constant shear stress, in order to eliminate the effect of viscosity, they are a relative measure of elasticity. Higher Δ P 0 and S o indicate a higher level of LCB and correlate with poorer optical properties and drawdown in films.
Evaluation of the Efficiency of a Soft Dosage Form for the Treatment of Osteoarthritis: Influence on the Level of Pro-inflammatory Cytokines (2023)

Introduction. Osteoarthritis is now considered to be a slowly progressive inflammatory disease that completely affects the joint. An important role in the development of this pathology is played by inflammation of the synovial membrane and ligaments (synovitis), supplemented by constant mechanical stress. Normally, a balance of anti-inflammatory and pro-inflammatory mediators is observed in cartilage, however, under the influence of risk factors, this balance shifts towards the latter. Aim. Evaluation of the effect of a previously developed soft dosage form containing meloxicam, a purine derivative and an immunomodulator M on the level of pro-inflammatory cytokines: IL-1α, IL-1β, IL-6 and TNF-α in osteoarthritis. Materials and methods. The experiment included 25 animals, which were divided into 5 groups by simple randomization: 1 – test (gel 0.5 %), 2 –test (gel 1 %), 3 – reference (Amelotex®, gel 1 %), 4 – control (gel base); 5 – intact. Preclinical modeling of the pathology was carried out by combined injection of 0.1 ml of a mixture of complete Freund's adjuvant with a 10 % suspension of talc in isotonic sodium chloride solution in a ratio of 1 : 10 into the cavity of the hock (tarsal) joint of Brown Norvay Catholic Rats male rats. Enzyme immunoassay of animal blood serum on the 28th day of the experiment was performed using standard ELISA plate kits (Cloud-Clone Corp., USA). Statistical data processing was performed using GraphPad Prism 8.0.2 software (GraphPad Software Inc., USA), differences were considered statistically significant at p &lt; 0.05. Results and discussion. The developed compositions contributed to a decrease in the level of pro-inflammatory cytokines (IL-1α, IL-6 and TNF-α) compared with the main and reference gel preparation. At the same time, differences were found between the effect observed from the use of the test agents (gel 0.5 %, gel 1 %) and the reference drug in terms of the effect on the level of IL-1α and TNF-α, which indicates a greater effectiveness of the selected combination of active substances, because, unlike the single-component gel Amelotex®, the compositions developed by us additionally included a purine derivative and an immunomodulator M. The data obtained are important from the point of view of understanding the mechanism of action of a soft dosage form. Conclusion. Based on the results of previous and present studies, it is assumed that the combined composition of the soft dosage form with a half (0.5 %) concentration of meloxicam is of greatest interest for clinical practice, since its use at a high level of effectiveness additionally reduces the likelihood of adverse reactions from the non-steroidal anti-inflammatory drug, which is important in the case of long-term therapy of osteoarthritis.
The negligible effect of strain on the low-temperature heat capacity of silica glass (1976)

In an attempt to affect the anomalous low-temperature heat capacity of glass, an unstrained sample of silica glass was heated to 1150\ifmmode^\circ\else\textdegree\fi{}C and quenched in oil which induced a large internal strain. The heat capacities before and after straining the sample are identical in the temperature range 0.4-1.4 K. In addition, a composite of available data shows that the representation $C=aT+b{T}^{3}$ is only valid between 0.4 and 1.7 K whereas below 0.3 K, $C\ensuremath{\propto}{T}^{1.22}$ and between 3 and 10 K, $C\ensuremath{\propto}{T}^{3.8}$.
Abstract 3568: CYP3A4 epoxygenase activity mediates ER+ mammary tumor growth and angiogenesis, in part, through EET biosynthesis and is inhibited by biguanides (2015)

Abstract While cytochrome P450 enzymes (CYPs) are implicated in tumor angiogenesis through biosynthesis of epoxyeicosatrienoic acids (EETs), little is known about breast cancer cell-intrinsic CYPs that exhibit epoxygenase activity, such as CYP3A4. In an orthotopic breast cancer model, silencing of epithelial CYP3A4 suppressed angiogenesis-related escape of ER+ breast tumors from dormancy. While the diabetes drug metformin inhibits mitochondrial complex I and inhibits tumor growth, how it does so is unknown. Metformin inhibited CYP epoxygenase activity and co-crystallized in the active site of CYP3A4, hydrogen bonding with arginine 212, allowing the development of hexyl-benzyl-biguanide (HBB) as a CYP3A4 inhibitor using molecular modeling. HBB exhibited more than 10-fold greater potency than metformin for inhibition of ER+ mammary tumor growth and inhibited associated tumor angiogenesis. HBB inhibited EET biosynthesis ∼40-fold more potently than metformin and was ∼40-fold more potent for activation of AMPK phosphorylation. EETs suppressed and CYP silencing promoted AMPK phosphorylation, linking CYPs with AMPK regulation in breast cancer. HBB depolarized mitochondria, reduced oxygen consumption rates and suppressed the Warburg effect, while EETs restored the mitochondrial membrane potential. CYP3A4 silencing and HBB treatment increased reactive oxygen species (ROS) production, suggesting that CYPs suppress cancer cell death, in part, through suppression of ROS. CYP3A4 silencing sensitized breast cancer cells to hormonal therapy and chemotherapy, abrogated by EETs. Because EETs are autocrine, paracrine and endocrine, these results implicate CYPs in tumor growth, in part, through cell-cell mediation of mitochondrial homeostasis and demonstrate the potential of CYP3A4 as a therapeutic target in breast cancer. Citation Format: Zhijun Guo, Irina F. Sevrioukova, Eric Hanse, Ilia Denisov, Xia Zhang, Ting-Lan Chiu, Daniel Swedien, Justin Stamschror, Juan Alvarez, William Marerro Ortiz, Monique Morgan, Michael Maher, Kathryn J. Chavez, Dafydd Thomas, Young Kyung Bae, Jonathan Henriksen, Beverly Norris, Robert J. Schumacher, Henry Wang, Robin Bliss, Haitao Chu, Rebecca Cuellar, Thomas L. Poulos, Stephen G. Sligar, William Atkins, Stephen Schmechel, Jorge Capdevila, John Falck, Ian Blair, Jeffrey P. Jones, Gunda Georg, Kalpna Gupta, Ameeta Kelekar, Elizabeth Amin, David A. Potter. CYP3A4 epoxygenase activity mediates ER+ mammary tumor growth and angiogenesis, in part, through EET biosynthesis and is inhibited by biguanides. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3568. doi:10.1158/1538-7445.AM2015-3568
EFFICIENT ESTIMATION OF PARAMETERS IN MOVING-AVERAGE MODELS (1959)

EFFICIENT ESTIMATION OF PARAMETERS IN MOVING-AVERAGE MODELS Get access J. DURBIN J. DURBIN Research Techniques Division, London School of Economics Search for other works by this author on: Oxford Academic Google Scholar Biometrika, Volume 46, Issue 3-4, December 1959, Pages 306–316, https://doi.org/10.1093/biomet/46.3-4.306 Published: 01 December 1959
Calcitonin gene-related peptide and menopause (2010)

The review summarizes recent findings with respect to pathophysiological role of calcitonin gene-related peptide (CGRP), in postmenopausal symptoms and diseases, which has opened horizons in understanding pathophysiology of menopause in a better way. Current evidences strongly propose a need to develop CGRP receptor antagonists, which may prove beneficial in many prevalent menopausal symptom/diseases such as vasomotor symptoms, cardiovascular risk, obesity, and major depressive disorder, in which CGRP levels are elevated.
Mobilisation and analyses of publicly available SARS-CoV-2 data for pandemic responses (2023)

Abstract The COVID-19 pandemic has seen large-scale pathogen genomic sequencing efforts, becoming part of the toolbox for surveillance and epidemic research. This resulted in an unprecedented level of data sharing to open repositories, which has actively supported the identification of SARS-CoV-2 structure, molecular interactions, mutations and variants, and facilitated vaccine development and drug reuse studies and design. The European COVID-19 Data Platform was launched to support this data sharing, and has resulted in the deposition of several million SARS-CoV-2 raw reads. In this paper we describe (1) open data sharing, (2) tools for submission, analysis, visualisation and data claiming (e.g. ORCiD), (3) the systematic analysis of these datasets, at scale via the SARS-CoV-2 Data Hubs as well as (4) lessons learned. As a component of the Platform, the SARS-CoV-2 Data Hubs enabled the extension and set up of infrastructure that we intend to use more widely in the future for pathogen surveillance and pandemic preparedness.
An Electrocardiogram-Based Method for Early Detection of Abrupt Changes in Blood Pressure during Hemodialysis (2006)

Clinical techniques for early detection of acute hypotension during conventional hemodialysis treatment are lacking, even though intradialytic hypotension is the most common acute complication. In this article, intradialytic hypotension is identified by means of signal analysis of data recorded at two clinics. The database consists of 30 treatments with concurrently acquired signals: the 12-lead electrocardiogram, continuous blood pressure, hematocrit, oxygen saturation, relative blood volume, and important hemodialysis variables. This article presents two characteristics, a heart rate turbulence (HRT) measure called turbulence slope (TS), and the LF/HF ratio, which provide information, at the beginning of hemodialysis treatment, on the patient's propensity to hypotension (TS: p = 0.0038, and LF/HF ratio: p = 0.0028). The authors also present a novel dynamic echocardiography-based method for detecting intradialytic hypotension using complementary information on heart rate variability (HRV) and ectopic beat patterns. These two types of information reflect different mechanisms of cardiac activity. It is essential that both types are used for the detection of hypotension, because HRV analysis is inappropriate when several ectopic beats are present. The proposed dynamic echocardiography-based method offers early identification of the cases with acute intradialytic hypotension of the database.
Power quality prediction algorithms and analysis (2012)

By using the gray prediction adaptive system whose parameter is variable and structure is fixed, this paper revises data sequence of the distortion in the power by using improved model. This method also increases prediction accuracy. Theory analysis and derivation was made according to mathematic analytic method the in power.
ChemInform Abstract: SYNTHESIS AND PSYCHOTROPIC ACTIVITY OF TRICYCLIC ANALOGS OF PYRAZIDOLE (1984)

Abstract Wie im Formelschema skizziert, werden die im Titel genannten dem Pyrazidol (VIII) ähnlichen Verbindungen (VII) über die neuen Hydrazone (III) hergestellt.
Evaluation of finite difference and FFT-based solutions of the transport of intensity equation (2017)

A finite difference method is proposed for solving the transport of intensity equation. Simulation results show that although slower than fast Fourier transform (FFT)-based methods, finite difference methods are able to reconstruct the phase with better accuracy due to relaxed assumptions for solving the transport of intensity equation relative to FFT methods. Finite difference methods are also more flexible than FFT methods in dealing with different boundary conditions.
Toll‐like receptor 2 siRNA suppresses corneal inflammation and attenuates Aspergillus fumigatus keratitis in rats (2011)

Toll-like receptors (TLRs) are key components of innate immunity that detect microbial infection and trigger host defense responses. However, they are capable of initiating both protective and damaging immune responses, as exaggerated expression of inflammatory components can have devastating effects on the host. We previously reported that TLR2 in corneal epithelium has an important role in the pathogenesis of fungal keratitis, however, how the corneal inflammation is modulated remains to be elucidated. This study aims to investigate the effect of targeting TLR2 on Aspergillus fumigatus keratitis in rats. The control or TLR2 small interfering RNA (siRNA) was applied sub-conjunctively and topically to the cornea. TLR2 immunostaining was performed to determine the feasibility of TLR2 siRNA delivery. Production of inflammatory cytokines and chemokines were determined by real-time quantitative PCR. Polymorphonuclear leukocyte (PMN) infiltration was assessed by myeloperoxidase activity. It was found that rat corneas treated with TLR2 siRNA showed a significant reduction of TLR2 expression in corneal epithelium. TLR2 siRNA treatment improved the outcome of keratitis, which was characterized by decreased corneal opacity, less corneal perforation, suppressed PMN infiltration, reduced production of inflammatory cytokines and chemokines, and less fungal burden. In conclusion, TLR2 siRNA treatment attenuated A. fumigatus keratitis by suppressing corneal inflammation and preventing fungal invasion, suggesting a novel avenue to control fungal infection and avert damage caused by excessive inflammation.
Dietary supplementation contributes to lifestyle improvement in hypercholesterolemic patients in real-life contexts (2014)

Improvements in Nutritional Lifestyle scores, which included regular consumption of Phyto-SY over 4 months, was significantly linked to healthier lifestyles and to beneficial modifications in atherogenic lipid profiles, which reflected patient empowerment in a 'real life' context.
The Total Synthesis of Pantocin B (2000)

[reaction: see text] Pantocin B, an unusual antibiotic produced by Erwinia herbicola, effectively controls E. amylovora, the pathogen causing the plant disease fire blight. A total synthesis of pantocin B from L-alanine, glycine, and L-malic acid is reported.
Deep Learning Based Preamble Detection and TOA Estimation (2019)

Accurate Time of Arrival (TOA) estimation has many use cases, including 5G initial access and localization. However, due to multipath propagation and noise, the correlation-based TOA estimation may not be accurate. In this paper, a deep learning based framework is proposed for preamble detection and TOA estimation without the need of knowing the transmit waveform. Extensive simulations on both synthetic data and real measured data show that the proposed method improves prediction accuracy by about three times while keeping the same computational complexity in comparison to the correlation method. It also provides 1000x computational reduction compared to the template matching method without loss of accuracy.