gebhart/patrepeval huggingface dataset:
Nucleotide-induced mucin release from primary hamster tracheal surface epithelial cells involves the P2u purinoceptor (1996)

Mucin release by airway surface epithelial cells is regulated by extracellular adenosine triphosphate (ATP) via a P2 purinoceptor-mediated mechanism. The objective of the present experiment was to examine the possible involvement of uridine triphosphate (UTP) in this purinergic signal transduction pathway. Using primary hamster tracheal surface epithelial cells, ATP and UTP were compared in their abilities: 1) to displace ATP gamma S35-binding to intact cells; 2) to accumulate inositol phosphates; and 3) to stimulate mucin release. Finally, the presence of a P2u receptor message was examined. Our results showed that: 1) UTP was much less effective than ATP in displacing ATP gamma S35-binding (median inhibitory concentrations (IC50S) 240 vs 2.9 microM); 2) UTP was more potent than ATP in accumulating inositol phosphates (100 vs 43% increase at 2mM); 3) UTP was equipotent with ATP in stimulating mucin release; 4) Northern blot analysis of messenger ribonucleic acids (mRNAs) with a mouse P2u receptor complementary deoxyribonucleic acid (cDNA) probe revealed a single specific band (2.8 kb), partial sequencing of which showed a great homology with those of human or mouse P2u receptors. We conclude that, although both ATP and UTP are equipotent in stimulating mucin release, their binding kinetics to the cell surface are quite different, suggesting the presence of a common binding domain which may be responsible for the mucin release by these nucleotides. We suggest that the P2u purinoceptor is likely to be responsible for mucin release by these nucleotides, probably via activation of phospholipase C.
Luteinizing Hormone, a Reproductive Regulator That Modulates the Processing of Amyloid-β Precursor Protein and Amyloid-β Deposition (2004)

Hormonal changes associated with the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following menopause/andropause have been implicated in the pathogenesis of Alzheimer's disease (AD). Experimental support for this has come from studies demonstrating an increase in amyloid-beta (Abeta) deposition following ovariectomy/castration. Because sex steroids and gonadotropins are both part of the HPG feedback loop, any loss in sex steroids results in a proportionate increase in gonadotropins. To assess whether Abeta generation was due to the loss of serum 17beta-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins. Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain Abeta1-42 and Abeta1-40 concentrations, respectively, after 8 weeks of treatment. To further explore the role of gonadotropins in promoting amyloidogenesis, M17 neuroblastoma cells were treated with the gonadotropin luteinizing hormone (LH) at concentrations equivalent to early adulthood (10 mIU/ml) or post-menopause/andropause (30 mIU/ml). LH did not alter amyloid-beta precursor protein (AbetaPP) expression but did alter AbetaPP processing toward the amyloidogenic pathway as evidenced by increased secretion and insolubility of Abeta, decreased alphaAbetaPP secretion, and increased AbetaPP-C99 levels. These results suggest the marked increases in serum LH following menopause/andropause as a physiologically relevant signal that could promote Abeta secretion and deposition in the aging brain. Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD.
DENDRITIC CELL BASED VACCINES: PROGRESS IN IMMUNOTHERAPY STUDIES FOR PROSTATE CANCER (2004)

The new prospects opened by DC based vaccines for prostate cancer are fascinating. When compared to conventional treatments, DC vaccinations have few side effects. Improvements in patient selection, vaccine delivery strategies, immune monitoring and vaccine manufacturing will be crucial in moving DC based prostate cancer vaccines closer to the clinics.
Novel Matrix Metalloproteinase Inhibitor [18F]Marimastat-Aryltrifluoroborate as a Probe for <i>In vivo</i> Positron Emission Tomography Imaging in Cancer (2010)

Matrix metalloproteinases (MMP), strongly associated pathogenic markers of cancer, have undergone extensive drug development programs. Marimastat, a noncovalent MMP inhibitor, was conjugated with FITC to label cellular metalloproteinase cancer targets in MDA-MB-231 cells in vitro. Punctate localization of active transmembrane MMP14 was observed. For molecular-targeted positron emission tomography imaging of syngeneic 67NR murine mammary carcinoma in vivo, marimastat was (18)F-labeled using a shelf-stable arylboronic ester conjugate as a captor for aqueous [(18)F]fluoride in a novel, rapid one-step reaction at ambient temperature. [(18)F]Marimastat-aryltrifluoroborate localized to the tumors, with labeling being blocked in control animals first loaded with >10-fold excess unlabeled marimastat. The labeled drug cleared primarily via the hepatobiliary and gastrointestinal tract, with multiple animals imaged in independent experiments, confirming the ease of this new labeling strategy.
Composing graphical models with neural networks for structured representations and fast inference (2016)

We propose a general modeling and inference framework that composes probabilistic graphical models with deep learning methods and combines their respective strengths. Our model family augments graphical structure in latent variables with neural network observation models. For inference, we extend variational autoencoders to use graphical model approximating distributions with recognition networks that output conjugate potentials. All components of these models are learned simultaneously with a single objective, giving a scalable algorithm that leverages stochastic variational inference, natural gradients, graphical model message passing, and the reparameterization trick. We illustrate this framework with several example models and an application to mouse behavioral phenotyping.
Amphiphilic block copolymers featuring a reversible hetero Diels-Alder linkage (2014)

The present article reports the preparation of a novel class of switchable amphiphilic diblock copolymers with a temperature switchable linkage. Reversible addition fragmentation chain transfer (RAFT) polymerization was used to synthesize the individual blocks: for the preparation of the non-polar block, i.e. poly(isoprene-co-styrene) (P(I-co-S)) (9200 g mol−1 ≤ Mn ≤ 50 000 g mol−1, 1.22 ≤ Đ ≤ 1.36), a chain transfer agent (CTA, 3-((2-bromo-2-methylpropanoyl)oxy)propyl 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate) carrying a bromine group was employed, ready for subsequent cyclopentadienyl (Cp) transformation. For the preparation of the polar block, triethylene glycol methyl ether acrylate (TEGA) was polymerized (6600 g mol−1 ≤ Mn ≤ 35 000 g mol−1, 1.12 ≤ Đ ≤ 1.30) using a RAFT agent carrying a phosphoryl Z-group, which is able to undergo hetero Diels-Alder (HDA) ligation with Cp moieties. Both building blocks were conjugated at ambient temperature in the presence of ZnCl2 as catalyst yielding the amphiphilic block copolymer P(I-co-S)-b-PTEGA (16 000 g mol−1 ≤ Mn ≤ 68 000 g mol−1, 1.15 ≤ Đ ≤ 1.32). To investigate the bonding/debonding capability of the HDA linkage, high temperature nuclear magnetic resonance (HT-NMR) spectroscopy, high temperature dynamic light scattering (HT-DLS) and high temperature size exclusion chromatography (HT-SEC) were carried out, evidencing that efficiently switchable amphiphilic block copolymers were generated (>4 cycles).
Endothelial Nitric Oxide Synthase Traffic Inducer (NOSTRIN) is a Negative Regulator of Disease Aggressiveness in Pancreatic Cancer (2016)

Our findings showed that NOSTRIN is a potential negative regulator of disease aggressiveness, which may be targeted for designing improved treatment strategy in PDAC. Clin Cancer Res; 22(24); 5992-6001. ©2016 AACR.
Characterization of human immunodeficiency virus type 1 reverse transcriptase by using monoclonal antibodies: role of the C terminus in antibody reactivity and enzyme function (1988)

We describe the production of eight monoclonal antibodies reactive with human immunodeficiency virus type 1 reverse transcriptase (RT) by immunization of mice with purified recombinant RT. These antibodies were found to react with one or the other of two regions of the enzyme and were found to be useful in immunodeficiency purification of large amounts of the enzyme. One epitope located at the C terminus of the enzyme was of particular interest, since it was present in only the larger, 66-kilodalton (kDa) RT species and not its smaller, 51-kDa counterpart. To define this epitope, a series of mutants was made which synthesized C-terminally truncated RT. These mutants indicated that the same region of the enzyme, when deleted, both removed the C-terminal epitope and drastically reduced RT activity, indicating the importance of this region in the function of the enzyme; however, even the 51-kDa enzyme component had demonstrable activity.
Wideband High Power Doherty Amplifiers (2013)

Currently the Doherty Power Amplifier (DPA) is replacing the traditional Class B amplifier in base-station and broadcast applications, as such becoming the preferred choice of industry due to its simplicity and high efficiency performance. In spite of its success, so far practical DPA implementations can provide only a very limited RF bandwidth, which tends to narrow down even more at higher power levels. This narrowband behavior of the DPA is mostly caused by the use of traditional operating classes for the active devices and bandwidth restrictions related to use of a conventional impedance inverter. In this work, the bandwidth of different DPA topologies has been analyzed, followed by a discussion of recent techniques that can help to improve the DPA bandwidth. To overcome the remaining bandwidth limitations in a DPA design, a novel differential configuration was proposed. In this approach, transmission line based baluns are used to implement the desired wideband 2nd harmonic terminations of the active devices. By combining this technique with a novel wideband impedance inverter, excellent DPA wideband performance can be achieved. Unfortunately, when going to practical balun implementations, various imperfections come to light, which trouble the achievable DPA bandwidth performance. For this reason, three practical balun structures are investigated in detail, namely, the coaxial cable based balun, the vertically installed planar balun and suspended planar stripline balun. To explore the proposed DPA concept when using practical baluns, two DPAs featuring mixed-signal driven inputs are presented. A dedicated design procedure for these DPAs is also given. The first prototype is implemented using NXP GaN devices and coaxial cable based baluns. Simulation results show a maximum output power of 52dBm, but in 6dB power back-off we only reach 40% efficiency from 530MHz to 700MHz, which is significantly less than the intend bandwidth (450MHz-810MHz). Using the lessons learned of this first amplifier, a second design with NXP LDMOS devices and suspended planar stripline balun has been developed. According to simulation this later design provides a maximum output power of 59dBm with the efficiency above 55% at both full power and 6dB power back-off. According the simulations this second design can even achieve 50% efficiency at 8dB back-off. The related center frequency is 650MHz with a high-efficiency bandwidth at 6dB power back-off (efficiency within 10% of its maximum) from 460MHz to 790MHz.
Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation (2014)

Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis and inflammation and, in some patients, progressive fibrosis leading to cirrhosis. An understanding of the pathogenesis of NASH is still evolving but current evidence suggests multiple metabolic factors critically disrupt homeostasis and induce an inflammatory cascade and ensuing fibrosis. The mechanisms underlying these changes and the complex inter-cellular interactions that mediate fibrogenesis are yet to be fully elucidated. Lipotoxicity, in the setting of excess free fatty acids, obesity, and insulin resistance, appears to be the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence contribute to activation of the inflammasome via a variety of intra- and inter-cellular signalling mechanisms leading to fibrosis. Current evidence suggests that periportal components, including the ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the Th17 response may mediate disease progression. This review aims to provide an overview of the pathogenesis of NASH and summarises the evidence pertaining to key mechanisms implicated in the transition from steatosis and inflammation to fibrosis. Currently there are limited treatments for NASH although an increasing understanding of its pathogenesis will likely improve the development and use of interventions in the future.
(<i>E</i>)-1-Trimethylsilyl-1,3-butadiene (2001)

[71504-26-2] C7H14Si (MW 126.30) InChI = 1S/C7H14Si/c1-5-6-7-8(2,3)4/h5-7H,1H2,2-4H3/b7-6+ InChIKey = YFSJFUCGCAQAJA-VOTSOKGWSA-N (diene for Diels–Alder reactions,2, 3 creating allylsilanes that can be converted to a variety of functionalized cyclohexenes with a shift of the double bond from its original position in the cycloaddition;3 synthesis of a chiral allylborane;4 synthesis of allylsilanes5, 6 and trienes7) Physical Data: bp 110–115 °C, 70–74 °C/210 mmHg. Solubility: freely sol all organic solvents. Analysis of Reagent Purity: NMR: δ (CDCl3) 6.6–4.9 (5H, m), 0.02 (9H, s).3 UV: λmax (EtOH) 231 nm (ε 22 000).2 Preparative Method: prepared geometrically pure by Wittig2 or Peterson3 reactions on (E)-3-trimethylsilylpropenal,8 by pyrolysis of silylated 3-sulfolenes,9 and by coupling (E)-2-trimethylsilylvinyl bromide with Lithium Divinylcuprate.10 It can also be prepared geometrically impure, but largely (E), from Allyltrimethylsilane by a vinylogous Ramberg–Bäcklund reaction,11 and from 1,3‐Butadienyl‐1‐magnesium Chloride and Chlorotrimethylsilane.4 Handling, Storage, and Precautions: reasonably stable in the absence of air and radical initiators. It should be kept in a stoppered flask or sealed ampule in the presence of hydroquinone. Its toxicity is unknown, but the presence of a trimethylsilyl group is generally benign.
Fluorescence (Förster) resonance energy transfer imaging of oncogene activity in living cells (2005)

A hallmark of cancer cells is their uncontrolled activation of growth signal transduction cascades comprised of oncogene products. Overexpression and activating mutations of the growth factor receptors Ras and Raf are frequently observed in human cancer cells. Several research groups, including our own, have been developing probes based on the principle of fluorescence (Förster) resonance energy transfer (FRET) to visualize how signaling molecules, including oncogene products, are regulated in normal and cancerous cells in the living state. In this review, we will briefly introduce the principle of FRET-based probes, present an overview of the probes reported to date, and discuss the perspectives of these probes and fluorescent imaging systems in cancer biology.
Characterization of gas-water flow using electrical resistance imaging (2003)

This paper presents an impedance image based method, which is known as electrical resistance tomography (ERT), for characterization of gas-water two-phase flow in a 40m horizontal flow loop. An ERT sensor based on conductive ring technique is used to overcome the problem of measurement saturation caused by electrodes loosing electrical contact with conductive liquid, as it often occurs in stratified flow and slug or plug flow. In previous study, data implementation was constrained by the limited data collection speed and insufficient auxiliary sensing information. The quality of impedance images was also decayed due to the use of a linear back-projection algorithm. In order to gather sufficient information for the implementation of flow characteristics particularly flow pattern recognition and air cavity velocity, a fast data collection strategy was applied to a dual-plane ERT sensor and an iterative algorithm was used for image reconstruction. Results, in respect to flow patterns and velocity maps, are reported.
Effects of Age and Stocking Density on Leg Weakness in Broiler Chickens (2000)

The effects of stocking density (STD) on leg weakness in broiler chickens was assessed in two trials. The interaction between age and STD on leg weakness was further evaluated in one trial. In Trial 1, walking ability was assessed at 28, 42, and 49 d of age. Birds were stocked at 833, 625, or 435 cm2 per bird. In Trial 2, birds were stocked at 625 or 455 cm2 per bird and assessed for tibial dyschondroplasia (TD) by radiographic examination at 28 d and walking ability at 35 d. Foot pad burn, hock burn, and angulation of the hock joint were also assessed at slaughter on Day 42. Body weight was measured during both trials. At 4 wk of age, leg weakness was a relatively minor problem; few severely lame birds had a gait score (GS) of 4 or 5 at any density. However, 2 wk later, the birds had substantially poorer walking ability. Further deterioration had occurred by 7 wk of age. At all ages, males exhibited greater leg weakness than did females, and the proportion of severely lame birds increased with age of assessment. The effect of STD was consistent across both trials; higher STD were associated with poorer walking ability and reduced live weights. In Trial 2, higher STD resulted in more foot and hock burns. Females were more sensitive to STD than were males However, there was no effect of STD on the prevalence of TD or angulation of the hock joint. The effect of high STD on walking ability was apparent even at 4 wk of age. Adjusting the observations for differences in BW did not alter the findings. It was concluded that the lower STD substantially reduced the prevalence of leg weakness.
Human endogenous retrovirus-K (HML-2): a comprehensive review (2018)

The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these are defective or silenced through epigenetic changes, they were historically considered "junk DNA" and their potential role in human physiology or pathological circumstances have been poorly studied. The most recently acquired, human endogenous retrovirus-K (HERV-K), has multiple copies in the human genome and some of them have complete open reading frames that are transcribed and translated, especially in early embryogenesis. Phylogenetically, HERV-K is considered a supergroup of viruses. One of the subtypes, termed HML-2, seems to be the most active and hence, it is the best studied. Aberrant expression of HML-2 in adult tissues has been associated with certain types of cancer and with neurodegenerative diseases. This review discusses the discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis. Finally, it presents different therapeutic approaches being considered to target these viruses.
Alpha-terpineol promotes triterpenoid production of<i>Antrodia cinnamomea</i>in submerged culture (2014)

Antrodia cinnamomea is a medicinal mushroom producing potent bioactive triterpenoids. However, triterpenoids of A. cinnamomea in submerged culture are much less than those in fruiting bodies. Here we evaluated effects of different extracts from a host-related species, Cinnamomum camphora, on the mycelial growth and triterpenoid production of A. cinnamomea in submerged culture. The hot water extract of the stem showed the strongest promotion of the mycelial growth. The petroleum ether extract of the stem (PES) (0.05 g L(-1)) showed the greatest stimulatory effect on content and production of triterpenoids. A total of 39 compounds including terpenoids, phenolic and aromatic compounds were identified in the PES by GC-MS analysis. Furthermore, the effects of seven compounds contained in the PES on the mycelial growth and triterpenoid production of A. cinnamomea were evaluated. Among them, α-terpineol (0.5 mg L(-1)) showed the greatest stimulatory effect on the triterpenoid content (23.31 mg g(-1)) and triterpenoid production (91.33 mg L(-1)) of A. cinnamomea. Results of LC-MS analysis showed that α-terpineol (0.5 mg L(-1)) stimulated the syntheses of six triterpenoids in the mycelia of A. cinnamomea. This indicates that α-terpineol can act as an elicitor for triterpenoid biosynthesis in A. cinnamomea.
Horizontal Strain Field in Chinese Mainland and the Surrounding Areas (2004)

Abstract In the paper, two kinds of equations of block elastic motion are established: the equation with rotation in the entire block and homogeneous strain and the equation with rotation in the entire block and linear strain. Using the velocities of GPS sites located in the Western Region, Qinghai‐Xizang and North China blocks, both the elastic motion equations and the rigid motion equation are tested statistically for their unbiasedness and validity to simulate the site velocity of the block. The tested results indicate that the equation with rotation in the entire block and linear strain is the optimal model to describe the block motion; the equation with rotation in the entire block and homogeneous strain ranks the second; and the model of the block rigid rotation is the third. Dividing the Chinese mainland into 10 blocks, the rotation and strain parameters of each block are estimated using the equation with rotation in the entire block and linear strain and the velocities of GPS sites on the blocks. Then, the strain parameters of 1005 points in Chinese mainland and the surrounding areas are calculated with the spacing of 1° × 1°, and the strain field in Chinese mainland and the surrounding areas has been obtained. The basic characteristics of strain field in Chinese mainland and the surrounding areas are also analyzed in the paper. The direction of the principal compressive strain obtained by the method in the paper is well consistent with the principal compressive stress axes derived by the geological and seismological methods (except for South China block). The strain field has a very close relation with the main fault zones, and all the main fault zones of the block boundaries are the gradient zones with high‐level first shear strain rate. The fault zone is the result from the adjustment of strain‐stress field.
A dense pressure sensitive bedsheet design for unobtrusive sleep posture monitoring (2013)

Sleep plays a pivotal role in the quality of life, and sleep posture is related to many medical conditions such as sleep apnea. In this paper, we design a dense pressure-sensitive bedsheet for sleep posture monitoring. In contrast to existing techniques, our bedsheet system offers a completely unobtrusive method using comfortable textile sensors. Based on high-resolution pressure distributions from the bedsheet, we develop a novel framework for pressure image analysis to monitor sleep postures, including a set of geometrical features for sleep posture characterization and three sparse classifiers for posture recognition. We run a pilot study and evaluate the performance of our methods with 14 subjects to analyze 6 common postures. The experimental results show that our proposed method enables reliable sleep posture recognition and offers better overall performance than state-of-the-art methods, achieving up to 83.0% precision and 83.2% recall on average.