gebhart/patrepeval huggingface dataset:
Flavonoid Antioxidants (2001)

In order to ascertain the role of dietary flavonoids as antioxidants in vivo it is necessary to understand the chemical nature of the absorbed forms in the circulation in vivo and how the multiplicity of research findings in vitro reflect the bioactivity of flavonoids in vivo. Only when we gain adequate information on the circulating forms can we begin to understand the targeting to the tissues, whether flavonoids cross the blood-brain barrier, for example, and in what forms. Flavonoids are powerful antioxidants in vitro, but their overall function in vivo has yet to be clarified, whether antioxidant, anti-inflammatory, enzyme inhibitor, enzyme inducer, inhibitor of cell division, or some other role. It should also be emphasised that the reducing properties of flavonoids might contribute to redox regulation in cells, independently of their antioxidant properties, and thus might protect against cell ageing, for example, by working together with the intracellular reductant network. To gain understanding of these issues the factors influencing the absorption of flavonoids in the gastrointestinal tract needs to be established, namely the questions of: de-glycosylation before absorption, conjugation in the small intestine through glucuronidation, sulphation or methylation etc, metabolism and degradation in the colon to smaller phenolic molecules. The forms in which they circulate in vivo will influence their polarity and, thus, their localization and bioactivities in vivo. Finally if antioxidant activities are important, the elucidation of how such properties in vitro relate to the potential for conjugates and metabolites in vivo to act as antioxidants is required. The absorbed flavonoid components might function in the aqueous phase (like vitamin C) or in the lipophilic milieu (as vitamin E) in vivo. This will depend on their polarity properties on uptake, how they are metabolised on absorption, and their resulting structural forms in the circulation.
Effect of Changes in Light on Hormonal Secretion and Milk Production of Dairy Cows in Early Lactation (1994)

Abstract Two experiments were carried out to investigate the effect of a change in day length and light intensity on the concentration of prolactin in milk and plasma, on milk production during the first two months of lactation, and on the daily variation in plasma concentrations of prolactin, melatonin, growth hormone, Cortisol and insulin 24–48 h after calving. The light programmes used were 9.5 L:14.5 D and 17.5 L:6.5 D. During 4–8 weeks before calving one group was on the long day programme (LL group) and the other on the short day programme (DL group) in both experiments. After calving, both groups were on the long day programme. Indoor light intensity was 150 lux at the eye level of the cows in both experiments. Outdoor light intensity during the summer was also included in the calculationsln the second experiment. In the first study, with 6 cows and 6 first calvers, the plasma concentration of prolactin increased significantly in the LL group but not in the DL group during 30-3 days before calving (b = 1.88±0.70 μg/l/d, p<0.01). During weeks 1–8 after calving there was a similar increase in the DL group (b plasma = 12.03 μg/l/w, p < 0.001 and b milk = 0.88±0.37 μg/l/w, p <0.05), but no significant change in the LL group. The first calvers of the LL group produced 10–12% more energy-corrected milk (3.14 MJ/kg) and kg milk fat than those of the DL group (p<0.05). No production traits of the cows were influenced by the light programmes (p>0.40), but both groups of cows were severely affected by illness after calving. Melatonin, growth hormone and Cortisol concentrations in plasma showed no significant daily variation and no effect of light programmes (p>0.45). There was no significant difference in the insulin concentration between groups (p = 0.28), although the group on long days had lower concentrations at all hours. The concentration of plasma prolactin was lower during the dark hours than during the light hours (p<0.05). In the second experiment, 36 first calvers were stalled 6–8 weeks before expected calving following a period of grazing. The stalling involved a substantial decrease in daily maximum light intensity for the cows. From the first day in experiment to 10 days before expected calving, the plasma prolactin concentration decreased from 41.5 ± 3.7 to 29.0 ± 3.3 μg/l, p<0.05, equally in both groups. After calving, the plasma prolactin concentration increased in the DL group (b=4.20 ± 1.93 μg/l/w, p<0.05) to a higher level than at the start of the experiment. There was no difference in milk production (p>0.50). The results indicate that a continuously increasing secretion of prolactin in the last month of gestation may promote milk production in early lactation.
Stimulatory Effects of Prostaglandin E2 on Neurogenesis in the Dentate Gyrus of the Adult Rat (2002)

Neurogenesis in the dentate gyrus of adult rodents is elicited by transient global ischemia. Cyclooxygenase (COX) -2, a rate-limiting enzyme for prostanoid synthesis, is also induced by ischemia. We recently found that the administration of a non-selective COX inhibitor to ischemic animals suppressed cell proliferation in the subgranular zone (SGZ) at the dentate gyrus of the hippocampus. To clarify whether prostaglandin E2 (PGE2) synthesis by COX's is involved in neurogenesis, sulprostone, an analogue of PGE2, was injected into the rat hippocampus. Sulprostone injection increased the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the SGZ. BrdU-positive cells also expressed polysialylated isoforms of neural cell adhesion molecule and neuronal nuclear antigen. These results suggest that PGE2 plays an important role in the proliferation of cells in the SGZ.
Photoaffinity Labeling of Chromatin (1982)

The syntheses and properties of potential photoaffinity labels for the proteins in chromatin studies are described. One compound, N,N'-bis-(9-acridinyl)-4-aza-4-(4-azidobenzoyl)-1,7-diaminoheptane dihydrochloride, has been studied more closely. This photolabel shows high affinity towards DNA (Ka approximately 3 x 10(5) M-1) and photoreacts with histones at wavelengths in the range 260-450 nm. The photoreaction was monitored fluorimetrically, and labeling of histones H1, H2A/H2B and H3 was observed. When chromatin was photolabeled, labeling of H1 was exclusively quenched by NaCl at concentrations which are known to cause dissociation of this histone from the DNA. It is inferred that only DNA-associated proteins are photolabeled by the reagent.
Alpha and Beta Globin Messenger Ribonucleic Acid (1971)

Abstract This paper demonstrates that regulation of synthesis of the two globin chains in the rabbit reticulocyte is complex: cells contain about 1.5 times more ribosome-associated α mRNA than β, but ribosomes initiate translation of each α mRNA only about 65% as frequently as a β mRNA. Hence regulation of globin synthesis occurs not only as a result of mRNA availability, but also as a consequence of selective ratios of initiation. These experiments utilize seven antibiotics—emetine, anisomycin, sparsomycin, blasticidin, cycloheximide, fusidic acid, and streptovitacin. We show that at concentrations which inhibit protein synthesis in reticulocyte extracts 60 to 80%, all reduce the rate of propagation of nascent globin chains, but do not directly inhibit initiation of new chains. This results in accumulation of large polyribosomes, in which the mRNA molecules are saturated with ribosomes. Under these conditions protein synthesis is not limited by chain initiation and the relative amount of the two globin chains produced should be proportional to the relative amount of the mRNA; indeed we find that all drugs induce a change in the ratio of α:β globin synthesized from 1.0 to about 1.5. Using two techniques to determine the classes of polyribosomes which are synthesizing each globin chain, we have confirmed the finding of Hunt et al., (Hunt, T., Hunter, T., and Munro, A., Nature, 220, 481 (1968)) that β chains are made on larger polyribosomes than α chains. We believe that this is due solely to the decreased rate of ribosome attachment to an α mRNA relative to a β mRNA. In accord with this notion, we show that in the presence of any of the seven translation inhibitors, both classes of globin chains are made on the same classes of very large polyribosomes, and that these ribosomes contain relatively more nascent α chains than β chains.
Tissue Barriers to Arbovirus Infection in Mosquitoes (2015)

Arthropod-borne viruses (arboviruses) circulate in nature between arthropod vectors and vertebrate hosts. Arboviruses often cause devastating diseases in vertebrate hosts, but they typically do not cause significant pathology in their arthropod vectors. Following oral acquisition of a viremic bloodmeal from a vertebrate host, the arbovirus disease cycle requires replication in the cellular environment of the arthropod vector. Once the vector has become systemically and persistently infected, the vector is able to transmit the virus to an uninfected vertebrate host. In order to systemically infect the vector, the virus must cope with innate immune responses and overcome several tissue barriers associated with the midgut and the salivary glands. In this review we describe, in detail, the typical arbovirus infection route in competent mosquito vectors. Based on what is known from the literature, we explain the nature of the tissue barriers that arboviruses are confronted with in a mosquito vector and how arboviruses might surmount these barriers. We also point out controversial findings to highlight particular areas that are not well understood and require further research efforts.
Primary glomerulonephritis: A review of important recent discoveries (2013)

The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect.
An Efficient Data Evacuation Strategy for Sensor Networks in Postdisaster Applications (2013)

Disasters often result in a tremendous cost to our society. Previously, wireless sensor networks have been proposed to provide information for decision making in postdisaster relief operations. The existing WSN solutions for postdisaster operations normally assume that the deployed sensor network can tolerate the damage caused by disasters and maintain its connectivity and coverage, even though a significant portion of nodes have been physically destroyed. Inspired by the “blackbox” technique, we propose that preserving “the last snapshot” of the whole network and transferring those data to a safe zone would be the most logical approach to provide necessary information for rescuing lives and control damages. In this paper, we introduce data evacuation (DE), an original idea that takes advantage of the survival time of the WSN, that is, the gap from the time when the disaster hits and the time when the WSN is paralyzed, to transmit critical data to sensor nodes in the safe zone. Numerical investigations reveal the effectiveness of our proposed DE algorithm.
Analysis of a Vernier Motor with Concentrated Windings (2013)

This paper describes the operating principle and the performance analysis of the surface-permanent-magnet-type vernier motor with concentrated windings using finite element method analysis. To satisfy the structural relationship of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Z</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> = <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Z</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> ± <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> , the number of auxiliary teeth in the stator, pole pairs in the rotor and winding pole pairs are chosen as <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Z</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> =12, <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Z</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> =11 and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> =1 respectively. With this setup which operates at a gear ratio of 1/11, the cogging torque tends to be lower and therefore the output torque contains only smaller ripples. The iron loss computation and the efficiency calculation employing the two-frequency method are also investigated. Estimation of the iron loss has clarified that the hysteresis loss was dominant in the laminated core and that the magnet eddy current loss increased dramatically at higher speeds due to the rotating magnetic field.
5-azacytidine promotes terminal differentiation of hepatic progenitor cells (2015)

5-azacytidine (5-azaC) is known to induce cardiomyocyte differentiation. However, its function in hepatocyte differentiation is unclear. The present study investigated the in vitro capability of 5-azaC to promote maturation and differentiation of mouse embryonic hepatic progenitor cells, with the aim of developing an approach for improving hepatic differentiation. Mouse embryonic hepatic progenitor cells (HP14.5 cells) were treated with 5-azaC at concentrations from 0 to 20 μmol/l, in addition to hepatocyte induction culture medium. Hepatocyte induction medium induces HP14.5 cell differentiation. 5-azaC may enhance the albumin promotor-driven Gaussia luciferase (ALB-GLuc) activity in induced HP14.5 cells. In the present study 2 μmol/l was found to be the optimum concentration with which to achieve this. The expression of hepatocyte-associated factors was not significantly different between the group treated with 5-azaC alone and the control group. The mRNA levels of ALB; cytokeratin 18 (CK18); tyrosine aminotransferase (TAT); and cytochrome p450, family 1, member A1 (CYP1A1); in addition to the protein levels of ALB, CK18 and uridine diphosphate glucuronyltransferase 1A (UGT1A) in the induced group with 5-azaC, were higher than those in the induced group without 5-azaC, although no significant differences were detected in expression of the hepatic stem cell markers, DLK and α-fetoprotein, between the two groups. Treatment with 5-azaC alone did not affect glycogen synthesis or indocyanine green (ICG) metabolic function in HP14.5 cells, although it significantly increased ICG uptake and periodic acid-Schiff-positive cell numbers amongst HP14.5 cells. Therefore, the present study demonstrated that treatment with 5-azaC alone exerted no effects on the maturation and differentiation of HP14.5 cells. However, 5-azaC exhibited a synergistic effect on the terminal differentiation of induced hepatic progenitor cells in association with a hepatic induction medium.
The Benzo[c]phenanthridine Alkaloid, Sanguinarine, Is a Selective, Cell-active Inhibitor of Mitogen-activated Protein Kinase Phosphatase-1 (2005)

Mitogen-activated protein kinase phosphatase-1 (MKP-1) is a dual specificity phosphatase that is overexpressed in many human tumors and can protect cells from apoptosis caused by DNA-damaging agents or cellular stress. Small molecule inhibitors of MKP-1 have not been reported, in part because of the lack of structural guidance for inhibitor design and definitive assays for MKP-1 inhibition in intact cells. Herein we have exploited a high content chemical complementation assay to analyze a diverse collection of pure natural products for cellular MKP-1 inhibition. Using two-dimensional Kolmogorov-Smirnov statistics, we identified sanguinarine, a plant alkaloid with known antibiotic and antitumor activity but no primary cellular target, as a potent and selective inhibitor of MKP-1. Sanguinarine inhibited cellular MKP-1 with an IC50 of 10 microM and showed selectivity for MKP-1 over MKP-3. Sanguinarine also inhibited MKP-1 and the MKP-1 like phosphatase, MKP-L, in vitro with IC50 values of 17.3 and 12.5 microM, respectively, and showed 5-10-fold selectivity for MKP-3 and MKP-1 over VH-1-related phosphatase, Cdc25B2, or protein-tyrosine phosphatase 1B. In a human tumor cell line with high MKP-1 levels, sanguinarine caused enhanced ERK and JNK/SAPK phosphorylation. A close congener of sanguinarine, chelerythrine, also inhibited MKP-1 in vitro and in whole cells, and activated ERK and JNK/SAPK. In contrast, sanguinarine analogs lacking the benzophenanthridine scaffold did not inhibit MKP-1 in vitro or in cells nor did they cause ERK or JNK/SAPK phosphorylation. These data illustrate the utility of a chemical complementation assay linked with multiparameter high content cellular screening.
Acyclic diene metathesis (ADMET) depolymerization: Ethenolysis of 1,4-polybutadiene using a ruthenium complex (1999)

α,ω-Vinyl-terminated butadiene oligomers can be generated through the cross-metathesis of ethylene and high molecular weight 1,4-polybutadiene catalyzed by the complex RuCl2(CHPh)(PCy3)2. The effect of varied ethylene pressure is studied in order to obtain the highest conversion to the monomer 1,5-hexadiene. A dramatic increase in yield of this monomeric diene is realized relative to previous published attempts utilizing a well-defined group VI metal alkylidene in the same chemistry. Traces of side products are observed, and alternate mechanisms for their formation were proposed. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1857–1861, 1999
Generalized Reversible Computing (2018)

Landauer's Principle that information loss from a computation implies entropy increase can be rigorously proved from mathematical physics. However, carefully examining its detailed formulation reveals that the traditional identification of logically reversible computational operations with bijective transformations of the full digital state space is actually not the correct logical-level characterization of the full set of classical computational operations that can be carried out physically with asymptotically zero energy dissipation. To find the correct logical conditions for physical reversibility, we must account for initial-state probabilities when applying the Principle. The minimal logical-level requirement for the physical reversibility of deterministic computational operations is that the subset of initial states that exhibit nonzero probability in a given statistical operating context must be transformed one-to-one into final states. Thus, any computational operation is conditionally reversible relative to any sufficiently-restrictive precondition on its initial state, and the minimum dissipation required for any deterministic operation by Landauer's Principle asymptotically approaches 0 when the probability of meeting any preselected one of its suitable preconditions approaches 1. This realization facilitates simpler designs for asymptotically thermodynamically reversible computational hardware, compared to designs that are restricted to using only fully-bijective operations such as Toffoli type operations. Thus, this more general framework for reversible computing provides a more effective theoretical foundation to use for the design of practical reversible computers than does the more restrictive traditional model of reversible logic. In this paper, we formally develop the theoretical foundations of the generalized model, and briefly survey some of its applications.
hERG (KCNH2 or Kv11.1) K+ Channels: Screening for Cardiac Arrhythmia Risk (2008)

Testing new compounds for pro-arrhythmic potential has focused in recent years on avoiding activity at the hERG K+ channel, as hERG block is a common feature of many pro-arrhythmic compounds associated with Torsades de Pointes in humans. Blockers of hERG are well known to prolong cardiac action potentials and lead to long QT syndrome, and activators, although rarer, can lead to short QT syndrome. The most reliable assays of hERG utilize stable cell lines, and include ligand binding, Rb+ flux and electrophysiology (both automated and manual). These assays can be followed by measurement of activity at other ion channels contributing to cardiac contractility and detailed action potential/repolarization measurements in cardiac tissue. An integrated risk assessment for pro-arrhythmic potential is ultimately required, as the constellation of ion channel activities and potencies, along with the mechanism/kinetics of ion channel block, may ultimately be the best predictor of cardiac risk in vivo.
Schizophrenia and cancer: an epidemiological study (2005)

We found no evidence that schizophrenia confers protection against cancer in general. Low rates of cancer are consistent with the hypothesis that sun exposure may influence the development of schizophrenia, although other explanations are also possible.
Xenopus Cell-Free Extracts to Study DNA Damage Checkpoints (2004)

Surveillance mechanisms monitoring genomic integrity operate through signal transduction pathways called checkpoints. Checkpoints are essential to delay cell cycle progression in response to deoxyribonucleic acid (DNA) damage (1,2). These pathways require the coordinated monitoring and sensing of the damaged DNA with downstream signaling ultimately leading to cell cycle arrest. Traditionally, the DNA damage response and its checkpoint’s component have been studied mostly using yeast and mammalian cells. Budding and fission yeasts have been instrumental to identify mutations in genes impaired in DNA damage cell cycle checkpoints. Genetic screens in yeast have been a successful approach to identify radiation-sensitive (rad mutants) and checkpoint genes (hus, mad, bub mutants) participating in the maintenance of genomic integrity (3). However, this approach has several limitations. Essential genes may never be isolated in standard genetic screens. DNA damage response is more complex in vertebrates than it is in yeast and critical regulators of the DNA damage response, such as p53 and BRCA1, are found only in vertebrates (2). Mammalian cell lines from diverse origins, including some derived from patients harboring defects in the DNA damage response, have also been used extensively to study the DNA damage response (4–6). However, these cell-based systems do not allow using specific biochemical readouts as they are based on phenotypes resulting from complex outputs such as cell growth or survival.