gebhart/patrepeval huggingface dataset:
Control of cell proliferation (1977)

Much effort has gone into understanding the factors which regulate the growth of mammalian cells. Normal cells can exist in a proliferating state, or they can leave the cell division cycle and pass into a resting state, where they remain viable and functional for long periods. It is the switch between these alternative possibilities of cycling growth and quiescence that is of paramount importance in growth regulation. In the normal situation, there is a balance between cell proliferation and cell death. The movement of cells between the quiescent and growing state is under precise regulation in order to ensure the correct balance. In cancer this regulation is altered such that the rate of cell proliferation exceeds the rate of cell death. It is thus important to learn about the regulatory processes and how they are disrupted in the cancer cell. Evidence for alterations in these control events in tumor cells comes from in vitro experiments. Several culture conditions that are suboptimal for cell growth, as well as certain drugs, reversibly shift normal tissue culture cells into a quiescent state, whereas under the same culture conditions or in the presence of the same drugs certain transformed, tumor-forming cells continue to traverse the cell cycle. This suggests a derangement of regulatory biochemical mechanisms. We are already in a position to take empirical advantage of these observations. In mice we are attempting to use “protective” drugs such as the ones which have been found to be effective in cell culture to shift reversibly and selectively the rapidly proliferating cells of the bone marrow, intestinal epithelium, and lymph nodes into a quiescent state. Such protective drugs would then protect these normal tissues, which are generally the most susceptible to the toxicity of anti-cancer drugs, from the cytotoxicity of growth-specific antineoplastic agents. The tumor cells, which would not be stopped by these protective drugs, would still be killed. This project is major, and full of uncertainties as to how all of the normal cells will respond and how each tumor type (which differs in its control characteristics, among other things) will respond. Studies of this sort should be applicable to the treatment of at least some tumors. As we apply these ideas, we will increasingly develop a stock of information on which to base further approaches to cancer chemotherapy.
A Single Enzyme Catalyzes Both Platelet-activating Factor Production and Membrane Biogenesis of Inflammatory Cells (2006)

Platelet-activating factor (PAF) is a potent proinflammatory lipid mediator eliciting a variety of cellular functions. Lipid mediators, including PAF are produced from membrane phospholipids by enzymatic cascades. Although a G protein-coupled PAF receptor and degradation enzymes have been cloned and characterized, the PAF biosynthetic enzyme, aceyl-CoA:lyso-PAF acetyltransferase, has not been identified. Here, we cloned lyso-PAF acetyltransferase, which is critical in stimulus-dependent formation of PAF. The enzyme is a 60-kDa microsomal protein with three putative membrane-spanning domains. The enzyme was induced by bacterial endotoxin (lipopolysaccharide), which was suppressed by dexamethasone treatment. Surprisingly, the enzyme catalyzed not only biosynthesis of PAF from lyso-PAF but also incorporation of arachidonoyl-CoA to produce PAF precursor membrane glycerophospholipids (lysophosphatidylcholine acyltransferase activity). Under resting conditions, the enzyme prefers arachidonoyl-CoA and contributes to membrane biogenesis. Upon acute inflammatory stimulation with lipopolysaccharide, the activated enzyme utilizes acetyl-CoA more efficiently and produces PAF. Thus, our findings provide a novel concept that a single enzyme catalyzes membrane biogenesis of inflammatory cells while producing a prophlogistic mediator in response to external stimuli.
Comparing Sampling and Estimation Strategies in Establishment Populations (2007)

Population structure is a key determinant of the efficiency of sampling plans and estimators. Variables in many establishment populations have structures that can be described by simple linear models with a single auxiliary variable and a variance related to some power of that auxiliary. If a working model can be devised that is a good approximation to the population structure, then very efficient sample designs and estimators are possible. This study compares alternative strategies of (i) selecting a pilot study to estimate the variance power and using that estimate to select a main sample and (ii) selecting a only main sample based on an educated guess about the variance power. We also examine a number of sampling plans, including probability proportional to size, deep stratification based on a measure of size, and weighted balanced sampling. Population totals are estimated by best linear unbiased predictors, general regression estimators, and some other choices often used in practice.
Maternal Immunity and Prevention of Congenital Cytomegalovirus Infection (2003)

Naturally acquired immunity results in a 69% reduction in the risk of congenital CMV infection in future pregnancies.
Hypertensive diseases and eclampsia (2002)

Worldwide, pre-eclampsia and eclampsia contribute to the death of a pregnant woman every 3 min. In the UK in recent decades, hypertensive disorders of pregnancy have remained one of the leading causes of both maternal and perinatal morbidity and mortality. The management of pregnancies complicated by hypertension has not significantly altered for many years, possibly as a result of little progress being made in our understanding of the condition. New insights, however, have recently been gained into the pathophysiology of pre-eclampsia. These have yet to be translated into new interventions or to make any impact on clinical management of these pregnancies. This review will therefore focus on recent advances relating to research into the aetiology and pathogenesis of pre-eclampsia, but will conclude with a brief update on current therapeutic strategies.
The Function of RH22, a DEAD RNA Helicase, in the Biogenesis of the 50S Ribosomal Subunits of Arabidopsis Chloroplasts (2011)

The chloroplast ribosome is a large and dynamic ribonucleoprotein machine that is composed of the 30S and 50S subunits. Although the components of the chloroplast ribosome have been identified in the last decade, the molecular mechanisms driving chloroplast ribosome biogenesis remain largely elusive. Here, we show that RNA helicase 22 (RH22), a putative DEAD RNA helicase, is involved in chloroplast ribosome assembly in Arabidopsis (Arabidopsis thaliana). A loss of RH22 was lethal, whereas a knockdown of RH22 expression resulted in virescent seedlings with clear defects in chloroplast ribosomal RNA (rRNA) accumulation. The precursors of 23S and 4.5S, but not 16S, rRNA accumulated in rh22 mutants. Further analysis showed that RH22 was associated with the precursors of 50S ribosomal subunits. These results suggest that RH22 may function in the assembly of 50S ribosomal subunits in chloroplasts. In addition, RH22 interacted with the 50S ribosomal protein RPL24 through yeast two-hybrid and pull-down assays, and it was also bound to a small 23S rRNA fragment encompassing RPL24-binding sites. This action of RH22 may be similar to, but distinct from, that of SrmB, a DEAD RNA helicase that is involved in the ribosomal assembly in Escherichia coli, which suggests that DEAD RNA helicases and rRNA structures may have coevolved with respect to ribosomal assembly and function.
Fluorescence and Absorption Contrast Mechanisms for Biomedical Optical Imaging Using Frequency‐Domain Techniques (1997)

The ability to optically image or detect diseased tissue volumes located deep within tissues depends upon the degree of contrast provided by differences in local optical properties. In this report, we show that the exogenous contrast offered by fluorescent compounds is superior to that provided by nonfluorescing, light-absorbing compounds when time-dependent measurements are employed. In addition, we show that the induced contrast is not only moderated by the preferential uptake of fluorescent agents into diseased tissue volumes of interest but also by the fluorescent optical properties and the fluorescence dynamics in the specific tissue volume. Using tissue phantom studies, we demonstrated experimentally that near-infrared-absorbing and fluorescent dyes such as indocyanine green can provide detection of diseased tissue volumes from fluorescence measurements made at the periphery of tissue when there is perfect, 100-fold and 10-fold partitioning in diseased tissues over that in surrounding normal tissues. Experimental results of common laser dyes show the contrast is also mediated by the quantum yield and lifetime parameters that may be dependent upon the local tissue environment.
Fractalkine activates NRF2/NFE2L2 and heme oxygenase 1 to restrain tauopathy-induced microgliosis (2013)

The chemokine fractalkine modulates microglial responses in neurodegenerative diseases, including tauopathies, but the mechanistic processes and their relevance in human brain pathologies is not yet known. Here, we show that hippocampal HT22 cells expressing human TAU(P301L) mutant protein produce fractalkine, which in microglia activates AKT, inhibits glycogen synthase kinase-3β and upregulates the transcription factor NRF2/NFE2L2 and its target genes including heme oxygenase 1. In a mouse model of tauopathy based on stereotaxic delivery in hippocampus of an adeno-associated viral vector for expression of TAU(P301L), we confirmed that tau-injured neurons express fractalkine. NRF2- and fractalkine receptor-knockout mice did not express heme oxygenase 1 in microglia and exhibited increased microgliosis and astrogliosis in response to neuronal TAU(P301L) expression, demonstrating a crucial role of the fractalkine/NRF2/heme oxygenase 1 pathway in attenuation of the pro-inflammatory phenotype. The hippocampus of patients with Alzheimer's disease also exhibits increased expression of fractalkine in TAU-injured neurons that recruit microglia. These events correlated with increased levels of NRF2 and heme oxygenase 1 proteins, suggesting an attempt of the diseased brain to limit microgliosis. Our combined results indicate that fractalkine mobilizes NRF2 to limit over-activation of microglia and identify this new target to control unremitting neuroinflammation in tauopathies.
Stages in Iron Storage in the Ferritin of Escherichia coli (EcFtnA):  Analysis of Mössbauer Spectra Reveals a New Intermediate (1999)

Iron uptake into the nonheme ferritin of Escherichia coli (EcFtnA) and its site-directed variants have been investigated by Mössbauer spectroscopy. EcFtnA, like recombinant human H chain ferritin (HuHF), oxidized Fe(II) at a dinuclear ferroxidase center situated at a central position within each subunit. As with HuHF, Mössbauer subspectra observed between 1 min and 24 h after Fe(II) addition were assigned to Fe(III) monomers, "c", mu-oxo-bridged dimers, "b", and clusters, "a", the latter showing magnetically split spectra, "d", at 4.1 K. Like those of HuHF, the mu-oxo-bridged dimers were formed at the ferroxidase centers. However, the analysis also revealed the presence of a new type of dimer, "e" (QS1 = 0.38 mm/s, IS1 = 0.51 mm/s and QS2 = 0.72 mm/s, IS2 = 0.50 mm/s), and this was also assigned to the ferroxidase center. Dimers "b" appeared to be converted to dimers "e" over time. Subspectra "e" became markedly asymmetric at temperatures above 90 K, suggesting that the two Fe(III) atoms of dimers "e" were more weakly coupled than in the mu-oxo-bridged dimers "b", possibly due to OH- bridging. Monomeric Fe(III), giving relaxation spectra "c", was assigned to a unique site C that is near the dinuclear center. In EcFtnA all three iron atoms seemed to be oxidized together. In contrast to HuHF, no Fe(III) clusters were observed 24 h after the aerobic addition of 48 Fe(II) atoms/molecule in wild-type EcFtnA. This implies that iron is more evenly distributed between molecules in the bacterial ferritins, which may account for its greater accessibility.
Microrrelatos. Literatura divertida en la clase de E/LE (2008)

Hoy en día los materiales literarios se encuentran infrautilizados en el aula. Muchos aducen que el lenguaje que en ellos se utiliza presenta rasgos peculiares que hacen que se aleje de las verdaderas necesidades comunicativas de los alumnos y de los objetivos didácticos establecidos en los programas de lengua.
Sex differences in lung CYP1A1 expression and DNA adduct levels among lung cancer patients. (1999)

Several epidemiological studies have indicated that female tobacco smokers may be at higher risk of lung cancer than males. In a study of lung cancer cases, we have found that female smokers had a significantly higher level of aromatic/hydrophobic DNA adducts in their nontumor lung tissue (15.39+/-9.47 adducts/10(8) nucleotides, n = 29) than male smokers (12.08+/-8.14, a = 93; P = 0.047). Females had significantly higher levels of adducts/pack-year (females 0.95+/-0.82 adducts/pack-year and males 0.46+/-0.46; P = 0.0004) and adducts/cigaret/day (females 1.48+/-1.29 and males 0.89+/-0.74, P = 0.015). By quantitative reverse transcription-PCR, it was found that female smokers exhibited a significantly higher expression level of lung CYP1A1 (494+/-334 CYP1A1 mRNA/10(6) glyceraldehyde-3-phophate dehydrogenase mRNA, n = 15) compared with males (210+/-208, n = 12; P = 0.016). Furthermore, for both sexes combined a significant correlation between CYP1A1 expression and DNA adduct level was found (r = 0.50, P = 0.009). In conclusion, the observed sex difference in aromatic/hydrophobic DNA adduct levels may at least in part be explained by different levels of CYP1A1 expression.
Ammonium Excretion by an l -Methionine- dl -Sulfoximine-Resistant Mutant of the Rice Field Cyanobacterium Anabaena siamensis (1990)

An ammonium-excreting mutant (SS1) of the rice field nitrogen-fixing cyanobacterium Anabaena siamensis was isolated after ethyl methanesulfonate mutagenesis by selection on 500 muM l-methionine-dl-sulfoximine. SS1 grew in the presence and absence of (l)-methionine-dl-sulfoximine at a rate comparable to that of the wild-type strain, with a doubling time of 5.6 h. The rate of ammonium release by SS1 depended on cell density; it peaked at the 12th hour of growth with 8.7 mumol mg of chlorophyll h (at a chlorophyll concentration of 5 mug ml) and slowed down to almost nil at the fourth day of growth. A similar pattern of release by immobilized SS1 was observed between 12 to 20 h after loading alginate beads in packed-bed reactors at the rate of 11.6 mumol mg of chlorophyll h. The rate was later reduced significantly due to the fast growth of SS1 on the substrate. Prolonged release of ammonium at the peak level was achieved only by maintaining SS1 under continuous cultivation at low chlorophyll levels (5 to 7 mug ml). Under these conditions, nitrogen fixation in the mutant was 30% higher than that in its parent and glutamine synthetase activity was less by 50%. Immunoblot analysis revealed that SS1 and its parent have similar quantities of glutamine synthetase protein under ammonium excretion conditions. In addition, a protein with a molecular weight of about 30,000 seems to have been lost, as seen by electrophoretic separation of total proteins from SS1.
Evolutionary origin and radiation of the avian-adapted non-motile salmonellae (1993)

Multilocus enzyme electrophoresis was employed to estimate chromosomal genotypic diversity and relationships among 131 isolates of the non-motile Salmonella biotypes Gallinarum and Pullorum (serotype 1, 9, 12:-:-) that cause fowl typhoid and pullorum disease, respectively. Thirteen electrophoretic types (ETs), marking clones, were distinguished, and construction of a neighbour-joining phylogenetic tree revealed three lineages: one consisted of five ETs of Gallinarum, a second included seven ETs of Pullorum, and a third was represented by a single ET (Ga/Pu 1) that is intermediate between those of the other two lineages in both multilocus enzyme genotype and biochemical properties. Enzyme genotype analysis and comparative nucleotide sequencing of the phase 1 flagellin gene (fliC), the hook-associated protein 1 gene (flgK), and the 6-phosphogluconate dehydrogenase gene (gnd) identified serotype Enteritidis (1, 9, 12:g, m:-) as a close relative of the non-motile salmonellae. In most strains of biotype Gallinarum, the fliC gene is complete, intact and identical in sequence to that of Enteritidis, but isolates of three ETs had a stop codon at position 495. The fliC sequences of the ETs of Pullorum differed from that of Enteritidis in having non-synonymous changes in either two or three codons and a synonymous change in one codon. The sharing of distinctive alleles at three metabolic enzyme loci and a stop codon in flgK indicates that the non-motile salmonellae are monophyletic and that their most recent common ancestor was non-motile. Since diverging from that ancestor, the Pullorum lineage has evolved more rapidly than the Gallinarum and Ga/Pu 1 lineages.
Glass transition temperature variation, cross-linking and structure in network glasses: A stochastic approach (1999)

We give general topological rules which very accurately predict the chemical trends in glass transition temperature $T_g$ variation as a function of cross-linking. In multicomponent glasses, these chemical trends permit to distinguish homogeneous compositions (random network) from inhomogeneous ones (local phase separation). The stochastic origin of the Gibbs-Di Marzio equation is predicted at low connectivity and the analytical expression of its parameter emerges naturally from the calculation.
Cost analysis of energy storage systems for electric utility applications (1997)

Under the sponsorship of the Department of Energy, Office of Utility Technologies, the Energy Storage System Analysis and Development Department at Sandia National Laboratories (SNL) conducted a cost analysis of energy storage systems for electric utility applications. The scope of the study included the analysis of costs for existing and planned battery, SMES, and flywheel energy storage systems. The analysis also identified the potential for cost reduction of key components.
Evidence to Support the Role of HLA-G5 in Allograft Acceptance through Induction of Immunosuppressive/ Regulatory T Cells (2006)

The soluble HLA-G5 isoform encoded by intron-4 retaining spliced transcript has been previously detected in vivo in sera and grafts from transplanted patients who had significantly better graft acceptance. These findings led us to investigate the role of HLA-G5 in tolerance induction in vitro and its biological relevance in allograft acceptance in vivo. We demonstrated that engagement of Ig-like transcript-2 and Ig-like transcript-4 receptors by HLA-G5 is involved in inhibition of T cell alloproliferative responses. Naive T cells sensitized in vitro with HLA-G5, for as little as 18 h, 1) lost their ability to respond to subsequent allogeneic stimulus, and 2) acquired regulatory properties because they inhibited the reactivity of other T cells. These HLA-G5-induced T cells act in an Ag-nonspecific fashion and through soluble factors. Biological relevance was provided by ex vivo analyzes of samples from liver-kidney cotransplanted patients who had high HLA-G5 serum levels and no graft rejection. We showed that addition of HLA-G5-containing sera from these patients inhibited T cell alloresponses and that serum HLA-G5 was responsible for this inhibition. Notably, PBMC from transplanted patients exposed to high levels of circulating HLA-G5 did not respond to allostimulation and inhibited alloreactivity of other T cells. These results demonstrate that HLA-G5-mediated tolerance involves the induction of immunosuppressive T cells. These findings provide evidence supporting the tolerogenic properties of HLA-G and emphasize its potential application as a relevant therapeutic candidate capable of limiting allograft rejection.
Three-Dimensional Digital Image Processing And Reconstruction Of Granular Particles (2005)

This thesis presents a method for digitization of the two-dimensional shape of granular particles by means of photo microscopy and image processing techniques implemented using a software package from Media Cybernetics, Inc: Image-Pro Plus 5.1 and the add-ins Scope-Pro 5.0, SharpStack 5.0 and 3D Constructor 5.0. With the use of these tools, it was possible to implement an efficient semi-automated routine that allows the digitization of large numbers of two-dimensional silhouettes of particles in minimum time, without endangering the quality and reliability of the shapes obtained. Different sample preparation techniques, illumination systems, deconvolution algorithms, mathematical functions, filtering techniques and programming commands are brought into play in order to transform the shape of the two-dimensional projection of particles (captured as a set of successive images acquired at different planes of focus) into a binary format (black and white). At the same time, measurements and statistical information such as grain size distribution can be analyzed from the shapes obtained for a particular granular soil. This information also includes but it is not limited to perimeter, area, diameter (minimum, maximum and mean), caliper (longest, smallest and mean), roundness, aspect ratio and fractal dimension. Results are presented for several sands collected from different places around the world. In addition, some alternatives for three-dimensional shape reconstruction such as X-ray nano tomography and serial sectioning are discussed.
Activating Transcription Factor 3 Is Integral to the Eukaryotic Initiation Factor 2 Kinase Stress Response (2004)

In response to environmental stress, cells induce a program of gene expression designed to remedy cellular damage or, alternatively, induce apoptosis. In this report, we explore the role of a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. We find that expression of activating transcription factor 3 (ATF3), a member of the ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in response to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively. Increased expression of ATF3 protein occurs early in response to stress by a mechanism requiring the related bZIP transcriptional regulator ATF4. ATF3 contributes to induction of the CHOP transcriptional factor in response to amino acid starvation, and loss of ATF3 function significantly lowers stress-induced expression of GADD34, an eIF2 protein phosphatase regulatory subunit implicated in feedback control of the eIF2 kinase stress response. Overexpression of ATF3 in mouse embryo fibroblasts partially bypasses the requirement for PEK for induction of GADD34 in response to ER stress, further supporting the idea that ATF3 functions directly or indirectly as a transcriptional activator of genes targeted by the eIF2 kinase stress pathway. These results indicate that ATF3 has an integral role in the coordinate gene expression induced by eIF2 kinases. Given that ATF3 is induced by a very large number of environmental insults, this study supports involvement of eIF2 kinases in the coordination of gene expression in response to a more diverse set of stress conditions than previously proposed.