gebhart/patrepeval huggingface dataset:
Esterification of Low Density Lipoprotein Cholesterol in Human Fibroblasts and Its Absence in Homozygous Familial Hypercholesterolemia (1974)

A new mechanism is described for the cellular esterification of cholesterol derived from extra-cellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30- to 40-fold increase in the rate of incorporation of either [(14)C]acetate or [(14)C]oleate into the fatty acid fraction of cholesteryl [(14)C]esters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterfication process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells.
The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation (2003)

This review outlines the mechanisms underlying the interaction between the nervous and immune systems of the host in response to an immune challenge. The main focus is the cholinergic anti-inflammatory pathway, which we recently described as a novel function of the efferent vagus nerve. This pathway plays a critical role in controlling the inflammatory response through interaction with peripheral a7 subunit-containing nicotinic acetylcholine receptors expressed on macrophages. We describe the modulation of systemic and local inflammation by the cholinergic anti-inflammatory pathway and its function as an interface between the brain and the immune system. The clinical implications of this novel mechanism also are discussed.
Hypermethylation ofCXCR4Promoter in CD34+ Cells from Patients with Primary Myelofibrosis (2008)

Constitutive mobilization of CD34(+) cells in patients with primary myelofibrosis (PMF) has been attributed to proteolytic disruption of the CXCR4/SDF-1 axis and reduced CXCR4 expression. We document here that the number of circulating CD34(+)/CXCR4(+) cells in PMF patients, as well as the cellular CXCR4 expression, was directly related to CXCR4 mRNA level and that reduced CXCR4 mRNA level was not due to SDF-1-induced downregulation. To address whether epigenetic regulation contributes to defective CXCR4 expression, we studied the methylation status of the CXCR4 promoter using methylation-specific polymerase chain reaction and methylation-specific sequencing in the JAK2V617F-positive HEL cell line and in CD34(+) cells. We found that CD34(+) cells from PMF patients, unlike those from normal subjects, presented hypermethylation of CXCR4 promoter CpG island 1. Following incubation with the demethylating agent 5-Aza-2'-deoxycytidine (5-AzaD), the percentage of PMF CD34(+) cells expressing CXCR4 increased 3-10 times, whereas CXCR4 mRNA level increased approximately 4 times. 5-AzaD-treated PMF CD34(+) cells displayed almost complete reversal of CpG1 island 1 hypermethylation and showed enhanced migration in vitro in response to SDF-1. These data point to abnormal methylation of the CXCR4 promoter as a mechanism contributing to constitutive migration of CD34(+) cells in PMF. Disclosure of potential conflicts of interest is found at the end of this article.
Mutational analysis of domain antibodies reveals aggregation hotspots within and near the complementarity determining regions (2011)

High-affinity antibodies are critical for numerous diagnostic and therapeutic applications, yet their utility is limited by their variable propensity to aggregate either at low concentrations for antibody fragments or high concentrations for full-length antibodies. Therefore, determining the sequence and structural features that differentiate aggregation-resistant antibodies from aggregation-prone ones is critical to improving their activity. We have investigated the molecular origins of antibody aggregation for human V(H) domain antibodies that differ only in the sequence of the loops containing their complementarity determining regions (CDRs), yet such antibodies possess dramatically different aggregation propensities in a manner not correlated with their conformational stabilities. We find the propensity of these antibodies to aggregate after being transiently unfolded is not a distributed property of the CDR loops, but can be localized to aggregation hotspots within and near the first CDR (CDR1). Moreover, we have identified a triad of charged mutations within CDR1 and a single charged mutation adjacent to CDR1 that endow the poorly soluble variant with the desirable biophysical properties of the aggregation-resistant antibody. Importantly, we find that several other charged mutations in CDR1, non-CDR loops and the antibody scaffold are incapable of preventing aggregation. We expect that our identification of aggregation hotspots that govern antibody aggregation within and proximal to CDR loops will guide the design and selection of antibodies that not only possess high affinity and conformational stability, but also extreme resistance to aggregation.
Role of MHC class I expression and CD8+ T cells in the evolution of iodine-induced thyroiditis in NOD-H2h4 and NOD mice (2000)

Dietary iodine has long been known to influence the development of human autoimmune thyroid disease. In nonobese diabetic (NOD) and NOD-H2(h4) mice elevated dietary iodine has been shown to induce autoimmune thyroid disease. Immune responses to thyroid antigens can be detected in these mouse strains, including T cell responses in the NOD-H2(h4) mouse to thyroid peroxidase. Cell transfer studies and antibody depletion experiments reveal a requirement for both CD4(+) T cells and CD8(+) T cells in the development of thyroid autoimmunity. Histological analyses of the thyroids show that following 1 week of iodine administration MHC class I expression is elevated on thyroid follicular cells and CD4(+) and CD8(+) T cells have begun to infiltrate the gland. Although MHC class II expression on thyroid epithelial cells was also elevated, the tempo of expression was slower and the extent of expression was far less than that for MHC class I. Depletion of CD8(+) T cells at early stages of disease induction inhibited not only thyroid infiltration and autoantibody production but also reduced the levels of MHC expression in the thyroid, suggesting that cytokine production by infiltrating lymphocytes was responsible for the increased MHC expression.
Molecular Diversity of the Human T-Gamma Constant Region Genes (1987)

The human T cell antigen-receptor gamma chain, which is expressed on the surface of a subpopulation of CD3+ T lymphocytes, exhibits size polymorphism and varies in its ability to form disulfide bonds with a second polypeptide. Analysis of both genomic and complementary DNA clones encoding the human gamma polypeptide shows differences in lengths of the coding portions of the two constant region genes, C gamma 1 and C gamma 2. A single second-exon segment is always present in the C gamma 1 gene. C gamma 2 alleles containing either duplicated or triplicated second-exon segments are present in the normal human population and are expressed as messenger RNAs. Furthermore, a cysteine residue, encoded by the second exon of C gamma 1 and probably involved in interchain disulfide bridging, is absent in all C gamma 2 second-exon segments. These differences between C gamma 1 and the two alleles of C gamma 2 may explain the variability in molecular weight and disulfide bonding of gamma molecules expressed in different cells.
Antisense oligonucleotides selected by hybridisation to scanning arrays are effective reagents in vivo (2001)

Transcripts representing mRNAs of three Xenopus cyclins, B1, B4 and B5, were hybridised to arrays of oligonucleotides scanning the first 120 nt of the coding region to assess the ability of the immobilised oligonucleotides to form heteroduplexes with their targets. Oligonucleotides that produced high heteroduplex yield and others that showed little annealing were assayed for their effect on translation of endogenous cyclin mRNAs in Xenopus egg extracts and their ability to promote cleavage of cyclin mRNAs in oocytes by RNase H. Excellent correlation was found between antisense potency and affinity of oligonucleotides for the cyclin transcripts as measured by the array, despite the complexity of the cellular environment.
Studies on Improving PP Fiber Reinforced Concrete (2011)

Grafting method was used to modify polypropylene (PP) fiber to enhance the fiber reinforced concrete in this study. Polyacrylamide (PAM) was grafted onto PP surface by UV radiation using benzophenone (BP) as a photoinitiator. The microstructure of PP, and the interaction force between PP and the polar probe were observed with an atomic force microscopy (AFM). Experimental results showed that the roughness of PAM-grafted PP surface decreased significantly in comparison with that of the untreated PP surface. In addition, instead of smooth force curve as that of the untreated PP, the interaction between the probe and PAM-grafted PP surface appeared an oscillation. The above results gave the evidences that PAM had been successfully grafted onto the PP surface as discussed . The high hydrophilic property of PAM modifies the surface property of PP fiber and strengthens PP fiber reinforced concrete.
Microcirculation within grooved substrates regulates cell positioning and cell docking inside microfluidic channels (2008)

Immobilization of cells inside microfluidic devices is a promising approach for enabling studies related to drug screening and cell biology. Despite extensive studies in using grooved substrates for immobilizing cells inside channels, a systematic study of the effects of various parameters that influence cell docking and retention within grooved substrates has not been performed. We demonstrate using computational simulations that the fluid dynamic environment within microgrooves significantly varies with groove width, generating microcirculation areas in smaller microgrooves. Wall shear stress simulation predicted that shear stresses were in the opposite direction in smaller grooves (25 and 50 microm wide) in comparison to those in wider grooves (75 and 100 microm wide). To validate the simulations, cells were seeded within microfluidic devices, where microgrooves of different widths were aligned perpendicularly to the direction of the flow. Experimental results showed that, as predicted, the inversion of the local direction of shear stress within the smaller grooves resulted in alignment of cells on two opposite sides of the grooves under the same flow conditions. Also, the amplitude of shear stress within microgrooved channels significantly influenced cell retainment in the channels. Therefore, our studies suggest that microscale shear stresses greatly influence cellular docking, immobilization, and retention in fluidic systems and should be considered for the design of cell-based microdevices.
Platelet-activating factor stimulates metabolism of phosphoinositides via phospholipase A2 in primary cultured rat hepatocytes. (1987)

Addition of platelet-activating factor (PAF) to cells doubly labeled with [14C]glycerol plus [3H]arachidonic acid resulted in a transient decrease of [14C]glycerol-labeled phosphatidylinositol (PI) and a transient increase of [14C]glycerol-labeled lysophosphatidylinositol (LPI). [3H]Arachidonate-labeled PI, on the other hand, decreased in a time-dependent manner. The radioactivity in phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, and phosphatidylserine did not change significantly. The 3H/14C ratio decreased in PI in a time-dependent manner, suggesting the involvement of a phospholipase A2 activity. Although PAF also induced a gradual increase of diacylglycerol (DG), the increase of [14C]glycerol-labeled DG paralleled the loss of triacyl [14C]glycerol and the 3H/14C ratio of DG was 16 times smaller than that of PI. Thus, DG seemed not to be derived from PI. In myo- [3H]inositol-prelabeled cells, PAF induced a transient decrease of [3H]phosphatidylinositol-4,5-bis-phosphate (TPI) and [3H]phosphatidylinositol-4-phosphate (DPI) at 1 min. PAF stimulation of cultured hepatocytes prelabeled with 32Pi induced a transient decrease of [32P]polyphosphoinositides at 20 sec to 1 min. [32P]LPI appeared within 10 sec after stimulation and paralleled the loss of [32P]PI. [3H]Inositol triphosphate, [3H]inositol diphosphate, and [3H]inositol phosphate, which increased in a time-dependent manner upon stimulation with adrenaline, did not accumulate with the stimulation due to PAF. These observations indicate that PAF causes degradation of inositol phospholipids via phospholipase A2 and induces a subsequent resynthesis of these phospholipids.
Unique insertion sequence and pattern of CD4 expression in variants selected with immunotoxins from human immunodeficiency virus type 1-infected T cells (1995)

To study the variability of human immunodeficiency virus type 1 (HIV-1), we used immunotoxins to select for variants within a population of H9 cells persistently infected with a molecular clone of HIV-1 designated NL4-3. Chimeric immunotoxin CD4-PE40 (a chimeric fusion protein consisting of the amino-terminal two domains of CD4 and the carboxy-terminal domains of Pseudomonas exotoxin A) was used to select for cells lacking cell surface expression of HIV Env (envelope proteins gp160, gp120, and gp41). The cells described here (A1, A7, C9, and E9) fail to express HIV proteins because they have markedly diminished transcription of the integrated provirus (A1, A7, and E9) or no HIV provirus (C9). Analysis demonstrated that two different cloned variants, A1 and E9, contain the complementary sequence of tRNA(3Lys) (45 bp) inserted 3' to the primer-binding site, following by a 169-bp deletion through the start of the gag gene. No HIV mRNA was detected by Northern (RNA) blotting, but PCR demonstrated the presence of the viral message. These variants were found very infrequently in the unselected H9/NL4-3 cell population, and they contained proviruses distinct from that found in the dominant population. In addition, all of these variants had similar patterns of CD4 surface expression that allowed them to escape reinfection within the tissue culture. The data are discussed with regard to mechanisms and errors of HIV reverse transcription, as well as the evolution of mutants within a population of persistently infected cells.
Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3 (1999)

Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer.
Stress Genes: An Introductory Overview (1997)

Molecular sequence data, made available in the last 15 years or so, have led to the classification of living cells into three phylogenetic domains: Bacteria, Archaea, and Eucarya. All the organisms that have been tested belonging to either domain were capable of mounting a stress response with essentially the same characteristics, regardless of the stressor. The protagonists in the cell's stress response are the stress genes and their protein products. Some of the latter are molecular chaperones. Under physiological conditions, these chaperones aid other cellular proteins to fold properly and achieve a native -functional- configuration, and to translocate from the place of synthesis to the cell's locale in which they will operate. In a stressed cell, the stress proteins that are chaperones protect other molecules from denaturation and help those partially damaged to regain a functional configuration. Thus, cell death is avoided and recovery is enhanced. The study of stress genes and proteins has progressed considerably in organisms belonging to the domains Bacteria and Eucarya. Less is known about the archaeal stress genes. Here, research with an organism from the Archaea is discussed, focusing on the stress genes of the hsp70 (dnaK) locus. Future perspectives for basic and applied research within the health sciences and biotechnology industries are presented.
Effect of structural variations in cholesteryl-conjugated oligonucleotides on inhibitory activity toward HIV-1 (1991)

A number of oligonucleotide analogues containing internucleoside phosphorothioate linkages and a covalently attached cholesteryl residue was synthesized and tested for activity against HIV-1 in cultures of Molt3 cells. Structural features important for high antiviral activity are the presence of a cholesteryl moiety, a run of terminal phosphorothioate groups, and the presence of nucleoside residues. An increase in length of the tether between cholesteryl and phosphorus from six to 14 atoms has no significant effect on antiviral activity, and up to one-half of the internucleoside links in a cholesteryl-conjugated phosphorothioate oligomer and one-third of the internucleoside links in a nonconjugated phosphorothioate can be replaced with phosphodiester links without much change in antiviral activity. However, replacement of nucleoside units in the oligomers by a simple analogue (-OCH2CH2CH2O-) yields inactive or very weakly active compounds, even in the presence of a cholesteryl group. Dose-response patterns for assays in which cholesteryl-conjugated oligomers are added to test cells either simultaneously or subsequently to viral infection are similar for homooligomer derivatives and for oligomers containing "antisense" sequences, suggesting a similarity in mode of action for the two classes of oligomers in this system.
A Logit Analysis of Car Ownership in Hong Kong Based on Stated Intention Information (2000)

In this paper, disaggregate car ownership choice models are developedfor Hong Kong using the results of a survey with both revealed preference and stated preference questions. The car ownership choice (Iogit-type) models are calibrated to Investigate the effects of economic chonges andfiscal measures on the choice of car ownership. In the study, households are classified into non-car owning and car owning groups. These separoted groups arefurther sub-divided into those respondents who have no plans to bUy cars and those who plan to bUy cars. The revealed preference survey results were mainly used to collect the relevant data Of the respondents. The stated preference results revealed that monthly household Income, car purchose cost, annuai licence fee, monthly home-end parking and monthly car usage costs are the keyfactors Of pertaining to car ownership in Hong Kong.
Fast out-of-order processor simulation using memoization (1998)

Our new out-of-order processor simulatol; FastSim, uses two innovations to speed up simulation 8--15 times (vs. Wisconsin SimpleScalar) with no loss in simulation accuracy. First, FastSim uses speculative direct-execution to accelerate the functional emulation of speculatively executed program code. Second, it uses a variation on memoization---a well-known technique in programming language implementation---to cache microarchitecture states and the resulting simulator actions, and then "fast forwards" the simulation the next time a cached state is reached. Fast-forwarding accelerates simulation by an order of magnitude, while producing exactly the same, cycle-accurate result as conventional simulation.
Biofuel Cells Select for Microbial Consortia That Self-Mediate Electron Transfer (2004)

Microbial fuel cells hold great promise as a sustainable biotechnological solution to future energy needs. Current efforts to improve the efficiency of such fuel cells are limited by the lack of knowledge about the microbial ecology of these systems. The purposes of this study were (i) to elucidate whether a bacterial community, either suspended or attached to an electrode, can evolve in a microbial fuel cell to bring about higher power output, and (ii) to identify species responsible for the electricity generation. Enrichment by repeated transfer of a bacterial consortium harvested from the anode compartment of a biofuel cell in which glucose was used increased the output from an initial level of 0.6 W m(-2) of electrode surface to a maximal level of 4.31 W m(-2) (664 mV, 30.9 mA) when plain graphite electrodes were used. This result was obtained with an average loading rate of 1 g of glucose liter(-1) day(-1) and corresponded to 81% efficiency for electron transfer from glucose to electricity. Cyclic voltammetry indicated that the enhanced microbial consortium had either membrane-bound or excreted redox components that were not initially detected in the community. Dominant species of the enhanced culture were identified by denaturing gradient gel electrophoresis and culturing. The community consisted mainly of facultative anaerobic bacteria, such as Alcaligenes faecalis and Enterococcus gallinarum, which are capable of hydrogen production. Pseudomonas aeruginosa and other Pseudomonas species were also isolated. For several isolates, electrochemical activity was mainly due to excreted redox mediators, and one of these mediators, pyocyanin produced by P. aeruginosa, could be characterized. Overall, the enrichment procedure, irrespective of whether only attached or suspended bacteria were examined, selected for organisms capable of mediating the electron transfer either by direct bacterial transfer or by excretion of redox components.
Factors Affecting Purification of CD34 + Peripheral Blood Stem Cells Using the Baxter Isolex 300i (2002)

A total of 201 patients with breast cancer, ovarian cancer, or hematological malignancies underwent mobilization of peripheral blood stem cells (PBSC) using chemotherapy and granulocyte-colony stimulating factor (G-CSF). Stem cell products were collected using the Baxter CS3000 pheresis machine. The Baxter Isolex 300i was used to perform 240 CD34(+) cell separations on the apheresis products. Factors affecting yield and purity of the CD34(+) cells were analyzed. Overall yield was 55% and overall purity was 91.7%. T cell contamination was limited to 0.43% of total cells. Variables including red blood cells (RBC) concentration, platelet concentration, CD34(+) cell concentration, total WBCs selected, and time until processing had little effect on yields and purities. Installation of version 2.5 of the software in the Isolex 300i showed a modest improvement in yield and purity. Patients were reinfused with the cryopreserved CD34(+) selected cells following high-dose chemotherapy. No infusion-related side effects were noted. Analysis of engraftment data using the CD34(+)-selected cells revealed an increased risk of delayed or failed platelet engraftment when <5.0 x 10(6) CD34(+) cells per kilogram were transplanted. The Baxter Isolex 300i provides reproducible CD34(+) cell purification over a wide range of starting conditions. To provide prompt engraftment, >5.0 x 10(6) CD34(+) cells per kilogram should be infused for transplantation.
Role of emerging respiratory viruses in children with severe acute wheezing (2010)

The most prevalent viruses found in severe acute wheezing episodes were RSV and rhinovirus not only in childhood, but also in infancy. However, other emerging viruses such as HBoV and metapneumovirus also play an important role in wheezing episodes.