gebhart/patrepeval huggingface dataset:
Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. (1992)

Although it is a well-known fact that hemodynamic load is a major determinant of cardiac muscle mass and its phenotype, little is known as to how mechanical load is converted into intracellular signals of gene regulation. To address this question, we characterized the stretch-induced adaptation of cultured neonatal cardiocytes grown on a stretchable substrate in a serum-free medium. Static stretch (20%) of the cells was applied without cell injury. Stretch caused hypertrophy in myocytes and hyperplasia in non-myocytes. Stretch caused an induction of immediate-early genes such as c-fos, c-jun, c-myc, JE, and Egr-1, but not Hsp70. Immunostaining showed that the stretch-induced Fos protein localized in the nucleus of both myocytes and non-myocytes. Nuclear extracts from stretched myocytes contained DNA binding activity to the AP-1 and Egr-1 consensus sequences. In myocytes, the induction of immediate-early genes was followed by expression of "fetal" genes such as skeletal alpha-actin, atrial natriuretic factor, and beta-myosin heavy chain. DNA transfection experiments showed that the "stretch-response element" of the c-fos gene promoter is present within 356 base pairs of the 5'-flanking region, whereas that of the atrial natriuretic factor and the beta-myosin heavy chain genes is probably located outside of 3412 and 628 base pairs of the 5'-flanking region, respectively. These results demonstrate that the phenotype of stretched cardiocytes in this in vitro model closely mimics that of hemodynamic load-induced hypertrophy in vivo. This model seems to be a suitable system with which to dissect the molecular mechanisms of load-induced hypertrophy of cardiac muscle.
The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. (1988)

Study of very closely linked DNA variants at various loci has frequently shown linkage disequilibrium. We studied three closely linked RFLPs at the apolipoprotein AI-CIII locus. Two variants detected by MspI and SstI were in strong linkage disequilibrium; but when conventional statistical tests were used, a third variant (PstI), located between the MspI and SstI markers, appeared to be in linkage equilibrium with these two "outside" markers. Similar discrepancies from the expected monotone relationship between physical distance and linkage disequilibrium have been reported by others. To investigate these discrepancies, the power to detect linkage disequilibrium was calculated. It could be shown that, for the gene frequencies encountered, very large sample sizes would be required to demonstrate negative (i.e., repulsion-phase) linkage disequilibrium. Such numbers are usually very difficult to attain in human studies. Failure to demonstrate linkage disequilibrium by conventional methods therefore does not imply its absence. Appropriate nomograms and tables are provided.
Pattern Transfer Characteristics of Transparent Phase Shifting Mask (1991)

Phase shifting technologies achieve significant improvement in both resolution and depth of focus (DOF). We have proposed a “transparent-type” phase shifting mask which has a simple structure (no Cr layer) that considerably improves the resolution limit of optical lithography. 1) In this paper, we describe in detail pattern transfer characteristics of the transparent phase shifting mask with i-line steppers. The effects of numerical aperture (NA) and coherence factor (σ) on the resolution capability and DOF were investigated using simulations and experiments. Patterns are printed using i-line steppers with a numerical aperture (NA) of 0.45 and 0.65. A pattern of 0.23 µm lines and spaces is resolved with a 0.45 NA i-line stepper. DOF for 0.25-µm features is found to be in the 1.5-µm range. Well-resolved 0.18-µm lines and spaces are obtained with a 0.65-NA i-line stepper. Transparent phase shifting mask technologies extend the resolution limit of i-line lithography to the resist features below 0.2 µm.
IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes (2004)

Adult multipotent neural progenitor cells can differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.
Iminium carbonic acid derivative salts. XI. Synthesis of N,S‐containing heterobicycles from N‐protected 2‐methylthio‐1,3‐thiazinium and 2‐methylthiothiazoüum salts. Part 3. Reaction of N‐protected 2‐methylthio‐1,3‐thiazinium and 2‐methylthiothiazolium salts with 3‐amino‐2‐cyano‐3‐arylacrylonitriles (1996)

Abstract N ‐Boc‐protected 2‐memylthio‐1,3‐thiazinium 1 and 2‐methylthiothiazolium iodides 2, 3 obtained from the corresponding 3,4,5,6‐tetrahydro‐2 H ‐1,3‐thiazine‐2‐thiones and thiazolidine‐2‐thiones by the action of methyl iodide were reacted with 3‐armno‐2‐cyano‐3‐arylacrylonitriles forming the cyclic isothioureas 5–7 . The protection group was removed with trifluoroacetic acid whereupon the desired cyclisation to 3,4‐dihydro‐2 H ,6 H ‐pyrimido[2,1‐ b ][1,3]thiazines 8a‐c, 8a′‐c′ and thiazolo[3,2‐ b ]pyrimidines 9a,b, 9a′,b′, 10a,b took place.
Progressive cross-linking of fibrin gamma chains increases resistance to fibrinolysis. (1994)

In the presence of plasma transglutaminase (factor XIIIa) fibrin first undergoes intermolecular covalent cross-linking between its gamma chains to create gamma dimers followed by slower cross-linking among its alpha chains to form alpha polymers. Progressive cross-linking of gamma chain dimers occurs at the slowest rate, resulting in gamma trimers and gamma tetramers ("gamma multimers"). Most studies indicate that cross-linked fibrin clots become resistant to fibrinolysis, but the basis for this event is not clear. In this study, we explored the role of gamma chain multimerization compared with alpha polymerization as causal factors in time-dependent development of resistance to fibrinolysis. Fibrin clots prepared from native (intact) fibrinogen were incubated for up to 120 h at near physiological ionic strength and a factor XIIIa level approximating that in plasma. These clots were lysed by plasmin at rates that were inversely proportional to the level of gamma multimers, which increased progressively with the time of incubation. In contrast, fibrin cross-linked at high ionic strength (a condition under which only gamma dimers and alpha polymers form) or fibrin formed in the absence of factor XIII showed no time-dependent decrease in lysis rates. Fibrin cross-linked for a fixed time period with increasing amounts of factor XIIIa contained gamma multimer levels that were proportional to the factor XIIIa concentration and lysed at rates that were inversely proportional to the gamma multimer level. Furthermore, cross-linked fibrin formed from fibrinogen fraction I-9, which has limited potential for alpha polymerization, showed the same reduction in the lysis rate as native cross-linked fibrin. These findings indicate that development of resistance to fibrinolysis of cross-linked fibrin is not measurably dependent upon gamma dimer or alpha polymer formation but develops solely as a function of gamma multimerization.
Harmonisation of short-term in vitro culture for the expansion of antigen-specific CD8+ T cells with detection by ELISPOT and HLA-multimer staining (2014)

Ex vivo ELISPOT and multimer staining are well-established tests for the assessment of antigen-specific T cells. Many laboratories are now using a period of in vitro stimulation (IVS) to enhance detection. Here, we report the findings of a multi-centre panel organised by the Association for Cancer Immunotherapy Immunoguiding Program to investigate the impact of IVS protocols on the detection of antigen-specific T cells of varying ex vivo frequency. Five centres performed ELISPOT and multimer staining on centrally prepared PBMCs from 3 donors, both ex vivo and following IVS. A harmonised IVS protocol was designed based on the best-performing protocol(s), which was then evaluated in a second phase on 2 donors by 6 centres. All centres were able to reliably detect antigen-specific T cells of high/intermediate frequency both ex vivo (Phase I) and post-IVS (Phase I and II). The highest frequencies of antigen-specific T cells ex vivo were mirrored in the frequencies following IVS and in the detection rates. However, antigen-specific T cells of a low/undetectable frequency ex vivo were not reproducibly detected post-IVS. Harmonisation of the IVS protocol reduced the inter-laboratory variation observed for ELISPOT and multimer analyses by approximately 20 %. We further demonstrate that results from ELISPOT and multimer staining correlated after (P < 0.0001 and R (2) = 0.5113), but not before IVS. In summary, IVS was shown to be a reproducible method that benefitted from method harmonisation.
Cultured astrocytes express toll‐like receptors for bacterial products (2003)

It has become apparent that astrocytes may be important contributors to inflammatory immune responses within the brain in response to microbial challenges. To date, the mechanisms that underlie activation of this major glial cell type by such challenges have not been investigated. In the present study, we present evidence for members of a recently discovered family of receptors for highly conserved microbial components, the Toll-like receptors (TLRs), in isolated cultures of primary murine astrocytes. We describe the low-level constitutive expression of messenger RNA-encoding TLR2, TLR4, TLR5, and TLR9 in resting cultures of these cells. Importantly, the level of expression of messenger RNA for each of these receptors is markedly elevated following exposure to specific bacteria-derived ligands for these receptors. The functional expression of these receptor proteins is further supported by the ability of known ligands for each TLR to induce both message expression and protein secretion of the proinflammatory cytokine, interleukin-6. In addition, the recent availability of antibodies to TLR2 and TLR4 has enabled us to demonstrate directly the presence of these receptors on astrocytes by Western blot and immunofluorescence analysis, respectively. Furthermore, we have confirmed the sensitivity of such receptor expression to ligand stimulation. The present demonstration of Toll-like microbial pattern-recognition receptors on primary astrocytes provides a mechanistic link between bacterial challenge and inflammatory immune responses that may be an important component of the pathologies of bacterially induced inflammatory CNS disorders.
Ranking Risk Inequities (1995)

Comparing recent data on age-adjusted death rates for blacks and whites, the authors attempt to clarify how ranking risks based on degree of inequity might differ from ranking them according to frequency of health impairments in the overall population. They also identify problems in choosing a method for ranking causes of death that incorporates both frequency and equity and suggest that agreement will be difficult to reach.
Passionate Apologists: Haiti and the Unitea States in the Post-Occupation Years (1997)

Even after the end of the American Occupation in 1934 Haiti continued to be visible in terms of antithetical extremes — land of promise or land of savagery, where the natives were nobly or ignobly black. Either uncritically idealized or blindly denigrated, Haiti had become the stock in trade for cheap sensationalist fiction, such as Theodore Roscoe's Murder on the Way (1935) — a murder mystery complete with voodoo drums and malevolent zombies. However, at the end of the decade, Haitian-American relations entered a new phase. Politically and culturally a new 'order of things' was established, as Americans, like Plato's Cave dwellers, bravely turned away from what appeared to be Haiti's disturbing strangeness and tried to face the reality of Haiti.KeywordsAmerican OccupationFolk ReligionFolk CultureBlack NationalismAmerican ImperialismThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Macromol. Mater. Eng. 9/2016 (2016)

Front Cover: Polymer-Ag honeycomb films with regular morphology, indicated in the upper image, are fabricated via metal complexation induced phase separation at the air/water interface employing a functionalized graft copolymer as illustrated in the lower image. Pyrolysis of the film gives a translucent Ag honeycomb film potentially applicable for nanoelectronic applications. Further details can be found in the article by Sajjad Husain Mir and Bungo Ochiai* on page 1026.
Effects of low‐intensity laser therapy on the orthodontic movement velocity of human teeth: A preliminary study (2004)

Our findings suggest that LILT does accelerate human teeth movement and could therefore considerably shorten the whole treatment duration.
Old Dogs and New Tricks, Proteases, Inhibitors, and Cell Migration (2003)

A new model for the actions of plasminogen activator inhibitors (PAIs) on cell migration may resolve the conflicting research data on these proteins in metastasis and angiogenesis. Results from two groups reveal a role for PAI-1 in promoting cycles of attachment and detachment of the cell from the extracellular matrix that is independent of its role as an enzymatic inhibitor of urokinase-type plasminogen activator (uPA). Through the formation of a complex of integrins, uPA and its receptor, and the clearance receptors of the low-density lipoprotein family, PAI-1 may promote endocytosis and recycling of these adhesion-controlling proteins, allowing cycling of cellular attachment and detachment.
Structure-based design of a selective heparanase inhibitor as an antimetastatic agent (2004)

Heparanase is an endo-beta-D-glucuronidase that degrades heparan sulfate glycosaminoglycans in the extracellular matrix and the basement membrane and is well known to be involved in tumor cell invasion and angiogenesis. We have focused on heparanase as a target for antitumor agents, especially antimetastatic agents. (R)-3-hexadecanoyl-5-hydroxymethyltetronic acid (RK-682) was found to display an inhibitory activity against heparanase in our screening of natural sources. Because RK-682 has been reported to show inhibitory activities against several enzymes, we have tried to develop selective heparanase inhibitors using the method of rational drug design. Based on the structure of the heparanase/RK-682 complex, we speculated that selective inhibitory activity against heparanase could be acquired by arylalkylation, namely, by benzylation of the 4-position of RK-682. Among the rationally designed 4-alkyl-RK-682 derivatives, 4-benzyl-RK-682 has been found to possess a selective inhibitory activity for heparanase (IC50 for heparanase, 17 micromol/L; IC50 for other enzymes, >100 micromol/L). 4-Benzyl-RK-682 also inhibited the invasion and migration of human fibrosarcoma HT1080 cells (IC50 for invasion, 1.5 micromol/L; IC50 for migration, 3.0 micromol/L). On the other hand, RK-682 had no inhibitory effect on the invasion and migration of HT1080 cells at doses of up to 100 micromol/L.
Purification and properties of mitochondrial uracil-DNA glycosylase from rat liver (1988)

Uracil-DNA glycosylase from rat liver mitochondria, an inner membrane protein, has been purified approximately 575,000-fold to apparent homogeneity. During purification two distinct activity peaks, designated form I and form II, were resolved by phosphocellulose chromatography. Form I constituted approximately 85% while form II was approximately 15% of the total activity; no interconversion between the forms was observed. The major form was purified as a basic protein with an isoelectric point of 10.3. This enzyme consists of a single polypeptide with an apparent Mr of 24,000 as determined by recovering glycosylase activity from a sodium dodecyl sulfate-polyacrylamide gel. A native Mr of 29,000 was determined by glycerol gradient sedimentation. The purified enzyme had no detectable exonuclease, apurinic/apyrimidinic endonuclease, DNA polymerase, or hydroxymethyluracil-DNA glycosylase activity. A 2-fold preference for single-stranded uracil-DNA over a duplex substrate was observed. The apparent Km for uracil residues in DNA was 1.1 microM, and the turnover number is about 1000 uracil residues released per minute. Both free uracil and apyrimidinic sites inhibited glycosylase activity with Ki values of approximately 600 microM and 1.2 microM, respectively. Other uracil analogues including 5-(hydroxymethyl)uracil, 5-fluorouracil, 5-aminouracil, 6-azauracil, and 2-thiouracil or analogues of apyrimidinic sites such as deoxyribose and deoxyribose 5'-phosphate did not inhibit activity. Both form I and form II had virtually identical kinetic properties, and the catalytic fingerprints (specificity for uracil residues located in a defined nucleotide sequence) obtained on a 152-nucleotide restriction fragment of M13mp2 uracil-DNA were almost identical. These properties differentiated the mitochondrial enzyme from that of the uracil-DNA glycosylase purified from nuclei of the same source.
Optimizing routability in large-scale mixed-size placement (2013)

One of the necessary requirements for the placement process is that it should be capable of generating routable solutions. This paper describes a simple but effective method leading to the reduction of the routing congestion and the final routed wirelength for large-scale mixed-size designs. In order to reduce routing congestion and improve routability, we propose blocking narrow regions on the chip. We also propose dummy-cell insertion inside regions characterized by reduced fixed-macro density. Our placer consists of three major components: (i) narrow channel reduction by performing neighbor-based fixed-macro inflation; (ii) dummy-cell insertion inside large regions with reduced fixed-macro density; and (iii) pre-placement inflation by detecting tangled logic structures in the netlist and minimizing the maximum pin density. We evaluated the quality of our placer using the newly released DAC 2012 routability-driven placement contest designs and we compared our results to the top four teams that participated in the placement contest. The experimental results reveal that our placer improves the routability of the DAC 2012 placement contest designs and effectively reduces the routing congestion.
Debris studies for the tin-based droplet laser-plasma EUV source (2004)

We are developing a mass-limited, laser plasma target concept that utilizes excited state transitions in tin ions as the source of 13.5 nm radiation, offering in-band conversion efficiencies greater than 1%. The ultimate objective of this EUV source strategy is the utilization of a target that is completely ionized by the laser. To determine the viability of this source for EUVL, we are making extensive measurements of the debris emanating from the target. Here we report on some of these measurements. Also under investigation are various methods of debris mitigation. We have previously shown the effectiveness of electrostatic fields for repelling ions from mass-limited targets, demonstrating improvements in multilayer mirror lifetimes in excess of an order of magnitude, positioning water droplet targets within reach of the EUVL roadmap requirements. Our investigation of debris utilizes various diagnostic techniques including ion collection, ion sputtering and witness-plate capture of particulate debris, and extensive post-mortem microscopic materials analysis.
Transferable Force Field for Carbon Dioxide Adsorption in Zeolites (2009)

We have developed a complete force field that accurately reproduces the adsorption properties of carbon dioxide in a variety of zeolites with different topologies and compositions. The force field parameters were obtained by fitting to our own experimental data and validated with available data taken from the literature. The novelty of this force field is that it is fully transferable between different zeolite framework types, and therefore, it is applicable to all possible Si/Al ratios (with sodium as extra-framework cation) and for the first time affording the prediction of topology-specific and chemical composition-specific adsorption properties.
Loratadine: A Nonsedating Antihistamine with Once-Daily Dosing (1989)

Loratadine is an addition to the class of nonsedating antihistamines which includes terfenadine, astemizole, and acrivastine. Loratadine is chemically related to the tricyclic antidepressants. Animal data have shown that insignificant amounts of loratadine enter the brain, and it has a threefold greater affinity for peripheral as compared with central histamine 1-receptors. Loratadine has one main metabolite, descarbethoxyloratadine, which is four times more active than the parent drug. Loratadine reaches peak plasma concentration in 1-2 hours; the metabolite does so in 3-4 hours. Their respective elimination half-lives are about 10 and 20 hours. Onset of action is within 1 hour and duration is at least 24 hours. Once-daily dosing is recommended. Generally, loratadine is as efficacious as existing antihistamines in relieving symptoms of allergic rhinitis, urticaria, and in suppressing wheal formation. Reports of sedation and other adverse reactions are no more frequent than found with placebo. Tachyphylaxis has not been noted in humans, and there is minimal potential for drug interactions based on animal data. Loratadine and terfenadine have comparable therapeutic applications. Both have shown minimal adverse effects, but loratadine has a quicker onset and longer duration of action. These two agents are useful for acute allergic reactions. In contrast, astemizole has an onset of action of several days and is most useful for prophylactic treatment of seasonal allergies.
Characterization of the interaction of lambda exonuclease with the ends of DNA (1999)

Lambda exonuclease processively degrades one strand of double-stranded DNA (dsDNA) in the 5"-3" direction. To understand the mechanism through which this enzyme generates high processivity we are analyzing the first step in the reaction, namely the interaction of lambda exonuclease with the ends of substrate DNA. Endonuclease mapping of lambda exonuclease bound to DNA has shown that the enzyme protects approximately 13-14 bp on dsDNA, and no nucleo-tides on the single-stranded tail of the DNA product. We have developed a rapid fluorescence-based assay using 2-aminopurine and measured the steady-state rate constants for different end-structures of DNA. The relative k(cat)for 5" ends decreases in the order 5" recessed > blunt >> 5" overhang. However, k(cat)/K(m)remains relatively constant for these different structures suggesting they are all used equally efficiently as substrates. From these data we propose that a single-stranded 5" overhang end can bind non-productively to the enzyme and the non-hydrolyzed strand is required to aid in the proper alignment of the 5" end. We have also measured the length-dependence of the steady-state rate para-meters and find that they are consistent with a high degree of processivity.