gebhart/patrepeval huggingface dataset:
Hydrolysis of Triglycerides Using Solid Acid Catalysts (2009)

The commercial production of free fatty acids (FFAs) is carried out through the noncatalytic hydrolysis of triglycerides (TGs) using great amounts of superheated steam in large reactors made of expensive corrosion-resistant materials, making the process energy intensive and costly. In this study, the feasibility of a continuous reaction system using a solid acid for the hydrolysis of TGs at atmospheric pressure has been investigated. This research was to explore the viability of heterogeneous catalyzed hydrolysis of oils and fats for the synthesis of FFAs, a platform reaction of the oleochemical industry and a possible reaction in a novel two-step (hydrolysis−esterification) biodiesel synthesis process using low-cost feedstocks containing >5−15% FFAs. Tricaprylin (TCp) was used as a model compound representing TGs in order to obtain reliable intrinsic kinetics. Using tungstated zirconia (WZ) and the solid acid composite SAC-13 (Nafion resin nanoparticles supported on mesoporous silica) as catalysts, the hydrolysis of TCp was carried out at 110−150 °C in a semibatch reactor with continuous addition of water at low flow rates capable of achieving 100% selectivity of the carboxylic acid side chains on the triglyceride to HCp. The characteristics of the catalysts played an important role in reaction selectivity, apparent activation energy, and deactivation. Catalyst recycling experiments showed continuous activity loss for both catalysts. Characterization of the used catalysts indicated that deactivation was likely caused by the strong adsorption of bulky reaction intermediates on the catalytic acid sites, blocking reactant accessibility. For WZ, recalcination in air was an effective regeneration method resulting in the recovery of 100% of its original activity. Regeneration by calcination was not possible for SAC-13 due to its temperature sensitivity. Methanol washing of used WZ and SAC-13 catalysts only partially regenerated catalyst activity.
Partial chondroprotective effect of zoledronate in a rabbit model of inflammatory arthritis. (1999)

Zoledronate had a partial effect in a rabbit model of inflammatory arthritis. The chondroprotection may be due to the prevention of bone resorption. By maintaining an intact subchondral bone, normal joint loading may have been maintained and contact between the bone marrow and the articular cartilage averted.
Involvement of the Glu724–Pro760 Region of the Dihydropyridine Receptor II-III Loop in Skeletal Muscle-type Excitation-Contraction Coupling (1999)

Our previous study (El-Hayek, R., Antoniu, B., Wang, J. P., Hamilton, S. L., and Ikemoto, N. (1995) J. Biol. Chem. 270, 22116-22118) suggested the hypothesis that skeletal muscle-type excitation-contraction coupling is regulated by two domains (activating and blocking) of the II-III loop of the dihydropyridine receptor alpha1 subunit. We investigated this hypothesis by examining conformational changes in the ryanodine receptor induced by synthetic peptides and by transverse tubular system (T-tubule) depolarization. Peptide A, corresponding to the Thr671-Leu690 region, rapidly changed the ryanodine receptor conformation from a blocked state (low fluorescence of the conformational probe, methyl coumarin acetamide, attached specifically to the ryanodine receptor) to an activated state (high methyl coumarin acetamide fluorescence) as T-tubule depolarization did. Peptide C, corresponding to the Glu724-Pro760 region, blocked both conformational changes induced by peptide A and T-tubule depolarization. Its ability to block peptide A-induced and depolarization-induced activation was considerably impaired by replacing the portion of peptide C corresponding to the Phe725-Pro742 region of the loop with cardiac muscle-type sequence. These results are consistent with the model that depolarization-induced activation of excitation-contraction coupling and blocking/repriming are mediated by the peptide A region and the peptide C region (containing the critical Phe725-Pro742 sequence) of the II-III loop, respectively.
Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance (2017)

Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 <sup>Y537C</sup> and ESR1 <sup>Y537S</sup> mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.
Control of mitochondrial morphology by a human mitofusin (2001)

Although changes in mitochondrial size and arrangement accompany both cellular differentiation and human disease, the mechanisms that mediate mitochondrial fusion, fission and morphogenesis in mammalian cells are not understood. We have identified two human genes encoding potential mediators of mitochondrial fusion. The mitofusins (Mfn1 and Mfn2) are homologs of the Drosophila protein fuzzy onion (Fzo) that associate with mitochondria and alter mitochondrial morphology when expressed by transient transfection in tissue culture cells. An internal region including a predicted bipartite transmembrane domain (TM) is sufficient to target Mfn2 to mitochondria and requires hydrophobic residues within the TM. Co-expression of Mfn2 with a dominant interfering mutant dynamin-related protein (Drp1(K38A)) proposed to block mitochondrial fission resulted in long mitochondrial filaments and networks. Formation of mitochondrial filaments and networks required a wild-type Mfn2 GTPase domain, suggesting that the Mfn2 GTPase regulates or mediates mitochondrial fusion and that mitofusins and dynamin related GTPases play opposing roles in mitochondrial fusion and fission in mammals, as in yeast.
Mouse mast cell gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs and suppresses mast cell activation when coligated with the high-affinity Fc receptor for IgE. (1996)

Mouse mast cells express gp49B1, a cell-surface member of the Ig superfamily encoded by the gp49B gene. We now report that by ALIGN comparison of the amino acid sequence of gp49B1 with numerous receptors of the Ig superfamily, a newly recognized family has been established that includes gp49B1, the human myeloid cell Fc receptor for IgA, the bovine myeloid cell Fc receptor for IgG2, and the human killer cell inhibitory receptors expressed on natural killer cells and T lymphocyte subsets. Furthermore, the cytoplasmic domain of gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs that are also present in killer cell inhibitory receptors; these motifs downregulate natural killer cell and T-cell activation signals that lead to cytotoxic activity. As assessed by flow cytometry with transfectants that express either gp49B1 or gp49A, which are 89% identical in the amino acid sequences of their extracellular domains, mAb B23.1 was shown to recognize only gp49B1. Coligation of mAb B23.1 bound to gp49B1 and IgE fixed to the high-affinity Fc receptor for IgE on the surface of mouse bone marrow-derived mast cells inhibited exocytosis in a dose-related manner, as defined by the release of the secretory granule constituent beta-hexosaminidase, as well as the generation of the membrane-derived lipid mediator, leukotriene C4. Thus, gp49B1 is an immunoreceptor tyrosine-based inhibition motif-containing integral cell-surface protein that downregulates the high-affinity Fc receptor for IgE-mediated release of proinflammatory mediators from mast cells. Our findings establish a novel counterregulatory transmembrane pathway by which mast cell activation can be inhibited.
Mapping small DNA sequences by fluorescence in situ hybridization directly on banded metaphase chromosomes. (1990)

A procedure for mapping small DNA probes directly on banded human chromosomes by fluorescence in situ hybridization has been developed. This procedure allows for the simultaneous visualization of banded chromosomes and hybridization signal without overlaying two separate photographic images. This method is simple and rapid, requires only a typical fluorescence microscope, has proven successful with DNA probes as small as 1 kilobase, is applicable for larger probes, and will greatly facilitate mapping the vast number of probes being generated to study genetic disease and define the human genome. Human metaphase chromosomes were prepared from phytohemagglutinin-stimulated lymphocyte cultures synchronized with bromodeoxyuridine and thymidine. Probes were labeled with biotin-dUTP, and the hybridization signal was amplified by immunofluorescence. Chromosomes were stained with both propidium iodide and 4',6-diamidino-2-phenylindole (DAPI), producing R- and Q-banding patterns, respectively, allowing unambiguous chromosome and band identification while simultaneously visualizing the hybridization signal. Thirteen unique DNA segments have been localized to the long arm of chromosome 11 by using this technique, and localization of 10 additional probes by using radioactive in situ hybridization provides a comparison between the two procedures. These DNA segments have been mapped to all long-arm bands on chromosome 11 and in regions associated with neoplasias and inherited disorders.
The microRNAs of Caenorhabditis elegans (2003)

MicroRNAs (miRNAs) are an abundant class of tiny RNAs thought to regulate the expression of protein-coding genes in plants and animals. In the present study, we describe a computational procedure to identify miRNA genes conserved in more than one genome. Applying this program, known as MiRscan, together with molecular identification and validation methods, we have identified most of the miRNA genes in the nematode Caenorhabditis elegans. The total number of validated miRNA genes stands at 88, with no more than 35 genes remaining to be detected or validated. These 88 miRNA genes represent 48 gene families; 46 of these families (comprising 86 of the 88 genes) are conserved in Caenorhabditis briggsae, and 22 families are conserved in humans. More than a third of the worm miRNAs, including newly identified members of the lin-4 and let-7 gene families, are differentially expressed during larval development, suggesting a role for these miRNAs in mediating larval developmental transitions. Most are present at very high steady-state levels-more than 1000 molecules per cell, with some exceeding 50,000 molecules per cell. Our census of the worm miRNAs and their expression patterns helps define this class of noncoding RNAs, lays the groundwork for functional studies, and provides the tools for more comprehensive analyses of miRNA genes in other species.
Consensus molecular subtypes in colorectal cancer differ by geographic region. (2020)

4061 Background: The consensus molecular subtypes (CMS) have emerged as a novel classification in colorectal cancer (CRC). However, these subtypes, were mostly derived from a US/European population, and have scant data in other ethnic groups. This study aimed to demonstrate molecular subtypes of CRC across geographic regions. Methods: Formalin fixed paraffin embedded (FFPE) tissue from untreated patients with stage II-III colon cancer from Brazil, Canada, Mexico, Thailand, and the US were evaluated. Gene expression profiling was performed at the University of Texas MD Anderson Cancer Center using NanoString’s nCounter technology and an optimized classifier for FFPE. Results: A total of 366 samples were included in this study, evenly distributed between the 5 international sites. While the US population matched previously reported distributions, the distribution of CMS subtypes varied substantially by region (P &lt; 0.0001). While CMS1 was still associated with right-sided tumors (P &lt; 0.001) and deficient mismatch repair (dMMR) (P &lt; 0.001), the prevalence varied between 8% in Brazil to 30% in Mexico. CMS2 was found vary from 14% in Mexico to 47% in Brazil. The metabolic CMS3 subtype was present in only 3% in Thailand, but as high as 19% in Brazil. CMS4 was confirmed to be associated with higher stage (P = 0.047), and the prevalence was lowest in Brazil (14%) compared to 44% and 49% in US and Mexico, respectively. Expansion of study cohort is ongoing. Conclusions: CMS subtype prevalence differs substantially by geographic region in CRC. These variations suggest that transcriptomic-defined disease biology in international populations may be more heterogeneous than previously appreciated. Further studies in global populations are required to validate and extend these findings, which may have important impact for novel therapeutic development.
Genome editing of human pluripotent stem cells to generate human cellular disease models (2013)

Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.
Synthesis and antibacterial activity of cephalosporins having a catechol in the C3 side chain. (1993)

Cephalosporins having a catechol through a variety of linkages to the C3 position and a different C7 side chain were prepared. Among them, 3-(catechol-4- ylcarbonyloxy)methylcephalosporin (14) and 3-[(E)-3-(catechol-4-ylcarbonyloxy)-1-propen-1-yl]cephalospo rin (10) showed excellent activity against Gram-negative activity including ceftazidime-resistant Escherichia coli, Pseudomonas aeruginosa, Xanthomonas maltophilia and Pseudomonas cepacia.
On the Relative Roles of Free Volume and Activation Energy in the Viscosity of Liquids (1965)

The rate-theory approach of Eyring and the free-volume theory of Cohen and Turnbull for liquid viscosities have been reconsidered. The rate theory has been reformulated using the Cohen and Turnbull expression for the probability of finding a vacant site and yields an equation of the form η=A0exp[Ev*/RT+γV0/Vf].This result has been applied to many liquids ranging from fused silica to liquid argon and including polyatomic van der Waals as well as hydrogen-bonded liquids. Consistent fits to both temperature and pressure dependence of viscosity were obtained. A significant conclusion is that the free volume of liquids is considerably higher than that suggested by the WLF and Cohen and Turnbull equations.
Metathesis of Alkanes Catalyzed by Silica-Supported Transition Metal Hydrides (1997)

The silica-supported transition metal hydrides (=Si-O-Si=)(=Si-O-)2Ta-H and (=Si-O-)xM-H (M, chromium or tungsten) catalyze the metathesis reaction of linear or branched alkanes into the next higher and lower alkanes at moderate temperature (25degrees to 200degreesC). With (=Si-O-Si=)(=Si-O-)2Ta-H, ethane was transformed at room temperature into an equimolar mixture of propane and methane. Higher and lower homologs were obtained from propane, butane, and pentane as well as from branched alkanes such as isobutane and isopentane. The mechanism of the step leading to carbon-carbon bond cleavage and formation likely involves a four-centered transition state between a tantalum-alkyl intermediate and a carbon-carbon final sigma-bond of a second molecule of alkane.
Genetic alteration of soybean oil composition by a chemical mutagen (1984)

Abstract Soybean ( Glycine max [L.] Merr. cv. Century) seeds were treated with ethylmethanesulfonate (EMS) and the M 2 progeny were evaluated for fatty acid composition of the oil. Treatment with EMS significantly increased the variability in content of each of the fatty acids in comparison with those of the Century control. There was a strong inverse relationship between oleic and linoleic acids among seeds from M 2 plants. This supports the hypothesis of sequential desaturation as the method of formation of unsaturated fatty acids in soybean oil. A genetically stable mutant with 3.4% linolenic acid was identified that was similar to the cultivar Century in days to maturity, plant height and resistance to lodging.
Cooperative antithrombotic effect from the simultaneous inhibition of thrombin and factor Xa (2010)

Whereas heparin functions as an antithrombotic agent by promoting antithrombin III-based inhibition of thrombin and factor Xa, there is less appreciation for the combination behavior with small-molecule, direct inhibitors of these proteases. We conducted a study in a high-shear arterial environment to explore the potential for a cooperative antithrombotic effect with a thrombin inhibitor (argatroban), a factor Xa inhibitor (YM-60828), and a dual thrombin/factor Xa inhibitor (RWJ-445167). We employed a platelet-dependent vascular injury model in which rats were subjected to an acute electrical injury to the carotid artery. Antithrombotic efficacy was measured for thrombin inhibitor argatroban and factor Xa inhibitor YM-60828 administered alone or in combination. The results indicate that there is a cooperative antithrombotic effect in vivo when both thrombin and factor Xa are inhibited simultaneously. The dual thrombin/factor Xa inhibitor RWJ-445167 was found to have potent antithrombotic activity in this high-shear environment. A comparison of results for RWJ-445167 and argatroban showed additional efficacy with RWJ-445167, suggestive of drug synergy.
MPLS Label Stack Encoding (2001)

Multi-Protocol Label Switching (MPLS)" [1] requires a set of procedures for augmenting network layer packets with "label stacks", thereby turning them into "labeled packets".Routers which support MPLS are known as "Label Switching Routers", or "LSRs".In order to transmit a labeled packet on a particular data link, an LSR must support an encoding technique which, given a label stack and a network layer packet, produces a labeled packet.This document specifies the encoding to be used by an LSR in order to transmit labeled packets on Point-to-Point Protocol (PPP) data links, on LAN data links, and possibly on other data links as well.On some data links, the label at the top of the stack may be encoded in a different manner, but the techniques described here MUST be used to encode the remainder of the label stack.This document also specifies rules and procedures for processing the various fields of the label stack encoding.
Variation in the strength of selected codon usage bias among bacteria (2005)

Among bacteria, many species have synonymous codon usage patterns that have been influenced by natural selection for those codons that are translated more accurately and/or efficiently. However, in other species selection appears to have been ineffective. Here, we introduce a population genetics-based model for quantifying the extent to which selection has been effective. The approach is applied to 80 phylogenetically diverse bacterial species for which whole genome sequences are available. The strength of selected codon usage bias, S, is found to vary substantially among species; in 30% of the genomes examined, there was no significant evidence that selection had been effective. Values of S are highly positively correlated with both the number of rRNA operons and the number of tRNA genes. These results are consistent with the hypothesis that species exposed to selection for rapid growth have more rRNA operons, more tRNA genes and more strongly selected codon usage bias. For example, Clostridium perfringens, the species with the highest value of S, can have a generation time as short as 7 min.
The role of the immune system in regulating the microbiota (2010)

A diverse population of bacteria, archaea and fungi, collectively known as the microbiota, abounds within the gastrointestinal tract of the mammalian host. This microbial population makes many important contributions to host physiology through inter-kingdom signalling and by providing nutrients that have both local and systemic effects. In a healthy state the overall host-microbial interaction is symbiotic; however, a growing number of diseases have been associated with a dysregulated microbiota. To avoid these consequences, the host exerts substantial effort to maintain proper regulation of the microbiota with respect to localization and composition. Although important to maintaining microbial balance, the host immune response can also be the cause of a disrupted microbiota, contributing to disease severity. Here, we discuss the role of the host in both maintaining and disrupting a balanced gastrointestinal microbiota.
Use of limiting-dilution type long-term marrow cultures in frequency analysis of marrow-repopulating and spleen colony-forming hematopoietic stem cells in the mouse (1991)

We have developed an in vitro clonal assay of murine hematopoietic precursor cells that form spleen colonies (CFU-S day 12) or produce in vitro clonable progenitors in the marrow (MRA cells) of lethally irradiated mice. The assay is essentially a long-term bone marrow culture in microtiter wells containing marrow-derived stromal "feeders" depleted for hematopoietic activity by irradiation. To test the validity of the assay as a quantitative in vitro stem cell assay, a series of unsorted and physically sorted bone marrow cells were simultaneously assayed in vivo and overlaid on the feeders in a range of concentrations, while frequencies of cells forming hematopoietic clones (cobblestone area forming cells, CAFC) were calculated by means of Poisson statistics. Linear regression analysis of the data showed high correlations between the frequency of CFU-S day 12 and CAFC day 10, and between MRA cells and CAFC day 28. A majority of MRA activity and CAFC day 28 was separable from CFU-S day 12 and CAFC day 10. This correlation study validates the CAFC system as a clonal assay facilitation both the quantitative assessment of a series of subsets in the hematopoietic stem cell hierarchy and the study of single long-term repopulating cells in vitro.
Capture and Stimulated Release of Circulating Tumor Cells on Polymer‐Grafted Silicon Nanostructures (2012)

A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires. In this platform, integration of ligand-receptor recognition, nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells. Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.