gebhart/patrepeval huggingface dataset:
Left ventricular function of the isolated, genetically obese rat's heart (1985)

We sought to determine if left ventricular (LV) function of the heart from the adult, chronically obese animal is impaired. Hearts from 50 wk-old genetically obese female Zucker rats (624 +/- 13 g) and their lean littermate controls (275 +/- 5 g) were isolated during ether anesthesia, supported metabolically by retrograde aortic perfusion (6 ml/min, 35 degrees C) with physiological solution containing suspended canine erythrocytes (hematocrit, 20%), and the ventricles were paced at 180 beats/min. A distensible, fluid-filled balloon was placed in the LV, and pressure-volume (PV) relationships were obtained. The obese and lean end-diastolic PV curves were not different, and therefore the obese and lean LV chamber compliances were similar. Comparison of the systolic PV relationships demonstrated that the obese rat's heart had a greater pressure-generating capability, which probably was a reflection of its increased LV mass (0.96 +/- 0.03 vs. 0.72 +/- 0.02 g). The calculated average meridional (or circumferential) peak systolic wall stress in the LV of the obese rat's heart, however, was significantly reduced compared with control. This diminished ability to develop systolic stress from the same end-diastolic volumes suggests that the hypertrophied LV of the middle-aged obese rat's heart is dilated or that its contractility is depressed, or both.
High-sensitivity optical chemsensor based on etched D-fibre Bragg gratings (2004)

A novel and simple optical chemsensor concept based on cladding etched Bragg gratings UV-inscribed in D-fibre is reported. The sensitisation process of the Bragg structure to the refractive index of surrounding-medium under HF-etching has been investigated. Two etched devices were used to measure the concentrations of sugar solution, giving sensitivity as high as 0.02 nm/%.
Oral Defenses and Disease: Salivary Gland Function <sup>1</sup> (1984)

Recent studies on parotid gland flow rate and composition in healthy subjects do not support the conventional wisdom that there is a gradual deterioration in salivary gland function with aging. With gustatory stimulation a diminution in flow rate was observed only in post‐menopausal women taking medications. Studies of whole saliva and preliminary studies of submandibular saliva flow rate, however, suggest that these glands may exhibit functional changes not seen in the parotid. This would be consistent with histological findings. Reports to date on age effects on composition suggest modest selective changes in electrolytes (e.g. sodium) and only subtle changes in proteins (e.g. amylase isoenzymes). Clinical concerns (rampant caries, stomatitis, periodontal disease) arise largely because of the high number of elderly on medications or therapeutic interventions that affect salivary flow and the increase in incidence of diseases of the salivary gland (e.g. sialadeneitis, Sjogren's, sarcoidosis). Reduction in flow rate and alterations in composition diminish salivary protective mechanisms, i.e. antibacterial activity, lubrication and protection of soft tissues, and maintenance of hard tissue integrity. Recent research on structure of mucins, the nature of the salivary lipids and interactions among salivary proteins should stimulate a second generation of studies on both the effects of aging per se and aberrations resulting from disease. Stimulation of compromised function and development of more effective salivary substitutes are also important areas of research.
Mapping the Promoter DNA Sites Proximal to Conserved Regions of σ<sup>70</sup> in an <i>Escherichia coli </i>RNA Polymerase−<i>lac</i>UV5 Open Promoter Complex (1998)

Base-specific interactions between promoter DNA and Escherichia coli RNA polymerase are regulated by a sigma (sigma) protein during transcription initiation. To map spatial relations between evolutionarily conserved regions of the primary sigma (sigma 70) and each DNA strand along the lacUV5 promoter in the transcriptionally active "open" complex, we have used a cysteine-tethered cutting reagent to cleave DNA strands. The chemical nuclease FeBABE [iron (S)-1-(p-bromoacetamidobenzyl)ethylenediaminetetraacetate] was conjugated to single-cysteine mutants of sigma 70 at sites 132C, 376C, 396C, 422C, 496C, 517C, or 581C. After formation of open promoter complexes between lacUV5 DNA and RNA polymerase holoenzymes carrying conjugated sigma 70 subunits, we observed promoter DNA cleavage spanning at least 60 bases, between positions -48 and +12. The results show that sigma 70 region 2.1, otherwise implicated in core enzyme binding, is proximal to the nontemplate strand of lacUV5 DNA between the -10 promoter element and positions as far downstream of the transcription start site as +12. Conserved region 3.2 of sigma 70 is proximal to the template strand near the +1 transcription start site, and region 3.1 is positioned between the lacUV5-10 and -35 promoter elements. We propose a model for the orientation of sigma 70 and DNA in the open complex.
Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain (2011)

Thrombomodulin (TM) is a predominantly endothelial transmembrane glycoprotein that modulates hemostatic function through a domain that controls thrombin-mediated proteolysis and an N-terminal lectin-like domain that controls inflammatory processes. To test the hypothesis that TM is a determinant of malignancy and dissect the importance of these functional domains in cancer biology, metastatic potential was evaluated in TM(Pro) mice expressing a mutant form of TM with reduced thrombin affinity and TM(LeD) mice lacking the N-terminal lectin-like domain. Studies of TM(Pro) mice revealed that TM is a powerful determinant of hematogenous metastasis. TM(Pro) mice exhibited a strongly prometastatic phenotype relative to control mice that was found to result from increased survival of tumor cells newly localized to the lung rather than any alteration in tumor growth. The impact of the TM(Pro) mutation on metastasis was dependent on both tumor cell-associated tissue factor and thrombin procoagulant function. In contrast, expression of a mutant form of TM lacking the lectin-like domain had no significant impact on metastasis. These studies directly demonstrate for the first time that TM-mediated regulation of tumor cell-driven procoagulant function strongly influences metastatic potential and suggest that endothelial cell-associated modulators of hemostasis may represent novel therapeutic targets in limiting tumor dissemination.
Correlation of Fine Aggregate Imaging Shape Indices with Asphalt Mixture Performance (2001)

This study addresses the relationship between fine aggregate shape properties and the performance of hot-mix asphalt. Aggregate shape was expressed as three independent properties: form, angularity, and texture. Image analysis procedures and indices were developed to capture these properties. The indices were measured for 22 aggregate samples. The samples were related to the hot-mix asphalt rutting resistance measured under wet and dry conditions in the Purdue wheel-tracking device. Among the different aggregate shape properties, texture had the strongest correlation with rutting resistance. Resistance to rutting increased exponentially with an increase in aggregate texture.
Dextrinization of Potato Starch with Gaseous Hydrogen Chloride (1944)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDextrinization of Potato Starch with Gaseous Hydrogen ChlorideLee T. Smith and S. G. MorrisCite this: Ind. Eng. Chem. 1944, 36, 11, 1052–1054Publication Date (Print):November 1, 1944Publication History Published online1 May 2002Published inissue 1 November 1944https://pubs.acs.org/doi/10.1021/ie50419a020https://doi.org/10.1021/ie50419a020research-articleACS PublicationsRequest reuse permissionsArticle Views58Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Antibody-induced arthritis: disease mechanisms and genes involved at the effector phase of arthritis. (2006)

During the development of rheumatoid arthritis (RA) autoantibodies to IgG-Fc, citrullinated proteins, collagen type II (CII), glucose 6 phosphoisomerase (G6PI) and some other self-antigens appear. Of these, a pathogenic effect of the anti-CII and anti-G6PI antibodies is well demonstrated using animal models. These new antibody mediated arthritis models have proven to be very useful for studies involved in understanding the molecular pathways of the induction of arthritis in joints. Both the complement and FcgammaR systems have been found to play essential roles. Neutrophils and macrophages are important inflammatory cells and the secretion of tumour necrosis factor-alpha and IL-1beta is pathogenic. The identification of the genetic polymorphisms predisposing to arthritis is important for understanding the complexity of arthritis. Disease mechanisms and gene regions studied using the two antibody-induced arthritis mouse models (collagen antibody-induced arthritis and serum transfer-induced arthritis) are compared and discussed for their relevance in RA pathogenesis.
Effects of Mechanical Stimulation on the Biomechanics and Histology of Stem Cell–Collagen Sponge Constructs for Rabbit Patellar Tendon Repair (2006)

The objective of this study was to determine how mechanical stimulation affects the biomechanics and histology of stem cell-collagen sponge constructs used to repair central rabbit patellar tendon defects. Autogenous tissue-engineered constructs were created for both in vitro and in vivo analyses by seeding mesenchymal stem cells from 10 adult rabbits at 0.14x10(6) cells/construct in type I collagen sponges. Half of these constructs were mechanically stimulated once every 5 min for 8 h/day to a peak strain of 4% for 2 weeks. The other half remained in an incubator without mechanical stimulation for 2 weeks. Samples allocated for in vitro testing revealed that mechanically stimulated constructs had 2.5 times the linear stiffness of nonstimulated constructs. The remaining paired constructs for in vivo studies were implanted in bilateral full-thickness, full-length defects in the central third of rabbit patellar tendons. Twelve weeks after surgery, repair tissues were assigned for biomechanical (7 pairs) and histologic (3 pairs) analyses. Maximum force, linear stiffness, maximum stress, and linear modulus for the stimulated (vs. nonstimulated) repairs averaged 70% (vs. 55%), 85% (vs. 55%), 70% (vs. 50%), and 50% (vs. 40%) of corresponding values for the normal central third of the patellar tendons. The average force-elongation curve for the mechanically stimulated repairs also matched the corresponding curve for the normal patellar tendons, up to 150% of the peak in vivo force values recorded in a previous study. Construct and repair linear stiffness and linear modulus were also positively correlated (r = 0.6 and 0.7, respectively). Histologically both repairs showed excellent cellular alignment and mild staining for decorin and collagen type V, and moderate staining for fibronectin and collagen type III. This study shows that mechanical stimulation of stem cell-collagen sponge constructs can significantly improve tendon repair biomechanics up to and well beyond the functional limits of in vivo loading.
Dual-Fuel Diesel Engine Combustion With Hydrogen, Gasoline, and Ethanol as Fumigants: Effect of Diesel Injection Timing (2014)

Premixed compression ignition (CI) combustion has attracted increasing research effort recently due to its potential to achieve both high thermal efficiency and low emissions. Dual-fuel strategies for enabling premixed CI have been a focus using a low-reactivity fumigant and direct diesel injection to control ignition. Alternative fuels like hydrogen and ethanol have been used as fumigants in the past but typically with diesel injection systems that did not allow the same degree of control or mixing enabled by modern common rail systems. In this work, we experimentally investigated hydrogen, ethanol, and gasoline as fumigants and examined three levels of fumigant energy fraction (FEF) using gasoline over a large, direct diesel injection timing range with a single-cylinder diesel engine. It was found that the operable diesel injection timing range at constant FEF was dependent on the fumigant's propensity for autoignition. Peak indicated gross cycle efficiency occurred with advanced diesel injection timing and aligned well with combustion phasing near top dead center (TDC), as we found in an earlier work. The use of hydrogen as a fumigant resulted in very low hydrocarbon (HC) emissions compared with ethanol and gasoline, establishing that they mainly result from incomplete combustion of the fumigated fuel. Hydrogen emissions were independent of diesel injection timing, and HC emissions were strongly linked to combustion phasing, giving further indication that squish and crevice flows are responsible for partially burned species from fumigation combustion.
Experimental verification of the sectored annular phased array for MRI guided ultrasound surgery (2002)

To meet two of the requirements for MRI Guided Ultrasound Surgery, namely small surgical equipment and large focal volumes, a combined array encompassing the design parameters of the concentric-ring array and the sector-vortex array has been proposed. Simulations will show that the sectored annular array is capable of producing larger necrosed tissue volumes than the concentric-ring alone, while maintaining the ability of the concentric-ring array to move the focal volume in the axial direction of the array. These simulations are verified by measurements of the acoustic fields produced by an experimental array in water. In addition, the constructed array produced the necessary power required to coagulate tissue in rabbit thigh in vivo, while the temperature elevation was monitored using MRI.
A simple variational approach to optical rib waveguides (1991)

A simple method for the calculation of the mode properties of optical rib waveguides is presented. The method is based on a scalar variational principle combined with a vector perturbation analysis for the polarization correction. It is demonstrated that, with the proper trial functions, the approach can predict very accurately the dispersion characteristics with much less effort (in terms of formulation and computation) than the existing numerical techniques. The field patterns of the modes can be computed from the scalar analysis. The vector property of the mode can be taken into account by a perturbation formula. The computation is carried out on an IBM PC. The user-friendly computer program is written in Fortran.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
The Alpha Adrenergic Binding Properties of Terazosin in the Human Prostate Adenoma and Canine Brain (1988)

Clinical trials are currently underway to evaluate the efficacy of terazosin for the treatment of symptomatic benign prostatic hyperplasia (BPH). Terazosin is a potent and selective alpha 1 adrenergic blocking agent structurally similar to prazosin. The alpha adrenergic binding properties of terazosin were studied in human prostate adenomas and canine brains using radioligand receptor binding methods. Saturation analyses were performed at varying concentrations of [125I]-Heat and [3H]rauwolscine [( 3H]Ra) in human prostate adenomas and canine brains. The binding of [125I]-Heat and [3H]Ra in the human prostates and canine brains was consistently saturable and of high affinity. The equilibrium dissociation constant (Kd) for [125I]-Heat binding in the canine brains and human prostate adenomas was 84.4 +/- 4.3 pM and 65.4 +/- 19.2 pM, respectively (p greater than 0.05). The (Kd) for [3H]Ra binding in the human prostate adenomas and canine brains was 1.21 +/- 0.23 nM and 1.52 +/- 0.28 nM, respectively (p greater than 0.05). The density of alpha 1 (0.37 +/- 0.15 fmol/mg. wet wt.) and alpha 2 (0.29 +/- 0.09 fmol/mg. wet wt. adrenergic binding sites in the human adenomas were similar (p greater than 0.05). The IC50 corrected (IC50 corr) of terazosin for [125I]-Heat and [3H]Ra binding sites in the human prostate was 2.5 nM and 1.0 micron., respectively. The IC50 corr of terazosin for [125I]-Heat and [3H]Ra binding sites in the canine brain was 2.0 nM and 0.8 microM, respectively. The competitive binding assays indicate that terazosin binds selectively to alpha 1 adrenergic binding sites in the human prostate and canine brain.
5′ modifications to CRISPR–Cas9 gRNA can change the dynamics and size of R-loops and inhibit DNA cleavage (2020)

A key aim in exploiting CRISPR-Cas is gRNA engineering to introduce additional functionalities, ranging from individual nucleotide changes that increase efficiency of on-target binding to the inclusion of larger functional RNA aptamers or ribonucleoproteins (RNPs). Cas9-gRNA interactions are crucial for complex assembly, but several distinct regions of the gRNA are amenable to modification. We used in vitro ensemble and single-molecule assays to assess the impact of gRNA structural alterations on RNP complex formation, R-loop dynamics, and endonuclease activity. Our results indicate that RNP formation was unaffected by any of our modifications. R-loop formation and DNA cleavage activity were also essentially unaffected by modification of the Upper Stem, first Hairpin and 3' end. In contrast, we found that 5' additions of only two or three nucleotides could reduce R-loop formation and cleavage activity of the RuvC domain relative to a single nucleotide addition. Such modifications are a common by-product of in vitro transcribed gRNA. We also observed that addition of a 20 nt RNA hairpin to the 5' end of a gRNA still supported RNP formation but produced a stable ∼9 bp R-loop that could not activate DNA cleavage. Consideration of these observations will assist in successful gRNA design.
Mammalian Cell Display and Somatic Hypermutation In Vitro for Human Antibody Discovery (2014)

Human therapeutic antibody discovery has utilized a variety of systems, from in vivo immunization of human immunoglobulin-expressing mice, to in vitro display of antibody libraries. Of the in vitro antibody display technologies, mammalian cell display provides a number of advantages with the ability to co-select immunoglobulin molecules for high expression level in mammalian cells, native folding, and biophysical properties appropriate for drug development. Mammalian cell display has been achieved using either transient or stable expression systems, using a number of alternate transmembrane domains to present antibody on the cell surface. The unique capability of mammalian cells to present IgG in its fully post-translationally modified format also allows selection of antibodies for functional properties. One limitation of mammalian cell based systems, however, has been the smaller library size that can be presented compared to phage display approaches. Until recently, this has necessitated the use of libraries biased toward a particular antigen, such as libraries derived from immunized donors, to achieve success. An alternative approach has now been developed which recapitulates key aspects of the in vivo immune system through reproducing somatic hypermutation (SHM) in vitro. Libraries representing a naïve human B lymphocyte antibody repertoire are created by PCR amplification of the rearranged (D)J segments of heavy and light chain variable regions from human donors and incorporating the resulting sequence diversity into panels of human germline VH and VL genes. The resulting antibodies are presented as full length IgG on the surface of HEK293 cells. After isolation of antibodies binding to individual target antigens, subsequent affinity maturation using in vitro SHM is induced by expression of activation-induced cytidine deaminase (AID). Selection of antibodies from naïve fully human libraries using mammalian cell display coupled with in vitro SHM is an efficient methodology for the generation of high affinity human antibodies with excellent properties for drug development.
Ovorubin, a chromoprotein from the eggs of the gastropod mollusc <i>Pomacea canaliculata</i> (1958)

Abstract The eggs of Pomacea canaliculata australis (d’Orbigny), an amphibious freshwater prosobranch snail, have, as the most important nitrogenous constituent of the jelly surrounding the ovum, a red glycoprotein with a carotenoid prosthetic group. This protein, to which the name ovorubin has been given, has a high stability to denaturation by heat and by adsorption at interfaces. It is partially utilized during development of the ovum, although about two-thirds of the original ovorubin content of the egg is found in the visceral hump of the newly hatched animal. The carotenoid component is probably an ester or ether of astaxanthin, highly labile to alkali in the cold. The minimum molecular weight, calculated from the carotenoid content, lies in the region of 330 000. The carbohydrate component represents about 20% of the molecule. The carotenoid and the glycoprotein may readily be separated and recombined. Experiments on the apo-glycoprotein and the reconstituted caroteno-protein indicate that the carotenoid stabilizes the native configuration of the protein structure. It is suggested that stabilization of the configurations of protein molecules may be one of the roles of carotenoids in nature.
Naltrexone Modification of Drinking Effects in a Subacute Treatment and Bar‐Lab Paradigm: Influence of <i><scp>OPRM</scp>1</i> and Dopamine Transporter (<i><scp>SLC6A3</scp></i>) Genes (2012)

This study does not support a salient role for the OPRM1 asp40 alone in predicting drinking or naltrexone effects. However, although exploratory and in need of replication, it introduces the possibility that epistasis between the OPRM1 gene and DAT gene might need to be taken into account when examining differential genetic response to alcohol or medication treatment, especially in early-stage alcoholics.
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle (2010)

The hepatitis C virus (HCV) life cycle involves multiple steps, but most current drug candidates target only viral replication. The inability to systematically discover inhibitors targeting multiple steps of the HCV life cycle has hampered antiviral development. We present a simple screen for HCV antivirals based on the alleviation of HCV-mediated cytopathic effect in an engineered cell line-n4mBid. This approach obviates the need for a secondary screen to avoid cytotoxic false-positive hits. Application of our screen to 1280 compounds, many in clinical trials or approved for therapeutic use, yielded >200 hits. Of the 55 leading hits, 47 inhibited one or more aspects of the HCV life cycle by >40%. Six compounds blocked HCV entry to levels similar to an antibody (JS-81) targeting the HCV entry receptor CD81. Seven hits inhibited HCV replication and/or infectious virus production by >100-fold, with one (quinidine) inhibiting infectious virus production by 450-fold relative to HCV replication levels. This approach is simple and inexpensive and should enable the rapid discovery of new classes of HCV life cycle inhibitors.