gebhart/patrepeval huggingface dataset:
Pharmacological Treatment of Atrial Fibrillation: Mechanisms of Action and Efficacy of Class III Drugs (2006)

Atrial fibrillation represents a major clinical, social and economical matter, and its importance is expected to increase even more in the near future. The progressive ageing of population is associated with an inevitable rising in incidence and prevalence of this rhythm disorder, which limits functional capability, favours occurrence of cerebrovascular events and increases people's request for emergency room visits and hospital recovery. In spite of the increasing successes of the interventional non-pharmacological therapies, drug treatment of patients with atrial fibrillation in relation to conversion to sinus rhythm and prevention of recurrences, maintains a critical role. Several antiarrhythmic drugs are nowadays available, but their efficacy is limited by the high rate of arrhythmias recurrences and by side effects during acute and chronic treatment. Drugs interfering with potassium channels (Class III drugs) have been proposed and used in patients with atrial fibrillation. Aim of this review is to discuss the most recent data on the efficacy and feasibility of class III drugs in atrial fibrillation. Experimental and clinical data on dronedarone, ibutilide, dofetilide, azimilide, ersentilide and ambasilide will be hereby discussed.
A Green Fluorescent Protein Fusion to Actin-Binding Domain 2 of Arabidopsis Fimbrin Highlights New Features of a Dynamic Actin Cytoskeleton in Live Plant Cells (2004)

The actin cytoskeleton coordinates numerous cellular processes required for plant development. The functions of this network are intricately linked to its dynamic arrangement, and thus progress in understanding how actin orchestrates cellular processes relies on critical evaluation of actin organization and turnover. To investigate the dynamic nature of the actin cytoskeleton, we used a fusion protein between green fluorescent protein (GFP) and the second actin-binding domain (fABD2) of Arabidopsis (Arabidopsis thaliana) fimbrin, AtFIM1. The GFP-fABD2 fusion protein labeled highly dynamic and dense actin networks in diverse species and cell types, revealing structural detail not seen with alternative labeling methods, such as the commonly used mouse talin GFP fusion (GFP-mTalin). Further, we show that expression of the GFP-fABD2 fusion protein in Arabidopsis, unlike GFP-mTalin, has no detectable adverse effects on plant morphology or development. Time-lapse confocal microscopy and fluorescence recovery after photobleaching analyses of the actin cytoskeleton labeled with GFP-fABD2 revealed that lateral-filament migration and sliding of individual actin filaments or bundles are processes that contribute to the dynamic and continually reorganizing nature of the actin scaffold. These new observations of the dynamic actin cytoskeleton in plant cells using GFP-fABD2 reveal the value of this probe for future investigations of how actin filaments coordinate cellular processes required for plant development.
Polymerase Chain Reaction Assays for the Detection and Discrimination of the Soybean Rust PathogensPhakopsora pachyrhiziandP. meibomiae (2002)

ABSTRACT Soybean rust occurs in Australia and many countries throughout Africa, Asia, and South America. The causal agents of soybean rust are two closely related fungi, Phakopsora pachyrhizi and P. meibomiae, which are differentiated based upon morphological characteristics of the telia. Determination of the nucleotide sequence of the internal transcribed spacer (ITS) region revealed greater than 99% nucleotide sequence similarity among isolates of either P. pachyrhizi or P. meibomiae, but only 80% sequence similarity between the two species. Utilizing differences within the ITS region, four sets of polymerase chain reaction (PCR) primers were designed specifically for P. pachyrhizi and two sets for P. meibomiae. Classical and real-time fluorescent PCR assays were developed to identify and differentiate between P. pachyrhizi and P. meibomiae. Identification of P. pachyrhizi from infected soybean leaves using the real-time PCR assay will allow for more rapid diagnoses.
Lithium Ion Battery Aging Experiments and Algorithm Development for Life Estimation (2011)

Battery lifespan is one of the largest considerations when designing battery packs for electrified vehicles.Even during vehicle operation, it is essential to monitor the progression of a battery health as it degrades and predict battery life.This thesis presents a preliminary severity factor analysis based on available experimental data and details the development of an algorithm for predicting, while in operation, the remaining life of a battery based on the growth of internal resistance.Nine lithium ion batteries were systematically aged through severe aging protocols spanning multiple C-rates (2C, 4C and 8C), low ranges of SOC (0-10, 0-20 and 0-30%), and elevated temperature (55 deg C).Their internal resistance was continuously calculated at each sharp current transition, and these values were filtered and processed.Severity factors were calculated for each battery by determining the average rate of resistance growth over a battery life and a preliminary analysis of these factors was carried out.A resistance growth dynamic model was developed to identify rates of resistance growth on a local basis as resistance values were collected.These local rates of resistance growth were then used to calculate predicted future rates of resistance growth, which were in turn used to predict remaining life.The life prediction algorithm produced continuously updated predictions of remaining battery life that proved relatively accurate for cases of constant battery aging conditions.This computationally simple algorithm could be implemented onboard an iii electrified vehicle to provide estimates of remaining battery life based on resistance growth.This methodology can in principle be readily extended to track capacity degradation as well, provided that a feasible capacity estimator can be developed on the basis of vehicle measurements.Thank you to Giorgio Rizzoni and the entire OSU
Osteopontin is produced by mast cells and affects IgE‐mediated degranulation and migration of mast cells (2008)

Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and FcepsilonRI aggregation in bone marrow-derived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN(-/-)) and -sufficient (OPN(+/+)) mice without significant differences in yield, purity, granularity, and viability. Using OPN(-/-) FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin alphav). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN(-/-) mice compared with OPN(+/+) mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions.
ChemInform Abstract: 2‐Substituted Aminopyrido[2,3‐d]pyrimidin‐7(8H)‐ones. Structure—Activity Relationships Against Selected Tyrosine Kinases and in vitro and in vivo Anticancer Activity. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Role of transforming growth factor-β in hematologic malignancies (2006)

The transforming growth factor-beta (TGF-beta) signaling pathway is an essential regulator of cellular processes, including proliferation, differentiation, migration, and cell survival. During hematopoiesis, the TGF-beta signaling pathway is a potent negative regulator of proliferation while stimulating differentiation and apoptosis when appropriate. In hematologic malignancies, including leukemias, myeloproliferative disorders, lymphomas, and multiple myeloma, resistance to these homeostatic effects of TGF-beta develops. Mechanisms for this resistance include mutation or deletion of members of the TGF-beta signaling pathway and disruption of the pathway by oncoproteins. These alterations define a tumor suppressor role for the TGF-beta pathway in human hematologic malignancies. On the other hand, elevated levels of TGF-beta can promote myelofibrosis and the pathogenesis of some hematologic malignancies through their effects on the stroma and immune system. Advances in the TGF-beta signaling field should enable targeting of the TGF-beta signaling pathway for the treatment of hematologic malignancies.
Pseudotyping the adenovirus serotype 5 capsid with both the fibre and penton of serotype 35 enhances vascular smooth muscle cell transduction (2013)

Ex vivo gene therapy during coronary artery bypass grafting (CABG) holds great potential to prevent excessive smooth muscle cell (SMC) proliferation, neointima formation and graft failure. The most successful preclinical strategies to date have utilised vectors based on the species C adenovirus, Ad5, which engages the Coxsackie and Adenovirus receptor (CAR) as its primary attachment receptor. Profiling receptors on human SMCs demonstrated the absence of CAR but substantial expression of the species B receptor CD46. We performed transduction experiments using Ad5 and the CD46-utilising adenovirus Ad35, and found Ad35 significantly more efficient at transducing SMCs. To evaluate whether transduction could be further augmented, we evaluated chimeric CD46-utilising Ad5/Ad35 vectors comprising the Ad5 capsid pseudotyped with the Ad35 fibre alone (Ad5/F35) or in combination with the Ad35 penton (Ad5/F35/P35). In human smooth muscle cells (hSMCs), Ad5/F35/P35 mediated significantly higher levels of transduction than either parental vector or Ad5/F35. Ex vivo transduction experiments using mouse aortas from CD46 transgenics demonstrated that Ad5/F35/P35 was significantly more efficient at transducing SMCs than the other vectors tested. Finally, ex vivo transduction and immunofluorescent colocalisation experiments using human tissue from CABG procedures confirmed the preclinical potential of Ad5/F35/P35 as an efficient vector for vascular transduction during CABG.
Design of an image edge detection filter using the Sobel operator (1988)

The architecture of the edge detector presented is highly pipeline to perform the computations of gradient magnitude and direction for the output image samples. The chip design is based on a 2- mu m, double-metal, CMOS technology and was implemented using a silicon compiler system in less than 2 man-months. It is designed to operate with a 10-MHz two-phase clock, and it performs approximately 200*10/sup 6/ additions/s to provide the required magnitude and direction outputs every clock cycle. The function of the chip has been demonstrated with a prototype system that is performing image edge detection in real time.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dissolution Kinetics and Solubility of ZnO Nanoparticles Followed by AGNES (2012)

There is a current debate on whether the toxicity of engineered ZnO nanoparticles (NPs) can be traced back to their nanoscale properties or rather to the simple fact of their relatively high solubility and consequent release of Zn2+ ions. In this work, the emerging electroanalytical technique AGNES (Absence of Gradients and Nernstian Equilibrium Stripping), which is specially designed to determine free metal ion concentration, is shown to be able to measure the Zn2+ concentration resulting from dissolution of ZnO nanoparticles dispersed in aqueous salt solutions. Three NP samples from different sources (having average primary particle diameters of 6, 20, and 71 nm) were tested and compared with bulk ZnO material. The enhanced solubility of the nanoparticles with decreasing primary radius allows for an estimation of the surface energy of 0.32 J/m2. AGNES also allows the study of the kinetics of Zn2+ release as a response to a change in the solution parameters (e.g., pH, ZnO concentration). A physicochemical model has been developed to account for the observed kinetic behavior. With this model, only one kinetic parameter is required to describe the time dependence of the free Zn2+ concentration in solution. Good agreement with this prediction is obtained when, starting from an equilibrated NP dispersion, the pH of the medium is lowered. Also, the independence of this parameter from pH, as expected from the model, is obtained at least in the pH range 7–9. When dissolution is studied by dispersing ZnO nanoparticles in the medium, the kinetic parameter initially decreases with time. This decrease can be interpreted as resulting from the increase of the radius of the clusters due to the agglomeration/aggregation phenomena (independently confirmed). For the larger assayed NPs (i.e., 20 and 71 nm), a sufficiently large pH increase leads to a metastable solubility state, suggesting formation of a hydroxide interfacial layer.
Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo (1997)

Ursodeoxycholate (UDCA) has anti-inflammatory and chemoprotective effects in animal models of inflammatory bowel disease and colon cancer. Because overproduction of nitric oxide (NO) by the inducible isoform of NO synthase (iNOS) is implicated in the pathogenesis of these conditions, we investigated the ability of UDCA to inhibit NO production in transformed human intestinal epithelial (DLD-1) cells. Nitrite/nitrate production was measured by the Griess reaction, enzymatic activity of iNOS was assessed by conversion of L-arginine to L-citrulline, and protein and mRNA were measured by Western and Northern blotting. Dose-dependent inhibition of interleukin-1 beta- and interferon-gamma-stimulated nitrite/nitrate production was observed when cells were preincubated for 6 h with UDCA (0-800 microM), and a substantial inhibition (81 +/- 3.2%) was seen at 500 microM. In cytokine-stimulated cells, UDCA reduced iNOS mRNA, protein, and enzyme activity without exerting cytotoxicity. UDCA had a minimal direct inhibitory effect on iNOS enzyme activity. UDCA pretreatment also reduced the expression of iNOS in the colonic epithelium of rats treated with bacterial lipopolysaccharide. Thus UDCA inhibits the induction of epithelial iNOS in vitro and in vivo, and this effect may contribute to the anti-inflammatory and chemoprotective actions of UDCA.
Use of recombinant protein to identify a motif-negative human cytotoxic T-cell epitope presented by HLA-A2 in the hepatitis C virus NS3 region (1996)

To define cytotoxic T-cell (CTL) epitopes, the common approach involving the use of a series of overlapping synthetic peptides covering the whole protein sequence is impractical for large proteins. Motifs identify only a fraction of epitopes. To identify human CTL epitopes in the NS3 region of hepatitis C virus (HCV), we modified an approach using recombinant protein and the ability of short peptides to bind to class I major histocompatibility complex (MHC) molecules. Peripheral blood mononuclear cells from an HCV-infected patient were stimulated with a proteolytic digest of the recombinant NS3 protein to expand CTL to any active peptides in the digest. The digest was fractionated by reverse-phase high-performance liquid chromatography, and fractions were assessed for the ability to sensitize targets for lysis by CTL. The most active fraction was sequenced, identifying a 15-residue peptide (NS3-1J; TITTGAPVTYSTYGK). This sequence was confirmed to be the source of the activity by synthesis of the corresponding peptide. CTL lines specific for NS3-1J were established from two HCV-infected patients (both HLA-A2 and -B7 positive) by stimulation with the synthetic peptide in vitro. The CTL were HLA-A2 restricted, and the minimal epitope was mapped to a decapeptide NS3-1J (10.4). As this minimal epitope lacks the common HLA-A2-binding motif, this technique is useful for mapping CTL epitopes independent of known motifs and without the requirement for enormous numbers of overlapping peptides. Because this peptide is presented by the most common HLA class I molecule, present in almost half the population, it might be a useful component of a vaccine against HCV.
Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. (2001)

The expression level of the androgen receptor (AR) gene in androgen-dependent and -independent prostate cancer was determined by using real-time quantitative reverse transcription-PCR assay. Eight benign prostate hyperplasias, 33 untreated and 13 hormone-refractory locally recurrent carcinomas, as well as 10 prostate cancer xenografts, were analyzed. All hormone-refractory tumors expressed AR and showed, on average, 6-fold higher expression than androgen-dependent tumors or benign prostate hyperplasias (P < 0.001). Four of 13 (31%) hormone-refractory tumors contained AR gene amplification detected by fluorescence in situ hybridization. Androgen-independent tumors with gene amplification expressed, on average, a 2-fold higher level of AR than the refractory tumors without the gene amplification. Two xenografts (LuCaP 35 and 69) showed amplification and high-level expression of the AR gene. These xenografts are the first prostate cancer model systems containing the gene amplification. The findings demonstrate that AR is highly expressed in androgen-independent prostate cancer, suggesting that the AR signaling pathway is important in the progression of prostate cancer during endocrine treatment. The two xenografts with the AR gene amplification will enable studies evaluating the functional significance of the amplification and development of new treatment strategies based on high-level expression of AR.
Local anesthetic update. (1993)

The development of new local anesthetics has not been an area of particularly active research for a number of years. However, as the use of regional anesthesia has expanded, additional anesthetic requirements and techniques have stimulated the search for newer drugs and ways of modifying existing ones. This article reviews some of the more recent developments in this field.
The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase. (1992)

Lipoprotein lipase (LPL), the major lipolytic enzyme involved in the conversion of triglyceride-rich lipoproteins to remnants, was found to compete with binding of activated alpha 2-macroglobulin (alpha 2M*) to the low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor. Bovine milk LPL displaced both 125I-labeled alpha 2M* and 39-kDa alpha 2M receptor-associated protein (RAP) from the surface of cultured mutant fibroblasts lacking LDL receptors with apparent KI values at 4 degrees C of 6.8 and 30 nM, respectively. Furthermore, LPL inhibited the cellular degradation of 125I-alpha 2M* at 37 degrees C. Because both alpha 2M* and RAP interact with LRP, these data suggest that LPL binds specifically to this receptor. This was further supported by observing that an immunoaffinity-isolated polyclonal antibody against LRP blocked cellular degradation of 125I-LPL in a dose-dependent manner. In addition, 125I-LPL bound to highly purified LRP in a solid-phase assay with a KD of 18 nM, and this binding could be partially displaced with alpha 2M* (KI = 7 nM) and RAP (KI = 3 nM). Taken together, these data establish that LPL binds with high affinity to LRP and undergoes LRP-mediated cellular uptake. The implication of these findings for lipoprotein catabolism in vivo may be important if LRP binding is preserved when LPL is attached to lipoproteins. If so, LPL might facilitate LRP-mediated clearance of lipoproteins.
How Well Do MWL and CEL Preparations Represent the Whole Hardwood Lignin? (2014)

Hardwood lignin preparations were isolated using classical milled wood lignin (MWL) and cellulolytic enzyme lignin (CEL) protocols. Furthermore, we managed to produce a lignin preparation of a very high yield, above 90%, with high purity and minimal structural degradation. This was achieved by dissolution and regeneration of milled wood prior to enzymatic hydrolysis, along with the use of 80% dioxane for lignin extraction. This preparation (RCEL-80) yield was about 4.5 and 2.5 times higher than the yields of the traditional MWL and CEL preparations, correspondingly, at the same milling time. The preparations obtained were comprehensively analyzed with state-of-the-art quantitative NMR techniques and wet chemistry methods. CELs were representative preparations for hardwood lignins as the S/G ratios in the CELs were equivalent to those in lignin in situ. Degradation of the main lignin subunits was very low. Importantly, the structures of CELs were independent of the preparation yield and were very similar to the structure of the high-yield lignin, RCEL-80. In contrast, the structures of MWLs were noticeably dependent on the preparation yield, especially when the yield was below 15–20% of total wood lignin. In particular, the S/G ratio increased with increasing MWL yield, but was still lower than the S/G ratios of the whole lignins in situ, even at high MWL yields. The amounts of β-O-4 lignin units in MWL were lower than those in the corresponding CEL preparations. It has been concluded that CEL preparations were representative of the whole wood lignin whereas MWLs represent a fraction with a lower S/G ratio.
Characterization of Mouse Spleen Cells by Subtractive Proteomics (2005)

Major analytical challenges encountered by shotgun proteome analysis include both the diversity and dynamic range of protein expression. Often new instrumentation can provide breakthroughs in areas where other analytical improvements have not been successful. In the current study, we utilized new instrumentation (LTQ FT) to characterize complex protein samples by shotgun proteomics. Proteomic analyses were performed on murine spleen tissue separated by magnetic beads into distinct CD45- and CD45+ cell populations. Using shotgun protein analysis we identified approximately 2,000 proteins per cell group by over 12,000 peptides with mass deviations of less than 4.5 ppm. Datasets obtained by LTQ FT analysis provided a significant increase in the number of proteins identified and greater confidence in those identifications and improved reproducibility in replicate analyses. Because CD45- and not CD45+ cells are able to regenerate functional pancreatic islet cells in a mouse model of type I diabetes, protein expression was further compared by a subtractive proteomic approach in search of an exclusive protein expression profile in CD45- cells. Characterization of the proteins exclusively identified in CD45- cells was performed using gene ontology terms via the Javascript GoMiner. The CD45- cell subset readily revealed proteins involved in development, suggesting the persistence of a fetal stem cell in an adult animal.