gebhart/patrepeval huggingface dataset:
Rumen and Serum Metabolomes in Response to Endophyte-Infected Tall Fescue Seed and Isoflavone Supplementation in Beef Steers (2020)

Fescue toxicosis impacts beef cattle production via reductions in weight gain and muscle development. Isoflavone supplementation has displayed potential for mitigating these effects. The objective of the current study was to evaluate isoflavone supplementation with fescue seed consumption on rumen and serum metabolomes. Angus steers (<i>n</i> = 36) were allocated randomly in a 2 × 2 factorial arrangement of treatments including endophyte-infected (E+) or endophyte-free (E-) tall fescue seed, with (P+) or without (P-) isoflavones. Steers were provided a basal diet with fescue seed for 21 days, while isoflavones were orally administered daily. Following the trial, blood and rumen fluid were collected for metabolite analysis. Metabolites were extracted and then analyzed by UPLC-MS. The MAVEN program was implemented to identify metabolites for MetaboAnalyst 4.0 and SAS 9.4 statistical analysis. Seven differentially abundant metabolites were identified in serum by isoflavone treatment, and eleven metabolites in the rumen due to seed type (<i>p</i> < 0.05). Pathways affected by treatments were related to amino acid and nucleic acid metabolism in both rumen fluid and serum (<i>p</i> < 0.05). Therefore, metabolism was altered by fescue seed in the rumen; however, isoflavones altered metabolism systemically to potentially mitigate detrimental effects of seed and improve animal performance.
Amplifying the Red-Emission of Upconverting Nanoparticles for Biocompatible Clinically Used Prodrug-Induced Photodynamic Therapy (2014)

A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal β-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP-PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics.
MODIFIED SAUVÉ-KAPANDJI PROCEDURE FOR DISORDERS OF THE DISTAL RADIOULNAR JOINT IN PATIENTS WITH RHEUMATOID ARTHRITIS (2005)

Background: The Sauvé-Kapandji procedure has become popular for the treatment of disorders of the distal radioulnar joint in patients with rheumatoid arthritis, but this procedure is impossible to perform in patients with poor bone quality in the distal part of the ulna. We have modified the procedure for patients with poor bone quality in the distal part of the ulna. The modified procedure involves resecting the distal part of the ulna, making a drill-hole in the ulnar cortex of the distal part of the radius, rotating the resected portion of the ulna 90°, inserting it into the distal part of the radius, and fixing it at that site with use of an AO cancellous-bone screw. In the present report, we describe the new operative technique and report the results after a minimum duration of follow-up of three years. Methods: This operation was performed in fifty-six patients (sixty-six wrists) with rheumatoid arthritis. The mean age at the time of the operation was 59.3 years. The mean duration of follow-up was forty-eight months. Patients were evaluated in terms of wrist pain, grip strength, and range of motion. Radiographic evaluation included calculation of the carpal translation index to assess the extent of ulnar translation of the carpus. Results: Osseous union was achieved in all cases. Wrist pain resolved or decreased in all patients. The mean total range of forearm rotation increased from 144° preoperatively to 167° at the time of the most recent follow-up (p < 0.01). The mean carpal translation index did not change after the operation. Conclusions: The modified Sauvé-Kapandji procedure results in rigid fixation of the grafted bone. The technique provides sufficient osseous support of the carpus even in patients with rheumatoid arthritis and poor bone quality in the distal part of the ulna. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.
HER-2/neu transcriptionally activates Jab1 expression via the AKT/β-catenin pathway in breast cancer cells (2007)

Jab1 is a co-activator of activating protein-1 (AP-1) transcription factor and the fifth subunit of the constitutive photomorphogenesis 9 (COP9) signalosome, which has been shown to mediate nuclear exportation and ubiquitin-dependent degradation of the tumor suppressor p27(Kip1). Jab1 is overexpressed in several types of human cancer. However, de-regulation of Jab1 gene expression in cancer cells is largely unclear. In this study, we reported that expression of Jab1 was stimulated by HER-2/neu oncogene via transcriptional activation. Promoter deletion and mutation analysis indicated that HER-2/neu stimulated Jab1 via the T cell factor (TCF) binding site located at the -380/-368 region of the human Jab1 promoter. DNA affinity precipitation assay and chromatin immunoprecipitation assay verified that binding of beta-catenin and TCF-4 to this consensus site was increased by HER-2/neu. In addition, dominant-negative mutant of TCF significantly attenuated the stimulatory effect of HER-2/neu. We also demonstrated that HER-2/neu increased beta-catenin/TCF-mediated Jab1 expression via the AKT signaling pathway because chemical inhibitor or dominant-negative mutant of AKT effectively attenuated the stimulatory action of HER-2/neu. IGF-I, which is a well-known AKT activator, also up-regulated the expression of Jab1 in NIH/3T3 and MCF-7 cells. Knockdown of Jab1 by small interfering RNA (siRNA) preferentially inhibited proliferation of HER-2/neu-overexpressing breast cancer cells. Taken together, our results suggest that HER-2/neu transcriptionally activates Jab1 expression to promote proliferation of breast cancer cells.
Dual Inhibitors of Phosphodiesterase-4 and Serotonin Reuptake (2009)

A new class of multitarget compounds was synthesized by linking a novel selective serotonin reuptake inhibitor (SSRI) to a PDE4 inhibitor. The new dual PDE4 inhibitor/SSRI showed antidepressant-like activity in the forced swim test in mice The SSRIs 2-{5-[3-(5-fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethylamine (14) and 2-{5-[3-(5-fluoro-2-methoxy-phenyl)-propyl]-tetrahydro-furan-2-yl}-ethylamine (15) were both individually linked to the PDE4 inhibitor 4-(3,4-dimethoxy-phenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one (19), via a five-carbon chain. The dual PDE4 inhibitor/SSRI 2-{5-[3-(5-fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethylamine)-pentyl]-4,5,8,8a-tetrahydro-2H-phthalazin-1-one (21) showed potent and selective serotonin reuptake inhibition (IC(50) value of 127 nM). The dual PDE4 inhibitor/SSRI 21 also inhibited PDE4D3 with a K(i) value of 2.0 nM. The dual PDE4 inhibitor/SSRI was significantly more effective than the individual SSRI alone or fluoxetine in the forced swim test at standard doses. On a molar basis, the antidepressant-like effect of the dual PDE4 inhibitor/SSRI 21 showed a 129-fold increase in in vivo efficacy compared to fluoxetine.
Photoelectron Spectra and Electronic Structures of Substituted Pyrimidines (2005)

Abstract The electronic structures of pyrimidine ( 1 ) and its substituted derivatives 2 − 15 have been investigated by ultraviolet photoelectron spectroscopy and quantum chemical methods. The ionisation potentials corresponding to the π MOs π 1 ‐π 3 and the two n N orbitals of the pyrimidine unit could be determined and assigned for 1 − 15 . Multiple linear regression analyses of the IP s related to these orbitals with different substituent constants indicated that Hammett σ p values performed well for all these IP s, whereas the resonance parameters R and R + were satisfactory for π and poor for n N ionisations. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
Reproducibility of Performance and Certainty of Judgment in Maximal vs Feigned Muscular Effort (1999)

Detection of feigned muscular effort is a highly challenging topic in the medicolegal arena. Modern dynamometric methods have enabled a much higher accuracy in deciding whether the effort in question is indeed genuine or submaximal. Since in feigning the target, however, performance may fluctuate even within a single testing session, reproducibility cannot be assured. In actual claims, the statistical nature of certainty in proclaiming a feigned effort must be well understood by those involved in deciding the fate of a claim.
Stitching of heterogeneous images using depth information (2013)

We propose a novel heterogeneous image stitching algorithm, which employs disparity information as well as color information. It is challenging to stitch heterogeneous images that have different background colors and diverse foreground objects. To overcome this difficulty, we set the criterion that objects should preserve their shapes in the stitched image. To satisfy this criterion, we derive an energy function using color and disparity gradients. As the gradients are highly correlated with object boundaries, we can find the optimal seam from the energy function, along which two images are pasted. Moreover, we develop a retargeting scheme to reduce the size of the stitched image further. Experimental results demonstrate that the proposed algorithm is a promising tool for stitching heterogeneous images.
Phase I/II trial of gefitinib and RAD001 (everolimus) in patients (pts) with advanced non-small cell lung cancer (NSCLC) (2005)

7104 Background: The mechanisms of resistance to EGFR tyrosine kinase inhibitors remain poorly understood but may be related, in part, to dysregulation of downstream apoptotic pathways, such as the PI3K/Akt/PTEN axis. In preclinical models, inhibition of the PI3K/Akt pathway restores gefitinib (Iressa™) sensitivity in resistant cell lines. mTOR is a serine/threonine kinase located downstream of Akt that regulates cellular growth and G1/S cell cycle progression. RAD001 is an orally available mTOR inhibitor that inhibits growth of cancer cell lines, including A549. We undertook this phase I/II study to characterize the safety, pharmacokinetics (PK), and antitumor activity of the combination of gefitinib and RAD001 in pts with advanced NSCLC with no prior history of EGFR-directed therapy. Methods: Phase I: 3-pt cohorts with no intrapatient escalation, at RAD001 dose levels of 5 and 10 mg daily. All pts received gefitinib 250 mg daily. PK studies were performed over a 3-week period during which pts received a single dose of RAD001 on day 1, followed by daily gefitinib on day 8, and then daily RAD001 on day 22. 6 pts will be treated at the MTD or highest RAD001 dose level prior to expanding to the phase II portion. Results: 6 pts have been enrolled to date. Patient characteristics: Female: 3; Karnofsky Performance Status median 80%; age median 62; prior chemotherapy median 2 (1–4). Toxicity (≥ Grade 2): by RAD001 dose level, 5 mg (n=3): 1 patient developed G2 stomatitis; 10 mg (n=3): 1 pt developed G2 diarrhea and G3 stomatitis, 1 pt developed G3 diarrhea, hypokalemia, and creatinine elevation, and G4 acidosis. Preliminary PK studies demonstrate AUC ratios (combination/alone) of 1.32 ± 0.46 for RAD001 and 1.15 ± 0.14 for gefitinib. Within the 5 mg dose level, a 25 pack-year smoking male pt with squamous cell carcinoma experienced a confirmed partial response; no EGFR exon 19 or 21 mutation was identified. Conclusions: 2 patients experienced dose-limiting toxicity (DLT) in the 10 mg dose level. 3 more patients will be enrolled in the RAD001 5 mg dose level prior to expanding to the phase II portion. Preliminary PK data suggests no significant interactions between the agents. Supported, in part, by Novartis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis AstraZeneca, Novartis AstraZeneca
Preface/Front Matter (1994)

During the past decade, plant biology has been revolutionized by application of the methods and concepts of molecular genetics. During this period, the small mustard Arabidopsis thaliana has emerged as the most widely used and facile experimental organism for studies of a broad range of problems in development, metabolism, genetics, environmental adaptation, pathogen interactions, and many other areas. Although it is a typical higher plant in most respects, and is therefore a good model for approximately 250,000 other species, Arabidopsis has an unusually small genome, can be readily grown in confined laboratory environments, has convenient genetic properties such as a short generation time and prolific seed production, and is easily transformed. For these and related reasons, biological and genetic information about Arabidopsis is in a phase of explosive growth, and Arabidopsis has been chosen as the major organism for plant genome projects. This book represents a synthesis of currently available information about the biology of Arabidopsis, written by a consortium of authors and groups of authors representing the major fields of enquiry in plant biology. It provides up-to-date reviews, descriptions of recent and ongoing research in specific areas, and reference material. Plant molecular biology and, in particular, Arabidopsis molecular biology are rapidly changing fields, and the pace of change is increasing. Because of this, the authors of each chapter have been asked to include unpublished information as well as published work and to indicate the expected future directions of research in each area. Since Arabidopsis is of interest as a
E122 Development of a method for detecting nuclear fuel debris and water leaks at a nuclear reactor/containment vessel by flow visualization (2013)

It is the important issue to fill up each nuclear reactor/containment vessel with water and to take out debris of damaged fuel from them for decommissioning of Fukushima Daiichi nuclear power plants. It is necessary to detect the debris and water leaks at a nuclear reactor/containment vessel for the purpose However, the method is not completely developed in the present stage. Accordingly, we have developed a method for detecting debris and water leaks at a nuclear reactor/containment vessel by flow visualization Experiments of the flow visualization were conducted using two types of water tanks An optical fiber and a collimator lens were employed for modifying a straight laser beam into a sheet projection Some visualized images were obtained through the experiments. Particle Image Velocimetry, i.e. PIV, analysis was applied to the images for quantitative flow rate analysis. Consequently, it is considered that the flow visualization method has a possibility for the practical use.
Outcome of Debridement and Retention in Prosthetic Joint Infections by Methicillin-Resistant Staphylococci, with Special Reference to Rifampin and Fusidic Acid Combination Therapy (2012)

The management of prosthetic joint infections remains a clinical challenge, particularly infections due to methicillin-resistant staphylococci. Previously, this infection was considered a contraindication to debridement and retention strategies. This retrospective cohort study examined the treatment and outcomes of patients with arthroplasty infection by methicillin-resistant staphylococci managed by debridement and retention in conjunction with rifampin-fusidic acid combination therapy. Over an 11-year period, there were 43 patients with infection by methicillin-resistant staphylococci managed with debridement and retention. This consisted of close-interval repeated arthrotomies with pulsatile lavage. Rifampin was combined with fusidic acid for the majority of patients (88%). Patients were monitored for a median of 33.5 months (interquartile range, 20 to 54 months). Overall, 9 patients experienced treatment failure, with 12- and 24-month estimates of infection-free survival of 86% (95% confidence interval [CI], 71 to 93%) and 77% (95% CI, 60 to 87%), respectively. The following factors were associated with treatment failure: methicillin-resistant Staphylococcus aureus (MRSA) arthroplasty infection, a single surgical debridement or ≥4 debridements, and the receipt of less than 90 days of antibiotic therapy. Patients with infection by methicillin-resistant coagulase-negative staphylococci (MR-CNS) were less likely to fail treatment. The overall treatment success rate reported in this study is comparable to those of other treatment modalities for prosthetic joint infections by methicillin-resistant staphylococci. Therefore, the debridement and retention of the prosthesis and rifampin-based antibiotic therapy are a valid treatment option for carefully selected patients.
Physician computer skills: a prerequisite to the future in healthcare services. (2007)

Physicians in Kentucky have been slow to endorse and implement electronic medical records and other forms of information technology (IT), although this technology is available to them. Information was ob tained from medical relicensure data for all licensed Kentucky physicians and through two sample surveys to assess the use of IT in Kentucky medicine. Sixty-eight percent of licensed physicians recorded an e-mail address on their annual relicensure application, but more physicians were knowledgeable about IT than indicated by this relicensure response. A recorded e-mail address was more likely for younger physicians, physicians in hospital-based specialties, and those in larger medical specialty or academic physician groups. Those entering an email address were more likely to use IT for e-mail, word-processing, searching medical literature, and even consulting with other physicians. Only 10% of physicians with an e-mail address and 4.5% ofj those who did not list an e-mail address used e-mail to communicate with patients. Physicians entering an e-mail address were also more likely to employ an electronic medical record in their practice. Increased use of IT in medical practices is likely only if it can be associated with an increase in reimbursement or an improvement in quality of care.
Correspondence (2015)

*Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, Maryland †Department of Ophthalmology, Northwestern University, Chicago, Illinois None of the authors have any financial/conflicting interests to disclose.
Alteration of gene expression during progression of hypertension-induced cardiac dysfunction in rats (2008)

Hypertension induced by high-salt diet in Dahl salt-sensitive rats leads to compensatory cardiac hypertrophy by approximately 11 wk, cardiac dysfunction at approximately 17 wk, and death from cardiac dysfunction at approximately 21 wk. It is unclear what molecular hallmarks distinguish the compensatory hypertrophy from the decompensated cardiac dysfunction phase. Here we compared the gene expression in rat cardiac tissue from the compensatory hypertrophic phase (11 wk, n = 6) with the cardiac dysfunction phase (17 wk, n = 6) and with age-matched normotensive controls. Messenger RNA levels of 93 genes, selected based on predicted association with cardiac dysfunction, were measured by quantitative real-time PCR. In the hypertrophic phase, the expression of three genes, atrial natriuretic peptide (ANP; P = 0.0089), brain natriuretic peptide (P = 0.0012), and endothelin-1 precursor (P = 0.028), significantly increased, whereas there was decreased expression of 24 other genes including SOD2 (P = 0.0148), sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a (P = 0.0002), and ryanodine receptor 2 (P = 0.0319). In the subsequent heart cardiac dysfunction phase, the expression of an additional 20 genes including inducible nitric oxide synthase (NOS; P = 0.0135), angiotensin I-converting enzyme (P = 0.0082), and IL-1beta (P < 0.0001) increased, whereas the expression of seven genes decreased compared with those of age-matched controls. Furthermore, the expression of 22 genes, including prepro-endothelin-1, ANP, angiotensin I-converting enzyme, beta(1)-adrenergic receptor, SOD2, and endothelial NOS, significantly changed in the cardiac dysfunction phase compared with the compensatory hypertrophic phase. Finally, principal component analysis successfully segregated animals with decompensatory cardiac dysfunction from controls, as well as from animals at the compensated hypertrophy phase, suggesting that we have identified molecular markers for each stage of the disease.
Bisphosphonates as a Foundation of Drug Delivery to Bone (2002)

Bisphosphonates are organic analogues of pyrophosphate that are resistant to hydrolysis. Bisphosphonates exhibit an exceptional affinity to bone, which led to exploration of their utility for targeting pharmacological agents to bone. Among the pharmacological agents explored for bone delivery are radioisotopes, anti-neoplastic drugs, agents intended for augmentation of systemic bone mass, anti-inflammatory drugs and proteins. This review is intended to provide a summary of the literature on bisphosphonate-based drug delivery. A survey of therapeutic agents designed for bone targeting was provided in the first part of this review. Special emphasis was placed on the preclinical performance of the developed agents. In the second part, several aspects that were considered critical for the success of bisphosphonate-based drug delivery were explored. These aspects were oral bioavailability, protein binding of BPs, the nature of a BP-drug linkage and the choice of bone-affinity molecule. This article concludes with the author's perspective on the future of bisphosphonate-based drug delivery.
Miniaturized biocatalysis on polyacrylate‐based capillary monoliths (2010)

Abstract We developed a synthetic concept for the immobilization of enzymes onto monolithic supports. In addition, we elaborate on a generally applicable method for the rapid screening of the activity of such immobilized enzymes. For these purposes, we prepared monolithic acrylate‐based systems by electron‐beam (EB)‐triggered free‐radical polymerization within the confines of 200‐μm capillary columns. Aiming for protein immobilization, we subjected the polyacrylate‐based monoliths to EB‐mediated grafting processes to introduce functional surface‐located groups suited for the subsequent generation of functional units that themselves could bind different proteins. For the generation of the functional units, we used ring‐opening metathesis polymerization and free‐radical polymerization. The produced systems were tested for their ability to bind or repel proteins as exemplified by the use of the serine protease trypsin, which was used to catalyze the hydrolysis of N‐α‐benzoyl‐ L ‐arginine ethyl ester (BAEE). Finally, the monolith‐immobilized trypsin systems were used for enzymatic peptide synthesis purposes, such as the acyl transfer of BAEE to amino acid amides. Complementarily, we used an immobilized trypsin variant, which we additionally subjected to on‐column chemical modification with succinic anhydride to alter its synthetic properties. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011