gebhart/patrepeval huggingface dataset:
Relationships between topoisomerase II inhibition, sequence-specificity and DNA binding mode of dicationic diphenylfuran derivatives. (1999)

Four diphenylfuran derivatives possessing different dicationic terminal side chains were used to investigate sequence-specific binding to DNA and poisoning of human topoisomerase II. Footprinting experiments with a range of DNA substrates attest that all four drugs bind selectively to AT-rich sequences in DNA. However, the quantitative analysis of the footprinting profiles reveals significant differences in terms of AT-selectivity according to the nature of the basic side chains. Furimidazoline (DB60) shows a reduced capacity to interact selectively with A.T tetrads compared with furamidine (DB75) and the 3-pentyl-substituted diamidine analogue DB226. DB244, for which the two amidine ends are substituted with a cyclopentyl group, exhibits the most pronounced AT specificity. It binds tightly to sites composed of at least four adjacent AT base pairs, such as 5'-TAAT, AATT and TTTT. At low concentrations (< 2 microM) DB60 is also capable of forming stable complexes with AT sites but at higher concentrations the binding becomes totally non-specific due to additional intercalation of drug molecules into GC-rich sequences. Nevertheless, DB60 is the only drug is the series which stabilizes DNA-topoisomerase II covalent complexes. This compound effectively promotes DNA cleavage by topoisomerase II whereas DB75, DB226 and DB244 have practically no effect. The topoisomerase II poisoning activity of DB60 correlates with its ability to intercalate into GC sites in DNA whereas the three other diphenylfurans essentially behave as typical AT-selective minor groove binders. The study suggests that the antimicrobial activity of the diphenylfurans, which are active against the Pneumocystis carinii pathogen (PCP), depends essentially on their capacity to recognize AT-rich DNA sequences rather than their ability to interfere with topoisomerase II. In contrast, the cytotoxicity of drugs like DB60 would be connected with the formation of intercalation complexes and the stimulation of DNA cleavage by human topoisomerase II.
Undergraduate education in power electronics (1994)

This paper addresses the issue of undergraduate education in the field of power electronics. Based on the 1990 survey conducted by the Power Engineering Education Resources Subcommittee, we carefully study the collected data to address key issues regarding undergraduate education in power electronics. Suggested curriculum in power electronics is presented. Moreover, state-of-the-art power electronics laboratory set-up along with supporting simulation laboratory is described. Simulation design examples using Pspice program for some power electronics projects are given.
Performance Evaluation of Type II and Type IIa Box Beam End Terminals. Part III (2012)

This paper, part 3 of a multi-part series, reports on a study to evaluate the safety performance of the New York State Department of Transportation box beam Type II and Type IIA guide rail end terminals. A literature review on previous crash testing of relevant box beam guide rails, box beam median barriers and box beam end terminals first was undertaken, with emphasis on research and development efforts involving Type II and Type IIA end terminals. Next, a series of nine full-scale vehicle crash tests was performed on both types of end terminal systems. The tests were conducted according to AASHTO Manual for Assessing Safety Hardware (MASH) criteria with either a passenger car or a pickup truck. The test results were analyzed, evaluated and documented. The results showed that the Type II box beam end terminal system did not contain nor redirect the test vehicle. Significant deformations of, or intrusions into, the occupant compartment also occurred. These findings indicate that the Type II end terminal is unacceptable according to modified test designation no. 3-32 of the TL-3 safety performance criteria found in MASH.
Neuroprotective Effects of Transferrin in Experimental Glaucoma Models (2022)

Iron is essential for retinal metabolism, but an excess of ferrous iron causes oxidative stress. In glaucomatous eyes, retinal ganglion cell (RGC) death has been associated with dysregulation of iron homeostasis. Transferrin (TF) is an endogenous iron transporter that controls ocular iron levels. Intraocular administration of TF is neuroprotective in various models of retinal degeneration, preventing iron overload and reducing iron-induced oxidative stress. Herein, we assessed the protective effects of TF on RGC survival, using ex vivo rat retinal explants exposed to iron, NMDA-induced excitotoxicity, or CoCl<sub>2</sub>-induced hypoxia, and an in vivo rat model of ocular hypertension (OHT). TF significantly preserved RGCs against FeSO<sub>4</sub>-induced toxicity, NMDA-induced excitotoxicity, and CoCl<sub>2</sub>-induced hypoxia. TF protected RGCs from apoptosis, ferroptosis, and necrosis. In OHT rats, TF reduced RGC loss by about 70% compared to vehicle-treated animals and preserved about 47% of the axons. Finally, increased iron staining was shown in the retina of a glaucoma patient's eye as compared to non-glaucomatous eyes. These results indicate that TF can interfere with different cell-death mechanisms involved in glaucoma pathogenesis and demonstrate the ability of TF to protect RGCs exposed to elevated IOP. Altogether, these results suggest that TF is a promising treatment against glaucoma neuropathy.
Towards human exploration of space: The THESEUS review series on nutrition and metabolism research priorities (2016)

Nutrition has multiple roles during space flight from providing sufficient nutrients to meet the metabolic needs of the body and to maintain good health, to the beneficial psychosocial aspects related to the meals. Nutrition is central to the functioning of the body; poor nutrition compromises all the physiological systems. Nutrition is therefore likely to have a key role in counteracting the negative effects of space flight (e.g., radiation, immune deficits, oxidative stress, and bone and muscle loss). As missions increase in duration, any dietary/nutritional deficiencies will become progressively more detrimental. Moreover, it has been recognized that the human diet contains, in addition to essential macronutrients, a complex array of naturally occurring bioactive micronutrients that may confer significant long-term health benefits. It is therefore critical that astronauts be adequately nourished during missions. Problems of nutritional origin are often treatable by simply providing the appropriate nutrients and adequate recommendations. This review highlights six key issues that have been identified as space research priorities in nutrition field: in-flight energy balance; altered feeding behavior; development of metabolic stress; micronutrient deficiency; alteration of gut microflora; and altered fluid and electrolytes balance. For each of these topics, relevance for space exploration, knowledge gaps and proposed investigations are described. Finally, the nutritional questions related to bioastronautics research are very relevant to multiple ground-based-related health issues. The potential spin-offs are both interesting scientifically and potentially of great clinical importance.
A genome-wide linkage study of mammographic density, a risk factor for breast cancer (2011)

The suggestive peaks and the larger linkage signal seen in the subset of pedigrees with younger participants highlight regions of interest for further study to identify genes that determine MD, with the goal of understanding mammographic density and its involvement in susceptibility to breast cancer.
Measurement of the Parity-Violating Longitudinal Single-Spin Asymmetry forW±Boson Production in Polarized Proton-Proton Collisions ats=500  GeV (2011)

We report the first measurement of the parity-violating single-spin asymmetries for midrapidity decay positrons and electrons from W+ and W- boson production in longitudinally polarized proton-proton collisions at sqrt[s] = 500 GeV by the STAR experiment at RHIC. The measured asymmetries, A(L)(W+) = -0.27 ± 0.10(stat.) ± 0.02(syst.) ± 0.03(norm.) and A(L)(W-) = 0.14 ± 0.19(stat.) ± 0.02(syst.) ± 0.01(norm.), are consistent with theory predictions, which are large and of opposite sign. These predictions are based on polarized quark and antiquark distribution functions constrained by polarized deep-inelastic scattering measurements.
Efficient implementation of a variable projection order affine projection algorithm (2010)

Many fast affine projection (FAP) algorithms have been proposed in the last two decades. These algorithms offer a good tradeoff between convergence rate and computational complexity. Most of the existing FAP algorithms use a constant projection order. Recently, the evolutionary APA (E-APA) with a variable projection order has been proposed. In this paper, an efficient implementation of the E-APA based on dichotomous coordinate descent (DCD) method is proposed and investigated. It is shown that the proposed algorithm obtains both fast convergence speed and small steady-state error.
VACCINATION OF RHESUS MONKEYS WITH AN ANTI-IDIOTYPE ANTIBODY MIMICKING LEWIS Y (1994)

Journal of Immunotherapy with Emphasis on Tumor Immunology: October 1994 - Volume 16 - Issue 3 - p 240
Control-theoretic results on dynamic decision making (2008)

Several approaches to learning in dynamic decision making tasks are developed in this paper on the basis of the application of feedback control theory to the case study of the Sugar Production Factory task. Previous experimental models are not robust to workload change and require a large amount of information to be stored. The control model presented here not only avoids such shortcomings, but also significantly enhances the system efficiency, adaptivity and robustness. On the other hand, as trust and self-confidence are closely linked to the capacity of automation and manual control in a supervisory control system, it behooves us to develop a dynamic model to assist the operator in gaining a better understanding of capacities. A quantitative model of trust in automation is then proposed to accurately characterize operator's reliance on automation. Those results are demonstrated through simulation within a framework of a Sugar Factory supervisory control system.
<title>Simultaneous imaging and pH measurement with a single 250-micron-diameter optical fiber</title> (1993)

The distal tip of a 200 micrometers imaging fiber comprised of thousands of 2 micrometers fibers is coated with a thin layer of pH sensitive material. Polymerization is initiated thermally, and results in a uniform coating of polyHEMA/fluorescein on the order of 10 micrometers thick. Performance data for this fiber demonstrates it is capable of simultaneous pH measurements and near field imaging.
Uncertainty in AVO migration/inversion (1996)

AVO migration / inversion gives us estimates of elastic parameters from migrated prestack P-P reflection data. These estimates, as parameter images, can then be used for interpretation. In this work we examine the sources of uncertainty in these estimates and provide uncertainty images, in conjunction with the parameter images, to further aid interpretation. This area has recently begun to be explored (e.g., Beydoun et al, 1994; Tura and Hanitzsch, 1995). Here we further consider the specific sources of uncertainty and develop numerical methods for their measurement. The measured uncertainty can then be used in conjunction with the parameter images for enhanced interpretation.
Capacity and phase stability of metal-substituted α-Ni(OH)2 nanosheets in aqueous Ni–Zn batteries (2021)

Incorporating Al<sup>3+</sup> within α-Ni(OH)<sub>2</sub> nanosheets provides higher capacity in Ni–Zn cells with phase stability upon cycling compared to the other tested divalent substituents and unsubstituted α-Ni(OH)<sub>2</sub>.
Oxidation and epitaxy (1977)

The first order process models for silicon epitaxy and oxidation are described. Epitaxial dopant inclusion, autodoping and transient effects are discussed, and experimental results are presented. Silicon orientation, surface doping, and ambient effects are considered for silicon-oxidation rates. (Author)
Effects of a Synthetic Analogue of Vasopressin on Vascular Smooth Muscle. (1965)

SummaryPLV-2, a synthetic analogue of vasopressin, applied topically to the micro-vessels in the rat mesoappendix produces a graded dose response reduction in true capillary blood flow. The various vessel types contract from the venular to the arteriolar loops; the opposite of their normal profile of reactivity. This polypeptide, when injected i.v. in a single dose potentiates constrictor responses to topically applied catecholamines. In contrast to these microcirculatory effects, PLV-2 inhibits norepinephrine-induced contractions in the isolated rabbit aortic strip.
Subtype-specific secretomic characterization of pulmonary neuroendocrine tumor cells (2019)

Pulmonary neuroendocrine (NE) cancer, including small cell lung cancer (SCLC), is a particularly aggressive malignancy. The lineage-specific transcription factors Achaete-scute homolog 1 (ASCL1), NEUROD1 and POU2F3 have been reported to identify the different subtypes of pulmonary NE cancers. Using a large-scale mass spectrometric approach, here we perform quantitative secretome analysis in 13 cell lines that signify the different NE lung cancer subtypes. We quantify 1,626 proteins and identify IGFBP5 as a secreted marker for ASCL1<sup>High</sup> SCLC. ASCL1 binds to the E-box elements in IGFBP5 and directly regulates its transcription. Knockdown of ASCL1 decreases IGFBP5 expression, which, in turn, leads to hyperactivation of IGF-1R signaling. Pharmacological co-targeting of ASCL1 and IGF-1R results in markedly synergistic effects in ASCL1<sup>High</sup> SCLC in vitro and in mouse models. We expect that this secretome resource will provide the foundation for future mechanistic and biomarker discovery studies, helping to delineate the molecular underpinnings of pulmonary NE tumors.
The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines (2020)

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC <sub>50</sub> range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known DHODH requirements for immunomodulatory cytokine production, PTC299 inhibited the production of interleukin (IL)-6, IL-17A (also called IL-17), IL-17F, and vascular endothelial growth factor (VEGF) in tissue culture models. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and previously established favorable pharmacokinetic and human safety profiles render PTC299 a promising therapeutic for COVID-19.
Differences in the presentation and progression of Parkinson’s disease by sex (2020)

Abstract Objectives Identifying the contribution of biological sex to the heterogeneity in presentation and progression of Parkinson’s disease (PD). Background The different prevalence of Parkinson’s disease (PD) in men and women suggests that sex-associated mechanisms influence disease mechanisms. Investigating the contribution of sex to disease heterogeneity may uncover disease processes, and lead to new therapeutic targets. Also, understanding these differences in phenotypes will result in better patient management and the planning of more efficient clinical trials. Methods We tested 40 clinical phenotypes using longitudinal clinic-based patient cohorts consisting of 5,946 patients with a median follow-up of 3.1 years. For continuous outcomes, we used linear regressions at baseline to test the sex-associated differences in presentation, and linear mixed-effects models to test the sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox models for survival analyses. We adjusted for age, disease duration and dopaminergic medication usage. In the secondary analyses, data from 28,809 PD patients and 10,556 non-PD participants from Fox Insight, an online-only self-assessment cohort for PD research, were analyzed to check whether the sex-associated differences observed in the primary analyses were consistent in the cohort and whether the differences were unique to PD or not. Results Female PD patients had a higher risk for developing dyskinesia early during the follow-up period; with a slower progression in their difficulties of activities of daily living as measured by the Unified Parkinson’s Disease Rating Scale Part II (classic/MDS-revised version); and a lower risk of developing cognitive impairment than male patients. The findings in the longitudinal clinic-based cohorts were mostly consistent with the results in the online-only cohort. Conclusions This large-scale analysis observed the sex contribution to the heterogeneity of Parkinson’s disease. The results highlight the necessity of future research of the underlying mechanism and importance of personalized clinical management.
Heteroaryl-Fused 2-Phenylisothiazolone Inhibitors of Cartilage Breakdown (1994)

The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This effect is likely due to inhibition of MMP activation and a consequent reduction in MMP activity following IL-1 beta stimulation. Thus these compounds potentially represent simple, non-peptidic disease-modifying agents for the treatment of arthritic diseases. To examine the effects of structure on in vitro activity, three general features of the molecules were varied, substituents on the pendant N-phenyl group, the position of ring fusion to the isothiazolone, and substituents on the fused ring peri to the isothiazolone sulfur.
Towards an integrated understanding of cardiac arrhythmogenesis − Growing roles of experimental pathology (2016)

Cardiac arrhythmias have long been regarded as derangement of electrical impulse initiation and conduction within the heart. However, underlying mechanisms for arrhythmogenesis are not fully understood solely from the electrophysiological viewpoint. This review article discusses pathogenesis of arrhythmias from non‐electrical aspects, which were elucidated by spatiotemporal imaging of functional molecules in combination with morphological analysis of living heart tissues. Intracellular Ca 2+ ([Ca 2+ ] i ) overload, caused by myocardial injury, provokes Ca 2+ waves that could lead to abnormal excitations, i.e., triggered arrhythmias. Depressed Ca 2+ release from the sarcoplasmic reticulum, caused by ischemia, heart failure, or T‐tubular remodeling, results in spatiotemporally inhomogeneous [Ca 2+ ] i dynamics that could disturb impulse conduction, leading to reentrant tachyarrhythmias. Impairment of the gap junction‐mediated intercellular communications, which provokes derangement of impulse propagation of the myocardium, also leads to reentrant arrhythmias. Interpositions of non‐cardiomyocytes, especially fibroblasts, in the myocardium could also contribute to arrhythmogenesis via heterocellular gap‐junctional coupling with cardiomyocytes. Furthermore, alterations in myocardial histology, e.g., density and arrangements of myocytes in association with gap‐junctional distributions, could constitute important pathologic bases of atrial fibrillation. Integration of these molecular, functional, and morphological features of the myocardium, unveiled by experimental pathological approaches, would pave a new way for understanding pathogenesis of cardiac arrhythmias.
The IDET Procedure for Chronic Discogenic Low Back Pain (2004)

At 1-year post-IDET, half of patients were dissatisfied with their outcome. The percentage of patients on disability remained constant. The estimated proportion of patients undergoing fusion was predicted to be 15% at 1 year and 30% at 2 years.
Transport in a metallic nanotube at finite temperature (2009)

We consider the effect of thermal phonon displacements on the coherent transport in carbon nanotubes. The atomic displacements are generated using tight-binding molecular dynamics simulations, and the conductances are computed using a nonequilibrium Green's function technique. Atomic displacements due to lattice vibrations lead to different levels of conductance reduction and fluctuation on the massive and massless bands of a metallic nanotube. Different conduction regimes are studied by examining the resistance on different length scales. The temperature-induced displacements have a significant impact on the ballistic or diffusive transport in carbon nanotube.
Diddensiella caesifluorescens gen. nov., sp. nov., a riboflavin-producing yeast species of the family Trichomonascaceae (2012)

Four strains of a novel heterothallic yeast species were isolated from rotten wood collected in or near the Pilis Mountains in Hungary. The strains produced riboflavin in liquid culture. Analysis of gene sequences for the D1/D2 domains of the LSU nuclear rRNA, as well as analysis of concatenated gene sequences for the D1/D2 nuclear LSU rRNA, mitochondrial SSU rRNA and cytochrome oxidase II placed the novel species in a small clade including only two recognized species, Candida santjacobensis and Candida transvaalensis, in the family Trichomonascaceae. DNA sequence analyses demonstrated that the novel species was distinct from all currently recognized teleomorphic yeast genera. The name Diddensiella caesifluorescens gen nov., sp. nov. is proposed to accommodate the novel genus and species. The new genus proposed here can be recognized only from gene sequence analysis, because the characters of its asexual reproduction and ascospore formation are shared by several members of the genera Trichomonascus, Sugiyamaella and Spencermartinsiella. The type and isotype strains of D. caesifluorescens are NCAIM Y.01949(T) ( = NRRL Y-48781(T) = CBS 12613(T)) and NCAIM Y.01956(I) ( = NRRL Y-48782(I) = CBS 12614(I)), respectively. In view of their close relatedness to D. caesifluorescens, C. santjacobensis and C. transvaalensis are transferred to the genus Diddensiella as new combinations in accordance with changes in the International Code of Nomenclature for algae, fungi and plants.