gebhart/patrepeval huggingface dataset:
Handling missing values in the MDS‐UPDRS (2015)

This study was undertaken to define the number of missing values permissible to render valid total scores for each Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part. To handle missing values, imputation strategies serve as guidelines to reject an incomplete rating or create a surrogate score. We tested a rigorous, scale-specific, data-based approach to handling missing values for the MDS-UPDRS. From two large MDS-UPDRS datasets, we sequentially deleted item scores, either consistently (same items) or randomly (different items) across all subjects. Lin's Concordance Correlation Coefficient (CCC) compared scores calculated without missing values with prorated scores based on sequentially increasing missing values. The maximal number of missing values retaining a CCC greater than 0.95 determined the threshold for rendering a valid prorated score. A second confirmatory sample was selected from the MDS-UPDRS international translation program. To provide valid part scores applicable across all Hoehn and Yahr (H&Y) stages when the same items are consistently missing, one missing item from Part I, one from Part II, three from Part III, but none from Part IV can be allowed. To provide valid part scores applicable across all H&Y stages when random item entries are missing, one missing item from Part I, two from Part II, seven from Part III, but none from Part IV can be allowed. All cutoff values were confirmed in the validation sample. These analyses are useful for constructing valid surrogate part scores for MDS-UPDRS when missing items fall within the identified threshold and give scientific justification for rejecting partially completed ratings that fall below the threshold.
Localization and characterization of a heparin binding domain peptide of human von Willebrand factor. (1992)

Human von Willebrand factor, a plasma glycoprotein which plays a critical role in regulating hemostasis, binds heparin, but the physiological importance and mode of this interaction is poorly understood. Using the motif of an amino acid sequence of a consensus heparin binding synthetic peptide, a 23-residue sequence (Tyr565-Ala587) of human von Willebrand factor was identified that retains the consensus motif and binds heparin with affinity comparable with native von Willebrand factor and the consensus peptide. In a fluid phase binding assay, the Tyr565-Ala587 peptide competed effectively with von Willebrand factor for binding heparin. Synthesis and testing of peptides overlapping Tyr565-Ala587, as well as adjacent cationic regions, showed this core sequence to be the optimal linear binding domain. Far ultraviolet circular dichroism spectrometry of the Tyr565-Ala587 peptide suggested that the peptide undergoes conformational change upon binding heparin. The Tyr565-Ala587 peptide thus encompasses part (or all) of a functionally important heparin binding domain of von Willebrand factor. Further study of this and related peptides may be useful for exploring how heparin may influence von Willebrand factor-mediated platelet hemostasis.
Chloride ion conductivity in a plasticized quaternary ammonium polymer (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChloride ion conductivity in a plasticized quaternary ammonium polymerL. C. Hardy and D. F. ShriverCite this: Macromolecules 1984, 17, 4, 975–977Publication Date (Print):April 1, 1984Publication History Published online1 May 2002Published inissue 1 April 1984https://pubs.acs.org/doi/10.1021/ma00134a077https://doi.org/10.1021/ma00134a077research-articleACS PublicationsRequest reuse permissionsArticle Views337Altmetric-Citations42LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Multimodal Residual Learning for Visual QA (2016)

Deep neural networks continue to advance the state-of-the-art of image recognition tasks with various methods. However, applications of these methods to multimodality remain limited. We present Multimodal Residual Networks (MRN) for the multimodal residual learning of visual question-answering, which extends the idea of the deep residual learning. Unlike the deep residual learning, MRN effectively learns the joint representation from visual and language information. The main idea is to use element-wise multiplication for the joint residual mappings exploiting the residual learning of the attentional models in recent studies. Various alternative models introduced by multimodality are explored based on our study. We achieve the state-of-the-art results on the Visual QA dataset for both Open-Ended and Multiple-Choice tasks. Moreover, we introduce a novel method to visualize the attention effect of the joint representations for each learning block using back-propagation algorithm, even though the visual features are collapsed without spatial information.
Microtubule Affinity Regulating Kinase Activity in Living Neurons Was Examined by a Genetically Encoded Fluorescence Resonance Energy Transfer/Fluorescence Lifetime Imaging-based Biosensor (2011)

Protein kinases of the microtubule affinity regulating kinase (MARK)/Par-1 family play important roles in the establishment of cellular polarity, cell cycle control, and intracellular signal transduction. Disturbance of their function is linked to cancer and brain diseases, e.g. lissencephaly and Alzheimer disease. To understand the biological role of MARK family kinases, we searched for specific inhibitors and a biosensor for MARK activity. A screen of the ChemBioNet library containing ~18,000 substances yielded several compounds with inhibitory activity in the low micromolar range and capable of inhibiting MARK activity in cultured cells and primary neurons, as judged by MARK-dependent phosphorylation of microtubule-associated proteins and its consequences for microtubule integrity. Four of the compounds share a 9-oxo-9H-acridin-10-yl structure as a basis that will serve as a lead for optimization of inhibition efficiency. To test these inhibitors, we developed a cellular biosensor for MARK activity based on a MARK target sequence attached to the 14-3-3 scaffold protein and linked to enhanced cyan or teal and yellow fluorescent protein as FRET donor and acceptor pairs. Transfection of the teal/yellow fluorescent protein sensor into neurons and imaging by fluorescence lifetime imaging revealed that MARK was particularly active in the axons and growth cones of differentiating neurons.
Haptoglobin, hemopexin, and related defense pathwaysâ€”basic science, clinical perspectives, and drug development (2014)

Hemolysis, which occurs in many disease states, can trigger a diverse pathophysiologic cascade that is related to the specific biochemical activities of free Hb and its porphyrin component heme. Normal erythropoiesis and concomitant removal of senescent red blood cells (RBC) from the circulation occurs at rates of approximately 2 × 10(6) RBCs/second. Within this physiologic range of RBC turnover, a small fraction of hemoglobin (Hb) is released into plasma as free extracellular Hb. In humans, there is an efficient multicomponent system of Hb sequestration, oxidative neutralization and clearance. Haptoglobin (Hp) is the primary Hb-binding protein in human plasma, which attenuates the adverse biochemical and physiologic effects of extracellular Hb. The cellular receptor target of Hp is the monocyte/macrophage scavenger receptor, CD163. Following Hb-Hp binding to CD163, cellular internalization of the complex leads to globin and heme metabolism, which is followed by adaptive changes in antioxidant and iron metabolism pathways and macrophage phenotype polarization. When Hb is released from RBCs within the physiologic range of Hp, the potential deleterious effects of Hb are prevented. However, during hyper-hemolytic conditions or with chronic hemolysis, Hp is depleted and Hb readily distributes to tissues where it might be exposed to oxidative conditions. In such conditions, heme can be released from ferric Hb. The free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. Hemopexin (Hx) is another plasma glycoprotein able to bind heme with high affinity. Hx sequesters heme in an inert, non-toxic form and transports it to the liver for catabolism and excretion. In the present review we discuss the components of physiologic Hb/heme detoxification and their potential therapeutic application in a wide range of hemolytic conditions.
Isolation of a nonmitogenic angiogenesis factor from wound fluid. (1982)

Angiogenesis, or new capillary growth, is essential to normal growth and wound healing. It is also active in several pathologic states, including the growth of malignant tumors. An extracellular, nonneoplastic angiogenesis factor has been isolated from cell-free rabbit wound fluid by pore-limit dialysis and chromatography on a size-exclusion HPLC column. The isolated angiogenesis factor was purified 9,600-fold with a yield of 81% and has a molecular weight between 2,000 and 14,000. Wound fluid angiogenesis factor was completely separated from the mitogenic activity of wound fluid; it did not increase the number of capillary endothelial cells in vitro or stimulate [3H]thymidine uptake by these cells. The isolated angiogenesis factor stimulated endothelial cell migration in vitro, and less than 200 ng of the factor stimulated angiogenesis in vivo in the corneal implant assay.
DNA sequence characterization of theGgene region of bacteriophage Mu (1992)

The nucleotide sequence of a 1.2 kb region of bacteriophage Mu DNA was determined. This region contains the 3' end of the F gene, the complete G gene, and the 5' end of the I gene, all late genes involved in Mu virion morphogenesis. Identity of the G gene open reading frame was confirmed by sequencing four Gam mutations. The G open reading frame is predicted to encode proteins of 16.7 or 17.2 kDa, depending on which of two possible start codons are used to initiate translation. Four new nuB mutations in the DNA gyrase-binding site between the G and I genes were also sequenced and found to be identical to the nuB103 mutation sequenced previously.
Activity of Polyphenolic Crude Extracts as Scavangers of Superoxide Radicals and Inhibitors of Xanthine Oxidase (1992)

In view of the pharmacological interest in phenolic substances, we have determined the total amount of anthocyanins and polyphenols present in the berries of several cultivars of Ribes, Rubus, and Vaccinium genera. The in vitro antiradical activity of the crude extracts on chemically-generated superoxide radicals as well as the inhibitory activity towards the enzyme xanthine oxidase were studied. All the crude extracts examined showed a remarkably high activity towards chemically-generated superoxide radicals. The activities were greater than those expected on the basis of the quantities of anthocyanins and polyphenols present in the samples. Furthermore, the extracts showed a certain inhibitory activity towards xanthine oxidase. Ribes nigrum extracts exhibit the highest activity, being the richest in both anthocyanins and polyphenols. On the other hand, Ribes rubrum extracts seem to contain more active substances than the other crude extracts.
Collagen type IX from human cartilage: a structural profile of intermolecular cross-linking sites (1996)

Type IX collagen, a quantitatively minor collagenous component of cartilage, is known to be associated with and covalently cross-linked to type II collagen fibrils in chick and bovine cartilage. Type IX collagen molecules have also been shown to form covalent cross-links with each other in bovine cartilage. In the present study we demonstrate by structural analysis and location of cross-linking sites that, in human cartilage, type IX collagen is covalently cross-linked to type II collagen and to other molecules of type IX collagen. We also present evidence that, if the proteoglycan form of type IX collagen is present in human cartilage, it can only be a minor component of the matrix, similar to findings with bovine cartilage.
Virus-encoded microRNAs: future therapeutic targets? (2006)

The discovery of microRNAs (miRNAs) is a remarkable breakthrough in the field of molecular genetics, as miRNAs are key actors which regulate gene expression in diverse cellular processes from unicellular yeast to human. The recent discovery of virus-encoded miRNAs indicates that viruses also use this fundamental mode of gene regulation. Research into viral miRNAs function demonstrates that some miRNAs play an important role in regulating both the viral life cycle and the interaction between viruses and their hosts. The first in vivo "antagomir" study provides an exciting first step towards miRNA therapy, and the potential for ultimately designing molecular medicines based on the modulation of miRNAs seems good.
The central and multiple roles of B cells in lupus pathogenesis (1999)

A standard view of B cells in systemic autoimmunity is that they promote lupus by producing autoantibodies (autoAb). However, this view is incomplete because recent studies have revealed that autoimmune disease can be dissociated from autoAb deposition. Furthermore, the spontaneous T-cell activation and organ infiltration in systemic lupus erythematosus patients and animal models are difficult to explain entirely via a direct autoAb-mediated mechanism. In this review, we describe work addressing the B-cell functions of autoantigen presentation and autoAb production in lupus pathogenesis. In the JHD-MRL-Faslpr strain (JHD/lpr), a B-cell-deficient version of the lupus-prone MRL-Faslpr (MRL/lpr) mouse, spontaneous nephritis and dermatitis is abrogated, demonstrating that B cells have a primary role in disease. B cells play a similar role in Fas-intact, lupus-prone MRL mice. To address the role of autoantigen presentation, we analyzed transgenic mice which have B cells that cannot secrete immunoglobulin (mIgM transgenic mice). The restoration of B cells without antibody caused substantial interstitial nephritis and vasculitis although less marked than the intact MRL/lpr controls. To address the role of autoAb, we infused serum from aged MRL/lpr mice into JHD/lpr mice. At most, mild to no nephritis was observed in the infused mice. These results indicate that B cells are promoting autoimmunity in mechanisms other than autoAb secretion, and we describe a model depicting these B-cell roles in the context of other inflammatory events in lupus.
Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles (2015)

In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1).
beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity (1992)

In Alzheimer's disease (AD), abnormal accumulations of beta-amyloid are present in the brain and degenerating neurons exhibit cytoskeletal aberrations (neurofibrillary tangles). Roles for beta-amyloid in the neuronal degeneration of AD have been suggested based on recent data obtained in rodent studies demonstrating neurotoxic actions of beta-amyloid. However, the cellular mechanism of action of beta-amyloid is unknown, and there is no direct information concerning the biological activity of beta-amyloid in human neurons. We now report on experiments in human cerebral cortical cell cultures that tested the hypothesis that beta-amyloid can destabilize neuronal calcium regulation and render neurons more vulnerable to environmental stimuli that elevate intracellular calcium levels. Synthetic beta-amyloid peptides (beta APs) corresponding to amino acids 1-38 or 25-35 of the beta-amyloid protein enhanced glutamate neurotoxicity in cortical cultures, while a peptide with a scrambled sequence was without effect. beta APs alone had no effect on neuronal survival during a 4 d exposure period. beta APs enhanced both kainate and NMDA neurotoxicity, indicating that the effect was not specific for a particular subtype of glutamate receptor. The effects of beta APs on excitatory amino acid (EAA)-induced neuronal degeneration were concentration dependent and required prolonged (days) exposures. The beta APs also rendered neurons more vulnerable to calcium ionophore neurotoxicity, indicating that beta APs compromised the ability of the neurons to reduce intracellular calcium levels to normal limits. Direct measurements of intracellular calcium levels demonstrated that beta APs elevated rest levels of calcium and enhanced calcium responses to EAAs and calcium ionophore. The neurotoxicity caused by EAAs and potentiated by beta APs was dependent upon calcium influx since it did not occur in calcium-deficient culture medium. Finally, the beta APs made neurons more vulnerable to neurofibrillary tangle-like antigenic changes induced by EAAs or calcium ionophore (i.e., increased staining with tau and ubiquitin antibodies). Taken together, these data suggest that beta-amyloid destabilizes neuronal calcium homeostasis and thereby renders neurons more vulnerable to environmental insults.
Klotho reduces apoptosis in experimental ischaemic acute renal failure (2005)

The data suggest klotho to be involved in the pathophysiology of IRI. Downregulation of renal klotho exacerbates ischaemic acute renal failure, and klotho gene induction has therapeutic potential in managing ischaemic renal damage.
Multi-target multi-object radar tracking (2004)

In this paper, we present algorithms to exploit full capabilities of an automotive adaptive cruise control radar sensor. We propose model based filtering and data association techniques, guaranteeing sufficient noise suppression without constraining filter dynamics more than necessary. All measured data are considered and the tracking is extended to the multi-object case.
Homotopic shape deformation (2002)

An image warping method is presented that deforms an image continuously without foldover while observing a given set of trajectories of feature elements. Any intermediate image during the morph is homeomorphic to the initial image and the morphing process is a homotopy. The method permits points, line segments, and polygons to be included as features in the image. Techniques are described to make the deformation process smooth in spatial as well as temporal dimensions. An experimental result is included to demonstrate the feasibility of our approach and complexity of the algorithm is analyzed. Morphing between images that are topologically unequivalent is also briefly discussed.
Efficacy of Uniphyl, Salbutamol, and Their Combination in Asthmatic Patients on High-Dose Inhaled Steroids (1995)

A group of 32 patients with moderately severe, chronic asthma (mean FEV1 55% of predicted), maintained on moderately high doses of inhaled corticosteroids (mean dose 1,100 micrograms/d), participated in this double-blind, placebo-controlled crossover study. The effect on pulmonary function of adding theophylline (U, once daily Uniphyl), inhaled salbutamol (S, 200 micrograms four times per day), and their combination (C) or placebo (P) was assessed on Day 14 of each treatment phase. Patients recorded peak expiratory flow, asthma symptom severity (morning and evening), and use of rescue salbutamol inhaler in daily diaries. Mean FEV1 between 0730 and 1800 h and maximum FEV1 between 0730 and 1300 h were significantly higher on U, S, and C compared with P (p < 0.006). Morning peak flow and FEV1 (0730 h) were significantly higher on U and C compared with S and P (p < 0.01). Evening peak flow was higher on U than P (p < 0.001), and C was higher than S and P (p < 0.01). Rescue salbutamol inhaler use was significantly higher on P than on U, C, or S (p = 0.0001). Patient rating of asthma symptoms during C was significantly better than on S or P (p < 0.05). Patient rating of asthma control and study phase preference was significantly higher on combination and Uniphyl alone than on placebo, the combination also being superior to salbutamol alone. Addition of Uniphyl or a combination of Uniphyl and salbutamol significantly improves pulmonary function and asthma symptoms in patients treated with high doses of inhaled corticosteroids and as-needed beta agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Enalapril can prevent vascular amplifier development in spontaneously hypertensive rats. (1990)

Three groups of spontaneously hypertensive rats (SHR) were given enalapril (25 mg/kg/day) from 4 to 9 weeks, 4 to 14 weeks, and 14 to 20 weeks of age. The drug was stopped and observations continued for another 16-21 weeks. At selected times, we measured blood pressure, in vitro hindquarter vascular resistance properties, left ventricular weight/body weight ratio, and skeletal muscle vessel norepinephrine kinetics in treated and untreated SHR and in Wistar-Kyoto (WKY) rats. At the end of each treatment period, all cardiovascular variables were close to values of WKY rats and well below those of untreated SHR, and the norepinephrine or fractional rate constant was about 25% below those levels. After enalapril was stopped, blood pressure and left ventricular weight/body weight ratio increased in parallel to levels ranging from 30% to 50% of the normal difference between untreated SHR and WKY rats. However, in SHR treated from 4 to 9 weeks and from 4 to 14 weeks of age, hindquarter resistance properties remained close to WKY rat levels for the entire observation period of 16-21 weeks after treatment, suggesting suppression of the enhanced resistance responses of SHR (amplifier properties). In SHR treated from 14 to 20 weeks of age, suppression of amplifier properties was more transient, and they redeveloped partially 5-6 weeks after cessation of therapy. When enalapril was given up to 14 weeks of age, the long-term suppression of amplifier properties was probably mainly through prevention of smooth muscle hypertrophy in resistance vessels and possibly through other mechanisms (e.g., "rarefaction").(ABSTRACT TRUNCATED AT 250 WORDS)