bluuebunny/crossref_metadata_2025_split huggingface dataset:
α‐Actin isoform distribution in normal and failing human heart: a morphological, morphometric, and biochemical study
Authors: Suurmeijer Albert JH , Clément Sophie , Francesconi Arianna , Bocchi Leonardo , Angelini Annalisa , Van Veldhuisen Dirk J , Spagnoli Luigi Giusto , Gabbiani Giulio , Orlandi Augusto 
Published: February 2003

AbstractWe investigated the distribution of α‐skeletal, α‐cardiac, and α‐smooth muscle actin isoforms in human heart during development, hypertrophy, and failure. At 20 weeks of fetal life, α‐skeletal actin was localized in a small proportion of subendocardial and papillary muscle cardiomyocytes. At this gestation time, diffuse α‐cardiac actin staining was observed, associated with focal expression of α‐smooth muscle actin. In normal adult subjects, α‐skeletal actin positive cardiomyocytes were distributed in a transmural gradient with the highest proportion located subendocardially. In myocardial hypertrophy and cardiomyopathies, the amount of α‐skeletal actin was increased and diffuse staining was seen in all layers of ventricular myocardium, with the exception of idiopathic dilated cardiomyopathies. Cardiomyocytes were negative for α‐smooth muscle actin in all pathological situations studied. As expected, fibroblasts in post‐infarct scars expressed α‐smooth muscle actin and transforming growth factor‐β1 but, surprisingly, were negative for these proteins in interstitial fibrosis. Our results demonstrate that increased expression of α‐skeletal actin in the diseased human heart is associated with increased myocyte stretch, increased wall stress, and pressure overload, but not with idiopathic dilated cardiomyopathies. They also suggest that fibrotic changes develop with different mechanisms in scars versus interstitial fibrosis. Copyright © 2003 John Wiley & Sons, Ltd.
Functional groups expressed as graphs extracted from the Laplacian of the electron density
Authors: Popelier Paul L. A. , Burke James , Malcolm Nathaniel O. J. 
Published: February 2003

AbstractThe valence charge concentration shell, as determined by the Laplacian of the electron density, is used as a source of quantum topological graphs, called L‐graphs. A considerable number of such graphs are extracted from theab initiowave functions of 31 molecules calculated at the B3LYP/6‐311+G(2d,p)//B3LYP/6‐311+G(2d,p)level, covering common functional groups in organic chemistry. We show how L‐graphs can be constructed from a largely transferable subgraph called atomic L‐graph. We investigate the topological stability of the L‐graphs as a function of the basis set. Reliable and consistent atomic L‐graphs are only obtained with basis sets of triple‐zeta quality or higher. The recurrence of invariant motifs or subgraphs in the L‐graphs enables the isolation of 16 atomic L‐graphs. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Effects of age and sex on the disposition of retigabine
Authors: Hermann Robert , Ferron Geraldine M. , Erb Katharina , Knebel Norbert , Ruus Peter , Paul Jeffrey , Richards Lyette , Cnota Hans‐Peter , Troy Steven 
Published: February 2003

BackgroundThe novel antiepileptic drug retigabine is the first selective M‐current potassium channel opener for KCNQ2/3 and KCNQ3/5 channels. Retigabine undergoes phase II metabolism (N‐glucuronidation, acetylation) exclusively and renal excretion.ObjectiveOur objective was to evaluate the effects of age and sex on the pharmacokinetics of retigabine.MethodsHealthy young (age range, 18‐40 years) and elderly (age range, 66‐81 years) white subjects (12 men and 12 women in each group) received a single 200‐mg oral dose of retigabine. After dosing, blood was collected over a 72‐hour period to determine plasma concentrations of retigabine and its acetylated metabolite, AWD21‐360. Pharmacokinetics was compared for age group and sex by ANOVA.ResultsIn young men, retigabine was rapidly absorbed, with the maximum concentration occurring within 2 hours, and was eliminated with an apparent clearance of 0.67 L × h−1 × kg−1 and a mean terminal half‐life of 8.5 hours. Subjects were similarly exposed to AWD21‐360. Compared with young men, young women had higher retigabine maximum concentration (56%) and exposure (20%) but similar clearance (0.68 L × h−1 × kg−1); these differences were related to differences in body weight. Although maximum concentration was similar in elderly subjects, retigabine elimination was slower (30% lower apparent clearance normalized for weight), resulting in higher exposure (42%) and a longer half‐life (30%). Because phase II metabolism is scarcely affected by age, these differences may be related to the known decline of renal function with age.ConclusionsAlthough there are no substantial sex‐related differences in the disposition of retigabine, a relevant decrease in clearance resulting in higher exposure occurs in elderly patients. The results suggest that decline of renal function with age may account for some of the observed changes.Clinical Pharmacology & Therapeutics (2003) 73, 61–70; doi: 10.1067/mcp.2003.12
Metabolic-Flux Profiling of the Yeasts
Saccharomyces cerevisiae
and
Pichia stipitis
Authors: Fiaux Jocelyne , Çakar Z. Petek , Sonderegger Marco , Wüthrich Kurt , Szyperski Thomas , Sauer Uwe 
Published: February 2003

ABSTRACT

The so far largely uncharacterized central carbon metabolism of the yeast
Pichia stipitis
was explored in batch and glucose-limited chemostat cultures using metabolic-flux ratio analysis by nuclear magnetic resonance. The concomitantly characterized network of active metabolic pathways was compared to those identified in
Saccharomyces cerevisiae
, which led to the following conclusions. (i) There is a remarkably low use of the non-oxidative pentose phosphate (PP) pathway for glucose catabolism in
S. cerevisiae
when compared to
P. stipitis
batch cultures. (ii) Metabolism of
P. stipitis
batch cultures is fully respirative, which contrasts with the predominantly respiro-fermentative metabolic state of
S. cerevisiae
. (iii) Glucose catabolism in chemostat cultures of both yeasts is primarily oxidative. (iv) In both yeasts there is significant in vivo malic enzyme activity during growth on glucose. (v) The amino acid biosynthesis pathways are identical in both yeasts. The present investigation thus demonstrates the power of metabolic-flux ratio analysis for comparative profiling of central carbon metabolism in lower eukaryotes. Although not used for glucose catabolism in batch culture, we demonstrate that the PP pathway in
S. cerevisiae
has a generally high catabolic capacity by overexpressing the
Escherichia coli
transhydrogenase UdhA in phosphoglucose isomerase-deficient
S. cerevisiae
.
Development of a Controlled Drinking Self‐Efficacy Scale and appraising its relation to alcohol dependence
Authors: Sitharthan Thiagarajan , Job R.F. Soames , Kavanagh David J. , Sitharthan Gomathi , Hough Michael 
Published: February 2003

AbstractThere is no specific self‐efficacy measure that has been developed primarily for problem drinkers seeking a moderation drinking goal. In this article, we report the factor structure of a 20‐item Controlled Drinking Self‐Efficacy Scale (CDSES; Sitharthan et al., 1996; Sitharthan et al., 1997). The results indicate that the CDSES is highly reliable, and the factor analysis using the full sample identified four factors: negative affect, positive mood/social context, frequency of drinking, and consumption quantity. A similar factor structure was obtained for the subsample of men. In contrast, only three factors emerged in the analysis of data on female participants. Compared to women, men had low self‐efficacy to control their drinking in situations relating to positive mood/social context, and subjects with high alcohol dependence had low self‐efficacy for situations relating to negative affect, social situations, and drinking less frequently. The CDSES can be a useful measure in treatment programs providing a moderation drinking goal. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 351–362, 2003.
A polynomial‐time algorithm to find shortest paths with recourse
Authors: Provan J. Scott 
Published: February 2003

AbstractThe Shortest Path with Recourse Problem involves finding the shortest expected‐length paths in a directed network, each of whose arcs have stochastic traversal lengths (or delays) that become known only upon arrival at the tail of that arc. The traveler starts at a given source node and makes routing decisions at each node in such a way that the expected distance to a given sink node is minimized. We develop an extension of Dijkstra's algorithm to solve the version of the problem where arclengths are nonnegative and reset after each arc traversal. All known no‐reset versions of the problem are NP‐hard. We make a partial extension to the case where negative arclengths are present. © 2003 Wiley Periodicals, Inc.
Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection
Authors: Csajka Chantal , Marzolini Catia , Fattinger Karin , Décosterd Laurent A. , Fellay Jacques , Telenti Amalio , Biollaz Jérôme , Buclin Thierry 
Published: February 2003

ObjectiveThe reverse transcriptase inhibitor efavirenz is currently used at a fixed dose of 600 mg/d. However, dosage individualization based on plasma concentration monitoring might be indicated. This study aimed to assess the efavirenz pharmacokinetic profile and interpatient versus intrapatient variability in patients who are positive for human immunodeficiency virus, to explore the relationship between drug exposure, efficacy, and central nervous system toxicity and to build up a Bayesian approach for dosage adaptation.MethodsThe population pharmacokinetic analysis was performed by use of NONMEM based on plasma samples from a cohort of unselected patients receiving efavirenz. With the use of a 1‐compartment model with first‐order absorption, the influence of demographic and clinical characteristics on oral clearance and oral volume of distribution was examined. The average drug exposure during 1 dosing interval was estimated for each patient and correlated with markers of efficacy and toxicity. The population kinetic parameters and the variabilities were integrated into a Bayesian equation for dosage adaptation based on a single plasma sample.ResultsData from 235 patients with a total of 719 efavirenz concentrations were collected. Oral clearance was 9.4 L/h, oral volume of distribution was 252 L, and the absorption rate constant was 0.3 h−1. Neither the demographic covariates evaluated nor the comedications showed a clinically significant influence on efavirenz pharmacokinetics. A large interpatient variability was found to affect efavirenz relative bioavailability (coefficient of variation, 54.6%), whereas the intrapatient variability was small (coefficient of variation, 26%). An inverse correlation between average drug exposure and viral load and a trend with central nervous system toxicity were detected. This enabled the derivation of a dosing adaptation strategy suitable to bring the average concentration into a therapeutic target from 1000 to 4000 μg/L to optimize viral load suppression and to minimize central nervous system toxicity.ConclusionsThe high interpatient and low intrapatient variability values, as well as the potential relationship with markers of efficacy and toxicity, support the therapeutic drug monitoring of efavirenz. However, further evaluation is needed before individualization of an efavirenz dosage regimen based on routine drug level monitoring should be recommended for optimal patient management.Clinical Pharmacology & Therapeutics (2003) 73, 20–30; doi: 10.1067/mcp.2003.22
Origin Usage during
Euplotes
Ribosomal DNA Amplification
Authors: Tan Ming , Jahn Carolyn L. , Price Carolyn M. 
Published: February 2003

ABSTRACT

The macronuclear genome of the ciliate
Euplotes
is comprised of millions of small linear DNA molecules that have telomeres on each end. These molecules are generated during the sexual stage of the life cycle, when the new macronucleus is formed by a series of DNA processing events and multiple rounds of DNA amplification. We have used two-dimensional gels to compare the location of the replication origins used during vegetative growth and the two periods during macronuclear development when DNA amplification takes place. When we examined the pattern of ribosomal DNA (rDNA) replication intermediates, we observed almost identical Y arcs regardless of when in the
Euplotes
life cycle the DNA was isolated. No bubble or bubble-to-Y arcs could be detected. This indicates that replication of the macronuclear rDNA initiates at or near the telomere even when these molecules are being differentially amplified. Since replication rarely initiated from both ends of the rDNA, we examined the direction of replication fork movement to determine which end of the rDNA served as the origin. Fork movement gels indicated that replication initiated at the 5′ end. As transcription also starts near the telomere at the 5′ end, our findings suggest that the telomere and the promoter region cooperate to recruit
Euplotes
replication initiation complexes.
Plato and the "Socratic Fallacy"
Authors: Prior William 
Published: February 2003

AbstractSince Peter Geach coined the phrase in 1966 there has been much discussion among scholars of the "Socratic fallacy." No consensus presently exists on whether Socrates commits the "Socratic fallacy"; almost all scholars agree, however, that the "Socratic fallacy" is a bad thing and that Socrates has good reason to avoid it. I think that this consensus of scholars is mistaken. I think that what Geach has labeled a fallacy is no fallacy at all, but a perfectly innocent consequence of Platonic epistemology. The "Socratic fallacy" arises from the "Priority of Definition" principle (PD). Plato is committed to (PD) in the Meno. The Meno also contains a famous discussion of the difference between episteme and doxa (97a ff.). If we understand what Plato meant by episteme we can see that he must be committed to (PD); but we can also see that (PD) has none of the harmful consequences Geach attributes to it. Geach's view is indebted to Wittgenstein's philosophy of language. (PD) is implausible on this reading of the verb "to know," but not on Plato's. Plato claims that a demand for an explanation is appropriate wherever a claim to knowledge is made. Plato links the concept of episteme explicitly with the concept of logos; the connection between the terms may have been analytic. It does not follow from the Platonic conception of knowledge, as Geach argues, that it is "no use" using examples to establish general definitions. All that follows is that one cannot know that an alleged example of a term T is a genuine example until one has a general account of what it is to be T. Without the stronger conclusion, Geach cannot establish that the "Socratic fallacy" is a fallacy.
Platonic Causes
Authors: Sedley David 
Published: February 2003

AbstractThis paper examines Plato's ideas on cause-effect relations in the Phaedo. It maintains that he sees causes as things (not events, states of affairs or the like), with any information as to how that thing brings about the effect relegated to a strictly secondary status. This is argued to make good sense, so long as we recognise that aition means the "thing responsible" and exploit legal analogies in order to understand what this amounts to. Furthermore, provided that we do not presuppose that we already know what can and what cannot count as a cause, Plato proves to have an attractive case for his principle that all causation is a matter of like causing like. Once we appreciate this, we are a little closer to understanding his more idiosyncratic principle, which although puzzling is ubiquitous in his writings and often invoked as a premise in key arguments, that opposites cannot cause opposites. The last part of the paper turns to formal causes, defending Plato's advocacy of them, and examining their role in the Parmenides' Third Man Argument. The main proposal is that Plato's conception of Forms as causes opens the door to a better version of that argument's "Non-identity" premise than those currently available.
Physical Function Trajectories and Mortality in Older Adults With Multisensory Impairment
Authors: Vohra Varun , Simonsick Eleanor M. , Kamath Vidyulata , Bandeen-Roche Karen , Agrawal Yuri , Rowan Nicholas R. 
Published: January 2024

ImportanceSingle sensory impairment is associated with reduced functional resilience and increased mortality, though the effects of multiple sensory deficits are not known.ObjectiveTo investigate longitudinal associations of the type, severity, and number of sensory impairments with physical function trajectories and mortality in older adults.Design, Setting, and ParticipantsThis retrospective analysis of a longitudinal cohort study, the Health, Aging, and Body Composition (Health ABC) study, incorporated data from April 1997 to July 2013, featuring a 16-year follow-up with annual examinations and questionnaires. The cohort comprised 3075 men and women, aged 70 to 79 years at baseline, residing in Memphis, Tennessee, and Pittsburgh, Pennsylvania. All participants with complete sensory testing and covariate data at analytical baseline (year 5, 2002) were included. The data were analyzed September 1, 2022.ExposuresVisual, olfactory, auditory, and touch sensory functions were assessed between 2000 and 2002.Main OutcomesThe main outcomes included physical functioning trajectories and mortality risk. Physical function was assessed longitudinally using the Health ABC physical performance battery (HABCPPB).ResultsA total of 1825 individuals (mean [SD] age, 77.4 [3.2] years; 957 [52%] female) were included in this study. Multivariable analysis of HABCPPB decline indicated that having 1 sensory impairment (β estimate, −0.01 [95% CI, −0.02 to −0.001]); 2 sensory impairments (β estimate, −0.01 [95% CI, −0.02 to −0.01]); 3 sensory impairments (β estimate, −0.03 [95% CI, −0.04 to −0.02]); or 4 sensory impairments (β estimate, −0.04 [95% CI, −0.05,−0.03]) was significantly associated with a steeper HABCPPB score decline in a dose-dependent manner. Adjusted Cox proportional hazards models indicated that having 1 sensory impairment (hazard ratio [HR], 1.35 [95% CI, 1.01-1.81]), 2 sensory impairments (HR, 1.58 [95% CI, 1.19-2.11]), 3 sensory impairments (HR, 1.79 [95% CI, 1.33-2.42]), or 4 sensory impairments (HR, 1.97 [95% CI, 1.39-2.79]) was significantly associated with increased mortality risk in a similarly dose-dependent manner.ConclusionIn this retrospective cohort study, the degree and number of multiple sensory impairments were associated with worse physical functioning and increased mortality risk. These findings represent an opportunity for further investigation into the value of screening, prevention, and treatment of sensory impairments to reduce morbidity and mortality in older adults.
The neural correlates of topographical disorientation—a lesion analysis study
Authors: Blondiaux Eva , Diamantaras Andreas , Schumacher Rahel , Blanke Olaf , Müri René , Heydrich Lukas 
Published: January 2024

AbstractTopographical disorientation refers to the selective inability to orient oneself in familiar surroundings. However, to date its neural correlates remain poorly understood. Here we use quantitative lesion analysis and a lesion network mapping approach in order to investigate seven patients with topographical disorientation. Our findings link not only the posterior parahippocampal gyrus (PHG) and retrosplenial cortex but also the lingual gyrus, the precuneus and the fusiform gyrus to topographical disorientation. We propose that topographical disorientation is due to the inability to integrate familiar landmarks within a framework of allocentric and egocentric orientation, supported by a neural network including the posterior PHG, the retrosplenial and the lingual cortex.
Printed and Stretchable Triboelectric Energy Harvester Based on P(VDF‐TrFE) Porous Aerogel
Authors: Lozano Montero Karem , Calvo Guzman Remmi , Tewari Amit , Zou Haiyang , Wang Zhong Lin , Mäntysalo Matti , Laurila Mika‐Matti 
Published: January 2024

AbstractDeveloping energy harvesting devices is crucial to mitigate the dependence on conventional and rigid batteries in wearable electronics, ensuring their autonomous operation. Nanogenerators offer a cost‐effective solution for enabling continuous operation of wearable electronics. Herein, this study proposes a novel strategy that combines freeze‐casting, freeze‐drying, and printing technologies to fabricate a fully printed triboelectric nanogenerator (TENG) based on polyvinylidene fluorid‐etrifluoroethylene P(VDF‐TrFE) porous aerogel. First, the effects of porosity and poling on the stretchability and energy harvesting capabilities of P(VDF‐TrFE) are investigated, conducting a comprehensive analysis of this porous structure's impact on the mechanical, ferroelectric, and triboelectric properties compared to solid P(VDF‐TrFE) films. The results demonstrate that structural modification of P(VDF‐TrFE) significantly enhances stretchability increasing it from 7.7% (solid) to 66.4% (porous). This modification enhances output voltage by 66% and generated charges by 48% for non‐poled P(VDF‐TrFE) porous aerogel films compared to their non‐poled solid counterparts. Then, a fully printed TENG is demonstrated using stretchable materials, exhibiting a peak power of 62.8 mW m−2and an average power of 9.9 mW m−2over 100 tapping cycles at 0.75 Hz. It can illuminate light‐emitting diodes (LEDs) through the harvesting of mechanical energy from human motion. This study provides a significant advance in the development of energy harvesting devices.
Logic Gate Circuits Based on CeOx/WOy Memristor for the Odd/Even Checker and Encryption/Decryption of Image Applications
Authors: Wang Jiangqiu , Wang Hongyan , Cao Zelin , Zhu Shouhui , Du Junmei , Yang Chuan , Ke Chuan , Zhao Yong , Sun Bai 
Published: January 2024

AbstractDue to its powerful brain‐like parallel computing and efficient data processing capabilities, memristors are considered to be the core components for building the next generation of artificial intelligence systems. In this study, the CeOx/WOy heterojunction is employed as the functional layer, and various metal materials are utilized as the top electrode to fabricate the memristor. The results indicate that the memristive performance of the Ag/CeOx/WOy/ITO device can be improved by using Ag as the top electrode. By studying the conductivity mechanism of the device, a conductivity model is established that regulates oxygen vacancies and Ag conductive filaments. Furthermore, using the as‐prepared memristor, it is constructed four basic digital logic circuits: OR, AND, XOR, and XNOR, as well as a half adder and a full adder that can be used for digital arithmetic operations. Specifically, an odd/even checker is developed based on XOR and XNOR logic circuits to verify the correctness of data transmission. Finally, it is also designed and implemented a cryptographic array based on a memristor, which can be applied to encrypt and decrypt a series of numbers and images. Therefore, this work extends the application of memristor toward digital circuits, information transmission, data processing and image security encryption.