bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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
.
RePlacing Memory: the reorientation of Buchenwald
Authors: Azaryahu Maoz
Published: February 2003

This article examines the reconfiguration of memory at the former Buchenwald concentration camp following the reunification of Germany. Buchenwald’s complex history and its function as a national memorial of communist East Germany made the reorientation process a highly controversial issue. At the centre of the controversy was the distinction between heroes, victims and perpetrators. The reorientation of Buchenwald cast the successive chapters of Buchenwald’s history - as a Nazi concentration camp, as a Soviet detention camp and as an East German memorial shrine - in the mould of three geographically separated spheres of memory.
Rapid prototyping and rapid tooling—the key enablers for rapid manufacturing
Authors: Pham D T , Dimov S S
Published: February 2003

Rapid manufacturing is a new mode of operation that can greatly improve the competitive position of companies adopting it. The key enabling technologies of rapid manufacturing are rapid prototyping (RP) and rapid tooling (RT). This paper classifies the existing RP processes and briefly describes those with actual or potential commercial impact. The paper then discusses five important RP applications: building functional prototypes, producing casting patterns, making medical and surgical models, creating artworks and fabricating models to assist engineering analysis. Finally, the paper gives an overview of indirect and direct RT methods for quickly producing up to several thousand parts together with examples illustrating different applications of RT.
A study of recoating in stereolithography
Authors: Pham D T , Ji C
Published: February 2003

Recoating in a stereolithography apparatus (SLA) involves dipping the part being built into a vat containing liquid resin and sweeping a blade over the top of the part. There are two problems with the recoating opearation in existing SLA systems. Firstly, the process is slow because the blade sweep speed is usually restricted to minimize disturbances to the resin surface and also because, after each sweep, the machine has to wait idly for any disturbances to subside and the resin surface to become level before scanning by the laser can be performed. In a part made up of hundreds or thousands of layers, these measures considerably lengthen the build time. The second problem is the difficulty of ensuring that the thickness of the generated layers is even and accurate in parts that incorporate upward-facing concave areas. For such parts, recoated layers may be either thinner or thicker than specified. In the worst case, the part may become delaminated or the blade may strike the cured resin during recoating, resulting in build failure. This paper reports on an experimental study of the recoating operation. The paper discusses the setting of parameters controlling the operation and proposes guidelines for producing good quality SLA parts while reducing build times.
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

There 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

The 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.
Introduction: A New History of Russian Science
Authors: Kojevnikov Alexei
Published: February 2003

Like almost everything in the Soviet Union, the discipline of history of science and technology altered dramatically during the social upheaval of Gorbachev’s perestroika, in some ways that were predictable, and in other ways that were not. One new direction of research that has since grown into a bourgeoning field – the social history of Russian and Soviet science – is represented by the articles in this volume. This short introduction cannot substitute for a real historiographical study, which will probably appear in due course (see also Gerovitch 1996, Gerovitch 1998, Graham 1993). This is rather a personal memoir about the origin and motivations behind the approach; as incomplete as a participant’s memoir can be, but with some benefits of retrospective hindsight. Ten years ago, at a time of great fluidity in minds and intellectual agendas, many developments were driven primarily by intuition and the sheer momentum of Zeitgeist; now, as things have become somewhat settled, there is time for more reflection.
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

Objective

The 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.

Methods

The 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.

Results

Data 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.

Conclusions

The 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
Pacemaker Shift in the Rabbit Sinoatrial Node in Response to Vagal Nerve Stimulation
Authors: Shibata Nitaro , Inada Shin , Mitsui Kazuyuki , Honjo Haruo , Yamamoto Mitsuru , Niwa Ryoko , Boyett Mark R. , Kodama Itsuo
Published: February 2003

Effects of brief postganglionic vagal nerve stimulation on the activation sequence of the rabbit sinoatrial (SA) node were investigated. Activation sequences in a small area (7 mm × 7 mm) on the epicardial surface were measured in a beat‐to‐beat manner using an extracellular potential mapping system composed of 64 modified bipolar electrodes with high‐gain and low‐frequency band‐pass filtering. The leading pacemaker site was recognised clearly from both the activation sequence and the characteristic morphology of the potentials. Vagal stimulation resulted in a short‐lasting initial slowing of spontaneous rate followed by a long‐lasting secondary slowing; a brief period of relative or absolute acceleration was interposed between the two slowing phases. During these changes of spontaneous rate, the leading pacemaker site shifted in a complex beat‐to‐beat manner by 1‐6 mm alongside the crista terminalis in the superior or inferior direction. For the first spontaneous excitation following stimulation, the greater the slowing, the larger the distance of the pacemaker shift. There was no such linear relationship between the extent of slowing and the distance of pacemaker shift for the subsequent beats. These changes in the leading pacemaker site in response to vagal stimulation may be the result of the functional and morphological heterogeneity of the mammalian SA node in terms of innervation, receptor distribution and ion channel densities.
O2 Delivery and the Venous PO2‐O2 Uptake Relationship in Pump‐Perfused Canine Muscle
Authors: Kohzuki H. , Sakata S. , Misawa H. , Takaki M.
Published: February 2003

Under the conditions of both an increased red cell affinity for O2 at a constant rate of O2 delivery (arterial O2 content × flow) and a decrease in the rate of O2 delivery induced by hypoxic hypoxia at constant blood flow, we have obtained a linear relationship between the partial pressure of O2 in the muscle venous effluent (Pv,O2) and O2 uptake (V̇O2). The relationship is described by the equation V̇O2= Da× Pv,O2+V̇O2,conv where Da is the apparent O2 diffusion capacity and V̇O2,conv is O2 delivery‐limited V̇O2, and Da× Pv,O2 represents the O2 diffusion‐limited V̇O2 (V̇O2,diff). From these observations, we propose the hypothesis that V̇O2 consists of two additive values, V̇O2,conv and V̇O2,diff. The mechanism underlying the reduction in V̇O2 that is induced by reducing O2 delivery to markedly below the V̇O2,conv value has only been investigated using a model based on the single compartment of diffusion‐limited V̇O2, and has not been investigated in terms of this additive V̇O2 model. The single compartment analysis appears to overestimate the role of O2 diffusion in limiting the reduction of V̇O2 that occurs in response to a decrease in O2 diffusion capacity, as reflected by the V̇O2/Pv,O2 ratio. To gain better insight into the mechanism involved, we altered the rate of O2 delivery by changing arterial PO2 from normoxia (with inhalation of air) to hypoxia (by inhalation of 10‐11% O2) and blood flow (with high and low flow rates (n = 7 for both groups), and very low and ischaemic flow rates (n = 4 for both groups)) in pump‐perfused dog gastrocnemius preparations during tetanic isometric contractions at 1 Hz. As rates of O2 delivery were reduced from 23.2 to 10.9 ml min−1 (100 g)−1, significant decreases in Pv,O2 and V̇O2 were observed (P < 0.05). From the data of Pv,O2 and V̇O2 values within this range of O2 delivery rates, we obtained the regression equation V̇O2= 0.22 × Pv,O2+ 8.14 (r = 0.58). From the equation, the intercept of the V̇O2‐axis was significantly different from zero (P < 0.05), in accordance with the observation that the V̇O2/Pv,O2 ratio (ml min−1 (100 g)−1 Torr−1) increased from 0.54 to 1.35 (P < 0.05). However, at extremely low rates of O2 delivery (5.6 and 7.3 ml min−1 (100 g)−1 the V̇O2/Pv,O2 ratio was 1.51 and 2.80 (P < 0.05), respectively. This indicates a break in the linear V̇O2‐Pv,O2 relationship as the rate of O2 delivery was reduced to below the V̇O2,conv value of the V̇O2‐axis intercept. These results suggest that the reduction in V̇O2 caused by extreme reductions in the rate of O2 delivery is not attributable to a reduction in O2 diffusion capacity, as expected from the V̇O2/Pv,O2 ratio, but to a reduction in the O2 delivery‐limited V̇O2 component, as evaluated by the V̇O2‐axis intercept of the linear V̇O2‐Pv,O2 relationship.
Angiotensin Ii Type 1 (at1) Receptor Blockade Enhances the L‐NAME‐Induced Vasoconstriction in Rat Submandibular Gland
Authors: Vág J. , Kerémi Beáta , Hably Csilla , Bartha J. , Fazekas Á.
Published: February 2003

The vasoregulatory role of nitric oxide (NO) and angiotensin II type 1 (AT1) receptors in the circulation of the submandibular gland (SMG) of rats was studied. The glandular blood flow was determined by means of laser Doppler flowmetry and rubidium isotope technique. The data obtained by these two methods correlated well (r= 0.77; P < 0.01). The AT1 receptor antagonist candesartan (0.5 mg kg−1, I.V.) reduced the vascular resistance in the SMG by 37% (P < 0.05). By contrast, the NO synthase blocker L‐NAME (15 mg kg−1, I.V.) significantly increased vascular resistance in the SMG both in candesartan‐treated (P < 0.001) and non‐treated (P < 0.001) animals. The increase in resistance was greater (P < 0.05) after previous blockade of AT1 receptors. These findings suggest that the AT1 receptors have an important role in the vasoregulation of the SMG in the rat. As a result of AT1 blockade, NO‐dependent tone of glandular vessels may be enhanced significantly.
Influence of Genetically Predisposed Diabetes on Ethanol‐Induced Depression of Cardiac Contraction in Adult Rat Ventricular Myocytes
Authors: Ren Jun
Published: February 2003

Diabetes mellitus and alcohol (ethanol) intake are two positively correlated major risk factors for cardiovascular abnormalities. However, the interaction of the two on cardiac function is largely unknown. The purpose of the present study was to examine the impact of genetically predisposed diabetes on acute ethanol exposure‐induced cardiac contractile depression at the myocyte level. Ventricular myocytes from spontaneously biobreeding diabetes‐prone (BBDP) rats and their diabetes‐resistant littermates (BBDR) were stimulated to contract at 0.5 Hz. Contractile properties analysed include: peak shortening amplitude (PS), time‐to‐PS (TPS), time‐to‐90% relengthening (TR90) and maximal velocities of shortening/relengthening (± dL/dt). BBDP rats displayed hyperglycaemia, reduced body weight gain and increased cardiac, hepatic and renal size. Myocytes isolated from BBDP rat hearts exhibited prolonged TPS and TR90 associated with normal PS and ± dL/dt, compared with myocytes from the BBDR group. Acute ethanol exposure (80‐640 mg dl−1) caused a concentration‐dependent inhibition of PS in both BBDR and BBDP myocytes. However, the degree of inhibition of PS was significantly reduced in BBDP myocytes compared to that of BBDR myocytes. The maximal inhibition was 52.9% and 28.4% in BBDR and BBDP groups, respectively. Ethanol significantly depressed ± dL/dt in both BBDR and BBDP myocytes. In addition, ethanol did not affect TPS or TR90 in either the BBDR or BBDP group. Collectively, these results suggest that the ethanol‐induced depression in cardiac myocyte contraction may be ‘shadowed’ by genetically predisposed diabetes.
The ‘Novel’‘Uncoupling’ Proteins UCP2 and UCP3: What Do They Really do? Pros and Cons for Suggested Functions
Authors: Nedergaard Jan , Cannon Barbara
Published: February 2003

The scientifically novel, but evolutionarily ancient, so‐called uncoupling proteins 2 and 3 (UCP2, UCP3) are structually similar to the archetypical uncoupling protein UCP1. A series of suggestions have been forwarded for their physiological function. We discuss systematically here the pros and cons for these suggestions. We conclude that the novel UCPs do not seem to be physiologically relevant uncoupling proteins; the uncoupling property was apparently a late introduction into the subfamily through the evolution of UCP1. Physiological functions ascribed to UCP2 and UCP3 based on their purported uncoupling property may have to be revised (i.e. any type of thermogenesis, including protection against obesity, protection against the formation of reactive oxygen species and thermogenic involvement in the fever response). The presence of a mixed genetic background in most published studies of UCP2 or UCP3 gene‐ablated mice also means that data concerning marked differences in diabetes propensity, infection sensitivity and production of reactive oxygen species may require confirmation in backcrossed mice. The increased expression of UCP2 and UCP3 under conditions of increased fatty acid metabolism implies an as yet undefined role in lipid metabolism. Thus, the novel UCPs should probably be considered as mitochondrial carriers, and the challenge now is to identify the transported molecule.
The Role of Mitochondria in Cytoplasmic Ca2+ Cycling
Authors: Ganitkevich V. Y.
Published: February 2003

It has been known for a long time that isolated mitochondria are able to accumulate large amounts of calcium ions. Before the discovery that endoplasmic reticulum (ER) was the main Ca2+‐storing cellular organelle, mitochondria were thought to play a major role in cytoplasmic Ca2+ homeostasis (Carafoli, 2002). After IP3 was discovered and it was shown that IP3 receptors were localized in ER membrane and that Ca2+‐binding proteins such as calsequestrin could store large amounts of Ca2+ in the ER, the role of mitochondria in the regulation of cytoplasmic Ca2+ was questioned. However, in recent years, mostly due to the development of new methods, there has been increasing evidence that mitochondria could be an important cytoplasmic Ca2+ sink, especially under conditions of a high cellular Ca2+ load.
Origin Usage during
Euplotes
Ribosomal DNA Amplification
Authors: Tan Ming , Jahn Carolyn L. , Price Carolyn M.
Published: February 2003

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

Since 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

This 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.
Availability of Long-Acting Injectable Buprenorphine at Substance Use Treatment Facilities in 2021
Authors: Vidyasagar Nitin , Bunting Samuel R. , Arora Vineet M. , Ari Mim
Published: January 2024

This study assesses the proportion of US substance use and mental health care facilities that offered any medications for opioid use disorder and, specifically, long-acting injectable buprenorphine in 2021.
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

Importance

Single sensory impairment is associated with reduced functional resilience and increased mortality, though the effects of multiple sensory deficits are not known.

Objective

To investigate longitudinal associations of the type, severity, and number of sensory impairments with physical function trajectories and mortality in older adults.

Design, Setting, and Participants

This 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.

Exposures

Visual, olfactory, auditory, and touch sensory functions were assessed between 2000 and 2002.

Main Outcomes

The main outcomes included physical functioning trajectories and mortality risk. Physical function was assessed longitudinally using the Health ABC physical performance battery (HABCPPB).

Results

A 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.

Conclusion

In 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.
From synaptic dysfunction to atypical emotional processing in autism
Authors: Reis Sara L. , Monteiro Patricia
Published: January 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition mainly characterized by social impairments and repetitive behaviors. Among these core symptoms, a notable aspect of ASD is the presence of emotional complexities, including high rates of anxiety disorders. The inherent heterogeneity of ASD poses a unique challenge in understanding its etiological origins, yet the utilization of diverse animal models replicating ASD traits has enabled researchers to dissect the intricate relationship between autism and atypical emotional processing. In this review, we delve into the general findings about the neural circuits underpinning one of the most extensively researched and evolutionarily conserved emotional states: fear and anxiety. Additionally, we explore how distinct ASD animal models exhibit various anxiety phenotypes, making them a crucial tool for dissecting ASD's multifaceted nature. Overall, to a proper display of fear response, it is crucial to properly process and integrate sensorial and visceral cues to the fear‐induced stimuli. ASD individuals exhibit altered sensory processing, possibly contributing to the emergence of atypical phobias, a prevailing anxiety disorder manifested in this population. Moreover, these individuals display distinctive alterations in a pivotal fear and anxiety processing hub, the amygdala. By examining the neurobiological mechanisms underlying fear and anxiety regulation, we can gain insights into the factors contributing to the distinctive emotional profile observed in individuals with ASD. Such insights hold the potential to pave the way for more targeted interventions and therapies that address the emotional challenges faced by individuals within the autism spectrum.
STIM2 is involved in the regulation of apoptosis and the cell cycle in normal and malignant monocytic cells
Authors: Djordjevic Stefan , Itzykson Raphaël , Hague Frédéric , Lebon Delphine , Legrand Julien , Ouled‐Haddou Hakim , Jedraszak Guillaume , Harbonnier Juliette , Collet Louison , Paubelle Etienne , Marolleau Jean‐Pierre , Garçon Loïc , Boyer Thomas
Published: January 2024

Calcium is a ubiquitous messenger that regulates a wide range of cellular functions, but its involvement in the pathophysiology of acute myeloid leukemia (AML) is not widely investigated. Here, we identified, from an analysis of The Cancer Genome Atlas and genotype‐tissue expression databases, stromal interaction molecule 2 (STIM2) as being highly expressed in AML with monocytic differentiation and negatively correlated with overall survival. This was confirmed on a validation cohort of 407 AML patients. We then investigated the role of STIM2 in cell proliferation, differentiation, and survival in two leukemic cell lines with monocytic potential and in normal hematopoietic stem cells. STIM2 expression increased at the RNA and protein levels upon monocyte differentiation. Phenotypically, STIM2 knockdown drastically inhibited cell proliferation and induced genomic stress with DNA double‐strand breaks, as shown by increased levels of phosphorylate histone H2AXγ (p‐H2AXγ), followed by activation of the cellular tumor antigen p53 pathway, decreased expression of cell cycle regulators such as cyclin‐dependent kinase 1 (CDK1)–cyclin B1 and M‐phase inducer phosphatase 3 (CDC25c), and a decreased apoptosis threshold with a low antiapoptotic/proapoptotic protein ratio. Our study reports STIM2 as a new actor regulating genomic stability and p53 response in terms of cell cycle and apoptosis of human normal and malignant monocytic cells.
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

Topographical 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

Developing 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

Due 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.
Induced Self‐Assembly of Vitamin E‐Spermine/siRNA Nanocomplexes via Spermine/Helix Groove‐Specific Interaction for Efficient siRNA Delivery and Antitumor Therapy
Authors: Zhao Xiaoran , Xu Qi , Wang Qian , Liang Xingxing , Wang Jing , Jin Hongwei , Man Yizhi , Guo Dongyang , Gao Feng , Tang Xinjing
Published: January 2024

Gene therapy has been one of potential strategies for the treatment of different diseases, where efficient and safe gene delivery systems are also extremely in need. Current lipid nanoparticles (LNP) technology highly depends on the packing and condensation of nucleic acids with amine moieties. Here, an attempt to covalently link two natural compounds, spermine and vitamin E, is made to develop self‐assembled nucleic acid delivery systems. Among them, the spermine moieties specifically interact with the major groove of siRNA helix through salt bridge interaction, while vitamin E moieties are located around siRNA duplex. Such amphiphilic vitamin E‐spermine/siRNA complexes can further self‐assemble into nanocomplexes like multiblade wheels. Further studies indicate that these siRNA nanocomplexes with the neutrally charged surface of vitamin E can enter cells via caveolin/lipid raft mediated endocytosis pathway and bypass lysosome trapping. With these self‐assembled delivery systems, efficient siRNA delivery is successfully achieved for Eg5 and Survivin gene silencing as well as DNA plasmid delivery. Further in vivo study indicates that VE‐Su‐Sper/DSPE‐PEG2000/siSurvivin self‐assembled nanocomplexes can accumulate in cancer cells and gradually release siRNA in tumor tissues and show significant antitumor effect in vivo. The self‐assembled delivery system provides a novel strategy for highly efficient siRNA delivery.
A Holistic Review of C = C Crosslinkable Conjugated Molecules in Solution‐Processed Organic Electronics: Insights into Stability, Processibility, and Mechanical Properties
Authors: Sun Ning , Han Yamin , Huang Wenxin , Xu Man , Wang Jianguo , An Xiang , Lin Jinyi , Huang Wei
Published: January 2024

Solution‐processable organic conjugated molecules (OCMs) consist of a series of aromatic units linked by σ‐bonds, which present a relatively freedom intramolecular motion and intermolecular re‐arrangement under external stimulation. The cross‐linked strategy provides an effective platform to obtain OCMs network, which allows for outstanding optoelectronic, excellent physicochemical properties, and substantial improvement in device fabrication. An unsaturated double carbon–carbon bond (C = C) is universal segment to construct crosslinkable OCMs. In this review, the authors will set C = C cross‐linkable units as an example to summarize the development of cross‐linkable OCMs for solution‐processable optoelectronic applications. First, this review provides a comprehensive overview of the distinctive chemical, physical, and optoelectronic properties arising from the cross‐linking strategies employed in OCMs. Second, the methods for probing the C = C cross‐linking reaction are also emphasized based on the perturbations of chemical structure and physicochemical property. Third, a series of model C = C cross‐linkable units, including styrene, trifluoroethylene, and unsaturated acid ester, are further discussed to design and prepare novel OCMs. Furthermore, a concise overview of the optoelectronic applications associated with this approach is presented, including light‐emitting diodes (LEDs), solar cells (SCs), and field‐effect transistors (FETs). Lastly, the authors offer a concluding perspective and outlook for the improvement of OCMs and their optoelectronic application via the cross‐linking strategy.
Capillarity Enabled Large‐Array Liquid Metal Electrodes for Compact and High‐Throughput Dielectrophoretic Microfluidics
Authors: Chai Huichao , Zhu Junwen , Feng Yongxiang , Liang Fei , Wu Qiyan , Ju Zhongjian , Huang Liang , Wang Wenhui
Published: January 2024

Dielectrophoresis (DEP) particle separation has label‐free, well‐controllable, and low‐damage merits. Sidewall microelectrodes made of liquid metal alloy (LMA) inherits the additional advantage of thick electrodes to generate impactful DEP force. However, existing LMA electrode‐based devices lack the ability to integrate large‐array electrodes in a compact footprint, severely limiting flow rate and thus throughput. Herein, a facile and versatile method is proposed to integrate high‐density thick LMA electrodes in microfluidic devices, taking advantage of the passive control ability of capillary burst valves (CBVs). CBVs with carefully designed burst pressures are co‐designed in microfluidic channels, allowing self‐assembly of LMA electrode array through simple hand‐push injection. The arrayed electrode configuration brings the accumulative DEP deflection effect. Specifically, The fabricated 5000 pairs of sidewall electrodes in a compact chip are demonstrted to achieve ten times higher throughput in DEP deflection. The 5000‐electrode‐pair device is applied to successfully separate four mixed samples, including human peripheral blood mononuclear cells and A549 cells with the flow rate of 70 µL min−1. It is envisioned that this work can greatly facilitate LMA electrode array fabrication and offer a robust and versatile platform for DEP separation applications.
Concurrent Mechanisms of Hot Electrons and Interfacial Water Molecule Ordering in Plasmon‐Enhanced Nitrogen Fixation
Authors: Zhang Shaoce , Chen Dong , Chen Peigang , Zhang Rong , Hou Yue , Guo Ying , Li Pei , Liang Xiu , Xing Tingyang , Chen Jie , Zhao Yuwei , Huang Zhaodong , Lei Dangyuan , Zhi Chunyi
Published: January 2024

The participation of high‐energy hot electrons generated from the non‐radiative decay of localized surface plasmons is an important mechanism for promoting catalytic processes. Herein, another vital mechanism associated with the localized surface plasmon resonance (LSPR) effect, significantly contributing to the nitrogen reduction reaction (NRR), is found. That is to say, the LSPR‐induced strong localized electric fields can weaken the intermolecular hydrogen bonds and regulate the arrangement of water molecules at the solid–liquid interface. The AuCu pentacle nanoparticles with excellent light absorption ability and the capability to generate strong localized electric fields are chosen to demonstrate this effect. The in situ Raman spectra and theoretical calculations are employed to verify the mechanism at the molecular scale in a nitrogen fixation process. Meanwhile, due to the promoted electron transfer at the interface by the well‐ordered interfacial water, as well as the participation of high‐energy hot electrons, the optimal catalyst exhibits excellent performance with an NH3 yield of 52.09 µg h−1 cm−2 and Faradaic efficiency (FE) of 45.82% at ─0.20 V versus RHE. The results are significant for understanding the LSPR effect in catalysis and provide a new approach for regulating the reaction process.
Study on the Photothermal Conversion Performance of TiN Modified Carbon Fiber Fabric
Authors: Wang Lin , Xiong Tiantian , Zou Hantao , Gao Chao , Yan Wu , Liu Xueting
Published: January 2024

The application of solar thermal conversion is an effective means of utilizing solar energy. In this study, plain, honeycomb, and terry cotton fabrics are carbonized into carbon fiber fabrics at high temperatures, with subsequent Titanium nitride (TiN) modification. The dependence of the carbon fabric properties on structure is investigated. Fiber stability, high absorbance, and structural characteristics contribute to efficient performance in solar steam generation. The vertical loop array associated with the surface of the terry structure results in improved absorbance, limiting loss of TiN particles with a consequent enhancement of fiber photothermal conversion. The optimal TiN carbon fiber fabric (TiN CFF) based evaporator can achieve a water evaporation rate of 1.82 kg m−2 h−1 under one sun with up to 93.4% absorbance. Moreover, the fiber exhibits good cycling stability and seawater desalination performance. The synergism due to TiN modification and the terry fabric structure results in an efficient and low‐cost evaporator preparation method, which can be effectively applied in photothermal conversion materials and seawater desalination.
Reaction Space Charting as a Tool in Organic Chemistry Research and Development
Authors: Baró Eloy Lozano , Nadal Rodríguez Pau , Juárez‐Jiménez Jordi , Ghashghaei Ouldouz , Lavilla Rodolfo
Published: January 2024

The chemical and reaction spaces are incredibly vast and special procedures are required to study them. Their complex and multiparametric nature encompass myriads of compounds and interactions and endless modifications involving the distinct impact of relevant variables (temperature, solvent, stoichiometry, etc.). This often calls for the design, collection, and analysis/interpretation of large datasets. Reaction charting, the systematic scanning, description, analysis, and guided modifications of a given process, stands as the most promising approach. It offers fast and accurate solutions as well as expanding the knowledge about the systems. This deeper understanding enables reliable predictions, improvement of the productivity (yields, scope), eventually leading to sustainable, economic, and safe applications. The present review introduces the topic, analyzing selected examples and recent advancements in different organic chemistry‐related fields. The covered methodologies range from classical experimentation modifying one factor at a time, to Design of Experiments and more modern computational approaches involving Machine Learning and Artificial Intelligence. In this way, the impact of charting in process development, biological and medicinal chemistry, catalysis, reaction discovery and computational methods is accounted. Finally, the conclusion/outlook section gives a general appraisal and a prospect on the future implementation of the methodology.
Multi‐ and Gray‐Scale Thermal Lithography of Silk Fibroin as Water‐Developable Resist for Micro and Nanofabrication
Authors: Rostami Mohammadreza , Marković Aleksandra , Wang Ya , Pernollet Joffrey , Zhang Xiaosheng , Liu Xia , Brugger Juergen
Published: January 2024

Silk fibroin (SF) is a natural material with polymorphic structures that determine its water solubility and biodegradability, which can be altered by exposing it to heat. Here, a hybrid thermal lithography method combining scalable microscale laser‐based patterning with nanoscale patterning based on thermal scanning probe lithography is developed. The latter enables in addition grayscale patterns to be made. The resolution limit of the writing in silk fibroin is studied by using a nanoscale heat source from a scanned nanoprobe. The heat thereby induces local water solubility change in the film, which can subsequently be developed in deionized water. Nanopatterns and grayscale patterns down to 50 nm lateral resolution are successfully written in the silk fibroin that behaves like a positive tone resist. The resulting patterned silk fibroin is then applied as a mask for dry etching of SiO2 to form a hard mask for further nano‐processing. A very high selectivity of 42:1 between SiO2 and silk fibroin is obtained allowing for high‐aspect ratio structure to be fabricated. The fabricated nanostructures have very low line edge roughness of 5 ± 2 nm. The results demonstrate the potential of silk fibroin as a water‐soluble resist for hybrid thermal lithography and precise micro/nanofabrication.