bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetic acid bacteria encode two levansucrase types of different ecological relationship
Authors: Jakob Frank , Quintero Yamira , Musacchio Alexis , Estrada‐de los Santos Paulina , Hernández Lázaro , Vogel Rudi F.
Published: August 2019

Acetic acid bacteria (AAB) are associated with plants and insects. Determinants for the targeting and occupation of these widely different environments are unknown. However, most of these natural habitats share plant‐derived sucrose, which can be metabolized by some AAB via polyfructose building levansucrases (LS) known to be involved in biofilm formation. Here, we propose two LS types (T) encoded by AAB as determinants for habitat selection, which emerged from vertical (T1) and horizontal (T2) lines of evolution and differ in their genetic organization, structural features and secretion mechanism, as well as their occurrence in proteobacteria. T1‐LS are secreted by plant‐pathogenic α‐ and γ‐proteobacteria, while T2‐LS genes are common in diazotrophic, plant‐growth‐promoting α‐, β‐ and γ‐proteobacteria. This knowledge may be exploited for a better understanding of microbial ecology, plant health and biofilm formation by sucrase‐secreting proteobacteria in eukaryotic hosts.
The Causal Effect of Retirement on Health: Understanding the Mechanisms
Authors: Binh Tran Dai , Zikos Vasileios
Published: August 2019

This article examines the direct effects of retirement on health, as well as its indirect effects, through a mediation analysis. Using Australian panel data, analysis reveals that changes in retirement status and retirement duration imply positive causal effects on self‐assessed health as well as physical health and mental health. Gender plays an important role in shaping these relationships. For women, the positive relationship between retirement duration and health can be attributed to physical activity. In contrast, men appear to enjoy better health when staying retired for longer because they participate more in outdoor activities.
The Langevin diffusion as a continuous‐time model of animal movement and habitat selection
Authors: Michelot Théo , Gloaguen Pierre , Blackwell Paul G. , Étienne Marie‐Pierre
Published: August 2019

The utilization distribution of an animal describes the relative probability of space use. It is natural to think of it as the long‐term consequence of the animal's short‐term movement decisions: it is the accumulation of small displacements which, over time, gives rise to global patterns of space use. However, many estimation methods for the utilization distribution either assume the independence of observed locations and ignore the underlying movement (e.g. kernel density estimation), or are based on simple Brownian motion movement rules (e.g. Brownian bridges).

We introduce a new continuous‐time model of animal movement, based on the Langevin diffusion. This stochastic process has an explicit stationary distribution, conceptually analogous to the idea of the utilization distribution, and thus provides an intuitive framework to integrate movement and space use. We model the stationary (utilization) distribution with a resource selection function to link the movement to spatial covariates, and allow inference about habitat preferences of animals.

Standard approximation techniques can be used to derive the pseudo‐likelihood of the Langevin diffusion movement model, and to estimate habitat preference and movement parameters from tracking data. We investigate the performance of the method on simulated data, and discuss its sensitivity to the time scale of the sampling. We present an example of its application to tracking data of Steller sea lions Eumetopias jubatus.

Due to its continuous‐time formulation, this method can be applied to irregular telemetry data. The movement model is specified using a habitat‐dependent utilization distribution, and it provides a rigorous framework to estimate long‐term habitat selection from correlated movement data. The Langevin movement model can be written as a linear model, which allows for very fast inference. Standard tools such as residuals can be used for model checking.
Evaluation of Acute Pain in Patients Undergoing Total Hip Arthroplasty: A Cohort Study
Authors: Luz Rodríguez Acelas Alba , Monteiro Mantovani Vanessa , Cañon Montañez Wilson , Engelman Bruna , Barragan da Silva Marcos , de Abreu Almeida Miriam
Published: August 2019

PURPOSE

To evaluate pain levels in patients who underwent total hip arthroplasty (THA) using the Nursing Outcomes Classification (NOC).

METHODS

Prospective cohort study conducted in the surgical hospitalization units of a university hospital in southern Brazil. Twenty‐four patients were evaluated and followed‐up for four consecutive days after THA.

FINDINGS

A significant difference was found between the first and last evaluations for the outcome pain level (2102). Two indicators also showed statistically significant differences overtime.

CONCLUSIONS

The NOC outcome and indicators demonstrated the different pain levels of patients who underwent THA.

IMPLICATIONS FOR NURSING PRACTICE

The NOC system is applicable to clinical practice, because it facilitated the follow‐up of patient progression.
Endocannabinoid Signaling in the Central Amygdala and Bed Nucleus of the Stria Terminalis: Implications for the Pathophysiology and Treatment of Alcohol Use Disorder
Authors: Bedse Gaurav , Centanni Samuel W. , Winder Danny G. , Patel Sachin
Published: August 2019

High rates of relapse are a chronic and debilitating obstacle to effective treatment of alcohol use disorder (AUD); however, no effective treatments are available to treat symptoms induced by protracted abstinence. In the first part of this 2‐part review series, we examine the literature supporting the effects of alcohol exposure within the extended amygdala (EA) neural circuitry. In Part 2, we focus on a potential way to combat negative affect associated with AUD, by exploring the therapeutic potential of the endogenous cannabinoid (eCB) system. The eCB system is a potent modulator of neural activity in the brain, and its ability to mitigate stress and negative affect has long been an area of interest for developing novel therapeutics. This review details the recent advances in our understanding of eCB signaling in 2 key regions of the EA, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), and their role in regulating negative affect. Despite an established role for EA eCB signaling in reducing negative affect, few studies have examined the potential for eCB‐based therapies to treat AUD‐associated negative affect. In this review, we present an overview of studies focusing on eCB signaling in EA and cannabinoid modulation on EA synaptic activity. We further discuss studies suggesting dysregulation of eCB signaling in models of AUD and propose that pharmacological augmentation of eCB could be a novel approach to treat aspects of AUD. Lastly, future directions are proposed to advance our understanding of the relationship between AUD‐associated negative affect and the EA eCB system that could yield new pharmacotherapies targeting negative affective symptoms associated with AUD.
Shared gene signature between pterygium and meibomian gland dysfunction uncovered through gene‐expression meta‐analysis
Authors: Zhang Jing , Xiang Jun , Wu Dan , Dai Yiqin , Xu Jianjiang
Published: August 2019

Background

Pterygium and meibomian gland dysfunction (MGD) are two clinically correlated ocular diseases. We propose to investigate the shared gene signature between pterygium and MGD.

Methods

Microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database. Initial processing of the data was performed using the R programming package. Gene‐expression values were log2 transformed and normalized by quantile normalization. The differentially expressed genes (DEGs) in each individual dataset were analyzed by the limma package. The integration of different pterygium datasets and gene‐expression meta‐analysis was conducted by the NetworkAnalyst package. A Venn diagram was created to find the overlapped DEGs between MGD and pterygium datasets. Gene ontology enrichment and pathway analysis were performed using the ToppGene Suite.

Results

We found 193 DEGs significantly up‐regulated in pterygium, with the combined effect sizes ranging from 1.53 to 3.78. A gene signature consisting of 11 DEGs were found to be shared by pterygium and MGD (SPRR3, SERPINB13, NMU, KRT10, IL37, KRT6B, PI3, S100A2, MAL, AURKA, and RGCC), and bioinformatics analyses showed that these overlapped DEGs were significantly enriched in pathways related to keratinization, cell‐cycle regulation, and formation of the cornified envelope.

Conclusion

We identified a shared gene signature between pterygium and MGD through gene‐expression meta‐analysis. The analysis of this signature underlined that keratinization‐related pathways may play important roles in the development of these two clinically correlated pathologies.
Systemic arterial blood pressure determines the therapeutic window of non‐selective beta blockers in decompensated cirrhosis
Authors: Tergast Tammo L. , Kimmann Markus , Laser Hans , Gerbel Svetlana , Manns Michael P. , Cornberg Markus , Maasoumy Benjamin
Published: August 2019

Background

The safety of non‐selective β‐blockers in patients with advanced cirrhosis has been questioned in recent years. It was hypothesised that there is a particular therapeutic window. However, the specific limits still need to be determined.

Aim

To evaluate potential limits of the therapeutic window of non‐selective β‐blocker therapy in patients with cirrhosis and ascites

Methods

The impact of non‐selective β‐blockers on 28‐day transplant‐free survival was analysed in a cohort of 624 consecutive patients with decompensated cirrhosis and ascites. Three potential limits were investigated: spontaneous bacterial peritonitis, acute‐on‐chronic liver failure, mean arterial blood pressure ≤ 82 and < 65 mm Hg.

Results

Treatment with non‐selective β‐blockers was associated with a higher 28‐day transplant‐free survival in the overall cohort (hazard ratio: 0.621; P = .035) as well as in patients with acute‐on‐chronic liver failure (hazard ratio: 0.578; P = .031) and those with spontaneous bacterial peritonitis (hazard ratio: 0.594; P = .073). In contrast, survival benefits were markedly attenuated in patients with a mean arterial blood pressure ≤ 82 mm Hg and completely lost in those with mean arterial blood pressure < 65 mm Hg (P = .536). In spontaneous bacterial peritonitis patients with a mean arterial blood pressure < 65 mm Hg non‐selective β‐blocker treatment was associated with renal impairment. Of note, among those with a mean arterial blood pressure ≥ 65 mm Hg non‐selective β‐blocker intake was consistently associated with superior transplant‐free survival (hazard ratio: 0.582; P = .029) irrespective of the presence of spontaneous bacterial peritonitis (hazard ratio: 0.435; P = .028) or acute‐on‐chronic liver failure (hazard ratio: 0.480 P = .034).

Conclusions

Ascites, acute‐on‐chronic liver failure and spontaneous bacterial peritonitis do not limit the safe use of non‐selective β‐blockers in patients with cirrhosis. Mean arterial blood pressure might represent a better indicator to determine the therapeutic window of non‐selective β‐blocker treatment.
Hungry people prefer larger bodies and objects: The importance of testing boundary effects
Authors: Saxton Tamsin K. , McCarty Kristofor , Caizley Jasmine , McCarrick Dane , Pollet Thomas V.
Published: August 2019

Several lab‐based studies have indicated that when people are hungry, they judge larger women's bodies as more attractive, compared to when they are satiated. These satiety‐dependent judgements are assumed to provide explanatory power when it comes to the noted cross‐cultural differences in attitudes towards women's adiposity, whereby people who live in regions that are under greater nutritional stress tend to have more favourable attitudes towards bigger bodies. However, it is premature to assume that women's bodies are the proper or actual domain of the satiety‐dependent judgement shifts found within research study testing contexts until stimuli other than female bodies have also been tested: The research programme falls into the trap of confirmation bias unless we also seek out disconfirmatory evidence and test the boundaries of the effects of hunger. Accordingly, we collected attractiveness judgements of female and male bodies manipulated to vary in size by varying level of adiposity, and objects manipulated to vary in size, from 186 participants who also reported their current hunger level. We found that larger sizes of stimuli in general, and women's bodies in particular, especially when judged by women, were judged as more attractive by the hungrier participants. We discuss these patterns in the context of the Insurance Hypothesis, the Environmental Security Hypothesis, and the impact of hunger on acquisition.
Thermal niche variation among individuals of the poison frog, Oophaga pumilio, in forest and converted habitats
Authors: Rivera‐Ordonez Juana M. , Justin Nowakowski A. , Manansala Adrian , Thompson Michelle E. , Todd Brian D.
Published: August 2019

The conversion of natural habitats to human land uses often increases local temperatures, creating novel thermal environments for species. The variable responses of ectotherms to habitat conversion, where some species decline while others persist, can partly be explained by variation among species in their thermal niches. However, few studies have examined thermal niche variation within species and across forest‐land use ecotones, information that could provide clues about the capacity of species to adapt to changing temperatures. Here, we quantify individual‐level variation in thermal traits of the tropical poison frog, Oophaga pumilio, in thermally contrasting habitats. Specifically, we examined local environmental temperatures, field body temperatures (Tb), preferred body temperatures (Tpref), critical thermal maxima (CTmax), and thermal safety margins (TSM) of individuals from warm, converted habitats and cool forests. We found that frogs from converted habitats exhibited greater mean Tb and Tpref than those from forests. In contrast, CTmax and TSM did not differ significantly between habitats. However, CTmax did increase moderately with increasing Tb, suggesting that changes in CTmax may be driven by microscale temperature exposure within habitats rather than by mean habitat conditions. Although O. pumilio exhibited moderate divergence in Tpref, CTmax appears to be less labile between habitats, possibly due to the ability of frogs in converted habitats to maintain their Tb below air temperatures that reach or exceed CTmax. Selective pressures on thermal tolerances may increase, however, with the loss of buffering microhabitats and increased frequency of extreme temperatures expected under future habitat degradation and climate warming.

Abstract in Spanish is available with online material.
Depression, anxiety and stress in a cohort of Australian dentistry students
Authors: Stormon Nicole , Ford Pauline J. , Kisely Steve , Bartle Emma , Eley Diann S.
Published: August 2019

Introduction

Dentistry students face a challenging academic and clinical curriculum that can result in depression and anxiety. While studies usually report sources of stress for dentistry students, there is less information on levels of stress. This study used the Depression, Anxiety and Stress Scale (DASS‐21), to report perceived levels of depression, anxiety and stress in a cohort of Australian undergraduate dentistry students.

Methods

Students enrolled in years 1‐4 of the Bachelor of Dental Science (Honours) program at The University of Queensland were invited to complete the DASS‐21 using an online questionnaire. Students completed the same questionnaire 1 year later.

Results

At baseline, the mean DASS‐21 scores for this cohort (n = 179; females = 56%) were in the normal range for depression (4.69, SD 3.87) and stress (5.50, SD 3.65), and mild range for anxiety (4.25, SD 3.21). Overall, 24% (n = 42), 44% (n = 78) and 11% (n = 20) of students had moderate or above levels of depression, anxiety and stress, respectively. At 1‐year follow‐up, DASS‐21 scores were not significantly different.

Conclusions

Dental students have higher levels of depression, anxiety or stress than the general population, indicating they may be at risk for greater psychological distress. The information from this study should guide curriculum and learning environment design, as well as interventions to support students through this challenging degree.
Letter to the Editor: Prospective, randomised clinical trial of four different presurgical hand antiseptic techniques in equine surgery
Authors: Kampf G. , Verwilghen D.
Published: August 2019

See Article by Biermann et al
Seasonal changes in the biomass, distribution, and patchiness of zooplankton and fish in four lakes in the Sierra Nevada, California
Authors: Urmy Samuel S. , Warren Joseph D.
Published: August 2019

Zooplankton are important components of lentic ecosystems, affecting phytoplankton, water clarity, and nutrient cycling, as well as transferring primary production to upper trophic levels. Many of these processes are temporally and spatially heterogeneous, but are difficult to observe at fine scales with traditional sampling methods. High‐resolution sampling has been especially rare in remote and high‐altitude lakes.

We measured the vertical distribution of zooplankton and fish in four lakes in the Sierra Nevada Mountains of California, U.S.A. (Independence Lake, Lake Tahoe, Cherry Lake, and Lake Eleanor) using a dual‐frequency echosounder, and estimated lake‐wide biomass in all lakes except Tahoe. For zooplankton, we also quantified trends and patchiness in their horizontal distribution. In two of the lakes, Cherry and Eleanor, surveys were repeated four times at seasonal intervals between autumn 2013 and autumn 2014.

Zooplankton were most abundant in these lakes in the spring and summer of 2014, with peak wet‐weight biomasses estimated at 31,000 kg in Lake Eleanor in April and 68,000 kg in Cherry Lake in June. The biomass and vertical distribution of fish also varied, increasing and moving shallower in the water column in June in both Cherry Lake and Lake Eleanor.

Zooplankton density was not horizontally homogeneous, displaying gradients at the lake basin scale (5–6 km), and nested patchiness at a range of smaller scales (0–2 km). This small‐scale spatial variability may be generated biologically, not physically. While it is well‐known that the distribution of zooplankton is often patchy, this aspect of their ecology has not been quantified in most lakes, especially in remote montane locations.

These results illustrate how acoustic sampling can rapidly and simultaneously measure the biomass and spatial distribution of multiple trophic levels in small lakes. This capability provides unique opportunities to study the processes that generate and maintain gradients and patchiness in these components of the ecosystem.
‘It's not acceptable for the husband to stay at home': Taking a discourse analytical approach to capture the gendering of work
Authors: Schnurr Stephanie , Zayts Olga , Schroeder Andreas , Le Coyte‐Hopkins Catherine
Published: August 2019

This article illustrates some of the ways in which the notion of (paid) work is actively being gendered, and how these gendering processes take place not only through organizational practices but also in discourses that circulate outside an organization in the private domain. Drawing on 15 in‐depth interviews with women who opted out of their own professional career in order to accompany their husbands on their overseas work assignment to Hong Kong, we demonstrate some of the benefits of using a discourse analytical approach to capturing and identifying the processes through which these women actively (although not necessarily consciously) gender the notion of work, thereby reinforcing the gender order and its male bias. We argue that identifying and making visible these gendered and gendering practices is an important component of, and a potential trigger for, change both in organizations as well as private contexts.
Immunomorphology and molecular biology of mixed primary liver cancers: is Nestin a marker of intermediate‐cell carcinoma?
Authors: Malvi Deborah , de Biase Dario , Fittipaldi Silvia , Grillini Marco , Visani Michela , Pession Annalisa , D'Errico Antonia , Vasuri Francesco
Published: August 2019

Aims

Primary mixed liver cancers (PLCs), combined hepatocellular‐cholangiocellular (cHCC‐CC) and intermediate‐cell carcinomas are rare tumours characterised by different molecular mechanisms. Nestin is a marker of progenitor cells with a promising application in human tumours. The aims of the present paper are (i) to determine the expression of Nestin in mixed PLCs; and (ii) to correlate the PLC immunoprofile with the gene expression in each tumour component.

Methods and results

We selected 28 mixed PLCs, 13 (46.4%) cHCC‐CC and 15 (53.6%) intermediate‐cell carcinomas. The immunohistochemistry panel consisted of keratin 7, keratin 19, CD56 and Nestin. Next‐generation sequencing analysis was performed on 17 cases (27 specimens) using a multi‐gene custom panel. The differentiated HCC and CC components of cHCC‐CC were negative for Nestin in all cases. The intermediate areas of cHCC‐CC were immunoreactive for Nestin in 92.3% of cases, for CD56 in 76.9% and for K7/K19 in all cases. The immunoprofile of the intermediate‐cell carcinomas showed 73.3% of cases positive for Nestin and 66.7% for CD56. TP53 and TERT were the most frequently mutated genes (31.3% and 17.6% of samples, respectively). Mutations were also found in IDH1, IDH2, PIK3CA and NRAS genes. Intermediate and HCC areas of cHCC‐CC seemed to share the same mutational profile, and both harboured different mutations than the CC component.

Conclusions

According to our preliminary data, Nestin was not expressed by hepatocellular or cholangiocellular‐cell components, but was expressed by most of the intermediate cells in PLCs, and therefore could be considered in the differential diagnosis of PLCs, together with mutational profile.
Ribavirin facilitates early viral kinetics in chronic hepatitis C patients receiving daclatasvir/asunaprevir
Authors: Huang Chung‐Feng , Yeh Ming‐Lun , Huang Ching‐I , Liang Po‐Cheng , Lin Yi‐Hung , Hsieh Ming‐Yen , Chen Kuan‐Yu , Ko Yu‐Min , Lin Zu‐Yau , Chen Shinn‐Cherng , Huang Jee‐Fu , Dai Chia‐Yen , Chuang Wan‐Long , Yu Ming‐Lung
Published: August 2019

Background and Aim

Ribavirin (RBV) remains crucial in difficult‐to‐cure chronic hepatitis C patients receiving directly acting antivirals (DAAs). The current study aimed to address whether RBV enhanced early viral kinetics in patients with DAAs.

Methods

Hepatitis C virus (HCV) genotype‐1b patients were allocated to daclatasvir/asunaprevir +weight‐based RBV (1000–1200 mg/day) for 12–24 weeks. HCV RNA levels were compared at day 1, week 1, week 2, and week 4 of treatment.

Results

The sustained virological response rate was 100% (67/67) and 96.7% (59/61) in the RBV and non‐RBV group, respectively. The HCV RNA levels at treatment week 2 (W2) were significantly lower in the RBV group than in the non‐RBV group (0.42 ± 0.81 log IU/mL vs 0.79 ± 1.03 log IU/mL, P = 0.04). Among the intermediate responders who remained to have detectable RNA after W1 of treatment, patients with RBV had a significantly higher rate of undetectable HCV RNA (71.4% vs 36.0%, P = 0.003) and lower HCV RNA level at W2 (0.55 ± 0.89 log IU/mL vs 1.32 ± 1.04 log IU/mL, P = 0.001). A more significant magnitude of HCV RNA reduction was also noted from baseline to day 1 (3.15 ± 0.38 log IU/mL vs 2.80 ± 0.70 log IU/mL, P = 0.009) and W1 to W2 (1.40 ± 0.65 log IU/mL vs 0.88 ± 0.78 log IU/mL, P = 0.007) in the RBV group compared to the non‐RBV group among the intermediate responders. Logistic regression analysis revealed that adding RBV independently predicted undetectable HCV RNA at W2 (odds ratio/confidence interval: 4.74/1.54–14.57, P = 0.007) in the intermediate responders.

Conclusions

Adding RBV to DAAs improved early viral kinetic, in particular, for intermediate responders.
Earthquakes, grants, and public expenditure: How municipalities respond to natural disasters
Authors: Masiero Giuliano , Santarossa Michael
Published: August 2019

We analyze the response of municipalities to the occurrence of natural disasters in terms of spending behavior, use of upper‐tier transfers and recovery, using balance sheet data of about 8,000 Italian municipalities for the period 2000–2015, and the universe of earthquakes events. We find evidence of increasing expenditure for about 12 years after the shocks, with asymmetric responses between earthquake‐related and unconditional grants, and heterogeneous flypaper effects across the country. While in northern municipalities expenditure tends to regress to pre‐earthquake levels, southern municipalities stick to higher expenditure levels when grants drop. This evidence is coupled with a faster recovery of private income and housing prices in northern municipalities.
Distribution of Practice Effects in the Acquisition and Retention of L2 Mandarin Tonal Word Production
Authors: LI MAN , DEKEYSER ROBERT
Published: August 2019

This study investigated the effects of temporal distribution of practice on the learning and retention of Mandarin tonal word production. Eighty native English‐speaking adults with no prior knowledge of a tonal language participated in this study. They were randomly assigned to four experimental conditions varying in intersession interval (ISI) and retention interval (RI): Condition A with a 1‐day ISI and a 1‐week RI, Condition B with a 1‐day ISI and a 4‐week RI, Condition C with a 1‐week ISI and a 1‐week RI, and Condition D with a 1‐week ISI and a 4‐week RI. Participants underwent 3 training sessions followed by a final retention test. Results showed that the effects of ISI and RI differed depending on the type of knowledge to be retained. For the retention of declarative knowledge, RI had a robust effect: the longer the RI, the worse the retention. Compared to shorter spaced practice (1‐day ISI), longer spaced practice (1‐week ISI) seemed to improve long‐term retention (4‐week RI) of declarative knowledge; however, this ISI effect was much weaker. For procedural knowledge retention, ISI played an important role, but not RI, and it was the shorter spaced practice schedule that had an advantage over the longer spaced practice schedule.
Should We Listen or Read? Modality Effects in Implicit and Explicit Knowledge
Authors: KIM KATHY MINHYE , GODFROID ALINE
Published: August 2019

We examined the role of modality in learning second language (L2) grammar and forming implicit (unconscious) and explicit (conscious) knowledge. To this end, we isolated the effects of the physical medium of input (i.e., aural or visual) from those of the presentation method (i.e., word‐by‐word or simultaneous). We also explored the role of test modality in L2 performance, by including L2 knowledge tests in both aural and visual modes. Native English speakers engaged in meaning‐focused integrated practice of 3 German syntactic rules. In Experiment 1, learners were given aural or visual word‐by‐word (rapid serial visual presentation; RSVP) input and in Experiment 2, they were given aural or natural written input. We found evidence of learning across all 4 groups, but different types of resultant knowledge. In particular, learners gained explicit knowledge in all input modalities, yet only those trained with natural written input also developed robust implicit knowledge. We conclude that the permanence of visual input may be a critical advantage for beginning learners to develop implicit knowledge of word order rules. Support in the form of written materials can ease the cognitive burden on beginning learners, with better outcomes as a result.
Muscarinic receptor 1 allosteric modulators stimulate colorectal emptying in dog, mouse and rat and resolve constipation
Authors: Pustovit Ruslan V. , Itomi Yasuo , Ringuet Mitchell , Diwakarla Shanti , Chai Xin‐yi , McQuade Rachel M. , Tsukimi Yasuhiro , Furness John B.
Published: August 2019

Background

Because M1 muscarinic receptors are expressed by enteric neurons, we investigated whether positive allosteric modulators of these receptors (M1PAMs) would enhance colorectal propulsion and defecation in dogs, mice, and rats.

Methods

The potencies of the M1PAMs, T662 or T523, were investigated using M1 receptor‐expressing CHO cells. Effectiveness of M1PAMs on defecation was investigated by oral administration in mice and rats, by recording propulsive contractions in anaesthetized rats and by recording high amplitude propagating contractions in dogs.

Key Results

PAM EC50 values in M1 receptor‐expressing CHO cells were 0.7‐1.8 nmol/L for T662 and 8‐10 nmol/L for T523. The compounds had 1000‐fold lower potencies as agonists. In anesthetized rats, both compounds elicited propulsive colorectal contractions, and in dogs, mice, and rats, oral administration increased fecal output. No adverse effects were observed in conscious animals. M1PAMs triggered propagated high amplitude contractions and caused defecation in dogs. Nerve‐mediated contractions were enhanced in the isolated mouse colon. M1PAMs were equi‐effective in rats with or without the pelvic nerves being severed. In two models of constipation in mice, opiate‐induced constipation and constipation of aging, defecation was induced and constipation was reversed.

Conclusion and Inferences

M1PAMs act at targets sites in the colorectum to enhance colorectal propulsion. They are effective across species, and they reverse experimentally induced constipation. Previous studies have shown that they are safe in human. Because they provide an enhancement of physiological control rather than being direct agonists, they are predicted to provide effective treatment for constipation.
Arabidopsis glutathione reductase 2 is indispensable in plastids, while mitochondrial glutathione is safeguarded by additional reduction and transport systems
Authors: Marty Laurent , Bausewein Daniela , Müller Christopher , Bangash Sajid Ali Khan , Moseler Anna , Schwarzländer Markus , Müller‐Schüssele Stefanie J. , Zechmann Bernd , Riondet Christophe , Balk Janneke , Wirtz Markus , Hell Rüdiger , Reichheld Jean‐Philippe , Meyer Andreas J.
Published: August 2019

A highly negative glutathione redox potential (EGSH) is maintained in the cytosol, plastids and mitochondria of plant cells to support fundamental processes, including antioxidant defence, redox regulation and iron−sulfur cluster biogenesis. Out of two glutathione reductase (GR) proteins in Arabidopsis, GR2 is predicted to be dual‐targeted to plastids and mitochondria, but its differential roles in these organelles remain unclear.

We dissected the role of GR2 in organelle glutathione redox homeostasis and plant development using a combination of genetic complementation and stacked mutants, biochemical activity studies, immunogold labelling and in vivo biosensing.

Our data demonstrate that GR2 is dual‐targeted to plastids and mitochondria, but embryo lethality of gr2 null mutants is caused specifically in plastids. Whereas lack of mitochondrial GR2 leads to a partially oxidised glutathione pool in the matrix, the ATP‐binding cassette (ABC) transporter ATM3 and the mitochondrial thioredoxin system provide functional backup and maintain plant viability.

We identify GR2 as essential in the plastid stroma, where it counters GSSG accumulation and developmental arrest. By contrast a functional triad of GR2, ATM3 and the thioredoxin system in the mitochondria provides resilience to excessive glutathione oxidation.
Common and distinct brain responses to detecting top‐down and bottom‐up conflicts underlying numerical inductive reasoning
Authors: Xiao Feng , Sun Tie , Qi Senqing , Chen Qingfei
Published: August 2019

Complex reasoning problems are commonly influenced by a combination of top‐down and bottom‐up conflicts; however, the common and distinct brain responses to the two types of conflicts have remained unclear. Participants were required to identify the hidden rules in a number series completion task, which included identity condition (e.g., 13, 13, 13), perceptual mismatch condition (bottom‐up conflict, e.g., 13 13 +≡), and relational mismatch condition (top‐down conflict, e.g., 13 13 14). The ERP results showed that (a) both the perceptual and relational mismatch conditions triggered greater P200, N200, P300, and late positive component than the identity condition, reflecting attention reallocation, perceptual template deviations, feelings of uncertainty, and working memory updating, respectively, and (b) smaller N400 and decreased late negative component were found in the relational mismatch condition in contrast to other conditions, which suggested that changing number values violated rule expectancy as top‐down conflict. Therefore, multiple strategies were utilized to detect the conflicts underlying complex reasoning problems.
A generic space definition framework to support seamless indoor/outdoor navigation systems
Authors: Yan Jinjin , Diakité Abdoulaye A. , Zlatanova Sisi
Published: August 2019

Contemporary public buildings are becoming conglomerates of open, semi‐open and closed spaces, with indoor, outdoor and underground sections. For humans and robots to navigate seamlessly through such environments, new flexible approaches need to be developed. Navigation systems generally rely on a network (nodes and edges) as an abstraction of underlying space availability. However, indoor and outdoor networks have different origins. While indoor systems rely on indoor space subdivision approaches, current outdoor systems utilize road‐based network approaches. Linking such networks via particular nodes is possible but restrictive. Many spaces in the built environment are not strictly indoor or outdoor spaces and are thus often omitted from navigation networks, further limiting navigation options. To overcome these shortcomings, we introduce a new space definition framework in which the entire built environment is categorized into indoor, outdoor, semi‐indoor and semi‐outdoor spaces. We provide strict definitions for the four space categories. Our framework allows the same navigation network extraction approaches to be used and therefore enables seamless indoor/outdoor path computation for single or combinations of locomotion modes. The notions of semi‐indoor and semi‐outdoor spaces offer new options for further tailoring of the navigation path with respect to environmental factors, which we demonstrate with two use cases.
Dismantling the “Visual Ease Assumption:" A Review of Visual Narrative Processing in Clinical Populations
Authors: Coderre Emily L.
Published: August 2019

Visual narratives, such as wordless picture books and picture sequences like comics, have a long history in clinical testing, research, and intervention settings. The widespread “Visual Ease Assumption” rests on the premise that visual narratives, given their non‐linguistic nature, may alleviate processing difficulties in populations that struggle with language. In this paper, I review the evidence for and against this Visual Ease Assumption in three clinical populations in which language deficits are common or diagnostic: autism spectrum disorder (ASD), specific language impairment (SLI; now known as Developmental Language Disorder, DLD), and aphasia. I first redefine the Visual Ease Assumption as two testable predictions: (a) that visual narrative processing should be unimpaired for clinical populations compared to neurotypical (NT) populations; and (b) that in clinical populations, visual narrative processing should be less impaired than linguistic narrative processing. Through a review of the limited evidence available to test these predictions in ASD, SLI, and aphasia, I show that the Visual Ease Assumption is largely unsupported in empirical studies. Furthermore, I outline three additional limitations of the Visual Ease Assumption regarding the complexity of narrative processing, visual narrative tasks, and cognitive deficits in different clinical populations. Therefore, visual narratives should not be assumed to be “easier” for clinical populations that struggle with language; instead, a more thorough consideration of the cognitive processes involved in visual narrative processing is needed.
The Effects of Finite Ionic Sizes and Wall Slip on Entropy Generation in Electroosmotic Flows in a Soft Nanochannel
Authors: Liu Yongbo , Jian Yongjun
Published: August 2019

The combined effects of finite ionic sizes and boundary slip on the entropy generation in mixed pressure driven and electroosmotic flows (EOFs) in a soft nanochannel are investigated in this study. The soft nanochannel is represented by a rigid nanochannel covered by a charged polyelectrolyte layer (PEL) on its surface. The entropy generation analysis of EOFs in such a soft nanochannel is addressed for the first time. Under the assumption of high zeta potentials, the electric potential, velocity, and temperature distributions are obtained numerically by using the finite difference method. Subsequently, the thermal transport characteristic and the corresponding entropy generation analysis are discussed based on the obtained velocity and temperature distributions. Our results show that the soft nanochannel in the present model is not appropriate for cooling purposes. We also demonstrate that the steric factor v and the PEL thickness d can enhance the entropy generation rate. However, the slip boundary coefficient γ, the drag parameter α, and the equivalent electric double-layer (EDL) thickness λFCL can restrain this entropy generation rate. In addition, the contributions of Joule heating and viscous friction in the entropy generation rate are more prominent than the contribution due to heat transfer. The present theoretical research can be used to design the efficient thermofluidic devices.
Mobility Analysis of the Threefold-Symmetric Bricard Linkage and Its Network
Authors: Song Xiaoke , Guo Hongwei , Liu Ruiwei , Meng Fei , Chen Qiping , Xu Younan , Liu Rongqiang
Published: August 2019

In this study, the mobility of the threefold-symmetric Bricard linkage and its network are analyzed using screw theory. First, the screw motion equation of the linkage is derived. By applying the modified Grübler–Kutzbach criterion, we deduce that the degree of freedom (DOF) of the linkage is equal to 1. Then, we analyze the mechanical network constructed of threefold-symmetric Bricard linkages and provide its topological constraint graph. Using graph theory and screw theory, the constraint matrix of the mechanical network is obtained. Then, we solve the matrix rank via linear column transformation. Results show that the DOF of the mechanical network is equal to 1. The mobility analysis method of the mechanical network proposed in this study facilitates the solution of the constraint matrix rank and can be used as a reference for other mechanical networks constructed of single-loop linkages.
A Computational Fluid Dynamics-Based Sensitivity Analysis of the Chemical Vapor Analysis Process to Synthesize Carbon Nanotubes
Authors: Teixeira C. , Silva A. F. , Rocha L. A.
Published: August 2019

Over the last years, there has been a high interest in carbon nanotubes' (CNTs) applications due to their unique properties, mainly at mechanical and electrical levels. However, current synthesis processes, such as chemical vapor deposition (CVD), are highly unpredictable and inconsistent, which leads to an exhaustive trial-and-error methodology when extrapolating results. A sensitivity analysis based on computational fluid dynamics (CFD) is performed here to two distinct setups of the CVD process as a way to understand the synthesis process. Setups were computationally designed and simulated for various synthesis scenarios, where only the hydrocarbon flow and the process temperature were changed. Measuring synthesis conditions, such as concentrations and velocity, inside the tube furnace, for these scenarios allows the identification of which compound affects most each condition. Results showed that, when envisioning the process extrapolation, the synthesis conditions can be tuned via the accessed parameters.
A Combined Conduction–Radiation Model for Analyzing the Role of Radiation on Freezing of a Biological Tissue
Authors: Sukumar Siladitya , Kar Satya Prakash
Published: August 2019

Tissue freezing has significant applications in cryopreservation and cryosurgery processes. The freezing rate is an important factor during the cryopreservation process. To improve and make an accurate estimation of the freezing rate, radiation heat transfer plays a major role. To analyze in details, a two-dimensional coupled conduction–radiation model is developed. The tissue is frozen from the left side while the other sides are at the initial temperature. Finite volume method (FVM) is used to discretize both the radiative transfer equation (RTE) and energy equation. The algebraic equation after discretization is solved by the tri-diagonal matrix algorithm. The radiative heat flux is calculated by solving the RTE. The energy equation provides the temperature field. The enthalpy-porosity method is used to update the liquid volume fraction and thus the freezing front is captured. A linearization technique is proposed to linearize the radiative source term in the energy equation to avoid chances of divergence of the solution. The present model is first validated with the results of the existing literature and a good agreement is found. The effects of different parameters such as conduction–radiation parameter, scattering albedo, extinction coefficient and Stefan number on the prediction of temperature field, and the position of the freezing front are studied in details. It is found that a decrease in the values of conduction–radiation parameter, scattering albedo, and increase in the values of extinction coefficient and Stefan number cause more radiative heat loss. Hence, the freezing rate is improved and more frozen region is observed.
Robust MDSDO for Co-Design of Stochastic Dynamic Systems
Authors: Azad Saeed , Alexander-Ramos Michael J.
Published: August 2019

Optimization of dynamic engineering systems generally requires problem formulations that account for the coupling between embodiment design and control system design simultaneously. Such formulations are commonly known as combined optimal design and control (co-design) problems, and their application to deterministic systems is well established in the literature through a variety of methods. However, an issue that has not been addressed in the co-design literature is the impact of the inherent uncertainties within a dynamic system on its integrated design solution. Accounting for these uncertainties transforms the standard, deterministic co-design problem into a stochastic one, thus requiring appropriate stochastic optimization approaches for its solution. This paper serves as the starting point for research on stochastic co-design problems by proposing and solving a novel problem formulation based on robust design optimization (RDO) principles. Specifically, a co-design method known as multidisciplinary dynamic system design optimization (MDSDO) is used as the basis for an RDO problem formulation and implementation. The robust objective and inequality constraints are computed per usual as functions of their first-order-approximated means and variances, whereas analysis-based equality constraints are evaluated deterministically at the means of the random decision variables. The proposed stochastic co-design problem formulation is then implemented for two case studies, with the results indicating the importance of the robust approach on the integrated design solutions and performance measures.
Conceptual Insightful Synthesis of Spatial Compliant Mechanisms Using the Load Flow Formulation
Authors: Krishnan Girish , Patiballa Sree Kalyan
Published: August 2019

Conceptual design of spatial compliant mechanisms with distinct input and output ports may be hard because of its complex interconnected topology and is currently accomplished by computationally intensive automated techniques. This paper proposes a user insightful method for generating conceptual compliant topology solutions. The method builds on recent advances where the compliant mechanism deformation is represented as load flow in its constituent members. The nature of load flow enables functional decomposition of compliant mechanisms into maximally decoupled building blocks, namely, a transmitter member and a constraint member. The proposed design methodology seeks to synthesize spatial compliant designs by systematically combining transmitter-constraint members first, identifying kinematically feasible transmitter load paths between input(s) and output(s), and then selecting appropriate constraints that enforce the load path. The paper proposes four design steps to generate feasible solutions and four additional guidelines to optimize load paths and constraint orientations. The method is applied with equal ease to three spatial complaint mechanism examples that belong to single-input single-output, multiple-input single output, and single-input multiple-output mechanisms.
Effect of Grain Orientation on Indentation Induced Creep in Pure Zinc
Authors: Gokhale Aditya , Sarvesha R. , Prasad Rajesh , Singh Sudhanshu S. , Jain Jayant
Published: August 2019

The study presents the anisotropy in the indentation creep response of zinc. Indentation creep tests were conducted on grains with three different orientations, namely, 〈0001〉, ⟨112¯0⟩, and ⟨101¯0⟩. Indentation creep along the 〈c〉 axis showed a pronounced creep exhibiting a 25% higher creep displacement as compared with indentation perpendicular to the 〈c〉 axis. However, the recovery observed was the highest for basal-oriented grains wherein a recovery of 50% to its indented depth was observed, whereas for ⟨112¯0⟩ the recovery observed was 30%. The stress exponent, n, was obtained by employing two different approaches for each of the orientations and a difference in the stress exponent value was also observed, highlighting the anisotropic creep response. Basal and non-basal oriented grains showed a lower (n ≅ 1.6) and higher stress exponent (n ≅ 5), respectively, highlighting the different operable creep mechanism. Surface topography using atomic force microscope (AFM) revealed twinning and sink-in for ⟨112¯0⟩ and ⟨101¯0⟩, whereas uniform pile up was observed for basal grain.
Efficient Model-Assisted Probability of Detection and Sensitivity Analysis for Ultrasonic Testing Simulations Using Stochastic Metamodeling
Authors: Du Xiaosong , Leifsson Leifur , Meeker William , Gurrala Praveen , Song Jiming , Roberts Ronald
Published: August 2019

Model-assisted probability of detection (MAPOD) and sensitivity analysis (SA) are important for quantifying the inspection capability of nondestructive testing (NDT) systems. To improve the computational efficiency, this work proposes the use of polynomial chaos expansions (PCEs), integrated with least-angle regression (LARS), a basis-adaptive technique, and a hyperbolic truncation scheme, in lieu of the direct use of the physics-based measurement model in the MAPOD and SA calculations. The proposed method is demonstrated on three ultrasonic testing cases and compared with Monte Carlo sampling (MCS) of the physics model, MCS-based kriging, and the ordinary least-squares (OLS)-based PCE method. The results show that the probability of detection (POD) metrics of interests can be controlled within 1% accuracy relative to using the physics model directly. Comparison with metamodels shows that the LARS-based PCE method can provide up to an order of magnitude improvement in the computational efficiency.