bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural orifice transluminal endoscopic surgery with a snake‐mechanism using a movable pulley
Authors: Lee Hoyul , Kim Kwang Gi , Seo Jong Hyun , Sohn Dae Kyung
Published: March 2017

Background

Natural orifice transluminal endoscopic surgery is an emerging technique. We aimed to develop an advanced surgical robot mechanism for natural orifice surgery.

Methods

We propose the active‐controlled overtube‐type platform with multiple channels for an endoscopic camera and surgical tools. To make such a platform, we suggest an advanced snake mechanism comprising movable pulleys to make a snake mechanism with multiple degrees of freedom and high operating force.

Results

The stiffness and maneuverability of the active‐controlled platform appeared satisfactory. Using prototypes and ex vivo experiments, we confirmed that the mechanism was suitable for a snake‐like robotic platform for natural orifice surgery.

Conclusions

The suggested snake mechanism using movable pulleys has the advantages of stiffness and maneuverability. This new mechanism can be an alternative platform for natural orifice surgery.
Reliability and Validity of Eye Movement Measures of Children's Reading
Authors: Foster Tori E. , Ardoin Scott P. , Binder Katherine S.
Published: March 2017

Although strong claims have been made regarding the educational utility of eye tracking, such statements seem somewhat unfounded in the absence of clear evidence regarding the technical adequacy of eye movement (EM) data. Past studies have yielded direct and indirect evidence concerning the utility of EMs as measures of reading, but recent research explicitly investigating their reliability and validity has been lacking. The current study updates and extends past research by investigating the reliability and validity of recently used EM measures of children's reading. Participants were 175 second‐grade students whose EMs were monitored during silent reading of narrative text(s) at two timepoints. Participants were also individually administered measures of reading achievement. Results indicate adequate reliability and validity for passage‐level measures of fixation duration but suggest that elementary students’ reading behaviors relative to specific words are weakly associated with their normative levels of reading achievement.
A New Function of N719: N719 Based Solution‐Processible Binary Cathode Buffer Layer Enables High‐Efficiency Single‐Junction Polymer Solar Cells
Authors: Li Weiping , Yan Dong , Liu Wenxu , Chen Jie , Xu Wei , Zhan Chuanlang , Yao Jiannian
Published: March 2017

An N719 based high‐efficiency binary cathode buffer layer (CBL) was developed. The work‐function of the Al cathode was precisely modulated between −3.3 and −3.9 eV due to the cation re‐arrangement between the binary components, induced by finely controlling the binary‐components weight ratio. A 10.50%‐ and 11.46%‐efficiency organic solar cells were reported with the use of the N719 and the binary CBL, respectively.
An Ethical Defense of Citizenship
Authors: Thunder David
Published: March 2017

In many parts of the Western world, we have reached a low point in public confidence in the moral value and relevance of citizenship, in the integrity of our political institutions, and in the nobility of public office. Consequently, if we are to secure the political field for those among us virtuous enough to serve the common good, we need to restore public confidence in the ethical value of citizenship and public service. One small step in this direction would be to allay understandable moral qualms about the practice of citizenship. And that is precisely what I aim to do here. By deflating some serious ethical objections against citizenship, I aim to pave the way for the larger task of developing an ethical ideal of citizenship that can inspire citizens to put their talents at the service of the common good. The three objections I address here are rooted in (i) the alleged complicity of ordinary citizens in a range of collective and institutional evils, (ii) the alleged necessity of ruthless utilitarian reasoning in political life, and (iii) the alleged incompatibility of modern citizenship with the Christian way of life. I show that each of these objections can be answered, or at least significantly deflated.
Endoscopic Treatment of High‐Grade Dysplasia and Early Esophageal Cancer
Authors: Schlottmann Francisco , Patti Marco G. , Shaheen Nicholas J.
Published: March 2017

Background

The emergence of novel endoscopic modalities has challenged the role of surgery for patients with Barrett’s esophagus (BE) and high‐grade dysplasia (HGD) or early esophageal adenocarcinoma.

Aim

The aim of this study was to review the available evidence of the endoscopic treatment of HGD and early esopahgeal adenocarcinoma.

Results

For most patients with BE and HGD, endoscopic ablative therapy is the preferred treatment strategy. Patients with intramucosal adenocarcinoma (T1a) should be treated with endoscopic mucosal resection (EMR) followed by ablative therapy, in order to eradicate the remaining intestinal metaplasia. The best approach to treatment of adenocarcinoma with submucosal invasion (T1b) remains elusive. Endoscopic resection may be suitable for low‐risk T1b tumors (well differentiated, without lymphovascular invasion and with superficial submucosal invasion); however, further data are necessary to better risk stratify this group. Careful endoscopic surveillance is recommended following complete eradication of intestinal metaplasia to detect recurrent disease.

Conclusion

Patients with BE and HGD should undergo endoscopic ablative therapy. Patients with T1a adenocarcinoma should be treated with EMR and subsequent ablation of the entire BE segment. Low‐risk T1b tumors may be suitable for endoscopic resection.
Feeling cold and other underestimated symptoms in breast cancer: anecdotes or individual profiles for advanced patient stratification?
Authors: Golubnitschaja Olga
Published: March 2017

Breast cancer (BC) epidemic is recognised as being characteristic for the early twenty-first century. BC is a multifactorial disease, and a spectrum of modifiable (preventable) factors significantly increasing risks has been described. This article highlights a series of underestimated symptoms for consequent BC risk assessment and patient stratification. Phenomena of the deficient thermoregulation, altered sensitivity to different stimuli (pain, thirst, smell, light, stress provocation), dehydration, altered circadian and sleep patterns, tendency towards headache, migraine attacks and dizziness, as well as local and systemic hypoxic effects are discussed for BC patients providing functional links and proposing new approaches in the overall BC management.
On embedded minimal disks in convex bodies
Authors: Jost J. , Grüter M.
Published: March 2017

If

A ⊂ ℝ^3

is a convex body we prove the existence of an embedded minimal disk

M ⊂ A

meeting

∂A

orthogonally.

Si

A ⊂ ℝ^3

est un ensemble convexe, nous prouvons l’existence d’une sous-variété minimale

M ⊂ A

du type disque, intersectant

∂A

orthogonalement.
A finiteness result in the free boundary value problem for minimal surfaces
Authors: Tomi Friedrich
Published: March 2017

It is proved that if an analytic Η-convex body

M

in

ℝ^3

admits an infinite number of area minimizing disc type surfaces interior to

M

and supported by

∂M

then

M

must be diffeomorphic to a solid torus. Moreover, the set of these minimal surfaces then forms an analytic one-parameter family which foliates

M

.

On prouve le résultat suivant: si une partie

M

analytique et Η-convexe de

ℝ^3

admet dans son intérieur un nombre infini de surfaces minimisantes de type disques et supportées par

∂M

, il faut que

M

soit difféomorphe à un tore solide. En plus, l’ensemble des solutions forme une famille analytique de dimension 1 qui constitue un feuilletage de

M

.
Smooth invariant curves of singularities of vector fields on \( ℝ^{3} \)
Authors: Bonckaert Patrick
Published: March 2017

We describe singularities of

C^∞

vector fields, mainly in

ℝ^3

, in the neighbourhood of a given « generalized » direction (this is: the image of a

C^∞

germ

\gamma :(ℝ^{ + },\:0)\rightarrow (ℝ^{3},\:0)

with

γ'(0) ≠ 0

). It is a local study. One of the major results is: if

X

is a germ in

0 \in ℝ^{3}

of a

C^∞

vector field and if

X

is not infinitely flat along a direction

D

, then there exists a cone of finite contact around

D

in which four specific situations can occur. In three of these situations

D

is formally invariant under

X

(with formally we mean: up to the level of formal Taylor series) and there exists a

C^∞

one-dimensional invariant manifold having infinite contact with

D

. In particular, we obtain that the existence of a formally invariant direction

D

always implies the existence of a « real life » invariant direction having infinite contact with

D

, provided that

X

is not infinitely flat along

D

. Using the blowing up method for singularities of vector fields we reduce a singularity always to either a « flow box » or to a singularity with nonzero 1-jet and with a formally invariant direction. Finally we give topological models for the obtained situations.

I would like to thank Freddy Dumortier for suggesting me the problem and for his valuable help.

Nous décrivons les singularités de champs de vecteurs

C^∞

dans

ℝ^3

au voisinage d’une « direction » donnée, c’est-à-dire de l’image d’un germe

\gamma :(ℝ^{ + },0)\rightarrow (ℝ^{3},0)

, avec

γ'(0) ≠ 0

. C’est une étude locale. Nous montrons en particulier que si

X

est le germe àl’origine d’un champ

C^∞

et si

X

n’est pas plat dans une direction

D

, alors il existe un cône de contact d’ordre fini autour de

D

où quatre situations distinctes peuvent se produire. Dans trois d’entre elles,

D

est formellement invariant par

X

et il existe une courbe invariante

C^∞

présentant un contact d’ordre infini avec

D

. En utilisant la méthode de blow-up pour les singularités de champs de vecteurs, nous réduisons toutes les singularités soit à un « flow box », soit à une singularité au 1-jet non trivial possédant une direction formellement invariante. Enfin, nous fournissons des modèles topologiques pour les diverses situations obtenues.

Je remercie Freddy Dumortier pour m’avoir suggéré ce problème et pour son aide.
Lagrangian embeddings and critical point theory
Authors: Hofer Helmut
Published: March 2017

We derive a lower bound for the number of intersection points of an exact Lagrangian embedding of a compact manifold into its cotangent bundle with the zero section. To do this the intersection problem is converted into the problem of finding solutions of a Hamiltonian system satisfying canonical boundary conditions. The dynamical problem is then solved by global variational methods on a Hilbert manifold.

Soit

M

une variété différentiable, compacte et connexe,

T^*M → M

son fibré cotangent,

σ: M → T^*M

la section nulle,

φ: M → T^*M

un plongement lagrangien. Cet article démontre que

φ(M) ∩ σ(M)

contient du moins

c(M)

points, où

c(M)

est la catégorie cohomologique de

M

. Dans le cas

M = T^n

, tore à

n

dimensions, ce résultat avait été conjecturé par Arnold et démontré par M. Chaperon.
The Governance of EU Fundamental Rights
Authors: Dawson Mark
Published: March 2017

In spite of a continued increase in the substantive scope and reach of EU fundamental rights, little attention has been paid to their practical enforcement. In this book, Mark Dawson looks at the mechanisms through which EU fundamental rights are protected and enforced, closely examining the interrelation between the EU's pertinent legal and political bodies. He argues that in order to understand EU fundamental rights we must also understand the institutional, political and normative constraints that shape the EU's policies. The book examines the performance of different EU institutions in relation to rights and studies two important policy fields - social rights and rule of law protection - in depth.
Rulers, Religion, and Riches
Authors: Rubin Jared
Published: March 2017

For centuries following the spread of Islam, the Middle East was far ahead of Europe. Yet, the modern economy was born in Europe. Why was it not born in the Middle East? In this book Jared Rubin examines the role that Islam played in this reversal of fortunes. It argues that the religion itself is not to blame; the importance of religious legitimacy in Middle Eastern politics was the primary culprit. Muslim religious authorities were given an important seat at the political bargaining table, which they used to block important advancements such as the printing press and lending at interest. In Europe, however, the Church played a weaker role in legitimizing rule, especially where Protestantism spread (indeed, the Reformation was successful due to the spread of printing, which was blocked in the Middle East). It was precisely in those Protestant nations, especially England and the Dutch Republic, where the modern economy was born.
Latin America and the First World War
Authors: Rinke Stefan
Published: March 2017

Using a broad variety of textual and visual sources, Latin America and the First World War goes beyond traditional diplomatic history and analyzes the global dimension of the history of the Great War. Filling a significant gap in transnational histories of the war, Stefan Rinke addresses political, social, and economic aspects as well as the cultural impact of the war on Latin America and vice versa. Rinke's meticulous research is based on sources from the nineteen independent states of the entire subcontinent and promises to be the most comprehensive examination to date of Latin America before, during, and immediately after the war.
Beyond Shariati
Authors: Saffari Siavash
Published: March 2017

Ali Shariati (1933–77) has been called by many the 'ideologue of the Iranian Revolution'. An inspiration to many of the revolutionary generation, Shariati's combination of Islamic political thought and Left-leaning ideology continues to influence both in Iran and across the wider Muslim world. In this book, Siavash Saffari examines Shariati's long-standing legacy, and how new readings of his works by contemporary 'neo-Shariatis' have contributed to a deconstruction of the false binaries of Islam/modernity, Islam/West, and East/West. Saffari argues that through their critique of Eurocentric metanarratives on the one hand, and the essentialist conceptions of Islam on the other, Shariati and neo-Shariatis have carved out a new space in Islamic thought beyond the traps of Orientalism and Occidentalism. This unique perspective will hold great appeal to researchers of the politics and intellectual thought of post-revolutionary Iran and the greater Middle East.
Patient-Reported Benefits of Extracranial Venous Therapy: British Columbia CCSVI Registry
Authors: Sadovnick A. Dessa , Yee Irene M. , Attwell-Pope Kristen , Keyes Glenn , Kipp Lucas , Traboulsee Anthony L.
Published: March 2017

Objective Chronic cerebrospinal venous insufficiency (CCSVI) has been hypothesized to be a risk factor for multiple sclerosis (MS). Venoplasty has been proposed as a treatment for CCSVI. The aim of our study was to gain a better understanding of the “real-world” safety and longitudinal effectiveness of venoplasty Methods: British Columbia residents who self-reported having had venoplasty and consented to participate in the study were interviewed and followed for up to 24 months post-therapy using standardized structured questionnaires Results: Participants reported procedure-related complications (11.5%) and complications within the first month after the procedure (17.3%). Initially, more than 40% of participants perceived that the venoplasty had had positive effects on their health conditions, such as fatigue, numbness, balance, concentration/memory and mobility. However, this improvement was not maintained over time Conclusions: Follow-up patient-reported outcomes indicated that the initial perception of the positive impact of venoplasty on the health conditions of MS patients was not sustained over time. In addition, venoplasty was not without associated morbidity.
ACCURACY FOR BELIEVERS
Authors: Staffel Julia
Published: March 2017

In Accuracy and the Laws of Credence Richard Pettigrew assumes a particular view of belief, which states that people don't have any other doxastic states besides credences. This is in tension with the popular position that people have both credences and outright beliefs. Pettigrew claims that such a dual view of belief is incompatible with the accuracy-first approach. I argue in this paper that it is not. This is good news for Pettigrew, since it broadens the appeal of his framework.
The Impact of Reducing Antibiotics on the Transmission of Multidrug-Resistant Organisms
Authors: Barnes Sean L. , Rock Clare , Harris Anthony D. , Cosgrove Sara E. , Morgan Daniel J. , Thom Kerri A.
Published: March 2017

OBJECTIVE

Antibiotic resistance is a major threat to public health. Resistance is largely driven by antibiotic usage, which in many cases is unnecessary and can be improved. The impact of decreasing overall antibiotic usage on resistance is unknown and difficult to assess using standard study designs. The objective of this study was to explore the potential impact of reducing antibiotic usage on the transmission of multidrug-resistant organisms (MDROs).

DESIGN

We used agent-based modeling to simulate interactions between patients and healthcare workers (HCWs) using model inputs informed by the literature. We modeled the effect of antibiotic usage as (1) a microbiome effect, for which antibiotic usage decreases competing bacteria and increases the MDRO transmission probability between patients and HCWs and (2) a mutation effect that designates a proportion of patients who receive antibiotics to subsequently develop a MDRO via genetic mutation.

SETTING

Intensive care unit

INTERVENTIONS

Absolute reduction in overall antibiotic usage by experimental values of 10% and 25%

RESULTS

Reducing antibiotic usage absolutely by 10% (from 75% to 65%) and 25% (from 75% to 50%) reduced acquisition rates of high-prevalence MDROs by 11.2% (P<.001) and 28.3% (P<.001), respectively. We observed similar effect sizes for low-prevalence MDROs.

CONCLUSIONS

In a critical care setting, where up to 50% of antibiotic courses may be inappropriate, even a moderate reduction in antibiotic usage can reduce MDRO transmission.

Infect Control Hosp Epidemiol2017;38:663–669
Local linear stability analysis of cyclone separators
Authors: Grimble T. A. , Agarwal A. , Juniper M. P.
Published: March 2017

Local linear stability analysis is applied to the flow inside a cyclone separator to investigate the unsteady precession of the vortex core. The results of the stability analysis are compared with experimental measurements of the vortex oscillations using high-speed photography with particle seeding and hot-wire anemometry. The experiments reveal distinct spatial variation in the oscillation behaviour within the cyclone. The unsteady motion is focused at each end of the device, at both the narrow cone tip and just below the exhaust duct at the top of the cone, which is known as a vortex finder. The local stability analysis shows that an absolute instability is present throughout the flow for some non-zero azimuthal wavenumbers. The unsteady flow is observed to be driven by coupling between the shear layer and inertial waves confined within the vortex core. Comparison of the stability analysis with experiments shows the same frequency and mode shape behaviour and suggests that the local analysis accurately predicts the unstable modes of the system. The precessing vortex core is responsible for a narrow-band acoustic noise. Comparisons are also drawn with acoustic measurements made on cyclones in which the system is defined by key non-dimensional parameters, such as the swirl number and outlet diameter ratio. The results in this study demonstrate the applicability of local stability analysis to a complex swirling system and yield credible details about the underlying mechanisms of the unstable flow inside the cyclone.
Gut–brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease
Authors: Abautret-Daly Áine , Dempsey Elaine , Parra-Blanco Adolfo , Medina Carlos , Harkin Andrew
Published: March 2017

Introduction

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn’s disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD.

Results

The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut–brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic–pituitary–adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD.

Discussion

The impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse.

Conclusion

It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.
SOCIOECONOMIC STATUS AND ADVERSE BIRTH OUTCOMES: A POPULATION-BASED CANADIAN SAMPLE
Authors: Campbell Emily E. , Gilliland Jason , Dworatzek Paula D. N. , De Vrijer Barbra , Penava Debbie , Seabrook Jamie A.
Published: March 2017

This study assessed the strength of the association between socioeconomic status (SES) and low birth weight (LBW) and preterm birth (PTB) in Southwestern Ontario. Utilizing perinatal and neonatal databases at the London Health Science Centre, maternal postal codes were entered into a Geographic Information System to determine home neighbourhoods. Neighbourhoods were defined by dissemination areas (DAs). Median household income for each DA was extracted from the latest Canadian Census and linked to each mother. All singleton infants born between February 2009 and February 2014 were included. Of 26,654 live singleton births, 6.4% were LBW and 9.7% were PTB. Top risk factors for LBW were: maternal amphetamine use, chronic hypertension and maternal marijuana use (OR respectively: 17.51, 3.18, 2.72); previously diagnosed diabetes, maternal narcotic use and insulin-controlled gestational diabetes predicted PTB (OR respectively: 17.95, 2.69, 2.42). Overall, SES had little impact on adverse birth outcomes, although low maternal education increased the likelihood of a LBW neonate (OR: 1.01).
Predation on transmission stages reduces parasitism: sea anemones consume transmission stages of a barnacle parasite
Authors: FONG CAITLIN R. , KURIS ARMAND M.
Published: March 2017

While parasites serve as prey, it is unclear how the spatial distribution of parasite predators provides transmission control and influences patterns of parasitism. Because many of its organisms are sessile, the rocky intertidal zone is a valuable but little used system to understand spatial patterns of parasitism and elucidate the underlying mechanisms driving these patterns. Sea anemones and barnacles are important space competitors in the rocky intertidal zone along the Pacific coast of North America. Anemones are voracious, indiscriminate predators; thus, they may intercept infectious stages of parasites before they reach a host. We investigate whether a sea anemone protects an associated barnacle from parasitism by Hemioniscus balani, an isopod parasitic castrator. At Coal Oil Point, Santa Barbara, California USA, 29% of barnacles were within 1 cm from an anemone at the surveyed tidal height. Barnacles associated with anemones had reduced parasite prevalence and higher reproductive productivity than those remote from sea anemones. In the laboratory, anemones readily consumed the transmission stage of the parasite. Hence, anemone consumption of parasite transmission stages may provide a mechanism by which community context regulates parasite prevalence at a local scale. Our results suggest predation may be an important process providing parasite transmission control.
To see or not to see: non-invasive imaging for improved readout of drug treatment trials in the murine model of secondary alveolar echinococcosis
Authors: GORGAS D. , MARREROS N. , RUFENER R. , HEMPHILL A. , LUNDSTRÖM-STADELMANN B.
Published: March 2017

Alveolar echinococcosis (AE) is an emerging zoonotic disease caused by the cestode Echinococcus multilocularis. The secondary infection model of AE is based on intraperitoneal injection of disease-causing metacestodes into the peritoneal cavity of mice, which allows investigations on novel drugs or immunotherapeutical treatment options in vivo. So far, such in vivo studies assessed exclusively the parasite weight at the endpoint of a given treatment period. We here developed an ultrasound (US)-based scoring system that allows to follow-up parasite development in the living animal, and provides insights into parasite growth during the treatment phase. By this method a statistically significant difference between untreated and medicated mice with E. multilocularis infection was observed at 2 months post-infection, and the growth curve of the parasite load was described by a linear mixed model. High correlation and similar levels of variation were observed for the standard method based on parasite weight measurement, the novel US-based scoring system, as well volume segmentation by post-mortem magnetic resonance imaging. Thus, US-based scoring in the live animal has the potential to assist the 3R concept by contributing to the refinement and reduction of animal use in experimental echinococcosis.
Exploring the social and neighbourhood predictors of diabetes: a comparison between Toronto and Chicago
Authors: Kolpak Patrycja , Wang Lu
Published: March 2017

Objectives

This report examined the impact and extent that spatial access to primary care physicians (PCPs) and social neighbourhood-/community-level factors have on diabetes prevalence for Toronto and Chicago.

Methods

The two-step floating catchment area method was used to compute spatial access scores. Bivariate correlation and multivariate linear regression identified the factors that were associated with, and/or predicted, diabetes prevalence.

Results

Potential spatial access to PCPs had no strong associations with diabetes prevalence. Low socio-economic status factors and certain ethnic groups were strongly associated with diabetes prevalence for both cities. For Toronto, South American place of birth, households below poverty and high school-level education predicted diabetes prevalence. African ethnicity and households below poverty predicted diabetes prevalence for Chicago.

Conclusion

Although this report found no strong association between diabetes prevalence and access to PCPs, contextual factors significant in past individual-level diabetes studies were associated with diabetes prevalence at the neighbourhood/community level for Toronto and Chicago.
DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons
Authors: Zhao Jian-Yuan , Liang Lingli , Gu Xiyao , Li Zhisong , Wu Shaogen , Sun Linlin , Atianjoh Fidelis E. , Feng Jian , Mo Kai , Jia Shushan , Lutz Brianna Marie , Bekker Alex , Nestler Eric J. , Tao Yuan-Xiang
Published: March 2017

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG.
Reward type and behavioural patterns predict dogs’ success in a delay of gratification paradigm
Authors: Brucks Désirée , Soliani Matteo , Range Friederike , Marshall-Pescini Sarah
Published: March 2017

Inhibiting an immediate behaviour in favour of an alternative but more advantageous behaviour has been linked to individual success in life, especially in humans. Dogs, which have been living in the human environment for thousands of years, are exposed to daily situations that require inhibition different in context from other non-domesticated species. One task regularly used to study inhibitory control is the delay of gratification task, which requires individuals to choose between an immediate option of lower value and a delayed option of higher value. We tested sixteen dogs in a non-social delay of gratification task, conducting two different conditions: a quality and a quantity condition. While the majority of dogs failed to wait for more than 10 s, some dogs tolerated delays of up to 140 s, while one dog waited for 15 minutes. Moreover, dogs had more difficulties to wait if the reward increased in terms of quantity than quality. Interestingly, dogs were able to anticipate the delay duration and some dogs developed behavioural patterns that predicted waiting, which seems similar in some respects to ‘coping-strategies’ found in children, chimpanzees and parrots. Our results indicate that strategies to cope with impulsivity seem to be consistent and present across animal taxa.
Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments
Authors: Loo Lit-Hsin , Bougen-Zhukov Nicola Michelle , Tan Wei-Ling Cecilia
Published: March 2017

Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent.
Dynamics of laser-driven proton acceleration exhibited by measured laser absorptivity and reflectivity
Authors: Bin J. H. , Allinger K. , Khrennikov K. , Karsch S. , Bolton P. R. , Schreiber J.
Published: March 2017

Proton acceleration from nanometer thin foils with intense laser pulses is investigated experimentally. We analyzed the laser absorptivity by parallel monitoring of laser transmissivity and reflectivity with different laser intensities when moving the targets along the laser axis. A direct correlation between laser absorptivity and maximum proton energy is observed. Experimental results are interpreted in analytical estimation, exhibiting a coexistence of plasma expansion and light-sail form of radiation pressure acceleration (RPA-LS) mechanisms during the entire proton acceleration process based on the measured laser absorptivity and reflectivity.
Troponin-I is present as an essential component of muscles in echinoderm larvae
Authors: Yaguchi Shunsuke , Yaguchi Junko , Tanaka Hiroyuki
Published: March 2017

The troponin complex, composed of Troponin-I, Troponin-T and Troponin-C, is an essential mediator of the contraction of striated muscle downstream of calcium signaling in almost all bilaterians. However, in echinoderms and hemichordates, collectively termed Ambulacraria, the components of the troponin complex have never been isolated, thus suggesting that these organisms lost the troponin system during evolution. Here, by analyzing genomic information from sea urchins, we identify the troponin-I gene and isolate its complete mRNA sequence. Using this information, we reveal that the larval muscles express this gene and its translated product and that the protein is definitely a functional molecule expressed in sea urchin larvae by showing that Troponin-I morphants are unable to swallow algae. We conclude that muscular contraction in all bilaterians universally depends on a regulatory system mediated by Troponin-I, which emerged in the common ancestor of bilaterians.
Amigo2-upregulation in Tumour Cells Facilitates Their Attachment to Liver Endothelial Cells Resulting in Liver Metastases
Authors: Kanda Yusuke , Osaki Mitsuhiko , Onuma Kunishige , Sonoda Ayana , Kobayashi Masanobu , Hamada Junichi , Nicolson Garth L. , Ochiya Takahiro , Okada Futoshi
Published: March 2017

Since liver metastasis is the main cause of death in cancer patients, we attempted to identify the driver gene involved. QRsP-11 fibrosarcoma cells were injected into the spleens of syngeneic mice to isolate tumour sub-populations that colonize the liver. Cells from liver metastatic nodules were established and subsequently injected intrasplenically for selection. After 12 cycles, the cell subline LV12 was obtained. Intravenous injection of LV12 cells produced more liver metastases than QRsP-11 cells, whereas the incidence of lung metastases was similar to that of QRsP-11 cells. LV12 cells adhered to liver-derived but not to lung-derived endothelial cells. DNA chip analysis showed that amphoterin-induced gene and open reading frame 2 (Amigo2) was overexpressed in LV12 cells. siRNA-mediated knockdown of Amigo2 expression in LV12 cells attenuated liver endothelial cell adhesion. Ex vivo imaging showed that suppression of Amigo2 in luciferase-expressing LV12 cells reduced attachment/metastasis to liver to the same level as that observed with QRsP-11 cells. Forced expression of Amigo2 in QRsP-11 cells increased liver endothelial cell adhesion and liver metastasis. Additionally, Amigo2 expression in human cancers was higher in liver metastatic lesions than in primary lesions. Thus, Amigo2 regulated tumour cell adhesion to liver endothelial cells and formation of liver metastases.
Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling
Authors: Qi Xiaotian , Zhu Lei , Bai Ruopeng , Lan Yu
Published: March 2017

Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C–N radical–radical cross-coupling reaction. The concerted coupling pathway, in which a C–N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)–N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)–N species before C–N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)–N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)–N intermediate. The higher activation free energy for N–N radical–radical homo-coupling is attributed to the mismatch of Cu(II)–N species with the nitrogen radical because the electrophilicity for both is strong.
Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol
Authors: Dickens David , Chiduza George N. , Wright Gareth S. A. , Pirmohamed Munir , Antonyuk Svetlana V. , Hasnain S. Samar
Published: March 2017

LAT1 (SLC7A5) is a transporter for both the uptake of large neutral amino acids and a number of pharmaceutical drugs. It is expressed in numerous cell types including T-cells, cancer cells and brain endothelial cells. However, mechanistic knowledge of how it functions and its interactions with lipids are unknown or limited due to inability of obtaining stable purified protein in sufficient quantities. Our data show that depleting cellular cholesterol reduced the Vmax but not the Km of the LAT1 mediated uptake of a model substrate into cells (L-DOPA). A soluble cholesterol analogue was required for the stable purification of the LAT1 with its chaperon CD98 (4F2hc,SLC3A2) and that this stabilised complex retained the ability to interact with a substrate. We propose cholesterol interacts with the conserved regions in the LAT1 transporter that have been shown to bind to cholesterol/CHS in Drosophila melanogaster dopamine transporter. In conclusion, LAT1 is modulated by cholesterol impacting on its stability and transporter activity. This novel finding has implications for other SLC7 family members and additional eukaryotic transporters that contain the LeuT fold.
O-GlcNAcylation of SKN-1 modulates the lifespan and oxidative stress resistance in Caenorhabditis elegans
Authors: Li Hongyuan , Liu Xin , Wang Dan , Su Liangping , Zhao Tingting , Li Zhongwei , Lin Cong , Zhang Yu , Huang Baiqu , Lu Jun , Li Xiaoxue
Published: March 2017

In C. elegans, the transcription factor skinhead-1 (SKN-1), the ortholog of human NF-E2-related factor 2 (Nrf-2), plays important roles in oxidative stress defense and aging processes. It has been documented that the activity of SKN-1 is regulated by its phosphorylation modification. However, whether other posttranslational modifications of SKN-1 affect its function remains unclear to date. Here we report, for the first time, that SKN-1 is O-GlcNAcylated at Ser470 and Thr493 by O-GlcNActransferase OGT-1. By generating the double mutations of Ser470/Thr493 in the wild type and skn-1(zu67) worms, respectively, we found that disruption of O-GlcNAc modification on SKN-1 repressed the accumulation of SKN-1 in the intestinal nuclei, and decreased the activities of SKN-1 in modulating lifespan and oxidative stress resistance. Moreover, under oxidative stress, SKN-1 was highly O-GlcNAcylated, resulting in the decrease of GSK-3-mediated phosphorylation at Ser483 adjacent to the O-GlcNAcylated residues (Ser470 and Thr493). These data suggest that O-GlcNAcylation of SKN-1 is crucial for regulating lifespan and oxidative stress resistance via the crosstalk with its phosphorylation in C. elegans. These findings have important implications for studying the functions of O-GlcNAcylation on Nrf-2 in human aging-related diseases.
Anisotropic layered Bi2Te3-In2Te3 composites: control of interface density for tuning of thermoelectric properties
Authors: Liu Dongmei , Li Xinzhong , Borlido Pedro Miguel de Castro , Botti Silvana , Schmechel Roland , Rettenmayr Markus
Published: March 2017

Layered (Bi1−xInx)2Te3-In2Te3 (x = 0.075) composites of pronounced anisotropy in structure and thermoelectric properties were produced by zone melting and subsequent coherent precipitation of In2Te3 from a (Bi1−xInx)2Te3 (x > 0.075) matrix. Employing solid state phase transformation, the Bi2Te3/In2Te3 interface density was tuned by modifying the driving force for In2Te3 precipitation. The structure-property relationship in this strongly anisotropic material is characterized thoroughly and systematically for the first time. Unexpectedly, with increasing Bi2Te3/In2Te3 interface density, an increase in electrical conductivity and a decrease in the absolute Seebeck coefficient were found. This is likely to be due to electron accumulation layers at the Bi2Te3/In2Te3 interfaces and the interplay of bipolar transport in Bi2Te3. Significantly improved thermoelectric properties of Bi2Te3-In2Te3 composites as compared to the single phase (Bi1−xInx)2Te3 solid solution are obtained.
A network-based method for mechanistic investigation of Shexiang Baoxin Pill’s treatment of cardiovascular diseases
Authors: Fang Hai-Yang , Zeng Hua-Wu , Lin Li-Mei , Chen Xing , Shen Xiao-Na , Fu Peng , Lv Chao , Liu Qun , Liu Run-Hui , Zhang Wei-Dong , Zhao Jing
Published: March 2017

Shexiang Baoxin Pill (SBP), a traditional Chinese medicine formula, is commonly used to treat cardiovascular disease (CVD) in China. However, the complexity of composition and targets has deterred our understanding of its mechanism of action. Using network pharmacology-based approaches, we established the mechanism of action for SBP to treat CVD by analyzing protein-protein interactions and pathways. The computational results were confirmed at the gene expression level in microarray-based studies. Two of the SBP’s targets were further confirmed at the protein level by Western blot. In addition, we validated the theory that SBP’s plasma absorbed compounds play major therapeutic role in treating CVD.
Association between functional polymorphisms in the promoter of the miR-143/145 cluster and risk of intracranial aneurysm
Authors: Sima Xiutian , Sun Hong , Zhou Peizhi , You Chao , Cai Bowen
Published: March 2017

MicroRNAs (miRs)-143/145 are involved in various biological processes related to aneurysm formation and are downregulated in patients with intracranial aneurysm (IA). We aimed to determine whether two functional polymorphisms (i.e. rs4705342 and rs4705343) in the promoter of miR-143/145 are related to IA risk. A case-control study was undertaken to examine the association of rs4705342 and rs4705343 with IA risk, including 565 patients with IA and 622 age- and gender-matched controls. rs4705342 was analysed by TaqMan Assay, and rs4705343 was genotyped using polymerase chain reaction-restriction fragment length polymorphism. miR-143/145 expression was quantified using RT-PCR. rs4705342 was associated with a significantly lower risk of IA, with adjusted ORs of 0.74 (95% CI: 0.58–0.95) for TC genotype carriers and 0.74 (95% CI: 0.59–0.94) for TC/CC genotypes carriers. Individuals carrying the rs4705342 C allele had a reduced risk of IA (adjusted OR = 0.82; 95% CI: 0.68–0.98). Haplotype of the two loci of rs4705342 and rs4705343 showed that the CT haplotype carried a lower IA risk and higher miR-143 level. Moreover, the rs4705342 CC/CT genotypes were associated with higher miR-143 levels. Thus, the rs4705342C-rs4705343T haplotype in the promoter of miR-143/145 cluster may be related to IA development.
Self-Assembly and Anti-Amyloid Cytotoxicity Activity of Amyloid beta Peptide Derivatives
Authors: Castelletto V. , Ryumin P. , Cramer R. , Hamley I. W. , Taylor M. , Allsop D. , Reza M. , Ruokolainen J. , Arnold T. , Hermida-Merino D. , Garcia C. I. , Leal M. C. , Castaño E.
Published: March 2017

The self-assembly of two derivatives of KLVFF, a fragment Aβ(16–20) of the amyloid beta (Aβ) peptide, is investigated and recovery of viability of neuroblastoma cells exposed to Aβ (1–42) is observed at sub-stoichiometric peptide concentrations. Fluorescence assays show that NH2-KLVFF-CONH2 undergoes hydrophobic collapse and amyloid formation at the same critical aggregation concentration (cac). In contrast, NH2-K(Boc)LVFF-CONH2 undergoes hydrophobic collapse at a low concentration, followed by amyloid formation at a higher cac. These findings are supported by the β-sheet features observed by FTIR. Electrospray ionization mass spectrometry indicates that NH2-K(Boc)LVFF-CONH2 forms a significant population of oligomeric species above the cac. Cryo-TEM, used together with SAXS to determine fibril dimensions, shows that the length and degree of twisting of peptide fibrils seem to be influenced by the net peptide charge. Grazing incidence X-ray scattering from thin peptide films shows features of β-sheet ordering for both peptides, along with evidence for lamellar ordering of NH2-KLVFF-CONH2. This work provides a comprehensive picture of the aggregation properties of these two KLVFF derivatives and shows their utility, in unaggregated form, in restoring the viability of neuroblastoma cells against Aβ-induced toxicity.
Universal quantum gates for hybrid system assisted by atomic ensembles embedded in double-sided optical cavities
Authors: Liu A.-Peng , Cheng Liu-Yong , Guo Qi , Zhang Shou , Zhao Ming-Xia
Published: March 2017

We propose deterministic schemes for controlled-NOT (CNOT), Toffoli, and Fredkin gates between flying photon qubits and the collective spin wave (magnon) of an atomic ensemble inside double-sided optical microcavities. All the gates can be accomplished with 100% success probability in principle and no additional qubit is required. Atomic ensemble is employed so that light-matter coupling is remarkably improved by collective enhancement. We qualified the performance of the gates and the results show that they can be faithfully constituted with current experimental techniques.
Chemosensitivity of MCF-7 cells to eugenol: release of cytochrome-c and lactate dehydrogenase
Authors: Al Wafai Rana , El-Rabih Warde , Katerji Meghri , Safi Remi , El Sabban Marwan , El-Rifai Omar , Usta Julnar
Published: March 2017

Phytochemicals have been extensively researched for their potential anticancer effects. In previous study, direct exposure of rat liver mitochondria to eugenol main ingredient of clove, uncoupled mitochondria and increased F0F1ATPase activity. In the present study, we further investigated the effects of eugenol on MCF-7 cells in culture. Eugenol demonstrated: a dose-dependent decrease in viability (MTT assay), and proliferation (real time cell analysis) of MCF-7 cells, (EC50: 0.9 mM); an increase in reactive oxygen species; a decrease in ATP level and mitochondrial membrane potential (MitoPT JC-1 assay); and a release of cytochrome-c and lactate dehydrogenase (Cytotoxicity Detection Kit PLUS) into culture media at eugenol concentration >EC50. Pretreatment with the antioxidants Trolox and N-acetyl cysteine partially restored cell viability and decreased ROS, with Trolox being more potent. Expression levels of both anti- and pro-apoptotic markers (Bcl-2 and Bax, respectively) decreased with increasing eugenol concentration, with no variation in their relative ratios. Eugenol-treated MCF-7 cells overexpressing Bcl-2 exhibited results similar to those of MCF-7. Our findings indicate that eugenol toxicity is non-apoptotic Bcl-2 independent, affecting mitochondrial function and plasma membrane integrity with no effect on migration or invasion. We report here the chemo-sensitivity of MCF-7 cells to eugenol, a phytochemical with anticancer potential.