bluuebunny/crossref_metadata_2025 huggingface dataset:
Formalisation in higher-order logic and code generation to functional languages of the Gauss-Jordan algorithm
Authors: ARANSAY JESÚS , DIVASÓN JOSE
Published: July 2015

In this paper, we present a formalisation in a proof assistant, Isabelle/HOL, of anaiveversion of the Gauss-Jordan algorithm, with explicit proofs of some of its applications; and, additionally, a process to obtain versions of this algorithm in two different functional languages (SML and Haskell) by means of code generation techniques from the verified algorithm. The aim of this research is not to compete with specialised numerical implementations of Gauss-like algorithms, but to show that formal proofs in this area can be used to generate usable functional programs. The obtained programs show compelling performance in comparison to some other verified and functional versions, and accomplish some challenging tasks, such as the computation of determinants of matrices ofbigintegers and the computation of the homology of matrices representing digital images.
Successful ablation of incessant idiopathic right ventricular tachycardia arising from unusual sites in children
Authors: Wu Lin , Tian Hong , Wang Feng , Liang Xuecun , Chen Gang
Published: July 2015

Objective

Most idiopathic right ventricular tachycardias originate from the outflow tract. We present a case series of idiopathic incessant ventricular tachycardia arising from unusual sites of the right ventricle in children, which were well resolved by catheter ablation.

Methods

A retrospective review was performed of all three patients who underwent ablation of idiopathic ventricular tachycardia below the level of the right ventricular outflow tract using three-dimensional mapping in our institute.

Result

All three patients presented with tachycardia-induced cardiomyopathy due to incessant ventricular tachycardia on first admission. The sites of successful ablation were at the proximal right bundle branch, distal right bundle branch, and apex of the right ventricle, respectively. No complications occurred, and there has been no recurrence of ventricular tachycardia after the final ablation at an average follow-up period of 9 months. All three patients have achieved normalisation of left ventricular size and systolic function.

Conclusion

Incessant idiopathic ventricular tachycardia originating from unusual sites of the right ventricle in children, resulting in significant symptoms and impaired ventricular function, can be successfully treated with catheter ablation.
What does neuroimaging tell us about morphosyntactic processing in the brain of second language learners?
Authors: RONCAGLIA-DENISSEN M. PAULA , KOTZ SONJA A.
Published: July 2015

This review article provides an overview of the neural correlates of second language (L2) morphosyntactic processing of the past 20 years. Morphosyntactic processing is of great relevance for our understanding of second language acquisition as it is believed to be more sensitive to age of acquisition (AoA) and maturational constraints than other linguistic sub-processes, i.e., lexical- and semantic processing.

In this review we present the more general questions raised by the first neuroimaging studies, namely, whether L1 and L2 neural representation of morphosyntax is shared or segregated. Next, we present studies that addressed the impact of AoA, proficiency level, and language transfer on L2 morphosyntactic processing and representation and their findings. We then discuss these findings in light of the procedural/declarative and unified competition models. Finally, we suggest some future directions for studies investigating L2 morphosyntactic processing using neuroimaging techniques. With this article we aim to provide the reader with an overview of what is currently known in terms of L2 morphosyntactic representation and processing and emphasize aspects that have remained understudied.
Social inequalities in BMI trajectories: 8-year follow-up of the Pró-Saúde study in Rio de Janeiro, Brazil
Authors: Chor Dóra , Andreozzi Valeska , Fonseca Maria JM , Cardoso Letícia O , James Sherman A , Lopes Claudia S , Faerstein Eduardo
Published: July 2015

Objective

In a cohort of government employees in Rio de Janeiro, Brazil, we investigated prospectively, sex-specific associations between education and BMI trajectories and their potential effect modification by race.

Design

Of the 4030 participants in Phase 1 (1999), 3253 (81 %) participated in Phase 2 (2003) and 3058 (76 %) participated in Phase 3 (2006). Education was categorized as elementary, high school or college graduate. Study participants self-identified as White, Black orPardo. BMI was calculated from measured weight and height. BMI trajectories were modelled using a generalized additive regression model with mixed effects (GAMM).

Setting

The Pro-Saúde Study, a longitudinal investigation of social determinants of health.

Subjects

Women (n1441) and men (n1127) who participated in the three phases of data collection and had complete information for all study variables.

Results

Women and men with less than high school, or only a high school education, gained approximately 1 kg/m2more than college graduates (women: 1·06 kg/m2(P<0·001) and 1·06 kg/m2(P<0·001), respectively; men: 1·04 kg/m2(P=0·013) and 1·01 kg/m2(P=0·277), respectively). For women only, race was independently associated with weight gain. Women identifying asPardoor Black gained 1·03 kg/m2(P=0·01) and 1·02 kg/m2(P=0·10), respectively, more than Whites. No effect modification by race was observed for either men or women.

Conclusions

While both lower education and darker race were associated with greater weight gain, gender similarities and differences were observed in these associations. The relationship between weight gain and different indicators of social status are therefore complex and require careful consideration when addressing the obesity epidemic.
Socio-economic and lifestyle parameters associated with diet quality of children and adolescents using classification and regression tree analysis: the DIATROFI study
Authors: Yannakoulia Mary , Lykou Anastasia , Kastorini Christina Maria , Saranti Papasaranti Eirini , Petralias Athanassios , Veloudaki Afroditi , Linos Athena ,   on behalf of the DIATROFI Program Research Team
Published: July 2015

Objective

To explore factors affecting children’s and adolescents’ diet quality, in the framework of a food aid and promotion of healthy nutrition programme implemented in areas of low socio-economic status of Greece, during the current financial crisis.

Design

From a total of 162 schools participating in the programme during 2012–2013, we gathered 15 897 questionnaires recording sociodemographic characteristics, lifestyle parameters and dietary habits of children and their families. As a measure of socio-economic status, the Family Affluence Scale (FAS) was used; whereas for the assessment of diet quality, the KIDMED score was computed. Associations between KIDMED and FAS, physical activity and socio-economic parameters were examined using regression and classification–regression tree analysis (CART).

Results

The higher the FAS score, the greater the percentage of children and adolescents who reported to consume, on a daily basis, fruits and vegetables, dairy products and breakfast (P<0·001). Results from CART showed that children and adolescents in the medium or high FAS groups had higher KIDMED score, compared with those in the low FAS group. For those in the low FAS group, KIDMED score is expected to increase by 12·4 % when they spend more than 0·25 h/week in sports activities. The respective threshold for the medium and high FAS groups is 1·75 h/week, while education of the mother and father affected KIDMED score significantly as well.

Conclusions

Diet quality is strongly influenced by socio-economic parameters in children and adolescents living in economically disadvantaged areas of Greece, so that lower family affluence is associated with worse diet quality.
Maternal body image dissatisfaction and BMI change in school-age children
Authors: Duchin Ofra , Marin Constanza , Mora-Plazas Mercedes , Villamor Eduardo
Published: July 2015

Objective

Parental body image dissatisfaction (BID) is associated with children’s weight in cross-sectional studies; however, it is unknown whether BID predicts development of adiposity. The objective of the present study was to investigate the associations between maternal dissatisfaction with her or her child’s body and children’s BMI trajectories.

Design

Longitudinal study. Maternal dissatisfaction (BID) with her and her child’s body was calculated based on ratings of Stunkard scales obtained at recruitment, as current minus desired body image. Children’s height and weight were measured at baseline and annually for a median of 2·5 years. Mixed-effects models with restricted cubic splines were used to construct sex- and weight-specific BMI-for-age curves according to maternal BID levels.

Setting

Public primary schools in Bogotá, Colombia.

Subjects

Children (n1523) aged 5–12 years and their mothers.

Results

After multivariable adjustment, heavy boys and thin girls whose mothers desired a thinner child gained an estimated 1·7 kg/m2more BMI (P=0·04) and 2·4 kg/m2less BMI (P=0·004), respectively, between the age 6 and 14 years, than children of mothers without BID. Normal-weight boys whose mothers desired a thinner child’s body gained an estimated 1·8 kg/m2less BMI than normal-weight boys of mothers without BID (P=0·02). Maternal BID with herself was positively related to children’s BMI gain during follow-up.

Conclusions

Maternal BID is associated with child’s BMI trajectories in a sex- and weight-specific manner.
iSpectra: An Open Source Toolbox For The Analysis of Spectral Images Recorded on Scanning Electron Microscopes
Authors: Liebske Christian
Published: July 2015

iSpectra is an open source and system-independent toolbox for the analysis of spectral images (SIs) recorded on energy-dispersive spectroscopy (EDS) systems attached to scanning electron microscopes (SEMs). The aim of iSpectra is to assign pixels with similar spectral content to phases, accompanied by cumulative phase spectra with superior counting statistics for quantification. Pixel-to-phase assignment starts with a threshold-based pre-sorting of spectra to create groups of pixels with identical elemental budgets, similar to a method described by van Hoek (2014). Subsequent merging of groups and re-assignments of pixels using elemental or principle component histogram plots enables the user to generate chemically and texturally plausible phase maps. A variety of standard image processing algorithms can be applied to groups of pixels to optimize pixel-to-phase assignments, such as morphology operations to account for overlapping excitation volumes over pixels located at phase boundaries. iSpectra supports batch processing and allows pixel-to-phase assignments to be applied to an unlimited amount of SIs, thus enabling phase mapping of large area samples like petrographic thin sections.
Knowledge, attitudes and beliefs towards waterpipe tobacco smoking and electronic shisha (e-shisha) among young adults in London: a qualitative analysis
Authors: Kotecha Shrinal , Jawad Mohammed , Iliffe Steve
Published: July 2015

Introduction

Waterpipe tobacco smoking (WTS), known in the United Kingdom as shisha, is popular among adolescents worldwide. Some electronic cigarettes are marketed in the United Kingdom as ‘electronic shisha’ (e-shisha). This study aimed to understand how WTS users view e-shisha and whether it could be used as a harm-reduction or cessation aid.

Method

In-depth face-to-face interviews were conducted with 16 young adults recruited by snowball sampling in London, UK. Recurrent themes were derived iteratively through thematic analysis.

Results

WTS is a socially acceptable activity, carried out at home or in a café. Peer influence and flavour play a key role in its use. Participants were aware of some health risks of WTS, although many accepted this risk and reported a need for more health-related WTS information. Although participants were familiar with e-shisha, there was no evidence of its use as a harm-reduction or cessation product. E-shisha tasted different to flavoured waterpipe tobacco and removed the positive social attributes typically ascribed to WTS. Waterpipe users felt e-shisha may encourage non-users to initiate cigarettes or WTS.

Conclusion

Opinions of reduced risk in using WTS may be due to the lack of available information, misconceptions and its easy accessibility. E-shisha does not appear to play a role in WTS harm reduction or cessation. On-going research efforts should test educational interventions addressing the adverse health impacts of WTS in this population group.
Spirituality and/or religious faith: A means for coping with the effects of amyotrophic lateral sclerosis/motor neuron disease?
Authors: O'brien Mary R. , Clark David
Published: July 2015

Objective:

The notion of spirituality/religious belief is recognized internationally as a domain within end-of-life care and is important in patients' and carers' quality-of-life. When faced with incurable illness, patients often become more philosophical about their life; many seek comfort in spiritual or religious philosophies. Our intention was to understand how personal spirituality and religious faith might help those living with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) cope with their impending death.

Method:

Unsolicited narratives (internet and print-published) written by individuals diagnosed with the terminal condition of ALS/MND were analyzed thematically. Narratives from 161 individuals diagnosed with ALS/MND written over a period of 37 years (from 1968 to 2005) were included.

Results:

Our findings reveal that religious faith sustains and helps people to avoid despair, and personal spirituality helps them make sense of what is happening to them.

Significance of Results:

The use of personal narratives by people with ALS/MND has provided a vehicle for sharing their deepest spiritual and religious thoughts with others. The place of spirituality and religious faith within ALS/MND care should not be underestimated. Assessment of religious or spiritual needs should become a routine part of practice and is the responsibility of all members of the multidisciplinary team.
Lived-through past, experienced present, anticipated future: Understanding “existential loss” in the context of life-limiting illness
Authors: Harris Denise A.
Published: July 2015

Objective:

Motor Neurone Disease (MND) is a rare, devastating neurodegenerative disease of middle/later life, usually presenting in the sixth and seventh decades (McDermot & Shaw, 2008). People have to wait many months to receive a diagnosis of MND (Donaghy et al., 2008), and during this period they have already experienced the degenerative nature that characterizes MND (Bolmsjö, 2001). However, information on the meaning of life with MND through time is limited. The aim of the present research was to answer the research question “What does it mean to be a person living through the illness trajectory of MND?” and to research the phenomenon of existence when given a diagnosis of MND and in the context of receiving healthcare.

Method:

Hermeneutic phenomenology, inspired by the philosophers Heidegger and Gadamer, informed the methodological approach employed, which asked people to tell their story from when they first thought something untoward was happening to them. The hermeneutic analysis involved a five-stage process in order to understand (interpret) the lifeworld1of four people diagnosed with MND, and a lifeworld perspective helped to make sense of the meaning of existence when given a terminal diagnosis of MND.

Results:

The concept of “existential loss” identified in relation to MND was the loss of past ways of being-in-the-world, and the loss of embodiment, spatiality, and the future.

Significance of results:

The concept of existential loss requires closer attention by healthcare professionals from the time of diagnosis and on through the illness trajectory. The study findings are conceptualized into a framework, which when used as a clinical tool may prompt healthcare professionals to focus on their patients' existential loss and existential concerns. This research adds to the existing literature calling for a lifeworld approach to healthcare.
Tracing the remnants of medieval raspberries using molecular markers
Authors: Novak Vesna , Ivancic Anton , Susek Andrej , Sisko Metka
Published: July 2015

Our investigation was based on a molecular study of the genetic relationships among raspberry genotypes collected around selected medieval castles, Carthusian monasteries and nearby villages. We assumed that the hypothetical medieval raspberry genotypes could be traced to isolated medieval settlements that used to be highly prosperous during the feudal era but were later abandoned. Some of these genotypes could have survived in natural conditions without seed multiplication for at least three centuries. The molecular genetic analysis was based on microsatellite data. A total of 155 alleles were detected at 18 microsatellite loci. The clustering method grouped the analysed genotypes into seven main clusters. The analyses indicated that the most probable medieval genotypes had been collected around the ruins of two abandoned Carthusian monasteries: Zice and Jurkloster. They were morphologically very similar, vigorous and primitive but obviously not wild genotypes. The plants could be more than 2.3 m high, the canes were medium waxy, the lower and upper parts of the canes were covered by sparse short spines, the mid part was more or less completely smooth, the fully developed leaves were 15–25 cm long and the inflorescences were loose. In addition, the flowers were relatively small, the fruit setting was poor and the fruits were small, ovoid to conical and more aromatic than those of modern cultivars.
Identification and Characterization of Adolescent Internet User’s Profiles
Authors: Rial Antonio , Gómez Patricia , Picón Eduardo , Braña Teresa , Varela Jesús
Published: July 2015

The percentages of adolescent Internet use in general terms have been measured for nearly two decades now; however, it might be thought that not every teenager behaves online in the same way. This study aims to identify the different types or profiles of adolescents and to characterize them from an attitudinal, behavioral and socio-demographic viewpoint. A questionnaire was applied to a representative sample of 2,339 Compulsory Secondary School students (M = 13.77 years old) from Galicia (a North-Western region of Spain) for this purpose. A two-stage cluster analysis, based on the response pattern in relation to their attitudes toward Internet, was carried out. Four different segments with specific characteristics were identified: the first steppers, the trainees, the sensible users, and the heavy users. Besides the relevance of descriptive data, these results are of particular interest at an applied level, because they could lead to a better fit of programs to prevent risky behaviors and problematic Internet use in adolescents.
Pediatric Psychology at Georgia State University: Evaluation of Training With the Society of Pediatric Psychology Competencies
Authors: Cohen Lindsey L. , Rodrigues Nikita , Bishop Meredith , Griffin Anya , Sil Soumitri
Published: July 2015

The Task Force on Competencies and Best Training Practices in Pediatric Psychology recently proposed pediatric psychology training competencies organized into 6 cluster areas and a cross-cutting group. This blueprint allows programs to evaluate their training models and identify areas for improvement. The Georgia State University (GSU) pediatric psychology program provides training at the university, 3 children’s hospitals at Children’s Health Care of Atlanta, and other pediatric sites. To evaluate our pediatric psychology training, we used the Society of Pediatric Psychology (SPP) Task Force competencies and focused this paper on how training aligned with the Professionalism cluster. The self-evaluation included subjective evaluation of whether training was tied to competencies, outcome data on competency ratings, and broad performance outcomes. The GSU pediatric psychology program generally mapped onto the SPP Task Force professionalism cluster. At closer inspection, some areas are particularly well covered and others could be targeted for improvement. The self-assessment suggests that the GSU pediatric psychology program is providing excellent training in pediatric psychology. Subjective and objective (e.g., publications, internship, and professional placement) indices support this evaluation.
A novel intracellular mutualistic bacterium in the invasive antCardiocondyla obscurior
Authors: Klein Antonia , Schrader Lukas , Gil Rosario , Manzano-Marín Alejandro , Flórez Laura , Wheeler David , Werren John H , Latorre Amparo , Heinze Jürgen , Kaltenpoth Martin , Moya Andrés , Oettler Jan
Published: July 2015

The evolution of eukaryotic organisms is often strongly influenced by microbial symbionts that confer novel traits to their hosts. Here we describe the intracellular Enterobacteriaceae symbiont of the invasive ant Cardiocondyla obscurior, ‘Candidatus Westeberhardia cardiocondylae’. Upon metamorphosis, Westeberhardia is found in gut-associated bacteriomes that deteriorate following eclosion. Only queens maintain Westeberhardia in the ovarian nurse cells from where the symbionts are transmitted to late-stage oocytes during nurse cell depletion. Functional analyses of the streamlined genome of Westeberhardia (533 kb, 23.41% GC content) indicate that neither vitamins nor essential amino acids are provided for the host. However, the genome encodes for an almost complete shikimate pathway leading to 4-hydroxyphenylpyruvate, which could be converted into tyrosine by the host. Taken together with increasing titers of Westeberhardia during pupal stage, this suggests a contribution of Westeberhardia to cuticle formation. Despite a widespread occurrence of Westeberhardia across host populations, one ant lineage was found to be naturally symbiont-free, pointing to the loss of an otherwise prevalent endosymbiont. This study yields insights into a novel intracellular mutualist that could play a role in the invasive success of C. obscurior.
Spatial and temporal changes in cumulative human impacts on the world’s ocean
Authors: Halpern Benjamin S. , Frazier Melanie , Potapenko John , Casey Kenneth S. , Koenig Kellee , Longo Catherine , Lowndes Julia Stewart , Rockwood R. Cotton , Selig Elizabeth R. , Selkoe Kimberly A. , Walbridge Shaun
Published: July 2015

Human pressures on the ocean are thought to be increasing globally, yet we know little about their patterns of cumulative change, which pressures are most responsible for change, and which places are experiencing the greatest increases. Managers and policymakers require such information to make strategic decisions and monitor progress towards management objectives. Here we calculate and map recent change over 5 years in cumulative impacts to marine ecosystems globally from fishing, climate change, and ocean- and land-based stressors. Nearly 66% of the ocean and 77% of national jurisdictions show increased human impact, driven mostly by climate change pressures. Five percent of the ocean is heavily impacted with increasing pressures, requiring management attention. Ten percent has very low impact with decreasing pressures. Our results provide large-scale guidance about where to prioritize management efforts and affirm the importance of addressing climate change to maintain and improve the condition of marine ecosystems.
MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3
Authors: Zhang Lingyun , Ke Fang , Liu Zhaoyuan , Bai Jing , Liu Jinlin , Yan Sha , Xu Zhenyao , Lou Fangzhou , Wang Hong , Zhu Huiyuan , Sun Yang , Cai Wei , Gao Yuanyuan , Li Qun , Yu Xue-Zhong , Qian Youcun , Hua Zichun , Deng Jiong , Li Qi-Jing , Wang Honglin
Published: July 2015

Peripherally derived regulatory T (pTreg) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pTreg-cell generation. miR-31 conditional deletion results in enhanced induction of pTreg cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). Unexpectedly, we identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pTreg-cell induction and increased EAE severity. By generating miR-31 and Gprc5a double knockout mice, we show that miR-31 promotes the development of EAE through inhibiting Gprc5a. Thus, our data identify miR-31 and its target Gprc5a as critical regulators for pTreg-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional Treg cells in autoimmune diseases.
An itinerant antiferromagnetic metal without magnetic constituents
Authors: Svanidze E. , Wang Jiakui K. , Besara T. , Liu L. , Huang Q. , Siegrist T. , Frandsen B. , Lynn J. W. , Nevidomskyy Andriy H. , Gamża Monika B. , Aronson M. C. , Uemura Y. J. , Morosan E.
Published: July 2015

The origin of magnetism in metals has been traditionally discussed in two diametrically opposite limits: itinerant and local moments. Surprisingly, there are very few known examples of materials that are close to the itinerant limit, and their properties are not universally understood. In the case of the two such examples discovered several decades ago, the itinerant ferromagnets ZrZn2 and Sc3In, the understanding of their magnetic ground states draws on the existence of 3d electrons subject to strong spin fluctuations. Similarly, in Cr, an elemental itinerant antiferromagnet with a spin density wave ground state, its 3d electron character has been deemed crucial to it being magnetic. Here, we report evidence for an itinerant antiferromagnetic metal with no magnetic constituents: TiAu. Antiferromagnetic order occurs below a Néel temperature of 36 K, about an order of magnitude smaller than in Cr, rendering the spin fluctuations in TiAu more important at low temperatures. This itinerant antiferromagnet challenges the currently limited understanding of weak itinerant antiferromagnetism, while providing insights into the effects of spin fluctuations in itinerant–electron systems.
Storage and retrieval of vector beams of light in a multiple-degree-of-freedom quantum memory
Authors: Parigi Valentina , D’Ambrosio Vincenzo , Arnold Christophe , Marrucci Lorenzo , Sciarrino Fabio , Laurat Julien
Published: July 2015

The full structuration of light in the transverse plane, including intensity, phase and polarization, holds the promise of unprecedented capabilities for applications in classical optics as well as in quantum optics and information sciences. Harnessing special topologies can lead to enhanced focusing, data multiplexing or advanced sensing and metrology. Here we experimentally demonstrate the storage of such spatio-polarization-patterned beams into an optical memory. A set of vectorial vortex modes is generated via liquid crystal cell with topological charge in the optic axis distribution, and preservation of the phase and polarization singularities is demonstrated after retrieval, at the single-photon level. The realized multiple-degree-of-freedom memory can find applications in classical data processing but also in quantum network scenarios where structured states have been shown to provide promising attributes, such as rotational invariance.
A phosphorylation switch controls the spatiotemporal activation of Rho GTPases in directional cell migration
Authors: Cao Xuan , Kaneko Tomonori , Li Jenny S. , Liu An-Dong , Voss Courtney , Li Shawn S. C.
Published: July 2015

Although cell migration plays a central role in development and disease, the underlying molecular mechanism is not fully understood. Here we report that a phosphorylation-mediated molecular switch comprising deleted in liver cancer 1 (DLC1), tensin-3 (TNS3), phosphatase and tensin homologue (PTEN) and phosphoinositide-3-kinase (PI3K) controls the spatiotemporal activation of the small GTPases, Rac1 and RhoA, thereby initiating directional cell migration induced by growth factors. On epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) stimulation, TNS3 and PTEN are phosphorylated at specific Thr residues, which trigger the rearrangement of the TNS3–DLC1 and PTEN–PI3K complexes into the TNS3–PI3K and PTEN–DLC1 complexes. Subsequently, the TNS3–PI3K complex translocates to the leading edge of a migrating cell to promote Rac1 activation, whereas PTEN–DLC1 translocates to the posterior for localized RhoA activation. Our work identifies a core signalling mechanism by which an external motility stimulus is coupled to the spatiotemporal activation of Rac1 and RhoA to drive directional cell migration.
The key role of the scaffold on the efficiency of dendrimer nanodrugs
Authors: Caminade Anne-Marie , Fruchon Séverine , Turrin Cédric-Olivier , Poupot Mary , Ouali Armelle , Maraval Alexandrine , Garzoni Matteo , Maly Marek , Furer Victor , Kovalenko Valeri , Majoral Jean-Pierre , Pavan Giovanni M. , Poupot Rémy
Published: July 2015

Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an ‘innocent’ scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins.
Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices
Authors: Gjorevski Nikolce , S. Piotrowski Alexandra , Varner Victor D. , Nelson Celeste M.
Published: July 2015

Collective cell migration drives tissue remodeling during development, wound repair and metastatic invasion. The physical mechanisms by which cells move cohesively through dense three-dimensional (3D) extracellular matrix (ECM) remain incompletely understood. Here, we show directly that migration of multicellular cohorts through collagenous matrices occurs via a dynamic pulling mechanism, the nature of which had only been inferred previously in 3D. Tensile forces increase at the invasive front of cohorts, serving a physical, propelling role as well as a regulatory one by conditioning the cells and matrix for further extension. These forces elicit mechanosensitive signaling within the leading edge and align the ECM, creating microtracks conducive to further migration. Moreover, cell movements are highly correlated and in phase with ECM deformations. Migrating cohorts use spatially localized, long-range forces and consequent matrix alignment to navigate through the ECM. These results suggest biophysical forces are critical for 3D collective migration.
Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells
Authors: Jones Anna J , Gokhale Paul J , Allison Thomas F , Sampson Barry , Athwal Sharan , Grant Simon , Andrews Peter W , Allen Nicholas D , Patrick Case C
Published: July 2015

Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development.
Ultra-high-resolution 3D imaging of atherosclerosis in mice with synchrotron differential phase contrast: a proof of concept study
Authors: Bonanno Gabriele , Coppo Simone , Modregger Peter , Pellegrin Maxime , Stuber Annina , Stampanoni Marco , Mazzolai Lucia , Stuber Matthias , van Heeswijk Ruud B.
Published: July 2015

The goal of this study was to investigate the performance of 3D synchrotron differential phase contrast (DPC) imaging for the visualization of both macroscopic and microscopic aspects of atherosclerosis in the mouse vasculature ex vivo. The hearts and aortas of 2 atherosclerotic and 2 wild-type control mice were scanned with DPC imaging with an isotropic resolution of 15 μm. The coronary artery vessel walls were segmented in the DPC datasets to assess their thickness and histological staining was performed at the level of atherosclerotic plaques. The DPC imaging allowed for the visualization of complex structures such as the coronary arteries and their branches, the thin fibrous cap of atherosclerotic plaques as well as the chordae tendineae. The coronary vessel wall thickness ranged from 37.4 ± 5.6 μm in proximal coronary arteries to 13.6 ± 3.3 μm in distal branches. No consistent differences in coronary vessel wall thickness were detected between the wild-type and atherosclerotic hearts in this proof-of-concept study, although the standard deviation in the atherosclerotic mice was higher in most segments, consistent with the observation of occasional focal vessel wall thickening. Overall, DPC imaging of the cardiovascular system of the mice allowed for a simultaneous detailed 3D morphological assessment of both large structures and microscopic details.
T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia
Authors: Hao Han , Haas Michael J. , Wu Rongling , Gragnoli Claudia
Published: July 2015

Insomnia increases type-2 diabetes (T2D) risk. The 12q24 locus is linked to T2D, depression, bipolar disorder and anxiety. At the 12q24 locus, the Proteasome-Modulator 9 (PSMD9) single nucleotide polymorphisms (SNPs) rs74421874 [intervening sequence (IVS) 3+nt460-G>A], rs3825172 (IVS3+nt437-C>T) and rs14259 (E197G-A>G) are linked to: T2D, depression, anxiety, maturity-onset-diabetes-of the young 3/MODY3, obesity, waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular disease, T2D-microvascular disease, T2D-neuropathy, T2D-carpal-tunnel syndrome, T2D-nephropathy, T2D-retinopathy and non-diabetic retinopathy. PSMD9 SNP rs1043307/rs14259 (E197G-A>G) plays a role in anti-depressant therapy response, depression and schizophrenia. We aimed at determining PSMD9 rs74421874/rs3825172/rs14259 SNPs potential linkage to primary insomnia and sleep hours in T2D families. We recruited 200 Italian T2D families phenotyping them for primary insomnia and sleep hours per night. PSMD9-T2D-risk SNPs rs74421874/rs3825172 and rs1043307/rs14259 were tested for linkage with insomnia and sleep hours. Non-parametric-linkage analysis, linkage-disequilibrium-model analysis, single-SNP analysis, cluster-based-parametric analysis, quantitative-trait and variant-component analysis were performed using Merlin software. To validate data, 1000 replicates were executed for the significant non-parametric data. PSMD9 rs74421874 (IVS3+nt460-G>A), rs3825172 (IVS3+nt437-C>T) and rs1043307/rs14259 (E197G-A>G) SNPs are linked to insomnia in our Italian families.
Differential and coherent processing patterns from small RNAs
Authors: Pundhir Sachin , Gorodkin Jan
Published: July 2015

Post-transcriptional processing events related to short RNAs are often reflected in their read profile patterns emerging from high-throughput sequencing data. MicroRNA arm switching across different tissues is a well-known example of what we define as differential processing. Here, short RNAs from the nine cell lines of the ENCODE project, irrespective of their annotation status, were analyzed for genomic loci representing differential or coherent processing. We observed differential processing predominantly in RNAs annotated as miRNA, snoRNA or tRNA. Four out of five known cases of differentially processed miRNAs that were in the input dataset were recovered and several novel cases were discovered. In contrast to differential processing, coherent processing is observed widespread in both annotated and unannotated regions. While the annotated loci predominantly consist of ~24nt short RNAs, the unannotated loci comparatively consist of ~17nt short RNAs. Furthermore, these ~17nt short RNAs are significantly enriched for overlap to transcription start sites and DNase I hypersensitive sites (p-value < 0.01) that are characteristic features of transcription initiation RNAs. We discuss how the computational pipeline developed in this study has the potential to be applied to other forms of RNA-seq data for further transcriptome-wide studies of differential and coherent processing.
Radiofrequency treatment alters cancer cell phenotype
Authors: Ware Matthew J. , Tinger Sophia , Colbert Kevin L. , Corr Stuart J. , Rees Paul , Koshkina Nadezhda , Curley Steven , Summers H. D. , Godin Biana
Published: July 2015

The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.
Curved singular beams for three-dimensional particle manipulation
Authors: Zhao Juanying , Chremmos Ioannis D. , Song Daohong , Christodoulides Demetrios N. , Efremidis Nikolaos K. , Chen Zhigang
Published: July 2015

For decades, singular beams carrying angular momentum have been a topic of considerable interest. Their intriguing applications are ubiquitous in a variety of fields, ranging from optical manipulation to photon entanglement and from microscopy and coronagraphy to free-space communications, detection of rotating black holes and even relativistic electrons and strong-field physics. In most applications, however, singular beams travel naturally along a straight line, expanding during linear propagation or breaking up in nonlinear media. Here, we design and demonstrate diffraction-resisting singular beams that travel along arbitrary trajectories in space. These curved beams not only maintain an invariant dark “hole” in the center but also preserve their angular momentum, exhibiting combined features of optical vortex, Bessel and Airy beams. Furthermore, we observe three-dimensional spiraling of microparticles driven by such fine-shaped dynamical beams. Our findings may open up new avenues for shaped light in various applications.
Cutting improves the productivity of lucerne-rich stands used in the revegetation of degraded arable land in a semi-arid environment
Authors: Yuan Zi-Qiang , Yu Kai-Liang , Wang Bin-Xian , Zhang Wang-Yun , Zhang Xu-Long , Siddique Kadambot H. M. , Stefanova Katia , Turner Neil C. , Li Feng-Min
Published: July 2015

Understanding the relationships between vegetative and environmental variables is important for revegetation and ecosystem management on the Loess Plateau, China. Lucerne (Medicago sativa L.) has been widely used in the region to improve revegetation, soil and water conservation and to enhance livestock production. However, there is little information on how environmental factors influence long-term succession in lucerne-rich vegetation. Our objective was to identify the main environmental variables controlling the succession process in lucerne-rich vegetation such that native species are not suppressed after sowing on the Loess Plateau. Vegetation and soil surveys were performed in 31 lucerne fields (three lucerne fields without any management from 2003–2013 and 28 fields containing 11-year-old lucerne with one cutting each year). Time after planting was the most important factor affecting plant species succession. Cutting significantly affected revegetation characteristics, such as aboveground biomass, plant density and diversity. Soil moisture content, soil organic carbon, soil available phosphorus and slope aspect were key environmental factors affecting plant species composition and aboveground biomass, density and diversity. Long-term cutting can cause self-thinning in lucerne, maintain the stability of lucerne production and slow its degradation. For effective management of lucerne fields, phosphate fertilizer should be applied and cutting performed.
Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment
Authors: Quintana D S , Westlye L T , Rustan Ø G , Tesli N , Poppy C L , Smevik H , Tesli M , Røine M , Mahmoud R A , Smerud K T , Djupesland P G , Andreassen O A
Published: July 2015

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered’ nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.
Interaction of Metal Ions with Proteins as a Source of Inspiration for Biomimetic Materials
Authors: Smith Andrew M.
Published: July 2015

Nature provides us with great inspiration for the development of new materials and molecules by showing us the breadth and range of possibilities that can be achieved. One such area is the use of metal ions for catalysis of chemical reactions, transport of molecules and the formation of materials. This is all achieved through coupling metal ions to proteins either directly or through the use of organic molecules such as porphyrin rings. In this chapter we will explore the wide range of functions that proteins containing metal ions are involved in to provide us with inspiration on what can potentially be achieved. This will include the role of zinc ions as an example of a specific ion followed by examination of enzymatic reactions of non-haem-oxygenases and binuclear metallohydrolases, as well as porphyrin-containing proteins and the use of the latter in transport. We will then look at the use of metal ions in the formation of materials such as silks, amyloids, and mussel byssus and glue.
Cationic poly(amidoamine) promotes cytosolic delivery of bovine RNase A in melanoma cells, while maintaining its cellular toxicity
Authors: Dubois Julie L. N. , Lavignac Nathalie
Published: July 2015

Poly(amidoamine)s enhance cellular uptake of wild-type RNase A in B16F1 melanoma cells and help its cytosolic delivery, inducing increased cell death.
Study on the treatment effect of Polygonum cuspidatum for hyperuricemia in rats using the UPLC-ESI-QTOF/MS metabolomics approach
Authors: Xu Chen , Chen Weijia , Liu Shu , Pi Zifeng , Song Fengrui , Liu Zhiqiang
Published: July 2015

UPLC-ESI-QTOF/MS-based metabolomics was applied to investigate the potential biomarkers in hyperuricemic rats treated withPolygonum cuspidatum.
Quantitative analysis of hormones in cosmetics by LC-MS/MS combined with an advanced calibration model
Authors: Shi Cai-Xia , Chen Zeng-Ping , Chen Yao , Yu Ru-Qin
Published: July 2015

Accurate quantitative analysis of hormones in cosmetics was achieved through the combination of an advanced model with LC-MS/MS, even when significant variations occur in the sensitivity and signal stability of LC-MS/MS.
A novel fluorescent probe for imaging endogenous hydrogen sulphide via the CSE enzymatic pathway
Authors: Zhang Lili , Zhu Huikun , Li Mimi , Gu Xianfeng
Published: July 2015

The capability of monitoring endogenous H2S via the CSE enzymatic pathway was proved by utilizing a novel designed probe.
Exploiting dimensional variability in coordination polymers: solvent promotes reversible conversion between 3D and chiral 1D architectures
Authors: Rancan Marzio , Armelao Lidia
Published: July 2015

DMSO promotes dimensional variability between coordination-driven architectures such as a 3D nanoporous network and a 1D chiral polymer self-assembled from achiral building blocks.
Rh-catalyzed sequential oxidative C–H activation/annulation with geminal-substituted vinyl acetates to access isoquinolines
Authors: Chu Haoke , Sun Song , Yu Jin-Tao , Cheng Jiang
Published: July 2015

The concise synthesis of 3-substituted or non-C3-substituted isoquinolines through Rh-catalyzed sequential oxidative C–H activation/annulation with geminal-substituted vinyl acetates was developed.