bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Chemical Bonding Interaction: An Insight into the Growth Process of 1D ZnO on Few‐Layer Graphene for Excellent Photocatalytic and Room Temperature Gas Sensing Applications
Authors: Rakkesh R. Ajay , Durgalakshmi D. , Balakumar S.
Published: July 2018

A facile chemical synthesis approach is reported for simultaneous reduction of graphene oxide (GO) and chemically planted 1D ZnO Nanorods (NRs) on the few‐layer graphene (FLG) through chemical bonding interaction. The chemically bonded 1D ZnO – few layer graphene nanostructures are investigated by high resolution scanning transmission electron microscopy, photoelectron spectroscopy, X‐ray diffraction and photoluminescence studies. This multifunctional nanostructure efficiently boosts the photocatalytic activity by photodegradation of industrial pollutants within 5 minutes under natural sunlight irradiation and also senses the very low concentration (10 ppm) of hydrogen gas at room temperature with very high sensing response. The emerging photocatalytic performance and the room temperature gas sensing characteristics of 1D ZnO – few layer graphene is attributed to the presence of C–Zn chemical bonds, which plays an essential role in the interfacial charge transfer process between the graphene layers and 1D ZnO NRs. The strong chemical bonding interaction and interfacial charge transfer effects have been experimentally elucidated from the ionization value and work function characteristics of the synthesized hybrid nanostructure. This work demonstrates the simple way of preparing hybrid nanostructure with exposed crystal facets, which could provide an exposure for developing multifunctional nanomaterials towards sensing and removal of hazardous pollutants from our environment.
Octadecyl Amine Functionalized Graphene Oxide towards Hydrophobic Chemical Resistant Epoxy Nanocomposites
Authors: Mousavi Seyyed Mojtaba , Hashemi Seyyed Alireza , Arjmand Mohammad , Amani Ali Mohammad , Sharif Farbod , Jahandideh Sara
Published: July 2018

In this research study, graphene oxide (GO) was synthesized using an improved Hummers method and thence oxygen‐based functional groups were replaced with octadecyl amine. Afterwards, epoxy‐based nanocomposites containing GO and GO‐octadecyl amine (GO‐ODA) were fabricated via a vacuum shock technique. The chemical resistance of the fabricated nanocomposites against various solvents, namely xylene, toluene and distilled water, was investigated and the effect of chemical degradation on the hardness and structural stability of the nanocomposites was examined. Besides, SEM, contact angle and AFM analyses were conducted to evaluate morphology, hydrophobicity and roughness of the nanocomposites prior to and following the chemical degradation. The obtained results illustrated that the reinforcement of the epoxy‐based nanocomposites with GO‐ODA and GO, in order, enhanced chemical resistance, hardness, roughness, and hydrophobicity of the nanocomposites. For instance, after incorporating GO and GO‐ODA into the epoxy resin, the average roughness of the neat epoxy resin reduced 84.0% and 94.1%, the hardness of the neat epoxy resin increased from 80 to 82 and 86 kgf/mm2, and the contact angle of the epoxy resin changed from 76° to 71° and 85°, respectively. In brief, outcome of this study reveals that GO‐ODA can be used as an efficient filler to develop effective hydrophobic polymeric shields against chemical degradation.
A novel reliability analysis approach for component‐based software based on the complex network theory
Authors: Li Kewen , Yu Mingxiao , Liu Lu , Zhai Jiannan , Liu Wenying
Published: July 2018

Traditional software reliability evaluation approaches lack the analysis of intercomponent interactions of component‐based software systems, necessitating software reliability evaluation based on the reliabilities of the overall architecture and each component. In this paper, we propose a reliability evaluation model and an importance assessment technique for component‐based software based on the complex network theory. The components of a software system are identified and divided into 2 categories, input/output components and ordinary components. Then, the impact factors of ordinary components and input/output components are calculated based on the complex network theory and execution probabilities, respectively. Finally, the impact factors are used to evaluate the reliability of the software system and assess the importance of each component. Experimental results show that the proposed approach is able to estimate the reliability of component‐based software and provide relative priorities of the components that can be used to guide the system reliability optimization.
A Formalization of the LLL Basis Reduction Algorithm
Authors: Divasón Jose , Joosten Sebastiaan , Thiemann René , Yamada Akihisa
Published: July 2018

The LLL basis reduction algorithm was the first polynomial-time algorithm to compute a reduced basis of a given lattice, and hence also a short vector in the lattice. It thereby approximates an NP-hard problem where the approximation quality solely depends on the dimension of the lattice, but not the lattice itself. The algorithm has several applications in number theory, computer algebra and cryptography.

In this paper, we develop the first mechanized soundness proof of the LLL algorithm using Isabelle/HOL. We additionally integrate one application of LLL, namely a verified factorization algorithm for univariate integer polynomials which runs in polynomial time.
Anomalous transport in holographic boundary conformal field theories
Authors: Chu Chong-Sun , Miao Rong-Xin
Published: July 2018

Abstract

Recently, it is found that when an external magnetic field parallel to the boundary is applied, Weyl anomaly gives rises to a new anomalous current transport in the vicinity of the boundary. At the leading order of closeness from the boundary, the current is determined universally by the central charge of the theory. In this paper, we give a holographic proof for the existence and universality for this transport phenomena. We show that the current is independent of boundary conditions in four dimensions while it depends on boundary conditions in other dimensions. We also study the backreaction of the bulk Maxwell fields on the AdS spacetime and obtain the holographic Weyl anomaly for 5d BCFTs in presence of the background field strength.
New properties of large-c conformal blocks from recursion relation
Authors: Kusuki Yuya
Published: July 2018

Abstract

We study large c conformal blocks outside the known limits. This work seems to be hard, but it is possible numerically by using the Zamolodchikov recursion relation. As a result, we find new some properties of large c conformal blocks with a pair of two different dimensions for any channel and with various internal dimensions. With light intermediate states, we find a Cardy-like asymptotic formula for large c conformal blocks and also we find that the qualitative behavior of various large c blocks drastically changes when the dimensions of external primary states reach the value c/32. And we proceed to the study of blocks with heavy intermediate states h

p
and we find some simple dependence on heavy h

p
for large c blocks. The results in this paper can be applied to, for example, the calculation of OTOC or Entanglement Entropy. In the end, we comment on the application to the conformal bootstrap in large c CFTs.
Correction to: The effect of magnesium on early osseointegration in osteoporotic bone: a histological and gene expression investigation
Authors: Galli S. , Stocchero M. , Andersson M. , Karlsson J. , He W. , Lilin T. , Wennerberg A. , Jimbo R.
Published: July 2018

This article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.
Places of Persistence: Slavery and the Geography of Intergenerational Mobility in the United States
Authors: Berger Thor
Published: July 2018

Intergenerational mobility has remained stable over recent decades in the United States but varies sharply across the country. In this article, I document that areas with more prevalent slavery by the outbreak of the Civil War exhibit substantially less upward mobility today. I find a negative link between prior slavery and contemporary mobility within states, when controlling for a wide range of historical and contemporary factors including income and inequality, focusing on the historical slave states, using a variety of mobility measures, and when exploiting geographical differences in the suitability for cultivating cotton as an instrument for the prevalence of slavery. As a first step to disentangle the underlying channels of persistence, I examine whether any of the five broad factors highlighted by Chetty et al. (2014a) as the most important correlates of upward mobility—family structure, income inequality, school quality, segregation, and social capital—can account for the link between earlier slavery and current mobility. More fragile family structures in areas where slavery was more prevalent, as reflected in lower marriage rates and a larger share of children living in single-parent households, is seemingly the most relevant to understand why it still shapes the geography of opportunity in the United States.
Mining sites in Australia benefit from using Osmoflo water treatment technology
Authors: Atkinson Simon
Published: July 2018

Water treatment company Osmoflo is currently involved in two major projects in the mining sector in Australia. Here, we briefly discuss each one and outline the technology that is being employed and will benefit the sites involved.
Evaluation of a Medically Supervised Concussion Protocol for Youth Hockey in Canada
Authors: Ellis Michael J. , Leiter Jeff , Cordingley Dean M. , Reimer Karen , Koenig James , Russell Kelly F.
Published: July 2018

Objectives:The objective of this study was to evaluate the feasibility and implementation of a standardized medically supervised concussion protocol established between a city-wide AAA hockey league and a multi-disciplinary concussion program.Methods:We conducted a retrospective review of injury surveillance, clinical and healthcare utilization data from all athletes evaluated and managed through the Winnipeg AAA Hockey concussion protocol during the 2016-2017 season. We also conducted post-season email surveys of head coaches and parents responsible for athletes who competed in the same season.Results:During the 2016-2017 season, 28 athletes were evaluated through the medically supervised concussion protocol, with two athletes undergoing evaluation for repeat injuries (a total of 30 suspected injuries and consultations). In all, 96.7% of the athletes managed through the concussion protocol were captured by the league-designated Concussion Protocol Coordinator and 100% of eligible athletes underwent complete medical follow-up and clearance to return to full hockey activities. Although 90% of responding head coaches and 91% of parents were aware of the concussion protocol, survey results suggest that some athletes who sustained suspected concussions were not managed through the protocol. Head coaches and parents also indicated that athlete education and communication between medical and sport stakeholders were other elements of the concussion protocol that could be improved.Conclusion:Successful implementation of a medically supervised concussion protocol for youth hockey requires clear communication between sport stakeholders and timely access to multi-disciplinary experts in traumatic brain and spine injuries. Standardized concussion protocols for youth sports may benefit from periodic evaluations by sport stakeholders and incorporation of national guideline best practices and resources.
Network Approaches to Understand Individual Differences in Brain Connectivity: Opportunities for Personality Neuroscience
Authors: Tompson Steven H. , Falk Emily B. , Vettel Jean M. , Bassett Danielle S.
Published: July 2018

Over the past decade, advances in the interdisciplinary field of network science have provided a framework for understanding the intrinsic structure and function of human brain networks. A particularly fruitful area of this work has focused on patterns of functional connectivity derived from noninvasive neuroimaging techniques such as functional magnetic resonance imaging. An important subset of these efforts has bridged the computational approaches of network science with the rich empirical data and biological hypotheses of neuroscience, and this research has begun to identify features of brain networks that explain individual differences in social, emotional, and cognitive functioning. The most common approach estimates connections assuming a single configuration of edges that is stable across the experimental session. In the literature, this is referred to as a static network approach, and researchers measure static brain networks while a subject is either at rest or performing a cognitively demanding task. Research on social and emotional functioning has primarily focused on linking static brain networks with individual differences, but recent advances have extended this work to examine temporal fluctuations in dynamic brain networks. Mounting evidence suggests that both the strength and flexibility of time-evolving brain networks influence individual differences in executive function, attention, working memory, and learning. In this review, we first examine the current evidence for brain networks involved in cognitive functioning. Then we review some preliminary evidence linking static network properties to individual differences in social and emotional functioning. We then discuss the applicability of emerging dynamic network methods for examining individual differences in social and emotional functioning. We close with an outline of important frontiers at the intersection between network science and neuroscience that will enhance our understanding of the neurobiological underpinnings of social behavior.
The Fixation of (Moral) Belief
Authors: Wilson Nicholas Hoover
Published: July 2018

This article argues that the transition between early-modern and modern organization of empires—especially the administrative outlooks and institutional logics used to govern them—revolved around how moral conflict was viewed within imperial organizations themselves and by metropolitan audiences. Early modern imperial organizations were deeply patrimonial, and hence relied on a style of embedded moral reasoning that distanced and segmented their affairs from the metropole. By contrast, modern empires order what they govern in hierarchies that are nominally objective and whose criteria seem universal. Using a case study of the British Empire’s crisis and transformation at the turn of the 19thcentury, I argue that modern imperial administration emerged because networks of moral justification, which provided the scaffolding for patrimonial early-modern empire, eroded in the face of “disinterested” metropolitan scrutiny. This scrutiny created an audience for bitter political and moral conflicts among imperial administrators, who then used disembedded moral claims to mobilize support.
Detection of tetracycline and other antimicrobial residues in milk from cows with clinical mastitis treated by combination therapy
Authors: Siljanoski Aleksandar , Ciglarič Renata , Pezdir Tomaž , Lainšček Petra R , Dolenc Jožica , Starič Jože , Šinigoj-Gačnik Ksenija
Published: July 2018

The purpose of this study was to determine tetracycline and other antimicrobial residues in milk from dairy cows treated for clinical mastitis. Data on cow health and drugs used were obtained from the farm veterinarians. A milk sample from each affected udder quarter of each cow was taken for bacterial identification before treatment. All 35 cows in the study were treated with an intramammary product containing tetracycline, neomycin, bacitracin, and prednisolone (tetracycline injector) and also simultaneously with other drugsviathe intramammary or parenteral route. The withhold period of the ‘tetracycline product’ was eight milkings but, in all cases, longer withhold periods were prescribed due to off-label application of additional combinations of drugs. Milk samples from treated udder quarters, taken two milkings before and two after the prescribed withhold period, were analysed for antimicrobial residues. Additionally, milk samples were taken from untreated healthy udder quarters to check if any crossover of drugs had occurred. Three screening tests were used for antimicrobial detection. In 15 (42·9%) cows the milk samples from the treated infected quarters contained tetracycline residues above the maximum residue limit (MRL) after the prescribed withhold period and, in two cases (5·7%) the same was true for neomycin and cefquinome residues. Cephalexin above the MRL was detected in only one case (2·9%). Beta-lactams did not exceed the MRL after the prescribed withhold period. Antimicrobial residues were not detected in milk samples from untreated quarters. Cow condition including parity, decreased milk production and severity of mastitis significantly influenced the excretion of antimicrobials in milk (P≤ 0·05). No significant differences were found between the tetracycline positive and tetracycline negative cows regarding the bacteria involved, combination antimicrobial therapy, or treatment interval and duration.
Automated Fall Detection Technology in Inpatient Geriatric Psychiatry: Nurses’ Perceptions and Lessons Learned
Authors: Coahran Marge , Hillier Loretta M. , Van Bussel Lisa , Black Edward , Churchyard Rebekah , Gutmanis Iris , Ioannou Yani , Michael Kathleen , Ross Tom , Mihailidis Alex
Published: July 2018

Les personnes âgées hospitalisées présentent un haut risque de chute. Le système HELPER est un système de détection des chutes fixé au plafond qui envoie une alerte à un téléphone intelligent lorsqu’une chute est détectée. Cet article décrit la performance du système HELPER, qui a été testé dans un projet pilote mené dans un centre de santé mentale gériatrique. La précision du système pour la détection des chutes a été comparée aux données de l’hôpital liées à la documentation des chutes. Au terme du projet pilote, le personnel infirmier a été interviewé afin de documenter comment cette technologie était perçue. Dans cette étude, le système HELPER n’a pas permis de détecter une chute qui a été documentée par le personnel, mais en a détecté 4 autres qui n’avaient pas été documentées. Bien que la sensibilité du système soit élevée (0.80), les fausses alarmes qu’il génère diminuent sa valeur prédictive (0.01). Les entrevues avec le personnel infirmier ont permis de recueillir plusieurs informations utiles liées au fonctionnement de cette technologie dans un environnement réel; ces données seront utiles aux ingénieurs travaillant sur de tels systèmes et sur des technologies associées aux soins de santé et aux services sociaux.
Human cumulus cell sensitivity to vitrification, an ultrastructural study
Authors: Taghizabet Neda , Khalili Mohammad Ali , Anbari Fatemeh , Agha-Rahimi Azam , Nottola Stefania Annarita , Macchiarelli Guido , Palmerini Maria Grazia
Published: July 2018

Cumulus cells (CCs) play an important role in the regulation of female gamete development, meiotic maturation, oocyte–sperm interaction, capacitation and acrosome reaction. However, their role in maintaining oocyte competence after vitrification is unclear as controversial data on their protecting action against oocyte cryoinjuries are available. Here we described the effects of vitrification on the ultrastructure of human CCs collected from women undergoing assisted reproductive technologies (ARTs). In total, 50 patches of CCs, sampled from high-quality human cumulus–oocyte complexes, were randomly allocated into two groups after patient informed consent: 1, fresh CCs (controls, n = 25); 2, vitrified CCs (n = 25). Samples were then prepared and observed by transmission electron microscopy. In fresh CCs, in which small cell clusters were visible, cell membranes were joined by focal gap junctions. Microvilli were rare and short. Nuclei, mitochondria, smooth endoplasmic reticulum (SER), Golgi apparatus and lipid droplets appeared well preserved; vacuoles were scarce. After vitrification, we observed two populations of CCs: light CCs, with a smooth appearance and few short microvilli; and dark CCs, with numerous and long microvilli. In both, most of the organelles appeared similar to those of fresh CCs. Lipid droplets were denser and more numerous, with respect to fresh CCs. They were mainly located in the peri-nuclear and sub-plasmalemmal regions. Numerous packed electron-negative vacuoles were visible. The vitrification procedure did not cause alterations in the fine structure of major organelles, except for an increased amount of lipid droplets and vacuoles. This specific sensitivity of human CCs to vitrification should be considered during ARTs.
Fiddling While Rome Burns? A Response to Weyland on Full Professor Promotions
Authors: Leal David L.
Published: July 2018

This article responds to the stimulating comments of Kurt Weyland (2015) about the important but seldom discussed full professor promotion process. He suggested a number of problems, particularly candidates who are too eager to “go up” and institutions with insufficiently rigorous publication standards. Rather than proposing a top-down solution, Weyland urged associate professors to wait until they cleared a high research bar. By contrast, I see few systemic problems with the current promotion process. Although research is important, our academic ecosystem requires the valuing of a wide range of faculty activities and contributions. In addition, asking faculty to jump through even more research hoops may be ‘fiddling while Rome burns.’ It overlooks the crucial issue that we all face: making the case for the value of higher education to taxpayers, parents, lawmakers, students, employers, philanthropists, voters, and society. I am optimistic that we can do so, but it may require a new set of academic priorities—less of the status games that can animate our academic lives and more of a focus on how our work benefits society.
The benefits of international cooperation under climate uncertainty: a dynamic game analysis
Authors: Zhang Xiao-Bing , Hennlock Magnus
Published: July 2018

This paper investigates the benefits of international cooperation under uncertainty about global warming through a stochastic dynamic game. We analyze the benefits of cooperation both for the case of symmetric and asymmetric players. It is shown that the players’ combined expected payoffs decrease as climate uncertainty becomes larger, whether or not they cooperate. However, the benefits from cooperation increase with climate uncertainty. In other words, it is more important to cooperate when facing higher uncertainty. At the same time, more transfers will be needed to ensure stable cooperation among asymmetric players.
Against Conservatism in Metaphysics
Authors: Fairchild Maegan , Hawthorne John
Published: July 2018

In his recent book, Daniel Korman contrasts ontological conservatives with permissivists and eliminativists about ontology. Roughly speaking, conservatives admit the existence of ‘ordinary objects' like trees, dogs, and snowballs, but deny the existence of ‘extraordinary objects', like composites of trees and dogs (‘trogs'). Eliminativists, on the other hand, deny many or all ordinary objects, while permissivists accept both ordinary and extraordinary objects. Our aim in this paper is to outline some of our reasons for being drawn to permissivism, as well as some of our misgivings about conservative metaphysics. In the first section, we discuss a tempting epistemic line of argument against conservatism. This isn’t a line of argument we find especially promising. Our most basic complaint against conservatism is not that conservatism has poor epistemic standing even if true, but instead that conservatism is weird. We develop this thought in the second part of the paper. In the final section we discuss some larger methodological issues about the project of ontology.
Fatherhood, gender and the making of professional identity in large law firms: bringing men into the frame
Authors: Collier Richard
Published: July 2018

This paper reframes debates about gender equality in the legal professions by interrogating the practices of men and interconnections between fatherhood, gender and parenting within the specific context of large corporate law firms. Drawing on interviews with male lawyer-fathers, it argues that closer exploration of fatherhood reveals much about the gendered dynamics of identity formation as a legal professional in this sector. A set of ideas about fatherhood, the paper suggests, shape how men's work can define a distinctive gender identity as a ‘family man’ and good lawyer. Political-economic and cultural shifts around fatherhood, however, are reconfiguring and adapting gender relations in law in a number of contradictory ways with implications for understanding the place of men in relation to gender-equality agendas. Ideas about fatherhood, family, work and career, I argue, are mobilised and enmeshed within the reproduction of distinctive law-firm cultures and gendered ideas of organisational commitment. What, in short, might it mean to bebotha ‘good father’ and a ‘good lawyer’?
Refractory Ascites in Liver Cirrhosis
Authors: Adebayo Danielle , Neong Shuet Fong , Wong Florence
Published: July 2018

Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.
Pyruvate kinase M2 isoform deletion in cone photoreceptors results in age-related cone degeneration
Authors: Rajala Ammaji , Wang Yuhong , Soni Krutik , Rajala Raju V. S.
Published: July 2018

The tumor form of pyruvate kinase M2 has been suggested to promote cellular anabolism by redirecting the metabolism to cause accumulation of glycolytic intermediates and increasing flux through the pentose phosphate pathway, which is a metabolic pathway parallel to glycolysis. Both rod and cone photoreceptors express the tumor form of pyruvate kinase M2. Recent studies from our laboratory show that PKM2 is functionally important for rod photoreceptor structure, function, and viability. However, the functional role of PKM2 in cones is not known. In this study, we conditionally deleted PKM2 in cones (cone-cre PKM2-KO) and found that loss of PKM2 results in the upregulation of PKM1 and a significant loss of cone function and cone degeneration in an age-dependent manner. Gene expression studies on cone-cre PKM2-KO show decreased expression of genes regulating glycolysis, PPP shunt, and fatty acid biosynthesis. Consistent with these observations, cones lacking PKM2 have significantly shorter cone outer segments than cones with PKM2. Our studies clearly suggest that PKM2 is essential for the anabolic process in cones to keep them alive for normal functioning and to support cone structure.
MiR-133b targets Sox9 to control pathogenesis and metastasis of breast cancer
Authors: Wang Qiu-Yu , Zhou Ci-Xiang , Zhan Meng-Na , Tang Jun , Wang Chen-Long , Ma Cheng-Ning , He Ming , Chen Guo-Qiang , He Jian-Rong , Zhao Qian
Published: July 2018

The miR-133b, a commonly recognized muscle-specific miRNA, was reported to be deregulated in many kinds of cancers. However, its potential roles in tumorigenesis remain greatly elusive. Herein, we demonstrate that miR-133b is significantly suppressed in human breast cancer specimens, which is reversely correlated to histological grade of the cancer. Ectopic expression of miR-133b suppresses clonogenic ability and metastasis-relevant traits in vitro, as well as carcinogenesis and pulmonary metastasis in vivo. Further studies have identified Sox9, c-MET, and WAVE2 as direct targets of miR-133b, in which Sox9 contributes to all miR-133b-endowed effects including cell proliferation, colony formation, as well as cell migration and invasion in vitro. Moreover, re-expression of Sox9 reverses miR-133b-mediated metastasis suppression in vivo. Taken together, these findings highlight an important role for miR-133b in the regulation of tumorigenesis and metastatic potential of breast cancer and suggest a potential application of miR-133b in cancer treatment.
Consequences of blunting the mevalonate pathway in cancer identified by a pluri-omics approach
Authors: Goulitquer Sophie , Croyal Mikaël , Lalande Julie , Royer Anne-Lise , Guitton Yann , Arzur Danielle , Durand Stéphanie , Le Jossic-Corcos Catherine , Bouchereau Alain , Potin Philippe , Akoka Serge , Antignac Jean-Philippe , Krempf Michel , Ferchaud-Roucher Véronique , Giraudeau Patrick , Corcos Laurent
Published: July 2018

We have previously shown that the combination of statins and taxanes was a powerful trigger of HGT-1 human gastric cancer cells’ apoptosis1. Importantly, several genes involved in the “Central carbon metabolism pathway in cancer”, as reported in the Kyoto Encyclopedia of Genes and Genomes, were either up- (ACLY, ERBB2, GCK, MYC, PGM, PKFB2, SLC1A5, SLC7A5, SLC16A3,) or down- (IDH, MDH1, OGDH, P53, PDK) regulated in response to the drug association. In the present study, we conducted non-targeted metabolomics and lipidomics analyses by complementary methods and cross-platform initiatives, namely mass spectrometry (GC-MS, LC-MS) and nuclear magnetic resonance (NMR), to analyze the changes resulting from these treatments. We identified several altered biochemical pathways involved in the anabolism and disposition of amino acids, sugars, and lipids. Using the Cytoscape environment with, as an input, the identified biochemical marker changes, we distinguished the functional links between pathways. Finally, looking at the overlap between metabolomics/lipidomics and transcriptome changes, we identified correlations between gene expression modifications and changes in metabolites/lipids. Among the metabolites commonly detected by all types of platforms, glutamine was the most induced (6–7-fold), pointing to an important metabolic adaptation of cancer cells. Taken together, our results demonstrated that combining robust biochemical and molecular approaches was efficient to identify both altered metabolic pathways and overlapping gene expression alterations in human gastric cancer cells engaging into apoptosis following blunting the cholesterol synthesis pathway.
Δ133p53α, a natural p53 isoform, contributes to conditional reprogramming and long-term proliferation of primary epithelial cells
Authors: Mondal Abdul M. , Zhou Hua , Horikawa Izumi , Suprynowicz Frank A. , Li Guangzhao , Dakic Aleksandra , Rosenthal Bernard , Ye Lin , Harris Curtis C. , Schlegel Richard , Liu Xuefeng
Published: July 2018

We previously developed the technique of conditional reprogramming (CR), which allows primary epithelial cells from fresh or cryopreserved specimens to be propagated long-term in vitro, while maintaining their genetic stability and differentiation potential. This method requires a combination of irradiated fibroblast feeder cells and a Rho-associated kinase (ROCK) inhibitor. In the present study, we demonstrate increased levels of full-length p53 and its natural isoform, Δ133p53α, in conditionally reprogrammed epithelial cells from primary prostate, foreskin, ectocervical, and mammary tissues. Increased Δ133p53α expression is critical for CR since cell proliferation is rapidly inhibited following siRNA knockdown of endogenous Δ133p53α. Importantly, overexpression of Δ133p53α consistently delays the onset of cellular senescence of primary cells when cultured under non-CR conditions in normal keratinocyte growth medium (KGM). More significantly, the combination of Δ133p53α overexpression and ROCK inhibitor, without feeder cells, enables primary epithelial cells to be propagated long-term in vitro. We also show that Δ133p53α overexpression induces hTERT expression and telomerase activity and that siRNA knockdown of hTERT causes rapid inhibition of cell proliferation, indicating a critical role of hTERT for mediating the effects of Δ133p53α. Altogether, these data demonstrate a functional and regulatory link between p53 pathways and hTERT expression during the conditional reprogramming of primary epithelial cells.
Epigenetic silencing of tumor suppressor gene CDKN1A by oncogenic long non-coding RNA SNHG1 in cholangiocarcinoma
Authors: Yu Yang , Zhang Mingjiong , Wang Ni , Li Quanpeng , Yang Jian , Yan Shuai , He Xuezhi , Ji Guozhong , Miao Lin
Published: July 2018

Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption.
Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells
Authors: Zhang Yingshi , Li Dandan , Jiang Qiyu , Cao Shuang , Sun Huiwei , Chai Yantao , Li Xiaojuan , Ren Tianshu , Yang Ruichuang , Feng Fan , Li Bo-an , Zhao Qingchun
Published: July 2018

Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial–mesenchymal transition (EMT), and also participate in the induction of multi-drug resistance (MDR). In the present study, we demonstrated the discovery of a novel inhibitor for Notch activating/cleaving enzyme ADAM-17, named ZLDI-8; it inhibited the cleavage of NOTCH protein, consequently decreased the expression of pro-survival/anti-apoptosis and EMT related proteins. ZLDI-8 treatment enhanced the susceptibility of HCC cells to a small molecular kinase inhibitor Sorafenib, and chemotherapy agents Etoposide and Paclitaxel. ZLDI-8 treatment enhanced the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model. These results suggest that ZLDI-8 can be a promising therapeutic agent to enhance Sorafenib’s anti-tumor effect and to overcome the MDR of HCC patients.
k-space imaging of anisotropic 2D electron gas in GaN/GaAlN high-electron-mobility transistor heterostructures
Authors: Lev L. L. , Maiboroda I. O. , Husanu M.-A. , Grichuk E. S. , Chumakov N. K. , Ezubchenko I. S. , Chernykh I. A. , Wang X. , Tobler B. , Schmitt T. , Zanaveskin M. L. , Valeyev V. G. , Strocov V. N.
Published: July 2018

Nanostructures based on buried interfaces and heterostructures are at the heart of modern semiconductor electronics as well as future devices utilizing spintronics, multiferroics, topological effects, and other novel operational principles. Knowledge of electronic structure of these systems resolved in electron momentum k delivers unprecedented insights into their physics. Here we explore 2D electron gas formed in GaN/AlGaN high-electron-mobility transistor heterostructures with an ultrathin barrier layer, key elements in current high-frequency and high-power electronics. Its electronic structure is accessed with angle-resolved photoelectron spectroscopy whose probing depth is pushed to a few nanometers using soft-X-ray synchrotron radiation. The experiment yields direct k-space images of the electronic structure fundamentals of this system—the Fermi surface, band dispersions and occupancy, and the Fourier composition of wavefunctions encoded in the k-dependent photoemission intensity. We discover significant planar anisotropy of the electron Fermi surface and effective mass connected with relaxation of the interfacial atomic positions, which translates into nonlinear (high-field) transport properties of the GaN/AlGaN heterostructures as an anisotropy of the saturation drift velocity of the 2D electrons.
Microtubule minus-end aster organization is driven by processive HSET-tubulin clusters
Authors: Norris Stephen R. , Jung Seungyeon , Singh Prashant , Strothman Claire E. , Erwin Amanda L. , Ohi Melanie D. , Zanic Marija , Ohi Ryoma
Published: July 2018

Higher-order structures of the microtubule (MT) cytoskeleton are comprised of two architectures: bundles and asters. Although both architectures are critical for cellular function, the molecular pathways that drive aster formation are poorly understood. Here, we study aster formation by human minus-end-directed kinesin-14 (HSET/KIFC1). We show that HSET is incapable of forming asters from preformed, nongrowing MTs, but rapidly forms MT asters in the presence of soluble (non-MT) tubulin. HSET binds soluble (non-MT) tubulin via its N-terminal tail domain to form heterogeneous HSET-tubulin clusters containing multiple motors. Cluster formation induces motor processivity and rescues the formation of asters from nongrowing MTs. We then show that excess soluble (non-MT) tubulin stimulates aster formation in HeLa cells overexpressing HSET during mitosis. We propose a model where HSET can toggle between MT bundle and aster formation in a manner governed by the availability of soluble (non-MT) tubulin.
Crystal and melt inclusion timescales reveal the evolution of magma migration before eruption
Authors: Ruth Dawn C. S. , Costa Fidel , Bouvet de Maisonneuve Caroline , Franco Luis , Cortés Joaquin A. , Calder Eliza S.
Published: July 2018

Volatile element concentrations measured in melt inclusions are a key tool used to understand magma migration and degassing, although their original values may be affected by different re-equilibration processes. Additionally, the inclusion-bearing crystals can have a wide range of origins and ages, further complicating the interpretation of magmatic processes. To clarify some of these issues, here we combined olivine diffusion chronometry and melt inclusion data from the 2008 eruption of Llaima volcano (Chile). We found that magma intrusion occurred about 4 years before the eruption at a minimum depth of approximately 8 km. Magma migration and reaction became shallower with time, and about 6 months before the eruption magma reached 3–4 km depth. This can be linked to reported seismicity and ash emissions. Although some ambiguities of interpretation still remain, crystal zoning and melt inclusion studies allow a more complete understanding of magma ascent, degassing, and volcano monitoring data.
Author Correction: Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice
Authors: Liu Yicong , Wu Zhou , Nakanishi Yurika , Ni Junjun , Hayashi Yoshinori , Takayama Fumiko , Zhou Yanmin , Kadowaki Tomoko , Nakanishi Hiroshi
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF version of this paper. The error has been fixed in the paper.
Radio-frequency current drive for thermonuclear fusion reactors
Authors: Cardinali A. , Castaldo C. , Cesario R. , Amicucci L. , Galli A. , Napoli F. , Panaccione L. , Riccardi C. , Santini F. , Schettini G. , Tuccillo A. A.
Published: July 2018

Principal research on energy from thermonuclear fusion uses Deuterium-Tritium plasmas magnetically trapped in toroidal devices. As major scientific problem for an economic (i.e., really feasible) reactor, we must understand how to lead strongly heated plasmas to sustain a high fusion gain while large fraction of current is self-produced via the presence of strong pressure gradient. To suppress turbulent eddies that impair thermal insulation and pressure tight of the plasma, current drive (CD) is necessary. However, tools envisaged so far in ITER (International Thermonuclear Experiment Rector) are unable accomplishing this task that requires efficiently and flexibly matching the natural current profiles of plasma. Consequently, viability of a thermonuclear reactor should be problematic. Multi-megawatt radio-frequency (RF) power coupled to plasma would produce the necessary CD, but modelling results based on previous understanding found difficult the extrapolation of this CD concept to reactor conditions of high temperature plasma, and greater flexibility of method would also be required. Here we present new model results based on standard quasilinear (QL) theory that allow establish conditions to drive efficiently and flexibly the RF-driven current at large radii of the plasma column, as necessary for the goal of a reactor.
Environmental DNA reveals quantitative patterns of fish biodiversity in large rivers despite its downstream transportation
Authors: Pont Didier , Rocle Mathieu , Valentini Alice , Civade Raphaël , Jean Pauline , Maire Anthony , Roset Nicolas , Schabuss Michael , Zornig Horst , Dejean Tony
Published: July 2018

Despite the ecological and societal importance of large rivers, fish sampling remains costly and limited to specific habitats (e.g., river banks). Using an eDNA metabarcoding approach, we regularly sampled 500 km of a large river (Rhône River). Comparisons with long-term electrofishing surveys demonstrated the ability of eDNA metabarcoding to qualitatively and quantitatively reveal fish assemblage structures (relative species abundance) but eDNA integrated a larger space than the classical sampling location. Combination of a literature review and field data showed that eDNA behaves in the water column like fine particulate organic matter. Its detection distance varied from a few km in a small stream to more than 100 km in a large river. To our knowledge, our results are the first demonstration of the capacity of eDNA metabarcoding to describe longitudinal fish assemblage patterns in a large river, and metabarcoding appears to be a reliable, cost-effective method for future monitoring.
Prolonged phloem ingestion by Diaphorina citri nymphs compared to adults is correlated with increased acquisition of citrus greening pathogen
Authors: George Justin , Ammar El-Desouky , Hall David G. , Shatters Robert G. , Lapointe Stephen L.
Published: July 2018

Citrus greening disease (huanglongbing), currently the most destructive citrus disease worldwide, is putatively caused by Candidatus Liberibacter asiaticus (CLas), a phloem-limited bacterium transmitted by the Asian citrus psyllid Diaphorina citri. Electrical penetration graph (EPG) recordings over 42 h were performed to compare the feeding behavior of D. citri adults and 4th or 5th instar nymphs feeding on CLas-infected or healthy citron plants. Nymphs performed more individual bouts of phloem ingestion (E2) and recorded longer phloem ingestion total time compared with adults, whereas adults performed more bouts of xylem ingestion (G) and recorded greater total time of xylem ingestion compared with nymphs. Quantitative polymerase chain reaction tests indicated that 58% of nymphs and 6% of adults acquired CLas during the 42 h EPG-recorded feeding on infected plants. In a histological study, a greater proportion of salivary sheaths produced by nymphs were branched compared to those of the adults. Our results strongly suggest that more bouts and longer feeding time in the phloem by nymphs may explain their more efficient CLas acquisition from infected plants compared to adults. This is the first EPG study comparing nymphs and adults of D. citri on healthy and infected citrus plants in relation to CLas acquisition.
Optimization of a MT1-MMP-targeting Peptide and Its Application in Near-infrared Fluorescence Tumor Imaging
Authors: Ren Li , Wang Ye , Zhu Lei , Shen Liqiao , Zhang Jinrui , Wang Jingjing , Li Haolong , Zheng Qingchuan , Yu Dahai , Fang Xuexun
Published: July 2018

Membrane type 1 metalloproteinase (MT1-MMP) is an important regulator of cancer invasion, growth and angiogenesis, thus making it an attractive target for cancer imaging and therapy. A non-substrate peptide (MT1-AF7p) that bonded to the “MT-Loop” region of MT1-MMP was identified by using a phage-displayed peptide library and was used to image the MT1-MMP expression in vivo through optical imaging. However, the substrate in the screening did not have a 3D structure, thus resulting in a loose bonding of MT1-AF7p. To simulate the real conformation of the “MT-Loop” and improve the performance of MT1-AF7p, molecular simulations were performed, because this strategy provides multiple methods for predicting the conformation and interaction of proteinase in 3D. In view of the binding site of the receptor–ligand interactions, histidine 4 was selected for mutation to achieve an increased affinity effect. The optimized peptides were further identified and conformed by atomic force microscopy, isothermal titration calorimetry, cell fluorescence imaging in vitro, and near-infrared fluorescence tumor optical imaging in vivo. The results revealed that the optimized peptide with a mutation of histidine 4 to arginine has the highest affinity and specificity, and exhibited an increased fluorescence intensity in the tumor site in optical imaging.