bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the oxidation states and structural stability of the Ce analogue of brannerite
Authors: Aluri Esther Rani , Bachiu Lisa M. , Grosvenor Andrew P. , Forbes Scott H. , Greedan John E.
Published: July 2017

The Ce‐containing analogue of brannerite (ie, UTi2O6) was previously considered to be stoichiometric (ie, CeTi2O6); however, it has recently been determined that the material is O deficient. This oxygen‐deficient material has been suggested to be charged balanced by the presence of a minor concentration of Ce3+ or by the A‐site being cation deficient with the Ce oxidation state being 4+. A variety of Ti‐containing oxides (including brannerite) have been investigated as potential nuclear wasteforms, and it is necessary to understand the electronic structure of a proposed nuclear wasteform material as well as how the structure responds to radiation from incorporated waste elements. The radiation resistance of a material can be simulated by ion implantation. The objective of this study was to confirm the Ce oxidation state in the cation‐ and oxygen‐deficient material (ie, Ce0.94Ti2O6 − δ) and to determine how radiation damage affects this material. X‐ray photoelectron spectroscopy (XPS) and X‐ray absorption near‐edge spectroscopy were used to study Ce0.94Ti2O6 − δ before and after being implanted with 2 MeV Au− ions. Analysis of the Ce 3d XPS spectra from the as‐synthesized samples by using a previously developed fitting method has unequivocally shown that Ce adopts both 4+ (major) and 3+ (minor) oxidation states, which was confirmed by examination of magnetic susceptibility data. Analysis of XPS and X‐ray absorption near‐edge spectroscopy spectra from ion‐implanted materials showed that both Ce and Ti were reduced because of radiation damage and that the local coordination environments of the cations are greatly affected by radiation damage.
The joining of composite materials: the best of both worlds
Authors: Kluke Martin
Published: July 2017

Over the past several years, lightweight construction has undeniably become a driving force in many areas of transportation.
Leibniz on Causation and Agency
Authors: Jorati Julia
Published: July 2017

This book presents a comprehensive examination of Gottfried Leibniz's views on the nature of agents and their actions. Julia Jorati offers a fresh look at controversial topics including Leibniz's doctrines of teleology, the causation of spontaneous changes within substances, divine concurrence, freedom, and contingency, and also discusses widely neglected issues such as his theories of moral responsibility, control, attributability, and compulsion. Rather than focusing exclusively on human agency, she explores the activities of non-rational substances and the differences between distinctive types of actions, showing how the will, appetitions, and teleology are key to Leibniz's discussions of agency. Her book reveals that Leibniz has a nuanced and compelling philosophy of action which has relevance for present-day discussions of agency. It will be of interest to scholars and students of early modern philosophy as well as to metaphysicians and philosophers of action.
Raising Children
Authors: Lancy David F.
Published: July 2017

Why in some parts of the world do parents rarely play with their babies and never with toddlers? Why in some cultures are children not fully recognized as individuals until they are older? How are routine habits of etiquette and hygiene taught - or not - to children in other societies? Drawing on a lifetime's experience as an anthropologist, David F. Lancy takes us on a journey across the globe to show how children are raised differently in different cultures. Intriguing, and sometimes shocking, his discoveries demonstrate that our ideas about children are recent, untested, and often contrast starkly with those in other parts of the world. Lancy argues that we are, by historical standards, guilty of over-parenting, of micro-managing our children's lives. Challenging many of our accepted truths, his book will encourage parents to think differently about children, and by doing so to feel more relaxed about their own parenting skills.
How Leaders Mobilize Workers
Authors: Vössing Konstantin
Published: July 2017

This book explains why leaders choose social democracy, revolution, or moderate syndicalism to mobilize workers, and why it matters. In some countries, leaders have responded effectively to their political environment, while others have made ill-fitting choices. Vössing explains not only why leaders make certain choices, but also how their choices affect the success of interest mobilization and subsequent political development. Using quantitative data and historical sources, this book combines an analysis of the formation of class politics in all twenty industrialized countries between 1863 and 1919 with a general theory of political mobilization. It integrates economic, political, and ideational factors into a comprehensive account that highlights the critical role of individual leaders.
Strange Bedfellows
Authors: Phinney Robin
Published: July 2017

How do advocates for the poor gain influence in American policymaking? Strange Bedfellows argues that groups representing low-income populations compensate for a lack of resources by collaborating with diverse partners in their lobbying efforts. This study develops a theory of coalition influence that explains the mechanisms and conditions of coalition formation and influence, and provides support for the theory through an analysis of one of the most significant social policy changes in recent history. The analysis shows that in the years preceding the federal welfare reform of 1996, advocates collaborated with diverse partners to influence policymaking, coalitions were used as a tool for pooling different types of resources and communicating information, and groups collaborated selectively across issues. Through rigorous theory and rich qualitative analysis, Strange Bedfellows sheds new light on lobbying and influence in policymaking while offering a theoretical framework for understanding the broader role of coalitions in American politics.
Stable isotope (δD–δ18O) relationships of ice facies and glaciological structures within the mid-latitude maritime Fox Glacier, New Zealand
Authors: Appleby John R. , Brook Martin S. , Horton Travis W. , Fuller Ian C. , Holt Katherine A. , Quincey Duncan J.
Published: July 2017

Relationships between stable isotopes (δD–δ18O), ice facies and glacier structures have hitherto gone untested in the mid-latitude maritime glaciers of the Southern Hemisphere. Here, we present δD–δ18O values as part of a broader study of the structural glaciology of Fox Glacier, New Zealand. We analyzed 94 samples of δD–δ18O from a range of ice facies to investigate whether isotopes have potential for structural glaciological studies of a rapidly deforming glacier. The δD–δ18O measurements were aided by structural mapping and imagery from terminus time-lapse cameras. The current retreat phase was preceded by an advance of 1 km between 1984 and 2009, with the isotopic sampling and analysis undertaken at the end of that advance (2010/11). Stable isotopes from debris-bearing shear planes near the terminus, interpreted as thrust faults, are isotopically enriched compared with the surrounding ice. When plotted on co-isotopic diagrams (δD–δ18O), ice sampled from the shear planes appears to show a subtle, but distinctive isotopic signal compared with the surrounding clean ice on the lower glacier. Hence, stable isotopes (δD–δ18O) have potential within the structural glaciology field, but larger sample numbers than reported here may be required to establish isotopic contrasts between a broad range of ice facies and glacier structures.
Universal continuous transition to turbulence in a planar shear flow
Authors: Chantry Matthew , Tuckerman Laurette S. , Barkley Dwight
Published: July 2017

We examine the onset of turbulence in Waleffe flow – the planar shear flow between stress-free boundaries driven by a sinusoidal body force. By truncating the wall-normal representation to four modes, we are able to simulate system sizes an order of magnitude larger than any previously simulated, and thereby to attack the question of universality for a planar shear flow. We demonstrate that the equilibrium turbulence fraction increases continuously from zero above a critical Reynolds number and that statistics of the turbulent structures exhibit the power-law scalings of the (2 + 1)-D directed-percolation universality class.
Austerity and Anti-Austerity: The Political Economy of Refusal in ‘Low-Resistance’ Models of Capitalism
Authors: Bailey David J. , Shibata Saori
Published: July 2017

In contrast to much of the political economy literature, this article explores acts of refusal that obstruct attempts to impose austerity measures on advanced industrial democracies. It thereby complements a literature that has thus far focused far more upon the (apparently unobstructed) imposition of austerity. In doing so, it uses two typically ‘low-resistance’ countries – Japan and the UK –as least-likely cases and finds that austerity is rarely uncontested. Using fuzzy set Qualitative Comparative Analysis, it highlights the ‘causal recipes’ sufficient for both (1) anti-austerity activity to have a significant impact on austerity proposals and (2) the smooth (unobstructed) imposition of austerity. The politics of austerity is shown to be better understood as an iterative interaction between proposals for austerity and the acts of refusal they encounter. These obstacles to austerity appear more straightforward to activate effectively in Japan’s coordinated model of capitalism, whilst the UK’s liberal market economy tends to generate more innovative forms of dissent that (if they are sufficiently militant) provide an alternative route towards the obstruction of austerity.
Not a one-trick pony: Diverse connectivity and functions of the rodent lateral geniculate complex
Authors: MONAVARFESHANI ABOOZAR , SABBAGH UBADAH , FOX MICHAEL A.
Published: July 2017

Often mislabeled as a simple relay of sensory information, the thalamus is a complicated structure with diverse functions. This diversity is exemplified by roles visual thalamus plays in processing and transmitting light-derived stimuli. Such light-derived signals are transmitted to the thalamus by retinal ganglion cells (RGCs), the sole projection neurons of the retina. Axons from RGCs innervate more than ten distinct nuclei within thalamus, including those of the lateral geniculate complex. Nuclei within the lateral geniculate complex of nocturnal rodents, which include the dorsal lateral geniculate nucleus (dLGN), ventral lateral geniculate nucleus (vLGN), and intergeniculate leaflet (IGL), are each densely innervated by retinal projections, yet, exhibit distinct cytoarchitecture and connectivity. These features suggest that each nucleus within this complex plays a unique role in processing and transmitting light-derived signals. Here, we review the diverse cytoarchitecture and connectivity of these nuclei in nocturnal rodents, in an effort to highlight roles for dLGN in vision and for vLGN and IGL in visuomotor, vestibular, ocular, and circadian function.
The yolk syncytial layer of loach,Misgurnus fossilis(Teleostei) during early development
Authors: Kondakova Ekaterina , Neklyudova Irina , Efremov Vladimir
Published: July 2017

The yolk syncytial layer (YSL) of Teleostei is a dynamic multifunctional temporary system. This paper describes the YSL structure ofMisgurnus fossilis(Cobitidae) during its early developmental stages, studied using histological methods. YSL formation is prolonged. From the late blastula stage, the basal surface of the YSL is uneven and has protuberances, but becomes smoother during development. There are syncytial ‘islands’ with 1–2 yolk syncytial nuclei in the yolk mass. During epiboly, gastrulation and early segmentation, loach YSL is of different thickness in different regions along the dorso-ventral and antero-posterior axes of an embryo. The YSL is thickened in the dorsal region of gastrulae compared with the ventral region. Although the development ofM.fossilisis similar to the development of zebrafish, there are important differences in YSL formation and organization that await further study and analysis. The study of YSL organization contributes to our knowledge of teleost developmental diversity and to the biology of temporary structures.
BUBBLES AND CROWDING-IN OF CAPITAL VIA A SAVINGS GLUT
Authors: Hillebrand Marten , Kikuchi Tomoo , Sakuragawa Masaya
Published: July 2017

This paper uncovers a mechanism by which bubbles crowd in capital investment. If capital formation is initially depressed by a binding credit constraint, a bubble triggers a savings glut. Higher returns in a new bubbly equilibrium attract additional savings, which are channeled to expand investment at the extensive margin, leading to permanently higher capital, output, and wages. We demonstrate that crowding-in through this channel is a robust phenomenon that occurs along the entire time path.
LIFE: BIOGRAPHY AS CONFLICTUAL COHERENCE
Authors: LA VOPA ANTHONY J.
Published: July 2017

In the early 1970s, when I was a graduate student, biography was considered “an unloved stepchild” of the historical discipline. The naive empiricism of its soup-to-nuts narratives seemed deaf to any theory that might call the biographer's craft into question. In 2009, the American Historical Review honored the genre of biography with a roundtable on its creative renewal. Oddly (and regrettably) there was no mention of the work of Jerrold Seigel in any of the roundtable essays, though he had published three innovative biographical works over the previous thirty years. Characterizing Seigel as a biographer by trade would, to be sure, seriously diminish the scope of his scholarship. But two of his seven books have been full biographies, and in two others a biographical approach has been central to his modus operandi. A leading figure in refashioning the genre, he has been quite conscious of the implications of that commitment. In 1987 he ended an article on Durkheim with a challenge: “our knowledge of the human world must be able to survive the recognition of its personal sources.” Three years later he concluded an article on “the personal roots of Foucault's thinking” with another provocation to recent preoccupations in the discipline: “the proclaimed death of the subject is not some newly discovered set of relations that produce the illusion of human will and intentions as residues of their silent operation, but the action of a subjectivity that will not speak its name.”
Influence of Various Cover Crop Species on Winter and Summer Annual Weed Emergence in Soybean
Authors: Cornelius Cody D. , Bradley Kevin W.
Published: July 2017

Field experiments were conducted in 2013, 2014, and 2015 in Columbia and Moberly, Missouri to determine the effects of cereal rye, Italian ryegrass, winter wheat, winter oat, crimson clover, Austrian winterpea, hairy vetch, oilseed radish, and cereal rye plus hairy vetch on winter and summer annual weed emergence in soybean. For comparison purposes, each experiment in each year included a Fall PRE, Spring PRE without residual, and Spring PRE residual herbicide programs. Cereal rye and cereal rye plus hairy vetch reduced winter annual weed emergence by 72 and 68%, respectively, but were not comparable to the Fall PRE which reduced winter annual weed emergence by 99%. The following spring, early-season waterhemp emergence was similar among treatments of cereal rye, cereal rye plus hairy vetch, and the Spring PRE residual herbicide program. In contrast, all cover crop species other than Italian ryegrass reduced late season waterhemp emergence between 21 and 40%, but were not comparable to the Spring PRE residual herbicide program, which reduced late season waterhemp emergence by 97%. All other summer annual weeds excluding waterhemp showed a similar response among cover crop and herbicide treatments. Overall, results from this experiment indicate that certain cover crops are able to suppress winter and summer annual weed emergence, but not to the extent of soil-applied residual herbicides.
The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair
Authors: Liao Jinfeng , Tian Taoran , Shi Sirong , Xie Xueping , Ma Quanquan , Li Guo , Lin Yunfeng
Published: July 2017

Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based on the density difference between the two layers via a thermally reactive, rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components. The pore sizes of the upper and lower hydrogels were ~187.4 and ~112.6 μm, respectively. The moduli of the upper and lower hydrogels were ~0.065 and ~0.261 MPa. This prepared bilayer hydrogel exhibited the characteristics of mimetic composition, mimetic structure and mimetic stiffness, which provided a microenvironment for sustaining cell attachment and viability. Meanwhile, the biodegradability and biocompatibility of the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect model was developed in rabbits, and the bilayer hydrogels were implanted into the defect. The regenerated tissues in the bilayer hydrogel group exhibited new translucent cartilage and repaired subchondral bone, indicating that the hydrogel can enhance the repair of osteochondral defects.
The association between the baseline bone resorption marker CTX and incident dysglycemia after 4 years
Authors: Liu Ting-ting , Liu Dong-mei , Xuan Yan , Zhao Lin , Sun Li-hao , Zhao Dian-dian , Wang Xiao-feng , He Yang , Guo Xing-Zhi , Du Rui , Wang Ji-qiu , Liu Jian-min , Zhao Hong-yan , Tao Bei
Published: July 2017

Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin (OCN) in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen (CTX) and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant (NGT) women at baseline were invited for follow-up. The incidence of diabetes and prediabetes (collectively defined as dysglycemia) was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% (95% confidence interval (CI), 6.8%–30.7%)] compared with the lower [31.0% (95% CI, 17.2%–46.1%)] and upper [46.5% (95% CI, 31.2%–62.6%)] tertiles of CTX, with a significant difference seen between the middle and upper tertiles (P=0.002 5). After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 (95% CI, 1.73–28.99) when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.
Structural insights into the mechanism of the membrane integral N-acyltransferase step in bacterial lipoprotein synthesis
Authors: Wiktor Maciej , Weichert Dietmar , Howe Nicole , Huang Chia-Ying , Olieric Vincent , Boland Coilín , Bailey Jonathan , Vogeley Lutz , Stansfeld Phillip J. , Buddelmeijer Nienke , Wang Meitian , Caffrey Martin
Published: July 2017

Lipoproteins serve essential roles in the bacterial cell envelope. The posttranslational modification pathway leading to lipoprotein synthesis involves three enzymes. All are potential targets for the development of new antibiotics. Here we report the crystal structure of the last enzyme in the pathway, apolipoprotein N-acyltransferase, Lnt, responsible for adding a third acyl chain to the lipoprotein’s invariant diacylated N-terminal cysteine. Structures of Lnt fromPseudomonas aeruginosaandEscherichia colihave been solved; they are remarkably similar. Both consist of a membrane domain on which sits a globular periplasmic domain. The active site resides above the membrane interface where the domains meet facing into the periplasm. The structures are consistent with the proposed ping-pong reaction mechanism and suggest plausible routes by which substrates and products enter and leave the active site. While Lnt may present challenges for antibiotic development, the structures described should facilitate design of therapeutics with reduced off-target effects.
Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals
Authors: Posth Cosimo , Wißing Christoph , Kitagawa Keiko , Pagani Luca , van Holstein Laura , Racimo Fernando , Wehrberger Kurt , Conard Nicholas J. , Kind Claus Joachim , Bocherens Hervé , Krause Johannes
Published: July 2017

Ancient DNA is revealing new insights into the genetic relationship between Pleistocene hominins and modern humans. Nuclear DNA indicated Neanderthals as a sister group of Denisovans after diverging from modern humans. However, the closer affinity of the Neanderthal mitochondrial DNA (mtDNA) to modern humans than Denisovans has recently been suggested as the result of gene flow from an African source into Neanderthals before 100,000 years ago. Here we report the complete mtDNA of an archaic femur from the Hohlenstein–Stadel (HST) cave in southwestern Germany. HST carries the deepest divergent mtDNA lineage that splits from other Neanderthals ∼270,000 years ago, providing a lower boundary for the time of the putative mtDNA introgression event. We demonstrate that a complete Neanderthal mtDNA replacement is feasible over this time interval even with minimal hominin introgression. The highly divergent HST branch is indicative of greater mtDNA diversity during the Middle Pleistocene than in later periods.
CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth Area in the Bone Defect Repair Process
Authors: Wang Jimeng , Gao Yi , Cheng Pengzhen , Li Donglin , Jiang Huijie , Ji Chuanlei , Zhang Shuaishuai , Shen Chao , Li Junqin , Song Yue , Cao Tianqing , Wang Chunmei , Yang Liu , Pei Guoxian
Published: July 2017

CD31hiEmcnhi vessels were a subtype of vessels in the murine skeletal system, with high levels of platelet and endothelial cell adhesion molecule-1 (PECAM-1/CD31) and endomucin (Emcn). They were reported coupling angiogenesis and osteogenesis during bone development. We investigated the distribution of these vessels in rat tibiae and their temporal and spatial distribution during the bone defect repair process to improve our understanding of the importance of these vessels. We confirmed that CD31hiEmcnhi vessels were specially distributed around the trabecular bones near metaphysis and endosteum in rat tibiae. At 3 days post bone injury, CD31hiEmcnhi vessels proliferated and were extensively distributed across the entire repair area. At 7 and 14 days post-injury, these vessels decreased but were specially distributed around the growing trabecular bones near the frontier growth area, suggesting that these vessels support new bone formation. The distribution of CD31hiEmcnhi vessels and the transcriptions of Hif-1α and VEGFA, as well as BMP2 and Osterix decreased at 7 and 14 days post-injury under osteoporotic conditions, in combination with insufficient osteogenesis. Our research is of great significance to help understand the important role of CD31hiEmcnhi vessels in supporting new trabecular bones formation during bone defect repair process.
A Simple Analytical Model for Magnetization and Coercivity of Hard/Soft Nanocomposite Magnets
Authors: Park Jihoon , Hong Yang-Ki , Lee Woncheol , Kim Seong-Gon , Rong Chuangbing , Poudyal Narayan , Liu J. Ping , Choi Chul-Jin
Published: July 2017

We present a simple analytical model to estimate the magnetization (σs) and intrinsic coercivity (Hci) of a hard/soft nanocomposite magnet using the mass fraction. Previously proposed models are based on the volume fraction of the hard phase of the composite. However, it is difficult to measure the volume of the hard or soft phase material of a composite. We synthesized Sm2Co7/Fe-Co, MnAl/Fe-Co, MnBi/Fe-Co, and BaFe12O19/Fe-Co composites for characterization of their σs and Hci. The experimental results are in good agreement with the present model. Therefore, this analytical model can be extended to predict the maximum energy product (BH)max of hard/soft composite.
Climate Classification is an Important Factor in Assessing Quality-of-Care Across Hospitals
Authors: Boland Mary Regina , Parhi Pradipta , Gentine Pierre , Tatonetti Nicholas P.
Published: July 2017

Climate is a known modulator of disease, but its impact on hospital performance metrics remains unstudied. We assess the relationship between Köppen-Geiger climate classification and hospital performance metrics, specifically 30-day mortality, as reported in Hospital Compare, and collected for the period July 2013 through June 2014 (7/1/2013–06/30/2014). A hospital-level multivariate linear regression analysis was performed while controlling for known socioeconomic factors to explore the relationship between all-cause mortality and climate. Hospital performance scores were obtained from 4,524 hospitals belonging to 15 distinct Köppen-Geiger climates and 2,373 unique counties. Model results revealed that hospital performance metrics for mortality showed significant climate dependence (p < 0.001) after adjusting for socioeconomic factors. Climate is a significant factor in evaluating hospital 30-day mortality rates. These results demonstrate that climate classification is an important factor when comparing hospital performance across the United States.
Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury
Authors: Hill Lisa J. , Di Pietro Valentina , Hazeldine Jon , Davies David , Toman Emma , Logan Ann , Belli Antonio
Published: July 2017

Traumatic brain injury (TBI) is set to become the leading cause of neurological disability across all age groups. Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries. Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions. Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins. Using the Proseek Multiplex Inflammation assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4–12 hr and 48–72 hr post injury. Changes were compared to healthy volunteers (HV). Our results identified CST5, AXIN1 and TRAIL as novel early biomarkers of TBI. CST5 identified patients with severe TBI from all other cohorts and importantly was able to do so within the first hour of injury. AXIN1 and TRAIL were able to discriminate between TBI and HV at <1 hr. We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.
Epidermal growth factor receptor intron-1 CA repeat polymorphism on protein expression and clinical outcome in Taiwanese oral squamous cell carcinoma
Authors: Huang Shiang-Fu , Chien Huei-Tzu , Chuang Wen-Yu , Lai Chih-Hsiung , Cheng Sou-De , Liao Chun-Ta , Wang Hung-Ming
Published: July 2017

This study was designed to explore the relationship between epidermal growth factor receptor (EGFR) CA repeats polymorphism and protein expression in oral cavity squamous cell carcinoma (OSCC). A total of 194 OSCCs were examined for EGFR protein overexpression, gene copy number and the length of their CA repeats. The length of the EGFR CA repeats was found not to be associated with EGFR gene copy number or with protein overexpression. To exclude the effect of EGFR gene copy number on protein overexpression, only those OSCC tumors with disomy of the EGFR gene were included in further analysis. In this subgroup, EGFR protein overexpression was significantly associated with poor differentiation of the tumor cells and lymph node metastasis, especially extra-capsular spread. However, EGFR CA repeats were not related to any clinicopathological factor. Interestingly, patients genetically found to have the EGFR CA repeats SS genotype and having tumors with EGFR protein overexpression were found to have a worst prognosis in terms of disease-free survival (DFS) (HR = 2.68; 95% CI, 1.03–6.98) after multivariate adjustment. The present study demonstrates that concurrent overexpression of EGFR protein in the presence genetically of the SS form CA repeats acts as a predictor for poor DFS.
Presence of diabetes autoantigens in extracellular vesicles derived from human islets
Authors: Hasilo Craig P. , Negi Sarita , Allaeys Isabelle , Cloutier Nathalie , Rutman Alissa K. , Gasparrini Marco , Bonneil Éric , Thibault Pierre , Boilard Éric , Paraskevas Steven
Published: July 2017

Beta-cell (β-cell) injury is the hallmark of autoimmune diabetes. However, the mechanisms by which autoreactive responses are generated in susceptible individuals are not well understood. Extracellular vesicles (EV) are produced by mammalian cells under normal and stressed physiological states. They are an important part of cellular communication, and may serve a role in antigen processing and presentation. We hypothesized that isolated human islets in culture produce EV that contain diabetes autoantigens (DAA) from these otherwise normal, non-diabetic donors. Here we report the caspase-independent production of EV by human islets in culture, and the characterization of DAA glutamic acid decarboxylase 65 (GAD65) and zinc transporter 8 (ZnT8), as well as the β-cell resident glucose transporter 2 (Glut2), present within the EV.
Laquinimod treatment in the R6/2 mouse model
Authors: Ellrichmann Gisa , Blusch Alina , Fatoba Oluwaseun , Brunner Janine , Reick Christiane , Hayardeny Liat , Hayden Michael , Sehr Dominik , Winklhofer Konstanze F. , Saft Carsten , Gold Ralf
Published: July 2017

The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-cell-line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-cell-line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.
The Pawnee earthquake as a result of the interplay among injection, faults and foreshocks
Authors: Chen Xiaowei , Nakata Nori , Pennington Colin , Haffener Jackson , Chang Jefferson C. , He Xiaohui , Zhan Zhongwen , Ni Sidao , Walter Jacob I.
Published: July 2017

The Pawnee M5.8 earthquake is the largest event in Oklahoma instrument recorded history. It occurred near the edge of active seismic zones, similar to other M5+ earthquakes since 2011. It ruptured a previously unmapped fault and triggered aftershocks along a complex conjugate fault system. With a high-resolution earthquake catalog, we observe propagating foreshocks leading to the mainshock within 0.5 km distance, suggesting existence of precursory aseismic slip. At approximately 100 days before the mainshock, two M ≥ 3.5 earthquakes occurred along a mapped fault that is conjugate to the mainshock fault. At about 40 days before, two earthquakes clusters started, with one M3 earthquake occurred two days before the mainshock. The three M ≥ 3 foreshocks all produced positive Coulomb stress at the mainshock hypocenter. These foreshock activities within the conjugate fault system are near-instantaneously responding to variations in injection rates at 95% confidence. The short time delay between injection and seismicity differs from both the hypothetical expected time scale of diffusion process and the long time delay observed in this region prior to 2016, suggesting a possible role of elastic stress transfer and critical stress state of the fault. Our results suggest that the Pawnee earthquake is a result of interplay among injection, tectonic faults, and foreshocks.
Climate change impacts on the threatened terrestrial vertebrates of the Pacific Islands
Authors: Kumar Lalit , Tehrany Mahyat Shafapour
Published: July 2017

The aim of this study was to undertake a broad-scale understanding of the distribution of vulnerable, endangered and critically endangered terrestrial vertebrate species in the Pacific and the assessment of impacts of climate change and sea level rise. 150 critically endangered, endangered and vulnerable terrestrial vertebrates found in 23 countries of the Pacific were linked to island susceptibility to climate change. Out of the 1779 islands making up the 23 countries, 674 of them hosted at least one species from the above categories. 84 of the 150 species are endemic to this study area and many of these occur on islands with high susceptibility to climate change, with many of them occurring on one island only. The species data, together with islands, was overlain with Mean Significant Wave Height (Hs) projections for 2081–2100 under RCP4.5 and 8.5, and further analysed for threat of extinction. A large number of critically endangered and endangered species fall in regions that have the highest Hs projections.
Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2
Authors: Zhang Lei , Song Jun , Bai Tao , Qian Wei , Hou Xiao-Hua
Published: July 2017

Psychological stress has been associated with intestinal epithelial hyperpermeability, the basic process in various functional and organic bowel diseases. In the present study, we aimed to clarify the differences and underlining mechanisms in stress-induced barrier disruption in functionally and structurally distinct epitheliums, including the villus epithelium (VE) and follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes of Peyer’s lymphoid follicles. Employing an Ussing Chamber system, the epithelial permeability was assessed in rats following water avoidance stress (WAS) in vivo and in mucosa tissues exposed to corticotropin-releasing factor (CRF) ex vivo. Decreased transepithelial resistance (TER) and increased paracellular and transcellular macromolecular permeability in colon, ileal VE and FAE had been observed in WAS rats and in CRF-exposed mucosa. Especially, the barrier dysfunction was more serious in the FAE. Moreover, WAS upregulated the expression of mast cell tryptase and protease-activated receptor-2 (PAR2), which positively correlated with epithelial conductance. Mast cell stabilizer cromolyn sodium obviously alleviated the barrier disruption induced by WAS in vivo and CRF in vitro. Serine protease inhibitor aprotinin and FUT-175, and selective PAR2 antagonist ENMD-1068 effectively inhibited the CRF-induced FAE hyperpermeability. Altogether, it concluded that the FAE was more susceptible to stress, and the mast cells and PAR2 signaling played crucial roles in this process.
Reachability and the sense of embodiment in amputees using prostheses
Authors: Gouzien Adrienne , de Vignemont Fréderique , Touillet Amélie , Martinet Noël , De Graaf Jozina , Jarrassé Nathanaël , Roby-Brami Agnès
Published: July 2017

Amputated patients are hardly satisfied with upper limb prostheses, and tend to favour the use of their contralateral arm to partially compensate their disability. This may seem surprising in light of recent evidences that external objects (rubber hand or tool) can easily be embodied, namely incorporated in the body representation. We investigated both implicit body representations (by evaluating the peripersonal space using a reachability judgement task) and the quality of bodily integration of the patient’s prosthesis (assessed via questionnaires). As expected, the patients estimated that they could reach further while wearing their prosthesis, showing an embodiment of their prosthesis in their judgement. Yet, the real reaching space was found to be smaller with their prosthesis than with their healthy limb, showing a large error between reachability judgement and actual capacity. An overestimation was also found on the healthy side (comparatively to healthy subjects) suggesting a bilateral modification of body representation in amputated patients. Finally, a correlation was found between the quality of integration of the prosthesis and the way the body representation changed. This study therefore illustrates the multifaceted nature of the phenomenon of prosthesis integration, which involves its incorporation as a tool, but also various specific subjective aspects.
C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
Authors: Blain Jennifer , Bédard Jessily , Thompson Maureen , Boisvert François-Michel , Boucher Marie-Josée
Published: July 2017

Since the generation of a mouse strain conditionally expressing the active intracellular domain of Notch1 (N1ICD), many laboratories have exploited this model (RosaN1-ICD) to assess the impact of constitutive Notch1 signalling activation in normal and pathological processes. It should be underscored that Cre-recombination leads to the expression of a C-terminally truncated form of N1ICD (N1ICDdC) in the RosaN1-ICD mutant mice. Given that no studies were undertaken to delineate whether deletion of this region leaves intact N1ICD function, stable cell lines with single targeted integration of inducible N1ICD and N1ICDdC were generated. We found that C-terminal deletion of N1ICD stabilized the protein but did not promote the activity of Notch responsive promoters. Furthermore, despite higher expression levels, N1ICDdC failed to phenocopy N1ICD in the promotion of anchorage-independent growth. Our results thus suggest that the C-terminal region of N1ICD plays a role in shaping the Notch response. Therefore, it should be taken into consideration that N1ICD is truncated when interpreting phenotypes of RosaN1-ICD mutant mice.
Gamma-ray vortices from nonlinear inverse Thomson scattering of circularly polarized light
Authors: Taira Yoshitaka , Hayakawa Takehito , Katoh Masahiro
Published: July 2017

Inverse Thomson scattering is a well-known radiation process that produces high-energy photons both in nature and in the laboratory. Nonlinear inverse Thomson scattering occurring inside an intense light field is a process which generates higher harmonic photons. In this paper, we theoretically show that the higher harmonic gamma-ray produced by nonlinear inverse Thomson scattering of circularly polarized light is a gamma-ray vortex, which means that it possesses a helical wave front and carries orbital angular momentum. Our work explains a recent experimental result regarding nonlinear inverse Thomson scattering that clearly shows an annular intensity distribution as a remarkable feature of a vortex beam. Our work implies that gamma-ray vortices should be produced in various situations in astrophysics in which high-energy electrons and intense circularly polarized light fields coexist. Nonlinear inverse Thomson scattering is a promising radiation process for realizing a gamma-ray vortex source based on currently available laser and accelerator technologies, which would be an indispensable tool for exploring gamma-ray vortex science.
Portable and Error-Free DNA-Based Data Storage
Authors: Yazdi S. M. Hossein Tabatabaei , Gabrys Ryan , Milenkovic Olgica
Published: July 2017

DNA-based data storage is an emerging nonvolatile memory technology of potentially unprecedented density, durability, and replication efficiency. The basic system implementation steps include synthesizing DNA strings that contain user information and subsequently retrieving them via high-throughput sequencing technologies. Existing architectures enable reading and writing but do not offer random-access and error-free data recovery from low-cost, portable devices, which is crucial for making the storage technology competitive with classical recorders. Here we show for the first time that a portable, random-access platform may be implemented in practice using nanopore sequencers. The novelty of our approach is to design an integrated processing pipeline that encodes data to avoid costly synthesis and sequencing errors, enables random access through addressing, and leverages efficient portable sequencing via new iterative alignment and deletion error-correcting codes. Our work represents the only known random access DNA-based data storage system that uses error-prone nanopore sequencers, while still producing error-free readouts with the highest reported information rate. As such, it represents a crucial step towards practical employment of DNA molecules as storage media.
Realism of modelled Indian summer monsoon correlation with the tropical Indo-Pacific affects projected monsoon changes
Authors: Li Ziguang , Lin Xiaopei , Cai Wenju
Published: July 2017

El Niño-Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD) tend to exert an offsetting impact on Indian summer monsoon rainfall (ISMR), with an El Niño event tending to lower, whereas a positive IOD tending to increase ISMR. Simulation of these relationships in Phase Five of the Coupled Model Intercomparison Project has not been fully assessed, nor is their impact on the response of ISMR to greenhouse warming. Here we show that the majority of models simulate an unrealistic present-day IOD-ISMR correlation due to an overly strong control by ENSO. As such, a positive IOD is associated with an ISMR reduction in the simulated present-day climate. This unrealistic present-day correlation is relevant to future ISMR projection, inducing an underestimation in the projected ISMR increase. Thus uncertainties in ISMR projection can be in part induced by present-day simulation of ENSO, the IOD, their relationship and their rainfall correlations.
The production of fibroblast growth factor 23 is controlled by TGF-β2
Authors: Feger Martina , Hase Philipp , Zhang Bingbing , Hirche Frank , Glosse Philipp , Lang Florian , Föller Michael
Published: July 2017

Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions. FGF23 production is dependent on Orai1-mediated SOCE and inflammation. Here, we explored a putative role of TGF-β2 in FGF23 synthesis. To this end, UMR106 osteoblast-like cells were cultured, Fgf23 transcript levels determined by qRT-PCR, FGF23 protein measured by ELISA, and SOCE analyzed by fluorescence optics. UMR106 cells expressed TGF-β receptors 1 and 2. TGF-β2 enhanced SOCE and potently stimulated the production of FGF23, an effect significantly attenuated by SB431542, an inhibitor of the transforming growth factor-β (TGF-β) type I receptor activin receptor-like kinases ALK5, ALK4, and ALK7. Furthermore, the TGF-β2 effect on FGF23 production was blunted by SOCE inhibitor 2-APB. We conclude that TGF-β2 induces FGF23 production, an effect involving up-regulation of SOCE.
Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
Authors: Katoh Mitsuhiko , Wu Bao , Nguyen Huy Bang , Thai Truc Quynh , Yamasaki Ryo , Lu Haiyan , Rietsch Anna M. , Zorlu Musab M. , Shinozaki Youichi , Saitoh Yurika , Saitoh Sei , Sakoh Takashi , Ikenaka Kazuhiro , Koizumi Schuichi , Ransohoff Richard M. , Ohno Nobuhiko
Published: July 2017

Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models. Mouse cerebral microgliain vitrodemonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to examine microglial reactions, caused the activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive oxygen species (ROS). The increase in the ROS level activated 5′ adenosine monophosphate-activated protein kinase (AMPK), and facilitated elongation of mitochondria along the microtubule tracks. These results suggest that the polymorphic regulation of mitochondrial fission and fusion in reactive microglia is mediated by distinct signaling under inflammatory conditions, and modulates microglial phenotypes through the production of ROS.
Graphene Oxide Sheets Combine into Conductive Coatings by Direct Oxidative Electropolymerization
Authors: Halevy S. , Bochlin Y. , Kadosh Y. , Kaplan A. , Avraham H. , Nissim A. , Ben Hamo R. , Ohaion-Raz T. , Korin E. , Bettelheim A.
Published: July 2017

New coatings are obtained when graphene oxide is further oxidized at moderate anodic potentials (≤~1.3 V vs. Ag/AgCl). Based on a variety of spectroscopic and electrochemical observations, the coatings are attributed to the direct electropolymerization of graphene oxide sheets via oxidation of the phenol edge groups on graphene. Depending on the applied potential, ether or carboxylic groups are formed. The coatings obtained via further oxidation are characterized by a lower O/C ratio due to decarboxylation and a higher content of C=C bonds. These bonds extend aromatic conjugation into the combined graphene oxide sheets and are responsible for the highly conductive nature of these coatings.