bluuebunny/crossref_metadata_2025 huggingface dataset:
High-throughput screening of high Monascus pigment-producing strain based on digital image processing
Authors: Xia Meng-lei , Wang Lan , Yang Zhi-xia , Chen Hong-zhang
Published: January 2016

This work proposed a new method which applied image processing and support vector machine (SVM) for screening of mold strains. Taking Monascus as example, morphological characteristics of Monascus colony were quantified by image processing. And the association between the characteristics and pigment production capability was determined by SVM. On this basis, a highly automated screening strategy was achieved. The accuracy of the proposed strategy is 80.6 %, which is compatible with the existing methods (81.1 % for microplate and 85.4 % for flask). Meanwhile, the screening of 500 colonies only takes 20–30 min, which is the highest rate among all published results. By applying this automated method, 13 strains with high-predicted production were obtained and the best one produced as 2.8-fold (226 U/mL) of pigment and 1.9-fold (51 mg/L) of lovastatin compared with the parent strain. The current study provides us with an effective and promising method for strain improvement.
The yajC gene from Lactobacillus buchneri and Escherichia coli and its role in ethanol tolerance
Authors: Liu Siqing , Skory Chris , Qureshi Nasib , Hughes Stephen
Published: January 2016

The yajC gene (Lbuc_0921) from Lactobacillus buchneri NRRL B-30929 was identified from previous proteomics analyses in response to ethanol treatment. The YajC protein expression was increased by 15-fold in response to 10 % ethanol vs 0 % ethanol. The yajC gene encodes the smaller subunit of the preprotein translocase complex, which interacts with membrane protein SecD and SecF to coordinate protein transport and secretion across cytoplasmic membrane in Escherichia coli. The YajC protein was linked to sensitivity to growth temperatures in E. coli, involved in translocation of virulence factors during Listeria infection, and stimulating a T cell-mediated response of Brucella abortus. In this study, the L. buchneri yajC gene was over-expressed in E. coli. The strain carrying pET28byajC that produces YajC after isopropyl β-d-1-thiogalactopyranoside induction showed tolerance to 4 % ethanol in growth media, compared to the control carrying pET28b. This is the first report linking YajC to ethanol stress and tolerance.
A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies
Authors: Cirkel Geert A. , Kerklaan Bojana Milojkovic , Vanhoutte Frédéric , der Aa Annegret Van , Lorenzon Giocondo , Namour Florence , Pujuguet Philippe , Darquenne Sophie , de Vos Filip Y. F. , Snijders Tom J. , Voest Emile E. , Schellens Jan H. M. , Lolkema Martijn P.
Published: January 2016

Background Integrin signaling is an attractive target for anti-cancer treatment. GLPG0187 is a broad spectrum integrin receptor antagonist (IRA). GLPG0187 inhibited tumor growth and metastasis in mouse models. Methods We aimed to determine the Recommended Phase II Dose (RP2D) and to assess safety and tolerability of continuous i.v. infusion in patients with advanced malignant solid tumors. Anticipated dose levels were 20, 40, 80, 160, 320, and 400 mg/day in a modified 3 + 3 design. Plasma concentrations of GLPG0187 were assessed to characterize the pharmacokinetics (PK). C-terminal telopeptide of type I collagen (CTX) was used as pharmacodynamics marker. Results Twenty patients received GLPG0187. No dose limiting toxicities (DLTs) were observed. The highest possible and tested dose was 400 mg/day. Fatigue was the most frequently reported side effect (25 %). Recurrent Port-A-Cath-related infections and skin toxicity suggest cutaneous integrin inhibition. No dose-dependent toxicity could be established. PK analysis showed a short average distribution (0.16 h) and elimination (3.8 h) half-life. Continuous infusion resulted in dose proportional PK profiles. We observed decreases in serum CTX levels independent of the dose given, suggesting target engagement at the lowest dose level tested. Single agent treatment did not result in tumor responses. Conclusions GLPG0187 was well tolerated with a dose-proportional PK profile upon continuous infusion. No formal maximal tolerated dose could be established. GLPG0187 showed signs of target engagement with a favourable toxicity profile. However, continuous infusion of GLPG0187 failed to show signs of monotherapy efficacy.
Audit of Atypical Femoral Fractures and a Description of Some of Their Features
Authors: Lian Kevin , Trollip Jacques , Sandhu Supna , Moosavi Mandana , Gill Amninder , Kendler David , Dian Larry , Lentle Brian
Published: January 2016

Purpose

Atypical femoral fractures (AFF) are recently described events related to osteoporosis and, potentially, a rare result of antiresorptive treatment.

Methods

We set out to audit the diagnosis of AFF in an acute hospital. Charts and radiographs were reviewed retrospectively from patients diagnosed with subtrochanteric femoral fractures according to hospital discharge coding at Vancouver General Hospital (VGH), Canada, from January 2005 to March 2013.

Results

A total of 3084 patients were discharged from the hospital with a diagnosis of hip fracture between 2005 and 2013. Of these, 204 were coded as having had subtrochanteric fractures; 178 of the patients thus coded had radiographic evidence of other fracture types—usually intertrochanteric fractures. Eleven patients did not have available radiographs. Of the remaining 193 patients whose radiographs were reviewed, 24 (12.4%) fulfilled the published criteria for AFF.

Our observations were

1) laterality: 13 of 24 AFF (54.2%) were right-sided; 2) there was only one incomplete AFF in this series: a completed fracture was an inclusion criterion, but 1 patient with an AFF had both that fracture and an incomplete fracture and further foci of periosteal or endosteal foci of new bone (PENB) involving the contralateral femur; 3) radiologists had only diagnosed AFF in only 1 of the 24 patients with characteristic radiographic signs of AFF; 4) all but 1 patient had a focus of periosteal and/or endosteal new bone (PENB) through which the fracture line invariably passed, and in the 1 exception the radiography was too poor to be sure of this but there was a symmetrical contralateral focus of PENB; 5) in 19 of 24 patients there was an adequate image of part of the contralateral femur and of these 12 (63%) had a contralateral focus of PENB situated ±2.5 cm from the index lesion site when measured from the upper aspect of the greater trochanter, and in another patient a prior fracture of the contralateral femur had been treated surgically and it was at a symmetrical contralateral location from the index fracture.; 6) in 3 of the 19 patients multiple foci of PENB were detected on the lateral aspect of the contralateral femur even though the examination was of limited extent; and 7) AFFs were associated with bisphosphonate medication in 75% of the patients studied.

Conclusions

Hospital discharge coding misclassified a great majority of femoral fractures as subtrochanteric. As an essential criteria for diagnosing AFF is their subtrochanteric location, this misclassification impaired our ability to retrospectively search for AFF patients. Radiologists tended not to report AFF when typical radiographic characteristics were present. Bilateral and multifocal disease is of interest in pointing to the diagnosis and in suggesting that the mechanism of injury in respect of these unusual fractures is more complex than simple low-energy trauma.
A BOUND ON EMBEDDING DIMENSIONS OF GEOMETRIC GENERIC FIBERS
Authors: MADDOCK ZACHARY
Published: January 2016

The author finds a limit on the singularities that arise in geometric generic fibers of morphisms between smooth varieties of positive characteristic by studying changes in embedding dimension under inseparable field extensions. This result is then used in the context of the minimal model program to rule out the existence of smooth varieties fibered by certain nonnormal del Pezzo surfaces over bases of small dimension.
Review of the feed industry from a historical perspective and implications for its future
Authors: Coffey D. , Dawson K. , Ferket P. , Connolly A.
Published: January 2016

The history of the feed industry is pertinent in terms of understanding how and why certain practices have evolved. Some of these practices have been superseded by modern, more natural alternatives, for example the traditional use of antibiotics in feed. In other cases, such as inorganic minerals, more natural versions akin to those found in plant and animal materials are available, although these new initiatives are still being taken up globally. Research continues to increase our knowledge and understanding of nutrient balance and digestion, and in some species this is more advanced than others. The following paper represents the first complete history of the feed industry, its major milestones, and projects how it might continue to utilise new technology developments to improve animal feeding practices.
Dairy consumption and CVD: a systematic review and meta-analysis
Authors: Alexander Dominik D. , Bylsma Lauren C. , Vargas Ashley J. , Cohen Sarah S. , Doucette Abigail , Mohamed Muhima , Irvin Sarah R. , Miller Paula E. , Watson Heather , Fryzek Jon P.
Published: January 2016

Inverse associations between dairy consumption and CVD have been reported in several epidemiological studies. Our objective was to conduct a meta-analysis of prospective cohort studies of dairy intake and CVD. A comprehensive literature search was conducted to identify studies that reported risk estimates for total dairy intake, individual dairy products, low/full-fat dairy intake, Ca from dairy sources and CVD, CHD and stroke. Random-effects meta-analyses were used to generate summary relative risk estimates (SRRE) for high v. low intake and stratified intake dose–response analyses. Additional dose–response analyses were performed. Heterogeneity was examined in sub-group and sensitivity analyses. In total, thirty-one unique cohort studies were identified and included in the meta-analysis. Several statistically significant SRRE below 1.0 were observed, namely for total dairy intake and stroke (SRRE=0·91; 95 % CI 0·83, 0·99), cheese intake and CHD (SRRE=0·82; 95 % CI 0·72, 0·93) and stroke (SRRE=0·87; 95 % CI 0·77, 0·99), and Ca from dairy sources and stroke (SRRE=0·69; 95 % CI 0·60, 0·81). However, there was little evidence for inverse dose–response relationships between the dairy variables and CHD and stroke after adjusting for within-study covariance. The results of this meta-analysis of prospective cohort studies have shown that dairy consumption may be associated with reduced risks of CVD, although additional data are needed to more comprehensively examine potential dose–response patterns.
Interactions between retinol,α-tocopherol and cholecalciferol need consideration in diets for farmed mink (Mustela vison)
Authors: Hymøller Lone , Clausen Tove N. , Jensen Søren K.
Published: January 2016

A sufficient but balanced vitamin supplementation is a prerequisite for a satisfactory growth pattern and an effective immune system in mink and all other species. The fat-soluble vitamins are very sensitive to over- or under-supply because they interact with each other with respect to dose–response and chemical form. The purpose of the present study was to investigate the effect of increasing the amount of retinol in combination with RRR-α-tocopherol orall-rac-α-tocopherol in the feed given to growing mink on their retinol, cholecalciferol andα-tocopherol concentrations in plasma and selected organs. The results showed that the mink met their retinol requirements from the basal diet, but there were no negative effects of supplying various amounts of retinol on their plasmaα-tocopherol concentrations. On the other hand, the study showed that the cholecalciferol status in plasma, assessed as the 25-hydroxycholecalciferol concentration, was low when retinol was supplemented in the feed at high levels. In addition, supplementation with RRR-α-tocopherol in the feed negatively affected the plasma concentration of 25-hydroxycholecalciferol compared with supplementation withall-rac-α-tocopherol. In general, female mink had higher concentrations of fat-soluble vitamins in plasma than male mink.
When Jews Speak Arabic: Dialectology and Difference in Colonial Morocco
Authors: Kosansky Oren
Published: January 2016

This article explores how Judeo-Arabic and its speaking population were constituted as objects of research and reformation in colonial Morocco. I argue that the colonial project of dialectology, which emphasized the differentiated linguistic terrain of indigenous society, operated at two opposing levels. On one hand, the study of Judeo-Arabic contributed to the idea of homogeneous orality attributed to native languages, which despite their diverse relationships with literate textuality were made to appear divorced from locally established systems of writing. On the other, the historical and affective relationship between Jews and their Arabic dialect was figured in terms that stressed Jewish alienation from their mother tongue and thereby cast native Jews as differentiated objects of francophone linguistic reform. I pay particular attention to the material mechanics of ethnographic methodology, orthographic entextualization, and editorial arrangement through which colonial dialectologists rendered the Jewish dialect as an essentially oral and Arabic dialect, despite the countervailing circulation of Judeo-Arabic texts written in the Hebrew script. This investigation contributes to our understanding of how dialectology operated as a colonial science through which the hierarchical social categories of colonial rule were established, sustained, and manipulated against the backdrop of linguistic practices that never fully conformed to their colonial representation.
Export-Import Theory and the Racialization of Anti-Semitism: Turkish- and Arab-Only Prevention Programs in Germany
Authors: Özyürek Esra
Published: January 2016

Since the year 2000, remembering the Holocaust and fighting anti-Semitism have come to be accepted as cornerstones of European identity. The flip side of this development has been racialization of Muslims by singling them out as the main contemporary anti-Semites. After discussing the emergence of the concept “Muslim anti-Semitism,” I scrutinize government-issued reports and anti-Semitism-prevention programs in Germany. I show how the recent wave of struggle against anti-Semitism depicts Muslims as outsiders who bring unwanted ideologies, evaluates their anti-Semitism as more dangerous than that of right-wing German nationals, and attributes to Muslims culturally transmitted psychopathologies that make Muslim nations prone to anti-Semitism. Experts locate the root of Turkish anti-Semitism in their “myth of tolerance toward Jews,” and of Arab anti-Semitism in their sense of a “false victimhood” and “desire for power and pride.” Educators focus on each nationality separately to distinguish these alleged group-specific myths and feelings. Efforts and money that go into producing nation-specific Muslim anti-Semitisms depict a new Germany that has fully liberated itself from any anti-democratic tendencies surviving from its Nazi past. It also obscures connections between anti-Semitism and anti-Muslim racism, both of which are active forces in mainstream German society.
Witchcraft, Shamanism, and Nostalgia.A Review Essay
Authors: Geschiere Peter
Published: January 2016

The study of witchcraft seems to be globalizing in many respects. Not only are witches themselves supposedly globalizing, but the people who try to study them are also adopting a more global outlook. Moreover, witchcraft as a topic is no longer tied to specific areas of the world, but seems to crop up everywhere. For this essay I purposely chose three recent studies, out of a wide array of possible books, which come from very different parts of the world. Reading them comparatively can highlight key trends in this field, and also important differences.
Effects of time and dose of organic fertilizers on soil fertility, nutrient content and yield of vegetables
Authors: HERENCIA J. F. , MAQUEDA C.
Published: January 2016

A comparative study of the effect of organic fertilization at different times and doses on soil fertility and crop yield was performed over 3 years in a calcareous loamy soil. Nutrient availability in the soil and macronutrient concentration in leaves and in the edible part of the plants was examined in plots that were previously handled conventionally and ecologically for several years. The organic fertilizers used were manure compost at two doses in plots after 4 years of organic management treatment, and green residues of previous crops in plots with 10 years of organic management. In general, soil organic carbon (C), nitrogen (N), phosphorous (P) and magnesium (Mg) contents were found to be considerably greater in organically fertilized soils in comparison with soil receiving mineral fertilizer (conventional treatment (CT)). For C and N, the highest contents were observed in the long-term organic treatment (OR). However, few differences were found for potassium (K) and sodium (Na). The results obtained for electrical conductivity and pH indicated that, in general, there were no significant differences between treatments. The differences in the values of EC and pH occurred among cultivation cycles irrespective of the type of fertilization, but there was a contradictory trend for each of the above parameters. The results obtained for leaves and the edible part of the plant indicated that, in general, there were no significant differences between treatments, except for P with a trend for higher P content in organic crops. The nitrate values in leaves showed great variability, making it difficult to draw conclusions. The associations of fertilization and the chemical properties of soil with nutrient content in crops were checked by principal component analysis (PCA). For soil data, different clusters were observed between CT and OR treatments. However, PCA showed that the influence of crop type on plant nutrient concentrations was greater than type of fertilization. The effect of fertilization on crop yield was variable depending on plant species. The results indicated that organic fertilization did not cause deficiencies in the nutrient content and yield of vegetables when compared with conventional fertilization, showing that ecological management can be used effectively.
Lusoga (Lutenga)
Authors: Nabirye Minah , de Schryver Gilles-Maurice , Verhoeven Jo
Published: January 2016

Lusoga is an interlacustrine Bantu language spoken in the eastern part of Uganda in the region of Busoga, which is surrounded by the Victoria Nile in the west, Lake Kyoga in the north, the River Mpologoma in the east and Lake Victoria in the south. According to the 2002 census, this language is spoken by slightly over two million people (UBOS 2006: 12).
Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later
Authors: Ryan Aoife M. , Power Derek G. , Daly Louise , Cushen Samantha J. , Ní Bhuachalla Ēadaoin , Prado Carla M.
Published: January 2016

An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50–80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20–70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40–60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.
Adoption, reinvention and amendment of renewable portfolio standards in the American states
Authors: Carley Sanya , Nicholson-Crotty Sean , Miller Chris J.
Published: January 2016

It has long been recognised that interstate diffusion of policy innovations is comprised of distinct decisions including adoption, reinvention and amendment. Interstate influences are an important driver of these diffusion processes, but studies to date have not investigated the degree to which external influences vary across these decisions. We theorise that geographical peers will have the largest impact in adoption decisions; that ideological peers are an important source of policy information when states make decisions about “reinventing” innovations adopted by others; and that internal factors will drive the decision by a state to amend a policy. We test these expectations for renewable portfolio standards in the American states between 1996 and 2009. Results suggest that state policymakers emulate peers in adoption or policy design choices, and that internal influences have a stronger influence on amendment decisions than do external influences. These findings further our understanding of policy diffusion and state-by-state relations.
Exploring the Changing Role of Chinese Entities in WMD Proliferation
Authors: Salisbury Daniel , Jones Lucy
Published: January 2016

This paper seeks to provide an original examination of the nature of the proliferation of sensitive materials and technologies by Chinese entities. A number of publications have attempted to understand the issue of proliferation stemming from businesses based in China, with many having commented on the efforts undertaken both by international actors and by the Chinese government to prevent it. However, relatively few scholars have sought, in any systematic and sustained way, to understand the types of Chinese companies involved in proliferation and the evolution of their behaviour. This paper seeks to argue and account for the declining role of, and concern regarding, Chinese state-owned enterprise in the global proliferation problem. Different accounts for this change, and the relating proliferation challenge posed by China, are examined.
Spatio-temporal patterns of IED usage by the Provisional Irish Republican Army
Authors: TENCH STEPHEN , FRY HANNAH , GILL PAUL
Published: January 2016

In this paper, a unique dataset of improvised explosive device attacks during “The Troubles” in Northern Ireland (NI) is analysed via a Hawkes process model. It is found that this past dependent model is a good fit to improvised explosive device attacks yielding key insights about the nature of terrorism in NI. We also present a novel approach to quantitatively investigate some of the sociological theory surrounding the Provisional Irish Republican Army which challenges previously held assumptions concerning changes seen in the organisation. Finally, we extend our use of the Hawkes process model by considering a multidimensional version which permits both self and mutual-excitations. This allows us to test how the Provisional Irish Republican Army responded to past improvised explosive device attacks on different geographical scales from which we find evidence for the autonomy of the organisation over the six counties of NI and Belfast. By incorporating a second dataset concerning British Security Force (BSF) interventions, the multidimensional model allows us to test counter-terrorism (CT) operations in NI where we find subsequent increases in violence.
Ashley, Two Born as One, and the Best Interests of a Child
Authors: GILLETT GRANT
Published: January 2016

What is in the best interests of a child, and could that ever include interventions that we might regard as prima facie detrimental to a child’s physical well-being? This question is raised a fortiori by growth attenuation treatments in children with severe neurological disorders causing extreme developmental delay. I argue that two principles that provide guidance in generating a conception of best interests for each individual child yield the right results in such cases. The principles are as follows: thepotentiality principle, whereby every child should be able to develop its potential and is entitled to receive certain help in doing so, and theprinciple of psychosomatic harmony, whereby every human being is entitled to treatment that is appropriate to or enables a life in which mind and body are in tune with each other. These principles indicate a certain response to what we can call Ashley-type cases and admit certain caveats.
Minors and Contested Medical-Surgical Treatment
Authors: SNELLING JEANNE
Published: January 2016

Use of the best-interests test as the legal standard to justify medical treatment (or its cessation) in respect to legally incompetent adults or minors has come under sustained critique over the years. “Best interests” has variously been alleged to be indeterminate as well as susceptible to majoritarian ideology and inherent bias. It has also been alleged to be inferior to rights-based approaches. Against the background of several particularly hard cases involving minors discussed by Gillett in a prior article in this journal, this article considers some of these critiques. It concludes that these critical accounts make significant contributions to enabling a more procedurally and substantively robust consideration of what might be in a child’s best interests. However, it is argued that none of these accounts alone provide a superior framework that would justify jettisoning the concept of best interests. Further, it is suggested that best interests still has an important role in achieving patient-centered decisionmaking in this context. It concludes by suggesting a taxonomy of considerations when determining best interests.
Neuroethics beyond Normal
Authors: SHOOK JOHN R. , GIORDANO JAMES
Published: January 2016

An integrated and principled neuroethics offers ethical guidelines able to transcend conventional and medical reliance on normality standards. Elsewhere we have proposed four principles for wise guidance on human transformations. Principles like these are already urgently needed, as bio- and cyberenhancements are rapidly emerging. Context matters. Neither “treatments” nor “enhancements” are objectively identifiable apart from performance expectations, social contexts, and civic orders. Lessons learned from disability studies about enablement and inclusion suggest a fresh way to categorize modifications to the body and its performance. The term “enhancement” should be broken apart to permit recognition of enablements and augmentations, and kinds of radical augmentation for specialized performance. Augmentations affecting the self, self-worth, and self-identity of persons require heightened ethical scrutiny. Reversibility becomes the core problem, not the easy answer, as augmented persons may not cooperate with either decommissioning or displacement into unaccommodating societies. We conclude by indicating how our four principles of self-creativity, nonobsolescence, empowerment, and citizenship establish a neuroethics beyond normal that is better prepared for a future in which humans and their societies are going so far beyond normal.
Introducing the Medical Ethics Bowl
Authors: MERRICK ALLISON , GREEN ROCHELLE , CUNNINGHAM THOMAS V. , EISENBERG LEAH R. , HESTER D. MICAH
Published: January 2016

Although ethics is an essential component of undergraduate medical education, research suggests that current medical ethics curricula face considerable challenges in improving students’ ethical reasoning. This article discusses these challenges and introduces a promising new mode of graduate and professional ethics instruction for overcoming them. We begin by describing common ethics curricula, focusing in particular on established problems with current approaches. Next, we describe a novel method of ethics education and assessment for medical students that we have devised: the Medical Ethics Bowl (MEB). Finally, we suggest the pedagogical advantages of the MEB when compared to other ethics curricula.
Cognition in the Emergency Department as a Predictor of Recovery after Pediatric Mild Traumatic Brain Injury
Authors: Brooks Brian L. , Daya Hussain , Khan Samna , Carlson Helen L. , Mikrogianakis Angelo , Barlow Karen M.
Published: January 2016

Cognitive abilities can be acutely disrupted in children and adolescents who sustain a mild traumatic brain injury (mTBI), with the potential that these disruptions may be predictive of recovery. The objective of this study was to determine if cognitive abilities in the emergency department (ED) can differentiate and predict poor symptom recovery following a pediatric mTBI. Participants included 77 male and female youth with a mTBI (mean age=13.6;SD=2.6). All participants completed computerized cognitive testing (four subtests from the CNS Vital Signs) when they presented to the ED. Symptom measurement occurred in the ED (for pre-injury), at 7–10 days, 1 month, 2 months, and 3 months post-mTBI using the post-concussion symptom inventory (PCSI). Recovery was determined using reliable change scores for symptom ratings from 28 orthopedic injury controls (mean age=13.9 years;SD=2.1). Significantly worse Reaction Time scores (i.e., rapid information processing) in the ED were found in those who remained symptomatic at 1 month. Performances on the Reaction Time and Cognitive Flexibility domain scores were predictive of symptom outcome at 1 month for youth (above and beyond sex and baseline symptom burden). Youth with low scores on Reaction Time and/or Cognitive Flexibility were nearly 15 times (95%CI=1.8–323.5) more likely to remain symptomatic at 1 month post-mTBI. No significant group differences were found at 7–10 days, 2 months, or 3 months post-injury. Rapid computerized cognitive testing in the ED following a mTBI may help clinicians predict which youth may or may not remain symptomatic at follow-up. (JINS, 2016,22, 379–387)
International legal structuralism: a primer
Authors: Desautels-Stein Justin
Published: January 2016

International legal structuralism arrived on the shores of international thought in the 1980s. The arrival was not well received, perhaps in part, because it was not well understood. This essay aims to reintroduce legal structuralism and hopefully pave the way for new, and more positive, receptions and understandings. This reintroduction is organized around two claims regarding the broader encounter between international lawyers and critical theory in the 1980s. The first was a jurisprudential claim about how the critics sought to show how international law was nothing more than a continuation of international politics by other means. The second was a historical claim about how the critics wanted to show that international law had never been anything but politics, and that it always would be. In the view of this essay, both of these claims about international legal structuralism were wrong, and they are still wrong today. For despite the tendency to think of it as a cover for postmodern nihilism or relentless deconstruction or both, legal structuralism offers international theorists an enriching and edifying method for rethinking the relation between law and politics on the one hand, and law and history on the other. It is in the effort to carry a brief for a reawakened legal structuralism that the essay brings focus to some of the early works of Koskenniemi and Kennedy, identifies the semiotic foundations of that work, and ultimately suggests the possibility of a second generation of international legal structuralism.
Early Agriculture Has Kept Earth Warm for Millennia
Authors: Stanley Sarah
Published: January 2016

Ice core data, archeological evidence, and other studies suggest humans had a significant influence on Earth's preindustrial climate.
Pulse-density modulation control of chemical oscillation far from equilibrium in a droplet open-reactor system
Authors: Sugiura Haruka , Ito Manami , Okuaki Tomoya , Mori Yoshihito , Kitahata Hiroyuki , Takinoue Masahiro
Published: January 2016

The design, construction and control of artificial self-organized systems modelled on dynamical behaviours of living systems are important issues in biologically inspired engineering. Such systems are usually based on complex reaction dynamics far from equilibrium; therefore, the control of non-equilibrium conditions is required. Here we report a droplet open-reactor system, based on droplet fusion and fission, that achieves dynamical control over chemical fluxes into/out of the reactor for chemical reactions far from equilibrium. We mathematically reveal that the control mechanism is formulated as pulse-density modulation control of the fusion–fission timing. We produce the droplet open-reactor system using microfluidic technologies and then perform external control and autonomous feedback control over autocatalytic chemical oscillation reactions far from equilibrium. We believe that this system will be valuable for the dynamical control over self-organized phenomena far from equilibrium in chemical and biomedical studies.
Nanoscale visualization of functional adhesion/excitability nodes at the intercalated disc
Authors: Leo-Macias Alejandra , Agullo-Pascual Esperanza , Sanchez-Alonso Jose L. , Keegan Sarah , Lin Xianming , Arcos Tatiana , Feng-Xia-Liang  , Korchev Yuri E. , Gorelik Julia , Fenyö David , Rothenberg Eli , Delmar Mario
Published: January 2016

Intercellular adhesion and electrical excitability are considered separate cellular properties. Studies of myelinated fibres, however, show that voltage-gated sodium channels (VGSCs) aggregate with cell adhesion molecules at discrete subcellular locations, such as the nodes of Ranvier. Demonstration of similar macromolecular organization in cardiac muscle is missing. Here we combine nanoscale-imaging (single-molecule localization microscopy; electron microscopy; and ‘angle view’ scanning patch clamp) with mathematical simulations to demonstrate distinct hubs at the cardiac intercalated disc, populated by clusters of the adhesion molecule N-cadherin and the VGSC NaV1.5. We show that the N-cadherin-NaV1.5 association is not random, that NaV1.5 molecules in these clusters are major contributors to cardiac sodium current, and that loss of NaV1.5 expression reduces intercellular adhesion strength. We speculate that adhesion/excitability nodes are key sites for crosstalk of the contractile and electrical molecular apparatus and may represent the structural substrate of cardiomyopathies in patients with mutations in molecules of the VGSC complex.
Unveiling the structural arrangements responsible for the atomic dynamics in metallic glasses during physical aging
Authors: Giordano V. M. , Ruta B
Published: January 2016

Understanding and controlling physical aging, that is, the spontaneous temporal evolution of out-of-equilibrium systems, represents one of the greatest tasks in material science. Recent studies have revealed the existence of a complex atomic motion in metallic glasses, with different aging regimes in contrast with the typical continuous aging observed in macroscopic quantities. By combining dynamical and structural synchrotron techniques, here for the first time we directly connect previously identified microscopic structural mechanisms with the peculiar atomic motion, providing a broader unique view of their complexity. We show that the atomic scale is dominated by the interplay between two processes: rearrangements releasing residual stresses related to a cascade mechanism of relaxation, and medium range ordering processes, which do not affect the local density, likely due to localized relaxations of liquid-like regions. As temperature increases, a surprising additional secondary relaxation process sets in, together with a faster medium range ordering, likely precursors of crystallization.
Protein unfolding as a switch from self-recognition to high-affinity client binding
Authors: Groitl Bastian , Horowitz Scott , Makepeace Karl A. T. , Petrotchenko Evgeniy V. , Borchers Christoph H. , Reichmann Dana , Bardwell James C. A. , Jakob Ursula
Published: January 2016

Stress-specific activation of the chaperone Hsp33 requires the unfolding of a central linker region. This activation mechanism suggests an intriguing functional relationship between the chaperone’s own partial unfolding and its ability to bind other partially folded client proteins. However, identifying where Hsp33 binds its clients has remained a major gap in our understanding of Hsp33’s working mechanism. By using site-specific Fluorine-19 nuclear magnetic resonance experiments guided by in vivo crosslinking studies, we now reveal that the partial unfolding of Hsp33’s linker region facilitates client binding to an amphipathic docking surface on Hsp33. Furthermore, our results provide experimental evidence for the direct involvement of conditionally disordered regions in unfolded protein binding. The observed structural similarities between Hsp33’s own metastable linker region and client proteins present a possible model for how Hsp33 uses protein unfolding as a switch from self-recognition to high-affinity client binding.
Giant phonon anomaly associated with superconducting fluctuations in the pseudogap phase of cuprates
Authors: Liu Ye-Hua , Konik Robert M. , Rice T. M. , Zhang Fu-Chun
Published: January 2016

The pseudogap in underdoped cuprates leads to significant changes in the electronic structure, and was later found to be accompanied by anomalous fluctuations of superconductivity and certain lattice phonons. Here we propose that the Fermi surface breakup due to the pseudogap, leads to a breakup of the pairing order into two weakly coupled sub-band amplitudes, and a concomitant low energy Leggett mode due to phase fluctuations between them. This increases the temperature range of superconducting fluctuations containing an overdamped Leggett mode. In this range inter-sub-band phonons show strong damping due to resonant scattering into an intermediate state with a pair of overdamped Leggett modes. In the ordered state, the Leggett mode develops a finite energy, changing the anomalous phonon damping into an anomaly in the dispersion. This proposal explains the intrinsic connection between the anomalous pseudogap phase, enhanced superconducting fluctuations and giant anomalies in the phonon spectra.
Bcl-xL promotes metastasis independent of its anti-apoptotic activity
Authors: Choi Soyoung , Chen Zhengming , Tang Laura H. , Fang Yuanzhang , Shin Sandra J. , Panarelli Nicole C. , Chen Yao-Tseng , Li Yi , Jiang Xuejun , Du Yi-Chieh Nancy
Published: January 2016

Bcl-xL suppresses mitochondria-mediated apoptosis and is frequently overexpressed in cancer to promote cancer cell survival. Bcl-xL also promotes metastasis. However, it is unclear whether this metastatic function is dependent on its anti-apoptotic activity in the mitochondria. Here we demonstrate that Bcl-xL promotes metastasis independent of its anti-apoptotic activity. We show that apoptosis-defective Bcl-xL mutants and an engineered Bcl-xL targeted to the nucleus promote epithelial–mesenchymal transition, migration, invasion and stemness in pancreatic neuroendocrine tumour (panNET) and breast cancer cell lines. However, Bcl-xL proteins targeted to the mitochondria or outside of the nucleus do not have these functions. We confirm our findings in spontaneous and xenograft mouse models. Furthermore, Bcl-xL exerts metastatic function through epigenetic modification of the TGFβ promoter to increase TGFβ signalling. Consistent with these findings, we detect nuclear Bcl-xL in human metastatic panNETs. Taken together, the metastatic function of Bcl-xL is independent of its anti-apoptotic activity and its residence in the mitochondria.
CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking
Authors: Chou Szu-Yi , Hsu Kuo-Shun , Otsu Wataru , Hsu Ya-Chu , Luo Yun-Cin , Yeh Celine , Shehab Syed S. , Chen Jie , Shieh Vincent , He Guo-an , Marean Michael B. , Felsen Diane , Ding Aihao , Poppas Dix P. , Chuang Jen-Zen , Sung Ching-Hwa
Published: January 2016

Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis. Adult CLIC4-null proximal tubules display aberrant dilation. In MDCK 3D cultures, CLIC4 is expressed on early endosome, recycling endosome and apical transport carriers before reaching its steady-state apical membrane localization in mature lumen. CLIC4 suppression causes impaired apical vesicle coalescence and central lumen formation, a phenotype that can be rescued by Rab8 and Cdc42. Furthermore, we show that retromer- and branched actin-mediated trafficking on early endosome regulates apical delivery during early luminogenesis. CLIC4 selectively modulates retromer-mediated apical transport by negatively regulating the formation of branched actin on early endosomes.
The role of mesenchymal stem cells in promoting the transformation of androgen-dependent human prostate cancer cells into androgen-independent manner
Authors: Cheng Jiwen , Yang Keqin , Zhang Qingyun , Yu Yang , Meng Qinggui , Mo Ning , Zhou Yang , Yi Xianlin , Ma Chengzhong , Lei Aming , Liu Yan
Published: January 2016

Mesenchymal stem cells (MSCs) play an important role in the development of human prostate cancer (PCa). However, the role of MSCs in the transformation of androgen-dependent human PCa cells into androgen-independent manner has been poorly understood. In this study, we investigated the underlying mechanism of MSCs in promoting PCa cells from androgen-dependent into androgen-independent manner. Firstly, we demonstrated that MSCs could affect the transformation of androgen-dependent human PCa cells into androgen-independent manner in vivo and in vitro. Then we found a substantial expression of TGF-β in MSCs. TGF-β blockade could significantly inhibit the promotive function of MSCs in PCa cells. Besides that, we also demonstrated androgen might inhibit the expression of TGF-β in MSCs. Furthermore, we found that either overexpression of SSEA-4 or the number of SSEA-4 positive MSCs in PCa tissues was associated with a shorter cancer-free survival interval (CFSI) and a worse overall survival (OS). Our results suggest that androgen blockade treatment in clinical PCa therapy may elicit the expression of TGF-β in MSCs, which will result in the transformation of androgen-dependent human PCa cells into androgen-independent manner.
Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
Authors: Wen Wanqing , Kato Norihiro , Hwang Joo-Yeon , Guo Xingyi , Tabara Yasuharu , Li Huaixing , Dorajoo Rajkumar , Yang Xiaobo , Tsai Fuu-Jen , Li Shengxu , Wu Ying , Wu Tangchun , Kim Soriul , Guo Xiuqing , Liang Jun , Shungin Dmitry , Adair Linda S. , Akiyama Koichi , Allison Matthew , Cai Qiuyin , Chang Li-Ching , Chen Chien-Hsiun , Chen Yuan-Tsong , Cho Yoon Shin , Choi Bo Youl , Gao Yutang , Go Min Jin , Gu Dongfeng , Han Bok-Ghee , He Meian , Hixson James E. , Hu Yanling , Huang Tao , Isono Masato , Jung Keum Ji , Kang Daehee , Kim Young Jin , Kita Yoshikuni , Lee Juyoung , Lee Nanette R. , Lee Jeannette , Wang Yiqin , Liu Jian-Jun , Long Jirong , Moon Sanghoon , Nakamura Yasuyuki , Nakatochi Masahiro , Ohnaka Keizo , Rao Dabeeru , Shi Jiajun , Sull Jae Woong , Tan Aihua , Ueshima Hirotsugu , Wu Chen , Xiang Yong-Bing , Yamamoto Ken , Yao Jie , Ye Xingwang , Yokota Mitsuhiro , Zhang Xiaomin , Zheng Yan , Qi Lu , Rotter Jerome I. , Jee Sun Ha , Lin Dongxin , Mohlke Karen L. , He Jiang , Mo Zengnan , Wu Jer-Yuarn , Tai E. Shyong , Lin Xu , Miki Tetsuro , Kim Bong-Jo , Takeuchi Fumihiko , Zheng Wei , Shu Xiao-Ou
Published: January 2016

Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2 and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI and three loci near the CEP120, TSC22D2 and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
Increased Dickkopf-1 in Recent-onset Rheumatoid Arthritis is a New Biomarker of Structural Severity. Data from the ESPOIR Cohort
Authors: Seror Raphaèle , Boudaoud Saida , Pavy Stephan , Nocturne Gaetane , Schaeverbeke Thierry , Saraux Alain , Chanson Philippe , Gottenberg Jacques-Eric , Devauchelle-Pensec Valérie , Tobón Gabriel J. , Mariette Xavier , Miceli-Richard Corinne
Published: January 2016

Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic condition over the world. RA is potentially disabling because chronic inflammation of the joints leads to joint destruction. To date, the best predictor of radiographic progression for patients with early RA is the presence of radiographic erosions at baseline, but a limited number of predictive biomarkers of structural progression are currently used in daily practice. Here, we investigated Dickkopf-1 (DKK-1) and sclerostin (SOST) serum levels in patients with recent inflammatory arthritis from the ESPOIR cohort. This cohort is a prospective, multicenter French cohort of 813 patients with early arthritis. We observed that mean baseline DKK-1 level was higher among RA patients with than without radiological progression within the first 2 years of evolution. DKK-1 level was still associated with radiographic progression in a model including other main predictors of severity (erosions at baseline and anti-CCP antibody positivity). This study demonstrates that increased DKK-1 level at baseline predicted structural progression after 2-year follow-up and suggests that DKK-1 might be a new structural biomarker for early RA.