bluuebunny/crossref_metadata_2025 huggingface dataset:
A Luther for 2017
Authors: Keen Ralph
Published: September 2017

The history of the Reformation begins, and often ends, with Martin Luther. The history of Luther's biography is a chronicle of the perspectives from which Luther has been approached. Throughout the twentieth century, with few exceptions, his greatness was accepted as being beyond question, with each interpreter offering a new explanation for the Reformer's heroic place in European religious history. Scott Hendrix has been contributing to Luther studies since Luther and the Papacy (1981); his Short Introduction (2010) and an earlier biography (2009) are marked by lucidity and accuracy. His careful work on the little-known Urbanus Rhegius (1489–1541) and other Reformers has brought these significant participants in the expansion of religious reform out of the shadows of historical oblivion. For care with material and clarity of exposition, Hendrix is well positioned to write the American Luther biography of this anniversary year.
Locked Out
Authors: JOHANSSON VERONICA , SOEKADAR SURJO R. , CLAUSEN JENS
Published: September 2017

Brain–computer interfaces (BCIs) can enable communication for persons in severe paralysis including locked-in syndrome (LIS); that is, being unable to move or speak while aware. In cases of complete loss of muscle control, termed “complete locked-in syndrome,” a BCI may be the only viable solution to restore communication. However, a widespread ignorance regarding quality of life in LIS, current BCIs, and their potential as an assistive technology for persons in LIS, needlessly causes a harmful situation for this cohort. In addition to their medical condition, these persons also face social barriers often perceived as more impairing than their physical condition. Through social exclusion, stigmatization, and frequently being underestimated in their abilities, these persons are being locked out in addition to being locked-in. In this article, we (1) show how persons in LIS are being locked out, including how key issues addressed in the existing literature on ethics, LIS, and BCIs for communication, such as autonomy, quality of life, and advance directives, may reinforce these confinements; (2) show how these practices violate the United Nations Convention on the Rights of Persons with Disabilities, and suggest that we have a moral responsibility to prevent and stop this exclusion; and (3) discuss the role of BCIs for communication as one means to this end and suggest that a novel approach to BCI research is necessary to acknowledge the moral responsibility toward the end users and avoid violating the human rights of persons in LIS.
Research Domain Criteria as Psychiatric Nosology
Authors: AKRAM FAISAL , GIORDANO JAMES
Published: September 2017

Diagnostic classification systems in psychiatry have continued to rely on clinical phenomenology, despite limitations inherent in that approach. In view of these limitations and recent progress in neuroscience, the National Institute of Mental Health (NIMH) has initiated the Research Domain Criteria (RDoC) project to develop a more neuroscientifically based system of characterizing and classifying psychiatric disorders. The RDoC initiative aims to transform psychiatry into an integrative science of psychopathology in which mental illnesses will be defined as involving putative dysfunctions in neural nodes and networks. However, conceptual, methodological, neuroethical, and social issues inherent in and/or derived from the use of RDoC need to be addressed before any attempt is made to implement their use in clinical psychiatry. This article describes current progress in RDoC; defines key technical, neuroethical, and social issues generated by RDoC adoption and use; and posits key questions that must be addressed and resolved if RDoC are to be employed for psychiatric diagnoses and therapeutics. Specifically, we posit that objectivization of complex mental phenomena may raise ethical questions about autonomy, the value of subjective experience, what constitutes normality, what constitutes a disorder, and what represents a treatment, enablement, and/or enhancement. Ethical issues may also arise from the (mis)use of biomarkers and phenotypes in predicting and treating mental disorders, and what such definitions, predictions, and interventions portend for concepts and views of sickness, criminality, professional competency, and social functioning. Given these issues, we offer that a preparatory neuroethical framework is required to define and guide the ways in which RDoC-oriented research can—and arguably should—be utilized in clinical psychiatry, and perhaps more broadly, in the social sphere.
Pesticides
Authors: CABRERA LAURA Y.
Published: September 2017

There is growing evidence about the influence of chemical exposures on specific molecular systems and mechanisms involved in cognitive and mental function. Evidence is also emerging about the negative impact of these chemical exposures on mental health, including depression, suicide, and other risks. Despite the growing appreciation of these factors, however, little attention has been paid to the ethical and social implications of their interactions. Drawing on recent work that argues for an environmental neuroethics approach that explicitly brings together ethics, environment, and conditions of the central nervous system, this article focuses on these critical issues for pesticides specifically.
Deep Brain Stimulation, Authenticity and Value
Authors: NYHOLM SVEN , O’NEILL ELIZABETH
Published: September 2017

In this article, we engage in dialogue with Jonathan Pugh, Hannah Maslen, and Julian Savulescu about how to best interpret the potential impacts of deep brain stimulation on the self. We consider whether ordinary peoples’ convictions about the true self should be interpreted in essentialist or existentialist ways. Like Pugh, Maslen, and Savulescu, we argue that it is useful to understand the notion of the true self as having both essentialist and existentialist components. We also consider two ideas from existentialist philosophy—Jean-Paul Sartre and Simone de Beauvoir’s ideas about “bad faith” and “ambiguity”—to argue that there can be value to patients in regarding themselves as having a certain amount of freedom to choose what aspects of themselves should be considered representative of their true selves. Lastly, we consider the case of an anorexia nervosa patient who shifts between conflicting mind-sets. We argue that mind-sets in which it is easier for the patient and his or her family to share values can plausibly be considered to be more representative of the patient’s true self, if this promotes a well-functioning relationship between the patient and the family. However, we also argue that families are well advised to give patients room to determine what such shared values mean to them, as it can be alienating for patients if they feel that others try to impose values on them from the outside.
Energy contribution of NOVA food groups and sociodemographic determinants of ultra-processed food consumption in the Mexican population
Authors: Marrón-Ponce Joaquín A , Sánchez-Pimienta Tania G , Louzada Maria Laura da Costa , Batis Carolina
Published: September 2017

Objective

To identify the energy contributions of NOVA food groups in the Mexican diet and the associations between individual sociodemographic characteristics and the energy contribution of ultra-processed foods (UPF).

Design

We classified foods and beverages reported in a 24 h recall according to the NOVA food framework into: (i) unprocessed or minimally processed foods; (ii) processed culinary ingredients; (iii) processed foods; and (iv) UPF. We estimated the energy contribution of each food group and ran a multiple linear regression to identify the associations between sociodemographic characteristics and UPF energy contribution.

Setting

Mexican National Health and Nutrition Survey 2012.

Subjects

Individuals ≥1 years old (n10 087).

Results

Unprocessed or minimally processed foods had the highest dietary energy contribution (54·0 % of energy), followed by UPF (29·8 %), processed culinary ingredients (10·2 %) and processed foods (6·0 %). The energy contribution of UPF was higher in: pre-school-aged childrenv. other age groups (3·8 to 12·5 percentage points difference (pp)); urban areasv. rural (5·6 pp); the Central and North regionsv. the South (2·7 and 8·4 pp, respectively); medium and high socio-economic statusv. low (4·5 pp, in both); and with higher head of household educational levelv. without education (3·4 to 7·8 pp).

Conclusions

In 2012, about 30 % of energy in the Mexican diet came from UPF. Our results showed that younger ages, urbanization, living in the North region, high socio-economic status and high head of household educational level are sociodemographic factors related to higher consumption of UPF in Mexico.
The Domestic Politics of Preferential Trade Agreements in Hard Times
Authors: MANSFIELD EDWARD D. , MILNER HELEN V.
Published: September 2017

There is evidence that some countries negotiate trade agreements during economic downturns. Why would a leader do this? We argue that political leaders can gain from such agreements because of the signals they send to their public. The public are less likely to blame leaders for adverse economic conditions when they have implemented sound economic policies, such as signing agreements designed to liberalize trade and prevent a slide into protectionism. In hard economic times, leaders – especially those in democratic environments – may find that trade agreements are a useful way to reassure the public. Since majorities in many countries around the world view trade favorably, leaders may see agreements that prevent them from adopting protectionism as a way to maintain support. We evaluate this argument by analyzing preferential trade agreements (PTAs) formed since 1962. We find that, on average, democratic countries are more likely to form PTAs during hard economic times. We also find that democratic leaders who sign PTAs during downturns enjoy a longer tenure than their counterparts who do not sign such agreements.
Moral agents and legal persons: the ethics and the law of state responsibility
Authors: Fleming Sean
Published: September 2017

Why, if at all, does it make sense to assign some responsibilities to states rather than to individuals? There are two contemporary answers. According to the agential theory, states can be held responsible because they are moral agents, much like human beings. According to the functional theory, states can be held responsible because they are legal persons that act vicariously through individuals, much like principals who act through agents. The two theories of state responsibility belong to parallel traditions of scholarship that have never been clearly distinguished. While the agential theory is dominant in IR, political theory, and philosophy, the functional theory prevails in International Law. The purpose of this article is to bridge the gulf between ethical and legal approaches to state responsibility. I argue that IR scholars and political theorists have much to gain from the functional theory. First, it provides a plausible alternative to the agential theory that avoids common objections to corporate moral agency. Second, the functional theory helps us to understand features of International Law that have puzzled IR scholars and political theorists, such as the fact that states are not held criminally responsible. I suggest that states can be ‘moral principals’ instead of moral agents.
Controlling Dinitroaniline-Resistant Goosegrass (Eleusine indica) in Turfgrass
Authors: Breeden Shane M. , Brosnan James T. , Breeden Gregory K. , Vargas Jose J. , Eichberger Gregor , Tresch Stefan , Laforest Martin
Published: September 2017

Prodiamine is a dinitroaniline herbicide labeled for PRE control of goosegrass in warm- and cool-season turfgrass. In 2013, several golf course roughs in Maryville, TN reported poor goosegrass control (< 20%) following prodiamine treatment at 1,120 g ai ha-1. We harvested suspected prodiamine-resistant (PR) and prodiamine-susceptible (S) goosegrass phenotypes from the field and exposed them to a range of increasing prodiamine concentrations in hydroponic culture. Exposure to prodiamine at 0.001 mM reduced root growth of the S phenotype to 11% of the non-treated check. By comparison, exposure to 0.001 mM prodiamine had minimal effect on the PR phenotype, as root growth was 94% of the non-treated check. Molecular analyses revealed that PR plants contained a threonine (Thr) to isoleucine (Ile) substitution at position 239 on the α-tubulin 1 (TUA1) protein. The substitution, found in all PR plants, is the mechanism of prodiamine resistance in this phenotype. In field studies, topramezone controlled PR goosegrass 72% to 89% by 50 d after treatment (DAT) compared to only 22% to 23% for foramsulfuron. Topramezone treatment injured bermudagrass 34% to 60% from 7 to 14 DAT; however, injury was≤6% 28 DAT and 0% by the end of the study. Our results indicate that POST applications of topramezone can control dinitroaniline-resistant goosegrass. In addition, we established an easy-to-use genotyping assay to quickly screen goosegrass phenotypes for a target-site mutation (Thr-239-Ile) on TUA1 associated with resistance to dinitroaniline herbicides such as prodiamine. Future research should work to expand this assay for use with other weed species and herbicidal modes of action.
Latent State-Trait Models for Longitudinal Family Data
Authors: Loncke Justine , Mayer Axel , Eichelsheim Veroni I. , Branje Susan J. T. , Meeus Wim H. J. , Koot Hans M. , Buysse Ann , Loeys Tom
Published: September 2017

Abstract. Support is key to healthy family functioning. Using the family social relations model (SRM), it has already been shown that variability in perceived support is mostly attributed to individual perceiver effects. Little is known, however, as to whether those effects are stable or occasion-specific. Several methods have been proposed within the structural equation modeling (SEM) framework for the investigation of hypotheses on stable and occasion-specific aspects of such psychological attributes. In this paper, we explore the applicability of different models for determining the consistency of SRM effects of perceived support: the multistate model, the singletrait-multistate model, and the trait-state occasion model. We provide a detailed description of the model building process and assumption verification, as well as the supporting R-code. In addition to the methodological contribution on how to combine these models with the SRM, we also provide substantive insights into the consistency of perceived family support. We rely on round robin data on relational support from the Dutch RADAR-Y (Research on Adolescent Development and Relationships – Younger Cohort) study, a 6-year longitudinal study of 500 families with a 13-year-old target adolescent at the start of the study.
A Flight Guidance Display Format on Smart Glasses for Private	Pilots
Authors: Haiduk Paul M.
Published: September 2017

Abstract. Keeping the pilot eyes-out is important, especially in general aviation (GA), because pilots mostly fly under visual flight rules (VFR). In this study, a display format for smart glasses was developed. Besides the primary flight state information, a curved arrow shows the pilot when to turn and dynamically straightens when the turn should be terminated. The behavior of the display format was developed to guide the pilot in a VFR traffic pattern. A reduction of in flight technical error and missed signals in a secondary task demonstrated the potential of the display format in GA applications. Subjective workload did not significantly change. Results suggest that low-cost consumer smart glasses used in GA could have the potential to support pilots in the future.
An Input–Process–Output Model of Pilot Core	Competencies
Authors: Mansikka Heikki , Harris Don , Virtanen Kai
Published: September 2017

Abstract. The aim of this study was to investigate the relationship between the flight-related core competencies for professional airline pilots and to structuralize them as components in a team performance framework. To achieve this, the core competency scores from a total of 2,560 OPC (Operator Proficiency Check) missions were analyzed. A principal component analysis (PCA) of pilots’ performance scores across the different competencies was conducted. Four principal components were extracted and a path analysis model was constructed on the basis of these factors. The path analysis utilizing the core competencies extracted adopted an input–process–output’ (IPO) model of team performance related directly to the activities on the flight deck. The results of the PCA and the path analysis strongly supported the proposed IPO model.
Training Flight Accidents
Authors: Lee Seung Yong , Bates Paul , Murray Patrick , Martin Wayne
Published: September 2017

Abstract. Civil aviation is broadly categorized into two sectors: air transportation and general aviation. While the former sector is considered to be ultrasafe the latter requires a stronger focus on safety improvement. There has been considerable research examining the causes of general aviation accidents with a view to improving safety. However, there has been very limited research specifically focused on accidents involving training flights and associated causal factors. A total of 293 training flight accident reports, comprising 111 fatal and 182 nonfatal accidents were reviewed and analyzed to identify causes of training-flight accidents. The study found that based on the odds ratio, if a fatal accident involving training flights occurred it was 4.05 times more likely to be a dual training flight. Other findings included that most accidents occurred during the landing phase and the majority of accidents related to skill deficiency (e.g., an improper/inadequate flare). This was a major causal factor in nonfatal accidents in both dual and solo training flights. However, on dual training flights there were more fatal accidents involving decision deficiencies and mechanical malfunctions (e.g., loss of engine power). A previous study suggested that lack of supervision of student pilots by flight instructors was found to be a main causal factor and thus flight instructor training and recurrency requirements need to be reviewed.
Shaping micro-clusters via inverse jamming and topographic close-packing of microbombs
Authors: Yu Seunggun , Cho Hyesung , Hong Jun Pyo , Park Hyunchul , Jolly Jason Christopher , Kang Hong Suk , Lee Jin Hong , Kim Junsoo , Lee Seung Hwan , Lee Albert S. , Hong Soon Man , Park Cheolmin , Yang Shu , Koo Chong Min
Published: September 2017

Designing topographic clusters is of significant interest, yet it remains challenging as they often lack mobility or deformability. Here we exploit the huge volumetric expansion (up to 3000%) of a new type of building block, thermally expandable microbombs. They consist of a viscoelastic polymeric shell and a volatile gas core, which, within structural confinement, create micro-clusters via inverse jamming and topographical close-packing. Upon heating, microbombs anchored in rigid confinement underwent balloon-like blowing up, allowing for dense clusters via soft interplay between viscoelastic shells. Importantly, the confinement is unyielding against the internal pressure of the microbombs, thereby enabling self-assembled clusters, which can be coupled with topographic inscription to introduce structural hierarchy on the clusters. Our strategy provides densely packed yet ultralight clusters with a variety of complex shapes, cleavages, curvatures, and hierarchy. In turn, these clusters will enrich our ability to explore the assemblies of the ever-increasing range of microparticle systems.
Transcriptional regulation of endothelial cell behavior during sprouting angiogenesis
Authors: Jeong Hyun-Woo , Hernández-Rodríguez Benjamín , Kim JungMo , Kim Kee-Pyo , Enriquez-Gasca Rocio , Yoon Juyong , Adams Susanne , Schöler Hans R. , Vaquerizas Juan M. , Adams Ralf H.
Published: September 2017

Mediating the expansion of vascular beds in many physiological and pathological settings, angiogenesis requires dynamic changes in endothelial cell behavior. However, the molecular mechanisms governing endothelial cell activity during different phases of vascular growth, remodeling, maturation, and quiescence remain elusive. Here, we characterize dynamic gene expression changes during postnatal development and identify critical angiogenic factors in mouse retinal endothelial cells. Using actively translating transcriptome analysis and in silico computational analyses, we determine candidate regulators controlling endothelial cell behavior at different developmental stages. We further show that one of the identified candidates, the transcription factor MafB, controls endothelial sprouting in vitro and in vivo, and perform an integrative analysis of RNA-Seq and ChIP-Seq data to define putative direct MafB targets, which are activated or repressed by the transcriptional regulator. Together, our results identify novel cell-autonomous regulatory mechanisms controlling sprouting angiogenesis.
Decoupled choice-driven and stimulus-related activity in parietal neurons may be misrepresented by choice probabilities
Authors: Zaidel Adam , DeAngelis Gregory C. , Angelaki Dora E.
Published: September 2017

Trial-by-trial correlations between neural responses and choices (choice probabilities) are often interpreted to reflect a causal contribution of neurons to task performance. However, choice probabilities may arise from top-down, rather than bottom-up, signals. We isolated distinct sensory and decision contributions to single-unit activity recorded from the dorsal medial superior temporal (MSTd) and ventral intraparietal (VIP) areas of monkeys during perception of self-motion. Superficially, neurons in both areas show similar tuning curves during task performance. However, tuning in MSTd neurons primarily reflects sensory inputs, whereas choice-related signals dominate tuning in VIP neurons. Importantly, the choice-related activity of VIP neurons is not predictable from their stimulus tuning, and these factors are often confounded in choice probability measurements. This finding was confirmed in a subset of neurons for which stimulus tuning was measured during passive fixation. Our findings reveal decoupled stimulus and choice signals in the VIP area, and challenge our understanding of choice signals in the brain.
Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner
Authors: Deczkowska Aleksandra , Matcovitch-Natan Orit , Tsitsou-Kampeli Afroditi , Ben-Hamo Sefi , Dvir-Szternfeld Raz , Spinrad Amit , Singer Oded , David Eyal , Winter Deborah R. , Smith Lucas K. , Kertser Alexander , Baruch Kuti , Rosenzweig Neta , Terem Anna , Prinz Marco , Villeda Saul , Citri Ami , Amit Ido , Schwartz Michal
Published: September 2017

During ageing, microglia acquire a phenotype that may negatively affect brain function. Here we show that ageing microglial phenotype is largely imposed by interferon type I (IFN-I) chronically present in aged brain milieu. Overexpression of IFN-β in the CNS of adult wild-type mice, but not of mice lacking IFN-I receptor on their microglia, induces an ageing-like transcriptional microglial signature, and impairs cognitive performance. Furthermore, we demonstrate that age-related IFN-I milieu downregulates microglial myocyte-specific enhancer factor 2C (Mef2C). Immune challenge in mice lacking Mef2C in microglia results in an exaggerated microglial response and has an adverse effect on mice behaviour. Overall, our data indicate that the chronic presence of IFN-I in the brain microenvironment, which negatively affects cognitive function, is mediated via modulation of microglial activity. These findings may shed new light on other neurological conditions characterized by elevated IFN-I signalling in the brain.
Loss of β-catenin in resident cardiac fibroblasts attenuates fibrosis induced by pressure overload in mice
Authors: Xiang Fu-Li , Fang Ming , Yutzey Katherine E.
Published: September 2017

Cardiac fibrosis is characterized by excessive extracellular matrix deposition that contributes to compromised cardiac function and potentially heart failure. Cardiac pressure overload resulting from trans-aortic constriction in mice leads to cardiac fibrosis and increased Wnt/β-catenin signaling in cardiac fibroblasts. Here, we conditionally induce β-catenin loss of function in resident cardiac fibroblasts using Tcf21
MerCreMer
or in activated cardiac fibroblasts using periostin (Postn)
MerCreMer
. We show that β-catenin loss of function in cardiac fibroblasts after trans-aortic constriction significantly preserves cardiac function, and reduces interstitial fibrosis but does not alter the numbers of activated or differentiated cardiac fibroblasts in vivo. However, β-catenin is specifically required in resident cardiac fibroblasts for fibrotic excessive extracellular matrix gene expression and binds Col3a1 and Postn gene sequences in cultured cardiac fibroblasts after induction of Wnt signaling. Moreover, cardiomyocyte hypertrophy is blunted with cardiac fibroblast-specific loss of β-catenin after trans-aortic constriction in vivo. Thus, Wnt/β-catenin signaling in resident cardiac fibroblasts is required for excessive extracellular matrix gene expression and collagen deposition after trans-aortic constriction.
Frequency-division multiplexer and demultiplexer for terahertz wireless links
Authors: Ma Jianjun , Karl Nicholas J. , Bretin Sara , Ducournau Guillaume , Mittleman Daniel M.
Published: September 2017

The development of components for terahertz wireless communications networks has become an active and growing research field. However, in most cases these components have been studied using a continuous or broadband-pulsed terahertz source, not using a modulated data stream. This limitation may mask important aspects of the performance of the device in a realistic system configuration. We report the characterization of one such device, a frequency multiplexer, using modulated data at rates up to 10 gigabits per second. We also demonstrate simultaneous error-free transmission of two signals at different carrier frequencies, with an aggregate data rate of 50 gigabits per second. We observe that the far-field spatial variation of the bit error rate is different from that of the emitted power, due to a small nonuniformity in the angular detection sensitivity. This is likely to be a common feature of any terahertz communication system in which signals propagate as diffracting beams not omnidirectional broadcasts.
High-harmonic generation in amorphous solids
Authors: You Yong Sing , Yin Yanchun , Wu Yi , Chew Andrew , Ren Xiaoming , Zhuang Fengjiang , Gholam-Mirzaei Shima , Chini Michael , Chang Zenghu , Ghimire Shambhu
Published: September 2017

High-harmonic generation in isolated atoms and molecules has been widely utilized in extreme ultraviolet photonics and attosecond pulse metrology. Recently, high-harmonic generation has been observed in solids, which could lead to important applications such as all-optical methods to image valance charge density and reconstruct electronic band structures, as well as compact extreme ultraviolet light sources. So far these studies are confined to crystalline solids; therefore, decoupling the respective roles of long-range periodicity and high density has been challenging. Here we report the observation of high-harmonic generation from amorphous fused silica. We decouple the role of long-range periodicity by comparing harmonics generated from fused silica and crystalline quartz, which contain the same atomic constituents but differ in long-range periodicity. Our results advance current understanding of the strong-field processes leading to high-harmonic generation in solids with implications for the development of robust and compact extreme ultraviolet light sources.
Chemically intuited, large-scale screening of MOFs by machine learning techniques
Authors: Borboudakis Giorgos , Stergiannakos Taxiarchis , Frysali Maria , Klontzas Emmanuel , Tsamardinos Ioannis , Froudakis George E.
Published: September 2017

A novel computational methodology for large-scale screening of MOFs is applied to gas storage with the use of machine learning technologies. This approach is a promising trade-off between the accuracy of ab initio methods and the speed of classical approaches, strategically combined with chemical intuition. The results demonstrate that the chemical properties of MOFs are indeed predictable (stochastically, not deterministically) using machine learning methods and automated analysis protocols, with the accuracy of predictions increasing with sample size. Our initial results indicate that this methodology is promising to apply not only to gas storage in MOFs but in many other material science projects.
Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas
Authors: Madubata Chioma J , Roshan-Ghias Alireza , Chu Timothy , Resnick Samuel , Zhao Junfei , Arnes Luis , Wang Jiguang , Rabadan Raul
Published: September 2017

Cancer is caused by germline and somatic mutations, which can share biological features such as amino acid change. However, integrated germline and somatic analysis remains uncommon. We present a framework that uses machine learning to learn features of recurrent somatic mutations to (1) predict somatic variants from tumor-only samples and (2) identify somatic-like germline variants for integrated analysis of tumor-normal DNA. Using data from 1769 patients from seven cancer types (bladder, glioblastoma, low-grade glioma, lung, melanoma, stomach, and pediatric glioma), we show that “somatic-like” germline variants are enriched for autosomal-dominant cancer-predisposition genes (p < 4.35 × 10−15), including TP53. Our framework identifies germline and somatic nonsense variants in BRCA2 and other Fanconi anemia genes in 11% (11/100) of bladder cancer cases, suggesting a potential genetic predisposition in these patients. The bladder carcinoma patients with Fanconi anemia nonsense variants display a BRCA-deficiency somatic mutation signature, suggesting treatment targeted to DNA repair.
Buckling analysis in stretchable electronics
Authors: Wang Bo , Bao Siyuan , Vinnikova Sandra , Ghanta Pravarsha , Wang Shuodao
Published: September 2017

In the last decade, stretchable electronics evolved as a class of novel systems that have electronic performances equal to established semiconductor technologies, but can be stretched, compressed, and twisted like a rubber band. The compliance and stretchability of these electronics allow them to conform and mount to soft, elastic biological organs and tissues, thereby providing attractive opportunities in health care and bio-sensing. Majority of stretchable electronic systems use an elastomeric substrate to carry an ultrathin circuit mesh that consists of sparsely distributed stiff, thin-film electronic components interconnected by various forms of stretchable metal strips or low-dimension materials. During the fabrication processes and application of stretchable electronics, the thin-film components or nanomaterials undergo different kinds of in-plane deformation that often leads to out-of-plane or lateral buckling, in-surface buckling, or a combination of all. A lot of creative concepts and ideas have been developed to control and harness buckling behaviors, commonly regarded as pervasive occurrences in structural designs, to facilitate fabrication of stretchable structures, or to enhance stretchability. This paper provides a brief review of recent progresses on buckling analysis in stretchable electronics. Detailed buckling mechanics reveals important correlations between the geometric/material properties and system performance (e.g., mechanical robustness, deformability, structural architecture, and control). These mechanics models and analysis provide insights to design and optimize stretchable electronics for a wide range of important applications.
Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest
Authors: Cheng Tingcai , Wu Jiaqi , Wu Yuqian , Chilukuri Rajendra V. , Huang Lihua , Yamamoto Kohji , Feng Li , Li Wanshun , Chen Zhiwei , Guo Huizhen , Liu Jianqiu , Li Shenglong , Wang Xiaoxiao , Peng Li , Liu Duolian , Guo Youbing , Fu Bohua , Li Zhiqing , Liu Chun , Chen Yuhui , Tomar Archana , Hilliou Frederique , Montagné Nicolas , Jacquin-Joly Emmanuelle , d’Alençon Emmanuelle , Seth Rakesh K. , Bhatnagar Raj K. , Jouraku Akiya , Shiotsuki Takahiro , Kadono-Okuda Keiko , Promboon Amornrat , Smagghe Guy , Arunkumar Kallare P. , Kishino Hirohisa , Goldsmith Marian R. , Feng Qili , Xia Qingyou , Mita Kazuei
Published: September 2017

The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect’s natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India–South China–Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.
Highly diversified expansions shaped the evolution of membrane bound proteins in metazoans
Authors: Attwood Misty M. , Krishnan Arunkumar , Almén Markus Sällman , Schiöth Helgi B.
Published: September 2017

The dramatic increase in membrane proteome complexity is arguably one of the most pivotal evolutionary events that underpins the origin of multicellular animals. However, the origin of a significant number of membrane families involved in metazoan development has not been clarified. In this study, we have manually curated the membrane proteomes of 22 metazoan and 2 unicellular holozoan species. We identify 123,014 membrane proteins in these 24 eukaryotic species and classify 86% of the dataset. We determine 604 functional clusters that are present from the last holozoan common ancestor (LHCA) through many metazoan species. Intriguingly, we show that more than 70% of the metazoan membrane protein families have a premetazoan origin. The data show that enzymes are more highly represented in the LHCA and expand less than threefold throughout metazoan species; in contrast to receptors that are relatively few in the LHCA but expand nearly eight fold within metazoans. Expansions related to cell adhesion, communication, immune defence, and developmental processes are shown in conjunction with emerging biological systems, such as neuronal development, cytoskeleton organization, and the adaptive immune response. This study defines the possible LHCA membrane proteome and describes the fundamental functional clusters that underlie metazoan diversity and innovation.
The Quasi-Coarse-Grained Dynamics Method to Unravel the Mesoscale Evolution of Defects/Damage during Shock Loading and Spall Failure of Polycrystalline Al Microstructures
Authors: Agarwal Garvit , Valisetty Ramakrishna R. , Namburu Raju R. , Rajendran Arunachalam M. , Dongare Avinash M.
Published: September 2017

A long-standing problem in modeling of shock response of metals is the ability to model defect nucleation and evolution mechanisms during plastic deformation and failure at the mesoscales. This paper demonstrates the capability of the “quasi-coarse-grained dynamics” (QCGD) simulation method to unravel microstructural evolution of polycrystalline Al microstructures at the mesoscales. The various QCGD simulations discussed here investigate the shock response of Al microstructures comprising of grain sizes ranging from 50 nm to 3.20 µm and correspond to system sizes ranging from 150 nm to 9.6 µm, respectively. The QCGD simulations are validated by demonstrating the capability to retain atomistic characteristics of the wave propagation behavior, plastic deformation mechanisms (dislocation nucleation, dissociation/recombination behavior, dislocation interactions/reactions), evolution of damage (voids), and evolution of temperature during shock loading. The capability to unravel the mesoscale evolution of microstructure is demonstrated by investigating the effect of grain size, shock pulse and system size on the shock response and spall failure of the metal. The computed values of spall strengths predicted using the QCGD simulations agree very well with the trend predicted by MD simulations and a strain rate dependence of the spall strength is proposed that fits the experimentally available values in the literature.
IRS1 DNA promoter methylation and expression in human adipose tissue are related to fat distribution and metabolic traits
Authors: Rohde Kerstin , Klös Matthias , Hopp Lydia , Liu Xuanshi , Keller Maria , Stumvoll Michael , Dietrich Arne , Schön Michael R. , Gärtner Daniel , Lohmann Tobias , Dreßler Miriam , Kovacs Peter , Binder Hans , Blüher Matthias , Böttcher Yvonne
Published: September 2017

The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively. Genotyping of rs2943650 was performed in all individuals (N = 146). We observed a significantly higher IRS1 promoter DNA methylation in OVAT compared to SAT (N = 146, P = 8.0 × 10−6), while expression levels show the opposite effect direction (N = 41, P = 0.011). OVAT and SAT methylation correlated negatively with IRS1 gene expression in obese subjects (N = 16, P = 0.007 and P = 0.010). The major T-allele is related to increased DNA methylation in OVAT (N = 146, P = 0.019). Finally, DNA methylation and gene expression in OVAT correlated with anthropometric traits (waist- circumference waist-to-hip ratio) and parameters of glucose metabolism in obese individuals. Our data suggest that the association between rs2943650 near the IRS1 gene locus with clinically relevant variables may at least be modulated by changes in DNA methylation that translates into altered IRS1 gene expression.
Discriminative Scale Learning (DiScrn): Applications to Prostate Cancer Detection from MRI and Needle Biopsies
Authors: Wang Haibo , Viswanath Satish , Madabhushi Anant
Published: September 2017

There has been recent substantial interest in extracting sub-visual features from medical images for improved disease characterization compared to what might be achievable via visual inspection alone. Features such as Haralick and Gabor can provide a multi-scale representation of the original image by extracting measurements across differently sized neighborhoods. While these multi-scale features are effective, on large-scale digital pathological images, the process of extracting these features is computationally expensive. Moreover for different problems, different scales and neighborhood sizes may be more or less important and thus a large number of features extracted might end up being redundant. In this paper, we present a Discriminative Scale learning (DiScrn) approach that attempts to automatically identify the distinctive scales at which features are able to best separate cancerous from non-cancerous regions on both radiologic and digital pathology tissue images. To evaluate the efficacy of our approach, our approach was employed to detect presence and extent of prostate cancer on a total of 60 MRI and digitized histopathology images. Compared to a multi-scale feature analysis approach invoking features across all scales, DiScrn achieved 66% computational efficiency while also achieving comparable or even better classifier performance.
The Role of Ubiquitination and Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate in the Degradation of the Adrenomedullin Type I Receptor
Authors: Roux Benoît T. , Bauer Claudia C. , McNeish Alister J. , Ward Stephen G. , Cottrell Graeme S.
Published: September 2017

Calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 2 (RAMP2) comprise a receptor for adrenomedullin (AM). Although it is known that AM induces internalization of CLR•RAMP2, little is known about the molecular mechanisms that regulate the trafficking of CLR•RAMP2. Using HEK and HMEC-1 cells, we observed that AM-induced activation of CLR•RAMP2 promoted ubiquitination of CLR. A mutant (CLRΔ9KR), lacking all intracellular lysine residues was functional and trafficked similar to the wild-type receptor, but was not ubiquitinated. Degradation of CLR•RAMP2 and CLRΔ9KR•RAMP2 was not dependent on the duration of AM stimulation or ubiquitination and occurred via a mechanism that was partially prevented by peptidase inhibitors. Degradation of CLR•RAMP2 was sensitive to overexpression of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), but not to HRS knockdown, whereas CLRΔ9KR•RAMP2 degradation was unaffected. Overexpression, but not knockdown of HRS, promoted hyperubiquitination of CLR under basal conditions. Thus, we propose a role for ubiquitin and HRS in the regulation of AM-induced degradation of CLR•RAMP2.
Synergistic effect of a drug loaded electrospun patch and systemic chemotherapy in pancreatic cancer xenograft
Authors: Jun Eunsung , Kim Song Cheol , Lee Chan Mi , Oh Juyun , Lee Song , Shim In Kyong
Published: September 2017

Pancreatic cancer has a high rate of local recurrence and poor prognosis even with adjuvant chemotherapy after curative resection. The aim of this study was to investigate if local drug delivery combined with low dose systemic chemotherapy can increase the therapeutic effect of chemotherapy while reducing systemic toxicities. Poly-L-lactic acid-based 5-FU releasing patch was fabricated by electrospinning, and its tumour killing effects were first confirmed in vitro. The 5-FU patch directly adhered to the tumour in subcutaneous and orthotopic murine models, and induced a significant decrease in tumour size. Systemic gemcitabine treatment group, 5-FU drug releasing patch group, and systemic gemcitabine plus 5-FU patch group were compared by tumour size measurement, non-invasive bio-imaging, and histology in subcutaneous models. Combination of local drug patch and systemic chemotherapy led to increased tumour suppression effects that lasted longer, as well as increased survival rate. Histology revealed higher degree of apoptosis in the combined group. Systemic toxicity was recovered within 7 days after the treatment in all mice. Conclusively, local drug delivery using biocompatible polymer patch significantly inhibited tumour growth, and combination with systemic chemotherapy was more effective than single systemic chemotherapy.
Ageing affects chondroitin sulfates and their synthetic enzymes in the intervertebral disc
Authors: Collin Estelle C , Carroll Oliver , Kilcoyne Michelle , Peroglio Marianna , See Eugene , Hendig Doris , Alini Mauro , Grad Sibylle , Pandit Abhay
Published: September 2017

The depletion of chondroitin sulfates (CSs) within the intervertebral disc (IVD) during degenerative disc disease (DDD) results in a decrease in tissue hydration, a loss of fluid movement, cell apoptosis, a loss of nerve growth inhibition and ultimately, the loss of disc function. To date, little is known with regards to the structure and content of chondroitin sulfates (CSs) during IVD ageing. The behavior of glycosaminoglycans (GAGs), specifically CSs, as well as xylosyltransferase I (XT-I) and glucuronyltransferase I (GT-I), two key enzymes involved in CS synthesis as a primer of glycosaminoglycan (GAG) chain elongation and GAG synthesis in the nucleus pulposus (NP), respectively, were evaluated in a bovine ageing IVD model. Here, we showed significant changes in the composition of GAGs during the disc ageing process (6-month-old, 2-year-old and 8-year-old IVDs representing the immature to mature skeleton). The CS quantity and composition of annulus fibrosus (AF) and NP were determined. The expression of both XT-I and GT-I was detected using immunohistochemistry. A significant decrease in GAGs was observed during the ageing process. CSs are affected at both the structural and quantitative levels with important changes in sulfation observed upon maturity, which correlated with a decrease in the expression of both XT-I and GT-I. A progressive switch of the sulfation profile was noted in both NP and AF tissues from 6 months to 8 years. These changes give an appreciation of the potential impact of CSs on the disc biology and the development of therapeutic approaches for disc regeneration and repair.
MicroRNA detection by an amplification-free biosensor based on controllable solid-state electrochemiluminescence quenched by charge transfer
Authors: Liu Chang , Wang Lin , Lu Liping , Kang Tianfang
Published: September 2017

A simple and amplification-free solid-state electrochemiluminescence (ECL) biosensor was developed for the sensitive and selective detection of miRNA.
Impact of cellular health conditions on the protein folding state in mammalian cells
Authors: Inomata Kohsuke , Kamoshida Hajime , Ikari Masaomi , Ito Yutaka , Kigawa Takanori
Published: September 2017

Cellular health conditions severely affect the protein folding state in mammalian cells.
Compositional nanodomain formation in hybrid formate perovskites
Authors: Donlan Edwina A. , Boström Hanna L. B. , Geddes Harry S. , Reynolds Emily M. , Goodwin Andrew L.
Published: September 2017

We discover compositional nanodomains in mixed-metal hybrid formate perovskites that are conceptually related to polar nanoregions in relaxor ferroelectrics.
Countercurrent liquid–liquid extraction on paper
Authors: Salentijn Gert IJ. , Grajewski Maciej , Verpoorte Elisabeth
Published: September 2017

We demonstrate the realization of two-phase countercurrent flow on paper and its use in a proof-of-concept liquid–liquid extraction.
Interlayer bond polarizability model for stacking-dependent low-frequency Raman scattering in layered materials
Authors: Liang Liangbo , Puretzky Alexander A. , Sumpter Bobby G. , Meunier Vincent
Published: September 2017

A simple model is developed to reveal the stacking dependence of Raman intensities of interlayer vibrations in 2D materials.
In situ synthesis of titanium doped hybrid metal–organic framework UiO-66 with enhanced adsorption capacity for organic dyes
Authors: Han Yitong , Liu Min , Li Keyan , Sun Qiao , Zhang Wensheng , Song Chunshan , Zhang Guoliang , Conrad Zhang Z. , Guo Xinwen
Published: September 2017

The adsorption ability of zirconium-based MOF UiO-66 for Congo red can be greatly promoted via the doping of Ti4+.
Transition-metal-free, visible-light-induced oxidative cross-coupling for constructing β-acetylamino acrylosulfones from sodium sulfinates and enamides
Authors: Sun Deli , Zhang Ronghua
Published: September 2017

A visible-light-induced, Rose Bengal catalyzed photoredox process for synthesizing β-acetylamino acrylosulfones has been discovered.
Cesium carbonate promoted cascade reaction involving DMF as a reactant for the synthesis of dihydropyrrolizino[3,2-b]indol-10-ones
Authors: Zhang Qianqian , Song Chuanjun , Huang He , Zhang Kun , Chang Junbiao
Published: September 2017

A cesium carbonate promoted cascade reaction for the synthesis of dihydropyrrolizino[3,2-b]indol-10-ones has been developed.