bluuebunny/crossref_metadata_2025 huggingface dataset:
Aircraft reliability assessment for an individual mission based on recordable flight parameters
Authors: Ma Xiaobing , Wang Zhihua , Guan Tianyu , Ma Tao
Published: June 2018

Reliability of aircraft varies with different missions, because load conditions are always diverse. In limited sample size circumstances, convention aircraft mission reliability assessment method can only give an average result for a kind of mission. Motivated by the practical need of reliability assessment for an individual mission, this paper constructs a novel method, which can assess reliability for a specific mission based on flight parameters. The mission reliability model can be established according to the relationship between flight loads, flight parameters, and reliability via adopting fault data and flight parameters synthetically. Statistical inference of aircraft failure rate is proposed, and then, the mission reliability can be assessed according to the fault data of the focused aircraft. It is worth noticing that the proposed method can also assess the reliability for a mission category via conducting an average calculation across all individual missions belonging to the target mission category. An illustrative example shows that the proposed method not only can give reliability assessments with a same precision with existing approaches for a specific mission category but also can reasonably assess the reliability regarding an individual mission.
Rare case of occult testosterone‐producing ovarian tumor that was diagnosed by selective venous hormone sampling
Authors: Kuno Yoshika , Baba Tsuyoshi , Kuroda Takafumi , Teramoto Mizue , Hirokawa Naoki , Endo Toshiaki , Saito Tsuyoshi
Published: June 2018

Case

A 32 year old woman was referred because of secondary amenorrhea, hirsutism, and voice deepening.

Outcome

The blood testosterone level was markedly high. A transvaginal ultrasound revealed a small region in the left ovary, but whether or not it was a tumor was unclear. Therefore, selective ovarian venous sampling was performed. Consequently, the testosterone level was selectively increased in a blood sample that was taken from the left ovarian vein, the tumor was successfully localized, and a laparoscopic left oophorectomy was performed. Although the left ovary appeared to be normal at laparoscopy, the androgen‐secreting tumor was located within it. The tumor was diagnosed as a Leydig cell tumor by histopathological analyses.

Conclusion

This report demonstrates that selective blood sampling from ovarian veins before an operation is effective in localizing an androgen‐producing ovarian tumor that is difficult to diagnose by imaging studies.
Correlating Three‐dimensional Morphology With Function in PBDB‐T:IT‐M Non‐Fullerene Organic Solar Cells
Authors: Li Wei , Cai Jinlong , Yan Yu , Cai Feilong , Li Sunsun , Gurney Robert S. , Liu Dan , McGettrick James D. , Watson Trystan M. , Li Zhe , Pearson Andrew J. , Lidzey David G. , Hou Jianhui , Wang Tao
Published: June 2018

In this work, the correlation between three‐dimensional morphology and device performance of PBDB‐T:IT‐M non‐fullerene organic solar cells is investigated. We found that a PBDB‐T‐rich top layer formed when the PBDB‐T:IT‐M film is cast on PEDOT:PSS, indicating a vertical component distribution that will hinder electron transport toward the cathode in a conventional device. This PBDB‐T‐rich top layer remained upon low‐temperature annealing at 80 °C, but disappeared when the annealing temperature is raised, resulting in an optimum annealing temperature of 160 °C for conventional devices as the removal of this polymer‐rich layer facilitates electron transport toward the top cathode layer. The PBDB‐T‐rich layer is also found in the surface region of the PBDB‐T:IT‐M film cast on a TiO2 substrate, but in this case it remained after thermal annealing at 80 or 160 °C, leading to a favorable vertical stratification for efficient charge collection in inverted devices. Although thermal annealing can enhance the crystallinity of PBDB‐T:IT‐M blend and lead to improved charge mobility, the correlation length of the PBDB‐T component increased excessively under annealing at 160 °C. Further, the packing of IT‐M clusters became loose upon high temperature annealing, an effect we believe results in more diffuse interfaces with PBDB‐T that result in reduced charge separation efficiency, consequently reducing the short‐circuit current in the inverted devices.
Preliminary in situ teeth study of the narrow‐ridged finless porpoises remains using microsynchrotron radiation X‐ray fluorescence and laser ablation inductively coupled plasma mass spectrometry
Authors: Zheng Yi , Zhang Ya , Tang Wenqiao , Guo Hongyi , Zhu Yan , Dong Zhaohui , Jiang Hui
Published: June 2018

In recent years, a growing number of the narrow‐ridged finless porpoises were found dead near the Yangtze River estuary. In this region lived two sympatric subspecies, respectively, the East Asian finless porpoise and the Yangtze finless porpoise. So far, it is difficult to distinguish these two subspecies due to their similar shape and unavailable molecular marker. In this work, synchrotron radiation X‐ray fluorescence (SRXRF) and laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) were applied for in situ teeth trace chemical analysis to study subspecies identification and migration near the Yangtze River estuary. Teeth Sr concentration and87Sr/86Sr ratios, determined by SRXRF and LA‐ICP‐MS techniques, have potential application in the identification of the finless porpoise subspecies. Only one (Sample S4) of the six samples was concluded as the Yangtze finless porpoise, and the others were the East Asian finless porpoise. This study also proved that the Sr/Ca and Zn/Ca ratios could be used as a useful environmental indicator to detect the migratory history of narrow‐ridged finless porpoises.
Holographic RG flows for four-dimensional $$ \mathcal{N}=2 $$ SCFTs
Authors: Bobev Nikolay , Cassani Davide , Triendl Hagen
Published: June 2018

Abstract

We study holographic renormalization group flows from four-dimensional

$$ \mathcal{N}=2 $$

N
=
2

SCFTs to either

$$ \mathcal{N}=2 $$

N
=
2

or

$$ \mathcal{N}=1 $$

N
=
1

SCFTs. Our approach is based on the framework of five-dimensional half-maximal supergravity with general gauging, which we use to study domain wall solutions interpolating between different supersymmetric AdS5 vacua. We show that a holographic RG flow connecting two

$$ \mathcal{N}=2 $$

N
=
2

SCFTs is only possible if the flavor symmetry of the UV theory admits an SO(3) subgroup. In this case the ratio of the IR and UV central charges satisfies a universal relation which we also establish in field theory. In addition we provide several general examples of holographic flows from

$$ \mathcal{N}=2 $$

N
=
2

to

$$ \mathcal{N}=1 $$

N
=
1

SCFTs and relate the ratio of the UV and IR central charges to the conformal dimension of the operator triggering the flow. Instrumental to our analysis is a derivation of the general conditions for AdS vacua preserving eight supercharges as well as for domain wall solutions preserving eight Poincaré supercharges in half-maximal supergravity.
Gravitational waves from first order electroweak phase transition in models with the U(1)
X
gauge symmetry
Authors: Hashino Katsuya , Kakizaki Mitsuru , Kanemura Shinya , Ko Pyungwon , Matsui Toshinori
Published: June 2018

Abstract

We consider a standard model extension equipped with a dark sector where the U(1)
X
Abelian gauge symmetry is spontaneously broken by the dark Higgs mechanism. In this framework, we investigate patterns of the electroweak phase transition as well as those of the dark phase transition, and examine detectability of gravitational waves (GWs) generated by such strongly first order phase transition. It is pointed out that the collider bounds on the properties of the discovered Higgs boson exclude a part of parameter space that could otherwise generate detectable GWs. After imposing various constraints on thi model, it is shown that GWs produced by multi-step phase transitions are detectable at future space-based interferometers, such as LISA and DECIGO, if the dark photon is heavier than 25 GeV. Furthermore, we discuss the complementarity of dark photon searches or dark matter searches with the GW observations in these models with the dark gauge symmetry.
Ethical adoption: A new imperative in the development of technology for dementia
Authors: Robillard Julie M. , Cleland Ian , Hoey Jesse , Nugent Chris
Published: June 2018

Introduction

Technology interventions are showing promise to assist persons with dementia and their carers. However, low adoption rates for these technologies and ethical considerations have impeded the realization of their full potential.

Methods

Building on recent evidence and an iterative framework development process, we propose the concept of “ethical adoption”: the deep integration of ethical principles into the design, development, deployment, and usage of technology.

Results

Ethical adoption is founded on five pillars, supported by empirical evidence: (1) inclusive participatory design; (2) emotional alignment; (3) adoption modelling; (4) ethical standards assessment; and (5) education and training. To close the gap between adoption research, ethics and practice, we propose a set of 18 practical recommendations based on these ethical adoption pillars.

Discussion

Through the implementation of these recommendations, researchers and technology developers alike will benefit from evidence‐informed guidance to ensure their solution is adopted in a way that maximizes the benefits to people with dementia and their carers while minimizing possible harm.
The International Law on Foreign Investment
Authors: Sornarajah M.
Published: June 2018

The climate surrounding foreign investment law is one of controversy and change, and with implications for human rights and environmental protection, foreign investment law has gained widespread public attention and visibility. This fully updated edition of Sornarajah's classic text offers thought-provoking analysis of the law in historical, political and economic contexts, capturing leading trends and charting the possible course of future developments. It takes into account the newer types of treaties that establish a regulatory space for states and moves away from inflexible investment protection, exploring the newly created defences relating to environment, human rights, indigenous rights and other areas ending the fragmentation of the law. It looks at the current debates on legitimacy of the system and current efforts at reform. Suitable for postgraduate and undergraduate students, The International Law on Foreign Investment is essential reading for anyone specialising in the law of foreign investments.
Linear Algebra
Authors: Meckes Elizabeth S. , Meckes Mark W.
Published: June 2018

Linear Algebra offers a unified treatment of both matrix-oriented and theoretical approaches to the course, which will be useful for classes with a mix of mathematics, physics, engineering, and computer science students. Major topics include singular value decomposition, the spectral theorem, linear systems of equations, vector spaces, linear maps, matrices, eigenvalues and eigenvectors, linear independence, bases, coordinates, dimension, matrix factorizations, inner products, norms, and determinants.
Visitor restriction policies and practices in children’s hospitals in North America: results of an Emerging Infections Network Survey
Authors: Pong Alice L. , Beekmann Susan E. , Faltamo Mekleet M. , Polgreen Philip M. , Shane Andi L.
Published: June 2018

Objective

To delineate the timing of, indications for, and assessment of visitor restriction policies and practices (VRPP) in pediatric facilities.

Design

An electronic survey to characterize VRPP in pediatric healthcare facilities.

Methods

The Infectious Diseases Society of America Emerging Infections Network surveyed 334 pediatric infectious disease consultants via an electronic link. Descriptive analyses were performed.

Results

A total of 170 eligible respondents completed a survey between 12 July and August 15, 2016, for a 51% response rate. Of the 104 respondents (61%) familiar with their VRPP, 92 (88%) had VRPP in all inpatient units. The respondents reported age-based VRPP (74%) symptom-based VRPP (97%), and outbreak-specific VRPP (75%). Symptom-based VRPP were reported to be seasonal by 24% of respondents and to be implemented year-round according to 70% of respondents. According to the respondents, communication of VRPP to families occurred at admission (87%) and through signage in care areas (64%), while communication of VRPP to staff occurred by email (77%), by meetings (55%), and by signage in staff-only areas (49%). Respondents reported that enforcement of VRPP was the responsibility of nursing (80%), registration clerks (58%), unit clerks (53%), the infection prevention team (31%), or clinicians 16 (16%). They also reported that the effectiveness of VRPP was assessed through active surveillance of hospital acquired respiratory infections (62%), through active surveillance of healthcare worker exposures (28%) and through patient/family satisfaction assessments (29%).

Conclusion

Visitor restriction policies and practices vary in scope, implementation, enforcement, and physician awareness in pediatric facilities. A prospective multisite evaluation of outcomes would facilitate the adoption of uniform guidance.
Leadership with Trustworthy Associates
Authors: DEWAN TORUN , SQUINTANI FRANCESCO
Published: June 2018

Group members value informed decisions and hold ideological preferences. A leader takes a decision on their behalf. Good leadership depends on characteristics of moderation and judgment. The latter emerges (endogenously) via advice communicated by “trustworthy associates.” Trustworthy advice requires ideological proximity to the leader. A group may choose a relatively extreme leader with a large number of such associates. Paradoxically, this can happen though it is in the group’s collective interest to choose a moderate leader. To assess whether these insights persist when political groups compete, we embed our analysis in a model of elections. Each of two parties chooses a leader who implements her preferred policy if elected. We find that a party may choose an extreme leader who defeats a moderate candidate chosen by the opposing party. Our results highlight the importance of party cohesion and the relations between a leader and her party. These can be more important to electoral success than proximity of a leader’s position to the median voter.
Cross-Border Intimacies: Marriage, migration, and citizenship in western India
Authors: IBRAHIM FARHANA
Published: June 2018

This article examines intersections between sexuality, migration, and citizenship in the context of cross-border and cross-region marriage migration in Kutch, Gujarat, to underscore that women's mobility across borders is one site on which national cultural and political anxieties unfold. It argues that contemporary cross-region marriage migration must be located within the larger political economy of such marriages, and should take into account the historical trajectories of marriage migration in particular regions. To this end, it examines three instances of marriage migration in Kutch: the princely state's marriages with Sindh, nineteenth-century marriages between merchants from Kutch and women from Africa, and contemporary marriage migration into Kutch from Bengal. The article asks whether the relative evaluation of these marriages by the state can be viewed in relation to the settlement policies undertaken after partition, where borderlands were to be settled with those who were deemed loyal citizens. Finally, by historicizing marriage—as structure, but also aspirational category—it seeks to move away from the singularity of marriage as framed in the dominant sociological discourse on marriage in South Asia.
How the Nation’s Largest Minority Became White: Race Politics and the Disability Rights Movement, 1970–1980
Authors: Erkulwater Jennifer L.
Published: June 2018

Scholars point out a tension between racial justice and disability rights activism. Although racial minorities are more likely to become disabled than whites, both disability activism and the historiography of disability politics tend to focus on the experience and achievements of whites. This article examines how disability rights activists of the 1970s sought to build a united movement of all people with disabilities and explains why these efforts were unable to overcome cleavages predicated on race. Activists drew from New Left ideas of community and self-help as well as the New Right rhetoric of market freedoms to articulate a vision of liberation for people with disabilities. Though they yearned for racial solidarity, in practice, activists could not overcome institutions that separated antipoverty and racial politics from disability policy, nor could they figure out how to incorporate minority voices in an identity-based movement forged around disability rather than color.
Perceptions and Policy Failure: Explaining President James Buchanan’s Policy Priorities Through Latent Opinion
Authors: Chamberlain Adam
Published: June 2018

This article evaluates the policy positions of President James Buchanan through the concept of latent opinion, or politicians worrying less about current public opinion and more about what it will be at the next election. Though Buchanan is often viewed as disconnected from the public’s opinions, the evidence shows that his positions on Kansas statehood and the acquisition of Cuba (or Mexican territory) were shaped by his perceptions of, and concerns over, what future public opinion would be in 1860. Though Buchanan was ultimately unsuccessful on both fronts, this study reveals that he was not simply unresponsive to public opinion, which is the common interpretation. Instead, the president’s policy positions were firmly tied to his views on latent opinion. Thus, the findings add a new dimension to scholarly understandings of James Buchanan’s policy priorities while displaying how latent opinion can be a beneficial construct in policy history.
Politics as Victimhood, Victimhood as Politics
Authors: Horwitz Robert B.
Published: June 2018

The victim has become among the most important identity positions in American politics. Victimhood is now a pivotal means by which individuals and groups see themselves and constitute themselves as political actors. Indeed, victimhood seems to have become a status that must be established before political claims can be advanced. Victimhood embodies the assertion that an individual or group has suffered wrongs that must be requited. What seems new is that wounded groups assert a self-righteous claim that they stand for something larger than their particular injury. The article explores how and why victimhood has become such a powerful theme in American politics. It suggests that victimhood as politics emerged from the contentious politics of the 1960s, specifically the civil rights movement and its aftermath. Key factors include the reaction to the minority rights and women’s movements, as well as internal dynamicswithinthe rights movements.
The F Words: Frauds, Forgeries, and Fakes in Antiquities Smuggling and the Role of Organized Crime
Authors: Sotiriou Konstantinos-Orfeas
Published: June 2018

The phenomenon of antiquities smuggling is a complicated issue. The lack of official data makes it difficult to do an integrated analysis of the problem. The aim of this article is to present an accurate view of antiquities smuggling in the recent past. After gaining official permission from the Greek police, we examined 246 official arrests made by the Greek Department against Antiquities Smuggling (Athens Office) that occurred between 1999 and 2009. First and foremost, our results revealed that many arrests showed instances of fake antiquities. Moreover, it seems that there is a connection between organized crime and antiquities forgery. In addition, people with higher status are more often involved in antiquities forgery. With respect to the stolen objects, coins were by far the most preferred objects when it comes to forgery, and forgers are also using mostly bronze when it comes to these forgeries. Antiquity looting seems to have many hidden aspects, and the varied natured of antiquities smuggling requires the cooperation of a range of competent authorities and an in-depth investigation of the data, which should be based on the principles of the scientific method.
Methods for Conducting Electron Backscattered Diffraction (EBSD) on Polycrystalline Organic Molecular Thin Films
Authors: Abbasi Kevin , Wang Danqi , Fusella Michael A. , Rand Barry P. , Avishai Amir
Published: June 2018

Electron backscattered diffraction (EBSD) is a technique regularly used to obtain crystallographic information from inorganic samples. When EBSD is acquired simultaneously with emitting diodes data, a sample can be thoroughly characterized both structurally and compositionally. For organic materials, coherent Kikuchi patterns do form when the electron beam interacts with crystalline material. However, such patterns tend to be weak due to the low average atomic number of organic materials. This is compounded by the fact that the patterns fade quickly and disappear completely once a critical electron dose is exceeded, inhibiting successful collection of EBSD maps from them. In this study, a new approach is presented that allows successful collection of EBSD maps from organic materials, here the extreme example of a hydrocarbon organic molecular thin film, and opens new avenues of characterization for crystalline organic materials.
From religious freedom to social justice: the human rights engagement of the ecumenical movement from the 1940s to the 1970s
Authors: Bouwman Bastiaan
Published: June 2018

This article contributes to the historiography on human rights and (religious) internationalism by tracing how the ecumenical movement in the post-war decades sought to protect the religious freedom of its co-religionists in Catholic and Muslim countries, specifically Italy, Nigeria, and Indonesia. In cooperation with local actors, the Commission of the Churches on International Affairs worked to anchor international human rights in the domestic sphere through constitutional provisions. These activities constituted a significant strand of Christian human rights engagement from the 1940s to the 1960s, which intersected with the Cold War and decolonization. The article then contrasts this with the turn to a more pluralistic and communitarian conception of human rights in the 1970s, animated by liberation theologies. As the World Council of Churches embraced a ‘revolutionary’ tradition and worked to resist military dictatorships in Latin America, racism, and global inequality, it gravitated towards Marxism-inflected and anti-colonial strands of human rights discourse.
Octave bandwidth S- and C-band GaN-HEMT power amplifiers for future 5G communication
Authors: Rautschke Felix , May Stefan , Drews Sebastian , Maassen Daniel , Boeck Georg
Published: June 2018

In this contribution, a design methodology for octave-bandwidth power amplifiers (PA) for 5G communication systems using surface mount dual-flat-no-lead packaged gallium-nitride high-electron-mobility transistor devices is presented. Systematic source- and load-pull simulations have been used to find the optimum impedances across 75% fractional bandwidth for S- (1.9–4.2 GHz) and C-band (3.8–8.4 GHz) PAs. The harmonic impact is considered to improve the output power and efficiency of the PAs. Utilizing the characteristic behavior of the transistors leads to modified optimum fundamental load impedances for the low-frequency range, which have higher gain compared with high-frequency range, and minimize the influence of the higher harmonics. Continuous wave large-signal measurements of the realized S-Band PA show a power added efficiency (PAE) of more than 40% from 1.9–4.2 GHz and a flat power gain of 11 dB while achieving a saturated output power of 10 W. The measured performance of the C-Band PA demonstrates a delivered power between 3.5 and 5 W across the frequency range of 3.8–8.4 GHz. A flat power gain of around 9 ± 0.5 dB with 26–40% PAE is achieved.
Microseismicity Cloud Can Be Substantially Larger Than the Associated Stimulated Fracture Volume: The Case of the Paralana Enhanced Geothermal System
Authors: Riffault Jeremy , Dempsey David , Karra Satish , Archer Rosalind
Published: June 2018

The goal of hydraulic stimulation is to increase formation permeability in the near vicinity of a well. However, there remain technical challenges around measuring the outcome of this operation. During two enhanced geothermal system stimulations in South Australia, Paralana in 2011 and Habanero in 2003, extensive catalogs of microseismicity were recovered. It is often assumed that shear failure of existing fractures is the main mechanism behind both the induced earthquakes and any permeability enhancement. This underpins a common notion that the seismically active volume is also the stimulated reservoir. Here we compute the density of earthquake hypocenters and provide evidence that, under certain conditions, this spatiotemporal quantity is a reasonable proxy for pore pressure increase. We then apply an inverse modeling approach that uses the earthquake observations and a modified reservoir simulator to estimate the parameters of a permeability evolution relation. The regime implied by the data indicates that most permeability enhancement occurred very near to the wellbore and was not coincident with the bulk of the seismicity, whose volume was about 2 orders of magnitude larger. Thus, we conclude that, in some cases, it is possible for permeability enhancement and induced seismicity to be decoupled, in which case the seismically active volume is a poor indicator of the stimulated reservoir. Our results raise serious questions about the effectiveness of hydroshearing as a stimulation mechanism in enhanced geothermal system. This study extends our understanding of the complex processes linking earthquakes, fluid pressure, and permeability in both natural and engineered settings.
A Centennial Episode of Weak East Asian Summer Monsoon in the Midst of the Medieval Warming
Authors: Jin Chunhan , Liu Jian , Wang Bin , Wang Zhiyuan , Yan Mi
Published: June 2018

Recent paleoproxy evidence has suggested that there is a centennial episode of weaker East Asian summer monsoon (EASM) within the Medieval Warm Period, in which the EASM is generally strong. This study aims to explore the causes of this phenomenon and determine what controls the centennial variability of the EASM. With the Community Earth System Model, a suite of control and forced experiments were conducted for the past 2,000 years. The model simulates a warm period over EA (East Asia) from CE 801–1250 with a generally increased summer mean precipitation over the northern EA; however, during CE 980–1100, the EASM is significantly weaker. On the multi‐decadal to centennial time scale, a strong EASM is associated with a La Niña‐like Indo‐Pacific warming, and a weak EASM with the El Niño‐like conditions. This sea surface temperature anomaly pattern represents the leading EOF (empirical orthogonal function) mode of centennial sea surface temperature variations, which are primarily forced by solar radiation and volcanic activity. In contrast, land use/land cover and greenhouse gases as well as internal dynamics play a negligible role. The weak EASM during CE 980–1100 is attributed to the relatively low solar radiation, which leads to a prevailing El Niño‐like Indo‐Pacific cooling with the strongest cooling occurring in the equatorial western Pacific. The suppressed convection over the equatorial western Pacific directly induces a Philippine Sea anticyclone anomaly, which increases the southern China precipitation, while suppressing Philippine Sea precipitation. The latter excites a meridional teleconnection that induces anomalous northerly winds and dry conditions over northern China.
Stronger Peak Ground Motion, Beyond the Threshold to Initiate a Response, Does Not Lead to Larger Stream Discharge Responses to Earthquakes
Authors: Mohr Christian H. , Manga Michael , Wald David
Published: June 2018

The impressive number of stream gauges in Chile, combined with a suite of past and recent large earthquakes, makes Chile a unique natural laboratory to study several streams that recorded responses to multiple seismic events. We document changes in discharge in eight streams in Chile following two or more large earthquakes. In all cases, discharge increases. Changes in discharge occur for peak ground velocities greater than about 7–11 cm/s. Above that threshold, the magnitude of both the increase in discharge and the total excess water do not increase with increasing peak ground velocities. While these observations are consistent with previous work in California, they conflict with lab experiments that show that the magnitude of permeability changes increases with increasing amplitude of ground motion. Instead, our study suggests that streamflow responses are binary.
Building the Magnetosphere From Magnetic Bubbles
Authors: Tsyganenko N. A. , Andreeva V. A.
Published: June 2018

A new approach has been developed to reconstruct the magnetospheric configurations from data by directly representing the magnetic field as a sum of divergence‐free contributions from a set of diffuse bubble‐like field sources, more or less evenly distributed over the modeling region. Unlike the earlier suggested method based on the radial basis functions, the new fully local approach does not involve toroidal and poloidal fields, which makes it conceptually simpler and computationally more straightforward. The method has been tested on artificial data sets generated using an empirical model and a global magnetohydrodynamic simulation. The new model was shown to faithfully reconstruct the high‐latitude magnetospheric structures, such as the field‐aligned currents and the diamagnetic depression in the outer polar cusp funnels. The new method can serve as a flexible tool with a tunable resolution and varied focus area, to be used in the data‐based modeling of the magnetosphere.
Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy
Authors: Talebi Ali , Dehairs Jonas , Rambow Florian , Rogiers Aljosja , Nittner David , Derua Rita , Vanderhoydonc Frank , Duarte Joao A. G. , Bosisio Francesca , Van den Eynde Kathleen , Nys Kris , Pérez Mónica Vara , Agostinis Patrizia , Waelkens Etienne , Van den Oord Joost , Fendt Sarah-Maria , Marine Jean-Christophe , Swinnen Johannes V.
Published: June 2018

Whereas significant anti-tumor responses are observed in most BRAFV600E-mutant melanoma patients exposed to MAPK-targeting agents, resistance almost invariably develops. Here, we show that in therapy-responsive cells BRAF inhibition induces downregulation of the processing of Sterol Regulator Element Binding (SREBP-1) and thereby lipogenesis. Irrespective of the escape mechanism, therapy-resistant cells invariably restore this process to promote lipid saturation and protect melanoma from ROS-induced damage and lipid peroxidation. Importantly, pharmacological SREBP-1 inhibition sensitizes BRAFV600E-mutant therapy-resistant melanoma to BRAFV600E inhibitors both in vitro and in a pre-clinical PDX in vivo model. Together, these data indicate that targeting SREBP-1-induced lipogenesis may offer a new avenue to overcome acquisition of resistance to BRAF-targeted therapy. This work also provides evidence that targeting vulnerabilities downstream of oncogenic signaling offers new possibilities in overcoming resistance to targeted therapies.
A dopaminergic switch for fear to safety transitions
Authors: Luo Ray , Uematsu Akira , Weitemier Adam , Aquili Luca , Koivumaa Jenny , McHugh Thomas J. , Johansen Joshua P.
Published: June 2018

Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate so that they can be extinguished. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signaling when a better-than-expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signaling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. In contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the canonical VTA-dopamine reward system and reveals opposing behavioral roles for different dopamine neuron projections in fear extinction learning.
C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains
Authors: Bhargava Ragini , Sandhu Manbir , Muk Sanychen , Lee Gabriella , Vaidehi Nagarajan , Stark Jeremy M.
Published: June 2018

To investigate the fidelity of canonical non-homologous end joining (C-NHEJ), we developed an assay to detect EJ between distal ends of two Cas9-induced chromosomal breaks that are joined without causing insertion/deletion mutations (indels). Here we find that such EJ requires several core C-NHEJ factors, including XLF. Using variants of this assay, we find that C-NHEJ is required for EJ events that use 1–2, but not ≥3, nucleotides of terminal microhomology. We also investigated XLF residues required for EJ without indels, finding that one of two binding domains is essential (L115 or C-terminal lysines that bind XRCC4 and KU/DNA, respectively), and that disruption of one of these domains sensitizes XLF to mutations that affect its dimer interface, which we examined with molecular dynamic simulations. Thus, C-NHEJ, including synergistic function of distinct XLF domains, is required for EJ of chromosomal breaks without indels.
Synthetic CRISPR-Cas gene activators for transcriptional reprogramming in bacteria
Authors: Dong Chen , Fontana Jason , Patel Anika , Carothers James M. , Zalatan Jesse G.
Published: June 2018

Methods to regulate gene expression programs in bacterial cells are limited by the absence of effective gene activators. To address this challenge, we have developed synthetic bacterial transcriptional activators in E. coli by linking activation domains to programmable CRISPR-Cas DNA binding domains. Effective gene activation requires target sites situated in a narrow region just upstream of the transcription start site, in sharp contrast to the relatively flexible target site requirements for gene activation in eukaryotic cells. Together with existing tools for CRISPRi gene repression, these bacterial activators enable programmable control over multiple genes with simultaneous activation and repression. Further, the entire gene expression program can be switched on by inducing expression of the CRISPR-Cas system. This work will provide a foundation for engineering synthetic bacterial cellular devices with applications including diagnostics, therapeutics, and industrial biosynthesis.
Personalising adherence-enhancing interventions using a smart inhaler in patients with COPD: an exploratory cost-effectiveness analysis
Authors: van Boven Job F. M. , Cushen Breda , Sulaiman Imran , Greene Garrett , MacHale Elaine , Mokoka Matshediso C. , Doyle Frank , Reilly Richard B. , Bennett Kathleen , Costello Richard W.
Published: June 2018

Four inhaler adherence clusters have been identified using the INCA audio device in COPD patients: (1) regular use/good technique, (2) regular use/frequent technique errors, (3) irregular use/good technique, and (4) irregular use/frequent technique errors. Their relationship with healthcare utilization and mortality was established, but the cost-effectiveness of adherence-enhancing interventions is unknown. In this exploratory study, we aimed to estimate the potential cost-effectiveness of reaching optimal adherence in the three suboptimal adherence clusters, i.e., a theoretical shift of clusters 2, 3, and 4 to cluster 1. Cost-effectiveness was estimated over a 5-year time horizon using the Irish healthcare payer perspective. We used a previously developed COPD health-economic model that was updated with INCA trial data and Irish national economic and epidemiological data. For each cluster, interventions would result in additional quality-adjusted life years gained at reasonable investment. Cost-effectiveness was most favorable in cluster 3, with possible cost savings of €845/annum/person.
Risk of weight gain for specific antipsychotic drugs: a meta-analysis
Authors: Spertus Jacob , Horvitz-Lennon Marcela , Abing Haley , Normand Sharon-Lise
Published: June 2018

People with schizophrenia are at considerably higher risk of cardiometabolic morbidity than the general population. Second-generation antipsychotic drugs contribute to that risk partly through their weight gain effects, exacerbating an already high burden of disease. While standard ‘as-randomized’ analyses of clinical trials provide valuable information, they ignore adherence patterns across treatment arms, confounding estimates of realized treatment exposure on outcome. We assess the effect of specific second-generation antipsychotics on weight gain, defined as at least a 7% increase in weight from randomization, using a Bayesian hierarchical model network meta-analysis with individual patient level data. Our data consisted of 14 randomized clinical trials contributing 5923 subjects (mean age = 39 [SD = 12]) assessing various combinations of olanzapine (n = 533), paliperidone (n = 3482), risperidone (n = 540), and placebo (n = 1368). The median time from randomization to dropout or trial completion was 6 weeks (range: 0–60 weeks). The unadjusted probability of weight gain in the placebo group was 4.8% across trials. For each 10 g chlorpromazine equivalent dose increase in olanzapine, the odds of weight gain increased by 5 (95% credible interval: 1.4, 5.3); the effect of risperidone (odds ratio = 1.6 [0.25, 9.1]) was estimated with considerable uncertainty but no different from paliperidone (odds ratio = 1.3 [1.2, 1.5]).
Selection and evaluation of an efficient method for the recovery of viral nucleic acids from complex biologicals
Authors: Sathiamoorthy Sarmitha , Malott Rebecca J. , Gisonni-Lex Lucy , Ng Siemon H. S.
Published: June 2018

There is a need for a broad and efficient testing strategy for the detection of both known and novel viral adventitious agents in vaccines and biologicals. High-throughput sequencing (HTS) is an approach for such testing; however, an optimized testing method is one with a sample-processing pipeline that can help detect any viral adventitious agent that may be present. In this study, 11 commercial methods were assessed for efficient extraction of nucleic acids from a panel of viruses. An extraction strategy with two parallel arms, consisting of both the Invitrogen PureLink™ Virus RNA/DNA kit for total nucleic acid extraction and the Wako DNA Extractor® kit with an RNase A digestion for enrichment of double-stranded nucleic acid, was selected as the strategy for the extraction of all viral nucleic acid types (ssRNA, dsRNA, and dsDNA). Downstream processes, such as double-strand DNA synthesis and whole-genome amplification (WGA), were also assessed for the retrieval of viral sequences. Double-stranded DNA synthesis yielded larger numbers of viral reads, whereas WGA exhibited a strong bias toward amplification of double-stranded DNA, including host cellular DNA. The final sample-processing strategy consisted of the dual extraction approach followed by double-stranded DNA synthesis, which yielded a viral population with increased detection of some viruses by 8600-fold. Here we describe an efficient extraction procedure to support viral adventitious agent detection in cell substrates used for biological products using HTS.
In-vivo topical mucosal delivery of a fluorescent deoxy-glucose delineates neoplasia from normal in a preclinical model of oral epithelial neoplasia
Authors: Pal Rahul , Villarreal Paula , Qiu Suimin , Vargas Gracie
Published: June 2018

Metabolic imaging of oral cavity mucosal surfaces could benefit early detection of oral squamous cell carcinoma (OSCC) and oral epithelial dysplasia (OED). Fluorescent deoxy-glucose agents provide contrast for glucose metabolism similar to 18FDG-PET imaging and allow use of optical imaging, which provides high resolution and lower potential cost. However, in-vivo topical mucosal delivery of fluorescent deoxy-glucose agents without injection or tissue resection has not been shown. We introduce in-vivo optical imaging of neoplasia following mucosal delivery of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) in an OSCC/OED hamster model and demonstrate uptake into epithelium across the mucosal surface without injection or disrupting the epithelium. 2-NBDG fluorescence intensity following 30-minutes topical application was 6-fold and 4-fold higher in OSCC and OED, respectively, compared to normal mucosa. Receiver operator characteristic analysis show 83% sensitivity and 73% specificity for detection of neoplasia vs benign (normal and inflammation). Faster 2-NBDG fluorescence temporal decay in neoplasia indicated higher uptake and glucose metabolic rate than normal mucosa. Mucosal delivery of 2-NBDG by topical application to the in-vivo oral surface is feasible and delineates neoplasia from normal mucosa, providing in-vivo noninvasive molecular imaging of dysregulated glucose metabolism, which could benefit preclinical studies of carcinogenesis or be developed for use in early detection.
Development and Validation of Nomogram to Predict Acute Kidney Injury in Patients with Acute Myocardial Infarction Treated Invasively
Authors: Zhou Xuejun , Sun Zhiqin , Zhuang Yi , Jiang Jianguang , Liu Nan , Zang Xuan , Chen Xin , Li Haiyan , Cao Haitao , Sun Ling , Wang Qingjie
Published: June 2018

To identify patients who are likely to develop contrast-induced acute kidney injury (CI-AKI) in patients with acute myocardial infarction (AMI), a nomogram was developed in AMI patients. Totally 920 patients with AMI were enrolled in our study. The discrimination and calibration of the model were validated. External validations were also carried out in a cohort of 386 AMI patients. Our results showed in the 920 eligible AMI patients, 114 patients (21.3%) developed CI-AKI in the derivation group (n = 534), while in the validation set (n = 386), 50 patients (13%) developed CI-AKI. CI-AKI model included the following six predictors: hemoglobin, contrast volume >100 ml, hypotension before procedure, eGFR, log BNP, and age. The area under the curve (AUC) was 0.775 (95% confidence interval [CI]: 0.732–0.819) in the derivation group and 0.715 (95% CI: 0.631–0.799) in the validation group. The Hosmer-Lemeshow test has a p value of 0.557, which confirms the model’s goodness of fit. The AUC of the Mehran risk score was 0.556 (95% CI: 0.498–0.615) in the derivation group. The validated nomogram provided a useful predictive value for CI-AKI in patients with AMI.
Automated detection and manipulation of sleep in C. elegans reveals depolarization of a sleep-active neuron during mechanical stimulation-induced sleep deprivation
Authors: Spies Jan , Bringmann Henrik
Published: June 2018

Across species, sleep is characterized by a complex architecture. Sleep deprivation is a classic method to study the consequences of sleep loss, which include alterations in the activity of sleep circuits and detrimental consequences on well being. Automating the observation and manipulation of sleep is advantageous to study its regulation and functions. Caenorhabditis elegans shows sleep behavior similar to other animals that have a nervous system. However, a method for real-time automatic sleep detection that allows sleep-specific manipulations has not been established for this model animal. Also, our understanding of how sleep deprivation affects sleep neurons in this system is incomplete. Here we describe a system for real-time automatic sleep detection of C. elegans grown in microfluidic devices based on a frame-subtraction algorithm using a dynamic threshold. As proof of principle for this setup, we used automated mechanical stimulation to perturb sleep behavior and followed the activity of the sleep-active RIS neuron. We show that our system can automatically detect sleep bouts and deprive worms of sleep. We found that mechanical stimulation generally leads to the activation of the sleep-active RIS neuron, and this stimulation-induced RIS depolarization is most prominent during sleep deprivation.
Author Correction: Multi-label Learning for Predicting the Activities of Antimicrobial Peptides
Authors: Wang Pu , Ge Ruiquan , Liu Liming , Xiao Xuan , Li Ye , Cai Yunpeng
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Identification of CTA-Based Predictive Findings for Temporary and Permanent Neurological Dysfunction after Repair in Acute Type A Aortic Dissection
Authors: Zhao Hongliang , Wen Didi , Duan Weixun , An Rui , Li Jian , Zheng Minwen
Published: June 2018

The aim of this study was to determine CT risk findings predictive of temporary neurological dysfunction (TND) and permanent neurological dysfunction (PND) after surgical repair for acute type A aortic dissection (ATAAD). A total of 255 patients (41 ± 16 years, 79% male) with ATAAD underwent aortic CT angiography (CTA) and surgical repair consecutively from January 2013 to June 2016. The CTA findings of the 255 patients for the thoracic aorta and carotid artery were analysed to identify risk factors predictive of TND and PND. Thirty-eight patients (15%) suffered TND, and 18 (7%) exhibited PND. Common carotid artery (CCA) dissection (OR = 4.63), lower enhancement of unilateral ICA (OR = 3.02) and aortic arch tears (OR = 2.83) were predictors of postoperative TND, while PND was best predicted by retrograde ascending aorta (aAO) dissection (OR = 5.62) and aortic arch tears (OR = 6.74). In CCA dissection, the extent of the entire CCA and proximal ICA (P = 0.014), a low-enhancement false lumen with re-entry (P = 0.000) and a severely narrowed true lumen without re-entry (P = 0.005) significantly increased the risk of postoperative TND. In patients with ATAAD, specific CT findings allow the individual risk of postoperative TND and PND to be identified and may guide subsequent surgical management.
Imperceptible electrooculography graphene sensor system for human–robot interface
Authors: Ameri Shideh Kabiri , Kim Myungsoo , Kuang Irene Agnes , Perera Withanage K. , Alshiekh Mohammed , Jeong Hyoyoung , Topcu Ufuk , Akinwande Deji , Lu Nanshu
Published: June 2018

Electrooculography (EOG) is a method to record the electrical potential between the cornea and the retina of human eyes. Despite many applications of EOG in both research and medical diagnosis for many decades, state-of-the-art EOG sensors are still bulky, stiff, and uncomfortable to wear. Since EOG has to be measured around the eye, a prominent area for appearance with delicate skin, mechanically and optically imperceptible EOG sensors are highly desirable. Here, we report an imperceptible EOG sensor system based on noninvasive graphene electronic tattoos (GET), which are ultrathin, ultrasoft, transparent, and breathable. The GET EOG sensors can be easily laminated around the eyes without using any adhesives and they impose no constraint on blinking or facial expressions. High-precision EOG with an angular resolution of 4° of eye movement can be recorded by the GET EOG and eye movement can be accurately interpreted. Imperceptible GET EOG sensors have been successfully applied for human–robot interface (HRI). To demonstrate the functionality of GET EOG sensors for HRI, we connected GET EOG sensors to a wireless transmitter attached to the collar such that we can use eyeball movements to wirelessly control a quadcopter in real time.