bluuebunny/crossref_metadata_2025 huggingface dataset:
Taylor series expansion approach for epistemic uncertainty propagation in queueing‐inventory models
Authors: Soufit Massinissa , Ouazine Sofiane , Abbas Karim
Published: June 2018

In this paper, we provide an uncertainty analysis for queueing‐inventory models, by extending the multivariate Taylor series expansion methodology to such stochastic models. Specifically, we derive a closed‐form expressions for the higher‐order sensitivity of discrete‐time Markov chain stationary distribution with respect to multiple parameter. We establish efficient bound on the remainder term corresponding to the multivariate Taylor series. Additionally, we estimate different quantities of interest of the output measures of the studied queueing‐inventory model. Using the copulas theory, we also include the effect of the dependence structure of parameters. The efficacy of the proposed method is shown with several numerical examples and obtained numerical results are compared with those of Monte Carlo simulation.
Orofacial strength, dysarthria, and dysphagia in congenital myotonic dystrophy
Authors: Berggren Kiera N. , Hung Man , Dixon Melissa M. , Bounsanga Jerry , Crockett Becky , Foye Mary D. , Gu Yushan , Campbell Craig , Butterfield Russell J. , Johnson Nicholas E.
Published: June 2018

Introduction: Herein we present an exploratory study of orofacial function in children with congenital myotonic dystrophy (CDM) vs. healthy controls. Methods: We evaluated 41 children with CDM and 29 healthy controls for speech and swallow function and for lingual and labial strength. Results: The Iowa Oral Performance Instrument (IOPI), measuring tongue strength, and a lip force meter (LFM), measuring lip strength, had excellent interrater reliability with intraclass correlation coefficients (ICCs) of 0.75 (n = 19, P < 0.001) and 0.96 (n = 20, P < 0.001), respectively. Mean overall lingual strength was 3.5‐fold less and labial strength was about 7‐fold less in CDM patients than in healthy controls. Eighteen of 24 children with CDM demonstrated dysarthria and an additional 11 participants were nonverbal. Dysarthria correlated moderately with lingual strength, age, and dysphagia. Strength measures correlated moderately with dysphagia. Discussion: Children with CDM have impaired orofacial functioning that affects communication and swallowing. Reliability of strength measures may be useful for future therapeutic trials. Muscle Nerve 58: 413–417, 2018
Combining remote sensing with physical flow laws to estimate river channel geometry
Authors: Harada Sho , Li S. Samuel
Published: June 2018

A reliable representation of river terrains is essential to river research. Field surveys of river channel geometry are time‐consuming, costly, and logistically constrained and thus would encounter difficulties to achieve sufficient spatial coverage, resolution, and frequency of resurvey. This paper aims to demonstrate an efficient approach to building a river terrain model (RTM), the emphasis being on how to combine bathymetry and topography derived from satellite images captured at different flow stages. A method for calculating the difference between high and low stages (DHLS) based on the uniform‐flow theory is proposed. Calculations are carried out for a 13‐km long meandering section of the gravel‐bed Goulais River in Canada, which features pools and riffles, alternating point bars, and midchannel bars. A RTM for this complex section has been successfully produced. It consists of three data components: bathymetry at low stage, topography at high stage, and DHLS. The results capture realistic characteristics, including thalweg shift, steep outer banks, and gradual inner banks. They also show realistic longitudinal and lateral locations of pools and riffles. To illustrate potential applications of RTM, this paper has computed extreme bed shear stresses at bankfull discharge through hydrodynamics simulations of depth‐averaged flow in the river section and further estimated bed‐sediment grain‐size distributions. The estimates compare well with field measurements. The DHLS can vary significantly along a river channel. The proposed method for determining it is not site‐specific, and hence applicable to other rivers. The novelty of the methodology discussed lies in combining remote sensing techniques with physical flow laws.
CuO Nanoparticles as An Efficient Heterogeneous Catalyst for the 1,3‐Dipolar Cycloaddition of Dicarbonyl Compounds to Azides
Authors: da S. Dias Cássio , de M. Lima Thiago , Lima Carolina G. S. , Zuekrman‐Schpector Julio , Schwab Ricardo S.
Published: June 2018

Substituted 1,2,3‐triazoles are important heterocyclic molecules with applications in diverse research areas. The organocatalytic (3+2) cycloaddition reaction of azides with active methylene compounds has proven to be a powerful strategy for the synthesis of a variety of 1,2,3‐triazoles with different substituents. However the reported methods in the literature, commonly used a homogenous organocatalyst. Considering this point, here we have reported a novel heterogeneous protocol for the synthesis of 1,4,5‐trisubstituted 1,2,3‐triazoles by reaction of different dicarbonyl compounds with aryl azides catalyzed by copper oxide nanoparticles under microwave irradiation. The important features of this methodology are high yield products, short reaction times and recyclability of the CuO catalyst.
Effects of workload on teachers' functioning: A moderated mediation model including sleeping problems and overcommitment
Authors: Huyghebaert Tiphaine , Gillet Nicolas , Beltou Nicolas , Tellier Fanny , Fouquereau Evelyne
Published: June 2018

This study investigated the mediating role of sleeping problems in the relationship between workload and outcomes (emotional exhaustion, presenteeism, job satisfaction, and performance), and overcommitment was examined as a moderator in the relationship between workload and sleeping problems. We conducted an empirical study using a sample of 884 teachers. Consistent with our predictions, results revealed that the positive indirect effects of workload on emotional exhaustion and presenteeism, and the negative indirect effects of workload on job satisfaction and performance, through sleeping problems, were only significant among overcommitted teachers. Workload and overcommitment were also directly related to all four outcomes, precisely, they both positively related to emotional exhaustion and presenteeism and negatively related to job satisfaction and performance. Theoretical contributions and perspectives and implications for practice are discussed.
Spanish, Arabic, and “English‐Only”: Making Meaning Across Languages in Two Classroom Communities
Authors: Pacheco Mark B.
Published: June 2018

This comparative case study explores the use of Spanish, Arabic, and English in two elementary classrooms where instruction is delivered primarily in English and teachers and students do not share proficiencies in students’ home languages. Using methods derived from ethnography of communication, the study examines how languages other than English (LOTEs) become part of a community's shared repertoire of meaning‐making resources. Furthermore, it examines how these resources shape and were shaped by the classroom community of practice. Discourse analysis of four separate classroom interactions shows that Spanish, Arabic, and English facilitated opportunities for classroom community members to negotiate new tools, activities, and forms of engagement, yet not all uses ofLOTEs afforded students’ meaning making in their communities of practice. Specifically, this study shows thatLOTEs can be productively included in English‐dominant environments, but community responsiveness to language use is critical for this success. Findings also reveal that multiple features of the classroom community, including member roles, community negotiation, and opportunities to engage in extended discourse, shaped meaning making withLOTEs. This study concludes with recommendations for leveragingLOTEs in similar classroom contexts.
Prevalence, antenatal management and perinatal outcome of monochorionic monoamniotic twin pregnancy: a collaborative multicenter study in England, 2000–2013
Authors: Glinianaia S. V. , Rankin J. , Khalil A. , Binder J. , Waring G. , Sturgiss S. N. , Thilaganathan B. , Hannon T.
Published: June 2018

Objectives

To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies.

Methods

In this multicenter cohort study, the prevalence of MCMA twinning was estimated using population‐based data on MCMA twin pregnancies, collected between 2000 and 2013 from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units. Pregnancy outcome at < 24 weeks' gestation, antenatal parameters and perinatal outcome (from ≥ 24 weeks to the first 28 days of age) were analyzed using combined data on pregnancies confirmed to be MCMA from NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000–2013.

Results

The estimated total prevalence of MCMA twin pregnancies in the North of England region was 8.2 per 1000 twin pregnancies (59/7170), and the birth prevalence was 0.08 per 1000 pregnancies overall (singleton and multiple). Using combined data from NorSTAMP and STORK, the rate of fetal death (at < 24 weeks' gestation), including terminations of pregnancy and selective feticide, was 31.8% (54/170); the overall perinatal mortality rate was 14.7% (17/116), ranging from 69.2% at < 30 weeks to 4.5% at ≥ 33 weeks' gestation. MCMA twins that survived in utero beyond 24 weeks were delivered, usually by Cesarean section, at a median of 33 (interquartile range, 32–34) weeks of gestation.

Conclusions

In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared with in previous decades, presumably due to early diagnosis, close surveillance and elective birth around 32–34 weeks of gestation. High perinatal mortality at early gestations was attributed mainly to extreme prematurity due to preterm spontaneous labor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Reactions of female cheetahs (Acinonyx jubatus) to urine volatiles from males of varying genetic distance
Authors: Mossotti Regina H. , Baskir Eli A. , Kozlowski Corinne P. , Franklin Ashley D. , Feldhamer George A. , Asa Cheryl S.
Published: June 2018

Understanding the factors used by female cheetahs (Acinonyx jubatus) to make mate choice decisions could benefit zoo breeding programs, which currently assign mates based primarily on genetic distance. Because transporting animals between institutions is costly and can be stressful, females are often limited in the number of males available for mating. One solution would be to determine if an easily transported substance could be used to gauge interest by a female to a potential mate. Here, we investigate female interest in urine samples from males of different genetic distances. Twelve females at five institutions were offered scents from 17 males of varying genetic relatedness in a pair‐wise choice paradigm. Behavioral responses of the females were recorded to determine preference. Results showed that females spent more time sniffing and in proximity to scents from the most distantly related males, but female response was not influenced by male urine testosterone concentration, female parity, age, or estrous cycling. Further research will be necessary to determine whether a female's interest in male urine translates to mate preference and acceptance before this technique can be applied to zoo breeding programs.
Prospective Risk Factor Analysis for the Development of Post‐operative Urinary Retention Following Ambulatory General Surgery
Authors: Scott A. J. , Mason S. E. , Langdon A. J. , Patel B. , Mayer E. , Moorthy K. , Purkayastha S.
Published: June 2018

Aims

Post‐operative urinary retention (POUR) is a common cause of unplanned admission following day‐case surgery and has negative effects on both patient and surgical institution. We aimed to prospectively evaluate potential risk factors for the development of POUR following day‐case general surgical procedures.

Methods

Over a 24‐week period, consecutive adult patients undergoing elective day‐case general surgery at a single institution were prospectively recruited. Data regarding urinary symptoms, comorbidities, drug history, surgery and perioperative anaesthetic drug use were collected. The primary outcome was the incidence of POUR, defined as an impairment of bladder voiding requiring either urethral catheterisation, unplanned overnight admission or both. Potential risk factors for the development of POUR were analysed by logistic regression.

Results

A total of 458 patients met the inclusion criteria during the study period, and data were collected on 382 (83%) patients (74.3% male). Sixteen patients (4.2%) experienced POUR. Unadjusted analysis demonstrated three significant risk factors for the development of POUR: age ≥ 56 years (OR 7.77 [2.18–27.78], p = 0.002), laparoscopic surgery (OR 3.37 [1.03–12.10], p = 0.044) and glycopyrrolate administration (OR 5.56 [2.00–15.46], p = 0.001). Male sex and lower urinary tract symptoms were not significant factors. Multivariate analysis combining type of surgery, age and glycopyrrolate use revealed that only age ≥ 56 years (OR 8.14 [2.18–30.32], p = 0.0018) and glycopyrrolate administration (OR 3.48 [1.08–11.24], p = 0.0370) were independently associated with POUR.

Conclusions

Patients aged at least 56 years and/or requiring glycopyrrolate—often administered during laparoscopic procedures—are at increased risk of POUR following ambulatory general surgery.
Consumer Advocacy for Luxury Brands
Authors: Shimul Anwar Sadat , Phau Ian
Published: June 2018

This paper explores consumer advocacy for luxury brands in relation to brand satisfaction, brand loyalty and luxury brand attachment. Data were collected from an online consumer panel ( n = 393) in Australia and were analysed through structural equation modelling. Luxury brand attachment has been found to have a stronger effect on consumer advocacy than that of brand satisfaction and brand loyalty. In addition to the moderating role of brand loyalty, luxury consumers’ dilemma with consumer advocacy has been discussed in this paper. These findings provide insight into the consumer advocacy for luxury branding academics and practitioners.
Sonographically Guided Plantaris Tendon Release: A Cadaveric Validation Study
Authors: Smith Jay , Alfredson Håkan , Masci Lorenzo , Sellon Jacob L. , Woods Charonn D.
Published: June 2018

Background

The plantaris tendon (PT) has been implicated in the pathogenesis of symptoms in a subset of patients with Achilles region pain syndromes and traditionally has been managed via open surgical resection. Although the PT can be visualized on ultrasound, a minimally invasive technique for sonographically guided PT release has not been formally described.

Objective

To validate a technique to perform sonographically guided PT release in an unembalmed cadaveric model.

Design

Prospective, cadaveric laboratory investigation.

Setting

Procedural skills laboratory in a tertiary medical center.

Subjects

Twenty unembalmed cadaveric knee–ankle–foot specimens (10 right, 10 left) obtained from 16 donors (6 male, 10 female) ages 55‐96 years (mean 82.6 years) with body mass indexes of 14.1‐33.2 kg/m2 (mean 23.3 kg/m2).

Methods

After simulated local anesthesia and sonographically guided hydrodissection of the plantaris tendon–Achilles tendon interval, a single experienced operator performed sonographically guided PT release on each specimen using an in‐plane, lateral‐to‐medial approach, a commercially available, disposable 3.0‐mm hook knife, and either a 17‐5 MHz or 15‐7 MHz linear array transducer. Each specimen was subsequently dissected to assess for PT release and iatrogenic injury.

Main Outcome

Status of the PT, Achilles tendon, and regional neurovascular structures as determined by dissection.

Results

All 20 PT releases were completed in a single attempt through a 3‐ to 5‐mm incision. Dissection confirmed complete PT release in all specimens without damage to the adjacent Achilles tendon or regional neurovascular structures.

Conclusion

Sonographically guided PT release is technically feasible and can be performed while avoiding injury to the Achilles tendon and regional neurovascular structures. Additional research is warranted to further define the role of sonographically guided PT release in patients with suspected PT‐mediated Achilles region pain syndromes.

Level of Evidence

IV
Statistical advances in clinical trials and clinical research
Authors: Shan Guogen , Banks Sarah , Miller Justin B. , Ritter Aaron , Bernick Charles , Lombardo Joseph , Cummings Jeffrey L.
Published: June 2018

Introduction

New treatments for neurodegenerative disease are urgently needed, and clinical trial methods are an essential component of new drug development. Although a parallel‐group study design for neurological disorder clinical trials is commonly used to test the effectiveness of a new treatment as compared to placebo, it does not efficiently use information from the on‐going study to increase the success rate of a trial or to stop a trial earlier when the new treatment is indeed ineffective.

Methods

We review some recent advances in designs for clinical trials, including futility designs and adaptive designs.

Results

Futility designs and noninferiority designs are used to test the nonsuperiority and the noninferiority of a new treatment, respectively. We provide some guidance on using these two designs and analyzing data from these studies properly. Adaptive designs are increasingly used in clinical trials to improve the flexibility and efficiency of trials with the potential to reduce resources, time, and costs. We review some typical adaptive designs and new statistical methods to handle the statistical challenges from adaptive designs.

Discussion

Statistical advances in clinical trial designs may be helpful to shorten study length and benefit more patients being treated with a better treatment during the discovery of new therapies for neurological disorders. Advancing statistical underpinnings of neuroscience research is a critical aspect of the core activities supported by the Center of Biomedical Research Excellence award supporting the Center for Neurodegeneration and Translational Neuroscience.
The Causal Effect of Radical Right Success on Mainstream Parties’ Policy Positions: A Regression Discontinuity Approach
Authors: Abou-Chadi Tarik , Krause Werner
Published: June 2018

This article investigates how the success of radical right parties affects the policy positions of mainstream parties. We do this using a regression discontinuity approach that allows us to causally attribute mainstream parties’ positional changes to radical right strength independent of public opinion as a potential confounder. Making use of exogenous variation created through differences in electoral thresholds, we empirically demonstrate that radical right success, indeed, causally affects mainstream parties’ positions. This is true for mainstream left as well as mainstream right parties. These findings make an important contribution to the broader literature on party competition as they indicate that other parties’ behavior and not only public opinion plays a crucial role in explaining parties’ policy shift.
AN EMENDATION TO APULEIUS,APOLOGIA47.1
Authors: Costantini Leonardo
Published: June 2018

The most authoritative testimony for the text of Apuleius’ defence-speech known asApologiaorPro Se De Magiais a Cassinese MS indicated with thesiglumF (Florence, Biblioteca Medicea Laurenziana, Plut. 68.2), written under the abbotship of Desiderius (1058–1087) in a mature Beneventan script, which also preserves the text of theMetamorphosesand theFlorida. The text that F preserves is unsurprisingly not flawless, and in this note I argue for the presence of a corruption affectingautinApol. 47.1. For the sake of clarity, I provide the passage fromApol. 46.6 to 47.2 below.
A Secular State for a Religious Nation: The Republic of Vietnam and Religious Nationalism, 1946–1963
Authors: Nguyen Phi-Vân
Published: June 2018

Most studies of the Republic of Vietnam's nation-building programs have focused on its security and land reforms. Yet spirituality was a fundamental element of Ngô Đình Diệm's Personalist Revolution. This article analyzes how the Republic of Vietnam attempted to channel the religious nationalism emerging from the First Indochina War. The spiritual dimension of the Republic's Personalist Revolution did not involve state interference in all religious activities. Instead, it promoted religious freedom and diversity, provided that the spiritual values they propagated opposed communism's atheism. In practice, this framework did not succeed in creating a religious alliance against communism. In fact, it strengthened a religious consciousness that would increasingly challenge the state, its assumption that religions opposed communism, and the very principle of religious diversity.
Path integrals for mean-field equations in nonlinear dynamos
Authors: Sokoloff Dmitry , Yokoi Nobumitsu
Published: June 2018

Mean-field dynamo equations are addressed with the aid of the path integral method. The evolution of magnetic field is treated as a three-dimensional Wiener random process, and the mean magnetic-field equations are obtained with the Wiener integrals taken over all the trajectories of the fluid particles. The form of the equations is just the same as the conventional mean-field equations, but here the equations are derived with the velocity field realisation affected by the force exerted by the magnetic field. In this sense, we derive nonlinear dynamo equations.
The importance of population density and inter-individual distance in conserving the European oysterOstrea edulis
Authors: Guy C. , Smyth D. , Roberts D.
Published: June 2018

Fertilization success will determine the rate at which a population can expand and is especially important when considering small, establishing or enduring communities. Introduced species frequently fail to establish reproductively functional populations due to strong Allee effects associated with low densities. The native European oyster,Ostrea edulisbroods its fertilized eggs in the pallial cavity for a period of 8–10 days before releasing the larvae. It is considered a partial broadcast spawner and was used as a model species to assess the importance of Allee effects such as inter-individual distance on reproductive success. Distances between individual oysters within test plots in areas of known oyster density were used in conjunction with standardized brood size (n larvae g−1total wet weight) to assess fertilization success. A significant, positive relationship was observed between brood size and oyster density. Oysters with a nearest neighbour ≤1.5 m were found to brood significantly more larvae than individuals with nearest neighbours ≥1.5 m. Therefore, high density sites need to be maintained to ensure the recovery and enhancement of this OSPAR Convention recognized species in decline.
The Strange Career of Johann Matthias Kramer: Transatlantic Migration, Language and the Circulation of Information in the Eighteenth Century
Authors: Häberlein Mark
Published: June 2018

This article examines the career of Johann Matthias Kramer, a language teacher and emigration agent, as a case study to illuminate the intersections between migration, colonialism, cultural transfer and the dissemination of information in the eighteenth century. Kramer’s career spanned diverse places and regions – his birthplace, Nuremberg, the commercial cities of Rotterdam and Hamburg, the university town of Göttingen and the North American colonies of Georgia and Pennsylvania – and it oscillated between two seemingly very different professions. The article argues, however, that both language teachers and emigration agents were highly mobile, usually lacked formal training, and had low reputations, but nonetheless helped to forge important social and cultural links.
Eurafrica: A Pan-European Vehicle for Central European Colonialism (1923–1939)
Authors: Thorpe Benjamin J.
Published: June 2018

‘Eurafrica’, the continental-scale fusion of Europe and Africa into one political entity, was first developed as a political concept in the 1920s by the Pan-European Union, and named as such in a 1929 article by its founder and leader Richard Coudenhove-Kalergi. Within five years, this neologism had become a commonplace, as Eurafrica exploded across public political discourse. This paper unpacks what Eurafrica entailed in its original expression, what made it a useful concept for the Pan-European Union to employ, and what made it so appealing to a wider (European) public. It does so with particular reference to the way in which Eurafrica was presented as a means of opening up colonialism to those European states that lacked their own colonies. Partly, this meant appealing to German colonialists resentful at the stripping of Germany’s colonies at Versailles. Crucially, however, it also meant appealing to the broader ‘historical injustices’ that meant that Central European countries did not have access to colonies, and promising a future in which these intra-European ‘injustices’ could be transcended and Central Europeans could thus become equal partners in Europe’smission civilisatricein Africa.
Atmospheric Response to Kilometer‐Scale Changes in Sea Ice Concentration Within the Marginal Ice Zone
Authors: Batrak Yurii , Müller Malte
Published: June 2018

Sea ice kilometer‐scale characteristics are not explicitly represented in weather and climate model systems. However, due to the large differences of the surface temperature between sea ice and ocean, sea ice‐free areas (leads, polynyas, etc.) can have a strong impact on the surface heat fluxes and, in turn, on atmospheric dynamics. In the present study we analyze the atmospheric response to changes in the sea ice characteristics in the marginal ice zone of the Fram Strait and Barents Sea. A kilometer‐scale convection permitting atmospheric modeling system is used. The model sensitivity experiment is idealized, since there is no complete information on sea ice on these scales available. Instead, we are merging information from the passive microwave satellite product of sea ice concentration with a sea ice lead product based on thermal infrared sensors. An important constraint is that the sea ice‐free areas are introduced locally, but on scales of 100 km the sea ice coverage is kept constant for both the experiments. The sensitivity of air‐sea fluxes, atmospheric temperature, and winds is analyzed between the model experiments. In general, the standard deviation of the changes in surface air temperature and winds is, on large scales, about 2 K and 2 m/s, respectively. Those values are in the same order as the mean 12‐hr forecast error of advanced weather forecast models in this region.
Prognostic Validation of a Neural Network Unified Physics Parameterization
Authors: Brenowitz N. D. , Bretherton C. S.
Published: June 2018

Weather and climate models approximate diabatic and sub‐grid‐scale processes in terms of grid‐scale variables using parameterizations. Current parameterizations are designed by humans based on physical understanding, observations, and process modeling. As a result, they are numerically efficient and interpretable, but potentially oversimplified. However, the advent of global high‐resolution simulations and observations enables a more robust approach based on machine learning. In this letter, a neural network‐based parameterization is trained using a near‐global aqua‐planet simulation with a 4‐km resolution (NG‐Aqua). The neural network predicts the apparent sources of heat and moisture averaged onto (160 km)2 grid boxes. A numerically stable scheme is obtained by minimizing the prediction error over multiple time steps rather than single one. In prognostic single‐column model tests, this scheme matches both the fluctuations and equilibrium of NG‐Aqua simulation better than the Community Atmosphere Model does.
East Asian Monsoon History and Paleoceanography of the Japan Sea Over the Last 460,000 Years
Authors: Gallagher Stephen J. , Sagawa Takuya , Henderson Andrew C. G. , Saavedra‐Pellitero Mariem , De Vleeschouwer David , Black Heather , Itaki Takuya , Toucanne Sam , Bassetti Maria‐Angela , Clemens Steve , Anderson William , Alvarez‐Zarikian Carlos , Tada Ryuji
Published: June 2018

The Japan Sea is directly influenced by the Asian monsoon, a system that transports moisture and heat across southeast Asia during the boreal summer, and is a major driver of the Earth's ocean‐atmospheric circulation. Foraminiferal and facies analyses of a 460‐kyr record from Integrated Ocean Drilling Program Expedition 346 Site U1427 in the Japan Sea reveal a record of nutrient flux and oxygenation that varied due to sea level and East Asian monsoon intensity. The East Asian summer monsoon (EASM) was most intense during marine isotope stage (MIS) 5e, MIS 7e, MIS 9e, and MIS 11c when the Tsushima Warm Current flowed into an unrestricted well‐mixed normal salinity Japan Sea, whereas East Asian winter monsoon (EAWM) conditions dominated MIS 2, MIS 4, MIS 6, and MIS 8 when sea level minima restricted the Japan Sea resulting in low‐salinity and oxygen conditions in the absence of Tsushima flow. Reduced oxygen stratified, low‐salinity, and higher productivity oceanic conditions characterize Terminations TV, TIII, TII, and TI when East China Sea coastal waters breached the Tsushima Strait. Chinese loess, cave, and Lake Biwa (Japan) and U1427 proxy records suggest EASM intensification during low to high insolation transitions, whereas the strongest EAWM prevailed during lowest insolation periods or high to low insolation transitions. Ice sheet/CO2 forcing leads to the strongest EAWM events in glacials and enhanced EASM in interglacials. Mismatches between proxy patterns suggest that latitudinal and land/sea thermal contrasts played a role in East Asian monsoon variability, suggesting that a complex interplay between ice sheet dynamics, insolation, and thermal gradients controls monsoonal intensity.
Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
Authors: Berglund Emelie , Maaskola Jonas , Schultz Niklas , Friedrich Stefanie , Marklund Maja , Bergenstråhle Joseph , Tarish Firas , Tanoglidi Anna , Vickovic Sanja , Larsson Ludvig , Salmén Fredrik , Ogris Christoph , Wallenborg Karolina , Lagergren Jens , Ståhl Patrik , Sonnhammer Erik , Helleday Thomas , Lundeberg Joakim
Published: June 2018

Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
Urinary cell-free DNA is a versatile analyte for monitoring infections of the urinary tract
Authors: Burnham Philip , Dadhania Darshana , Heyang Michael , Chen Fanny , Westblade Lars F. , Suthanthiran Manikkam , Lee John Richard , De Vlaminck Iwijn
Published: June 2018

Urinary tract infections are one of the most common infections in humans. Here we tested the utility of urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics in bacterial and viral urinary tract infections. We isolated cfDNA from 141 urine samples from a cohort of 82 kidney transplant recipients and performed next-generation sequencing. We found that urinary cfDNA is highly informative about bacterial and viral composition of the microbiome, antimicrobial susceptibility, bacterial growth dynamics, kidney allograft injury, and host response to infection. These different layers of information are accessible from a single assay and individually agree with corresponding clinical tests based on quantitative PCR, conventional bacterial culture, and urinalysis. In addition, cfDNA reveals the frequent occurrence of pathologies that remain undiagnosed with conventional diagnostic protocols. Our work identifies urinary cfDNA as a highly versatile analyte to monitor infections of the urinary tract.
Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease
Authors: Coffey Lark L. , Keesler Rebekah I. , Pesavento Patricia A. , Woolard Kevin , Singapuri Anil , Watanabe Jennifer , Cruzen Christina , Christe Kari L. , Usachenko Jodie , Yee JoAnn , Heng Victoria A. , Bliss-Moreau Eliza , Reader J. Rachel , von Morgenland Wilhelm , Gibbons Anne M. , Jackson Kenneth , Ardeshir Amir , Heimsath Holly , Permar Sallie , Senthamaraikannan Paranthaman , Presicce Pietro , Kallapur Suhas G. , Linnen Jeffrey M. , Gao Kui , Orr Robert , MacGill Tracy , McClure Michelle , McFarland Richard , Morrison John H. , Van Rompay Koen K. A.
Published: June 2018

Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions.
Advances in highly doped upconversion nanoparticles
Authors: Wen Shihui , Zhou Jiajia , Zheng Kezhi , Bednarkiewicz Artur , Liu Xiaogang , Jin Dayong
Published: June 2018

Lanthanide-doped upconversion nanoparticles (UCNPs) are capable of converting near-infra-red excitation into visible and ultraviolet emission. Their unique optical properties have advanced a broad range of applications, such as fluorescent microscopy, deep-tissue bioimaging, nanomedicine, optogenetics, security labelling and volumetric display. However, the constraint of concentration quenching on upconversion luminescence has hampered the nanoscience community to develop bright UCNPs with a large number of dopants. This review surveys recent advances in developing highly doped UCNPs, highlights the strategies that bypass the concentration quenching effect, and discusses new optical properties as well as emerging applications enabled by these nanoparticles.
Assigning the absolute configuration of single aliphatic molecules by visual inspection
Authors: Ebeling Daniel , Šekutor Marina , Stiefermann Marvin , Tschakert Jalmar , Dahl Jeremy E. P. , Carlson Robert M. K. , Schirmeisen André , Schreiner Peter R.
Published: June 2018

Deciphering absolute configuration of a single molecule by direct visual inspection is the next step in compound identification, with far-reaching implications for medicinal chemistry, pharmacology, and natural product synthesis. We demonstrate the feasibility of this approach utilizing low temperature atomic force microscopy (AFM) with a CO-functionalized tip to determine the absolute configuration and orientation of a single, adsorbed [123]tetramantane molecule, the smallest chiral diamondoid. We differentiate between single enantiomers on Cu(111) by direct visual inspection, and furthermore identify molecular dimers and molecular clusters. The experimental results are confirmed by a computational study that allowed quantification of the corresponding intermolecular interactions. The unique toolset of absolute configuration determination combined with AFM tip manipulation opens a route for studying molecular nucleation, including chirality-driven assembly or reaction mechanisms.
Hippocampal-Temporopolar Connectivity Contributes to Episodic Simulation During Social Cognition
Authors: Pehrs Corinna , Zaki Jamil , Taruffi Liila , Kuchinke Lars , Koelsch Stefan
Published: June 2018

People are better able to empathize with others when they are given information concerning the context driving that person’s experiences. This suggests that people draw on prior memories when empathizing, but the mechanisms underlying this connection remain largely unexplored. The present study investigates how variations in episodic information shape the emotional response towards a movie character. Episodic information is either absent or provided by a written context preceding empathic film clips. It was shown that sad context information increases empathic concern for a movie character. This was tracked by neural activity in the temporal pole (TP) and anterior hippocampus (aHP). Dynamic causal modeling with Bayesian Model Selection has shown that context changes the effective connectivity from left aHP to the right TP. The same crossed-hemispheric coupling was found during rest, when people are left to their own thoughts. We conclude that (i) that the integration of episodic memory also supports the specific case of integrating context into empathic judgments, (ii) the right TP supports emotion processing by integrating episodic memory into empathic inferences, and (iii) lateral integration is a key process for episodic simulation during rest and during task. We propose that a disruption of the mechanism may underlie empathy deficits in clinical conditions, such as autism spectrum disorder.
Reducing uncertainties in energy dissipation measurements in atomic force spectroscopy of molecular networks and cell-adhesion studies
Authors: Biswas Soma , Leitao Samuel , Theillaud Quentin , Erickson Blake W. , Fantner Georg E.
Published: June 2018

Atomic force microscope (AFM) based single molecule force spectroscopy (SMFS) is a valuable tool in biophysics to investigate the ligand-receptor interactions, cell adhesion and cell mechanics. However, the force spectroscopy data analysis needs to be done carefully to extract the required quantitative parameters correctly. Especially the large number of molecules, commonly involved in complex networks formation; leads to very complicated force spectroscopy curves. One therefore, generally characterizes the total dissipated energy over a whole pulling cycle, as it is difficult to decompose the complex force curves into individual single molecule events. However, calculating the energy dissipation directly from the transformed force spectroscopy curves can lead to a significant over-estimation of the dissipated energy during a pulling experiment. The over-estimation of dissipated energy arises from the finite stiffness of the cantilever used for AFM based SMFS. Although this error can be significant, it is generally not compensated for. This can lead to significant misinterpretation of the energy dissipation (up to the order of 30%). In this paper, we show how in complex SMFS the excess dissipated energy caused by the stiffness of the cantilever can be identified and corrected using a high throughput algorithm. This algorithm is then applied to experimental results from molecular networks and cell-adhesion measurements to quantify the improvement in the estimation of the total energy dissipation.
Human IgM antibody rHIgM22 promotes phagocytic clearance of myelin debris by microglia
Authors: Zorina Yana , Stricker Jason , Caggiano Anthony O. , Button Donald C.
Published: June 2018

In multiple sclerosis (MS), demyelinated CNS lesions fail to sufficiently remyelinate, despite the presence of oligodendrocyte precursor cells (OPCs) capable of differentiating into mature oligodendrocytes. MS lesions contain damaged myelin debris that can inhibit OPC maturation and hinder repair. rHIgM22 is an experimental human recombinant IgM antibody that promotes remyelination in animal models and is being examined in patients with MS. rHIgM22 binds to CNS myelin and partially rescues OPC process outgrowth on myelin. Since rHIgM22 does not affect OPC process outgrowth in vitro on permissive substrate, we examined the possibility that it acts by enhancing phagocytic clearance of myelin debris by microglia. In this study, we tested if rHIgM22 binding could tag myelin for microglial phagocytosis. A mouse microglial cell line and primary rat microglia were treated with myelin and rHIgM22 and assayed for myelin phagocytosis. We found that: 1) rHIgM22 stimulates myelin phagocytosis in a dose-dependent manner; 2) rHIgM22-mediated myelin phagocytosis requires actin polymerization; and 3) rHIgM22-stimulation of myelin phagocytosis requires activity of rHIgM22 Fc domain and activation of Complement Receptor 3. Since myelin inhibits OPC differentiation, stimulation of phagocytic clearance of damaged myelin may be an important means by which rHIgM22 promotes remyelination.
Author Correction: Elastic net regularized regression for time-series analysis of plasma metabolome stability under sub-optimal freezing condition
Authors: Gonzales Gerard Bryan , De Saeger Sarah
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 not been fixed in the paper.
Author Correction: A novel microRNA signature predicts survival in liver hepatocellular carcinoma after hepatectomy
Authors: Fu Qiang , Yang Fan , Xiang Tengxiao , Huai Guoli , Yang Xingxing , Wei Liang , Yang Hongji , Deng Shaoping
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 not been fixed in the paper.
The role of calretinin-expressing granule cells in olfactory bulb functions and odor behavior
Authors: Hardy Delphine , Malvaut Sarah , Breton-Provencher Vincent , Saghatelyan Armen
Published: June 2018

The adult mouse olfactory bulb is continuously supplied with new neurons that mostly differentiate into granule cells (GCs). Different subtypes of adult-born GCs have been identified, but their maturational profiles and their roles in bulbar network functioning and odor behavior remain elusive. It is also not known whether the same subpopulations of GCs born during early postnatal life (early-born) or during adulthood (adult-born) differ in their morpho-functional properties. Here, we show that adult-born calretinin-expressing (CR+) and non-expressing (CR−) GCs, as well as early-born CR+ GCs, display distinct inhibitory inputs but indistinguishable excitatory inputs and similar morphological characteristics. The frequencies of inhibitory post-synaptic currents were lower in early-born and adult-born CR+ GCs than in adult-born CR− neurons. These findings were corroborated by the reduced density of gephyrin+ puncta on CR+ GCs. CR+ GCs displayed a higher level of activation following olfactory tasks based on odor discrimination, as determined by an immediate early gene expression analysis. Pharmacogenetic inhibition of CR+ GCs diminished the ability of the mice to discriminate complex odor mixtures. Altogether, our results indicate that distinct inhibitory inputs are received by adult-born CR+ and CR− GCs, that early- and adult-born CR+ neurons have similar morpho-functional properties, and that CR+ GCs are involved in complex odor discrimination tasks.
Phenology drives species interactions and modularity in a plant - flower visitor network
Authors: Morente-López Javier , Lara-Romero Carlos , Ornosa Concepcion , Iriondo José M.
Published: June 2018

Phenology is often identified as one of the main structural driving forces of plant – flower visitor networks. Nevertheless, we do not yet have a full understanding of the effects of phenology in basic network build up mechanisms such as ecological modularity. In this study, we aimed to identify the effect of within-season temporal variation of plant and flower visitor activity on the network structural conformation. Thus, we analysed the temporal dynamics of a plant – flower visitor network in two Mediterranean alpine communities during one complete flowering season. In our approach, we built quantitative interaction networks and studied the dynamics through temporal beta diversity of species, interaction changes and modularity analysis. Within-season dissimilarity in the identity of interactions was mainly caused by species replacement through time (species turnover). Temporal replacement of species and interactions clearly impacted modularity, to the extent that species phenology emerged as a strong determinant of modularity in our networks. From an applied perspective, our results highlight the importance of considering the temporal variation of species interactions throughout the flowering season and the requirement of making comprehensive temporal sampling when aiming to build functionally consistent interaction networks.
Social jetlag impairs balance control
Authors: Umemura Guilherme Silva , Pinho João Pedro , da Silva Brandão Gonçalves Bruno , Furtado Fabianne , Forner-Cordero Arturo
Published: June 2018

We assessed the impact of a common sleep disturbance, the social jetlag, on postural control during a period involving workdays and free days. The sleep habits of 30 healthy subjects were registered with a wrist actimeter for nine days (starting on Friday) and they participated in a set of four postural control tests carried out on Friday and on Monday. In addition, the subjects filled questionnaires about their sleep conditions and preferences. Actimetry measurements were used to calculate the Mid Sleep Phase (MSP). The difference between the MSP values on the workdays and free days measures the social jetlag. There were significant differences in sleep variables between workdays and free days. Postural control performance improved on Monday, after free sleep over the weekend, when compared with the tests performed on Friday. It seems that social jetlag affects brain areas involved in the control of posture, such as thalamus and the prefrontal cortex as well as the cerebellum, resulting in a worse performance in postural control. The performance improvement in the posture tests after the free days could be attributed to a lower sleep debt.