bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits of fetal echocardiographic surveillance in pregnancies at risk of congenital heart block: single‐center study of 212 anti‐Ro52‐positive pregnancies
Authors: Sonesson S.‐E. , Ambrosi A. , Wahren‐Herlenius M.
Published: January 2019

Objectives

Assuming that autoimmune congenital heart block (CHB) is a progressive disease amenable to therapeutic modulation, we introduced a surveillance program for at‐risk pregnancies with the dual aim of investigating if fetal atrioventricular block (AVB) could be detected and treated before becoming complete and irreversible, and to establish the incidence of AVB I, II and III in a large prospective cohort.

Methods

This was a prospective study of 212 anti‐Ro52 antibody‐exposed pregnancies at risk of fetal AVB that were followed weekly between 18 and 24 weeks' gestation at our tertiary fetal cardiology center from 2000 to 2015. A 12‐lead electrocardiogram (ECG) was recorded within 1 week after birth. Fetal Doppler atrioventricular (AV) intervals were converted to Z‐scores using reference standard values derived from normal pregnancies. Each fetus was represented by the average value of the two recordings, obtained at two consecutive visits, which resulted in the longest AV interval. AV interval values were classified into normal AV conduction (Z‐score ≤ 2.0) and three levels of delayed AV conduction: Z‐score > 2.0 and ≤ 3.0, Z‐score > 3.0 and ≤ 4.0, and Z‐score > 4.0.

Results

AVB II or III developed in 6/204 (2.9%) pregnancies without a CHB history and 1/8 (12.5%) of those with a CHB history. AV intervals > 2 and ≤ 3, > 3 and ≤ 4, and > 4 were detected in 16.0%, 7.5% and 2.8% of cases, respectively, and were related to the PR interval on 185 available ECGs. Three of the five cases with AVB III and one of two cases with 2:1 AVB II developed within 1 week of AV interval Z‐score of 1.0, 1.9, 2.8 and 1.9, respectively. Transplacental treatment with betamethasone was associated with restoration of 1:1 AV conduction in the two fetuses with AVB II, with a better long‐term result (normal ECG vs AVB I or II) observed in the case in which treatment was started within 1 week after AVB developed. Betamethasone treatment did not reverse AVB III, although a temporary effect on AV conduction was observed in 1/5 cases. Notably, the three cases in which treatment was started within 1 week after AVB III development responded with a higher ventricular rate than the other two cases and did not require pacemaker implantation until a later age (2–5 years vs 1.5–2 months).

Conclusion

Fetal AV interval is a poor predictor of CHB progression, but CHB surveillance still allows detection of fetuses with AVB II or III shortly after its development, allowing for timely treatment initiation and potentially better outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors
Authors: Doi Toshihiko , Aramaki Takeshi , Yasui Hirofumi , Muro Kei , Ikeda Masafumi , Okusaka Takuji , Inaba Yoshitaka , Nakai Kenya , Ikezawa Hiroki , Nakajima Ryo
Published: January 2019

Background We conducted a first-in-Japanese, phase I study of ontuxizumab, a humanized, anti-endosialin monoclonal antibody, to confirm its tolerability, safety, and pharmacokinetics, and identify exploratory efficacy. Methods This was a multicenter, multiple-dose, open-label study in Japanese patients aged ≥20 years with solid tumors, including gastric cancer (GC) or advanced hepatocellular carcinoma (HCC), who had failed standard chemotherapy. The study comprised two parts: part 1 (dose-escalation; ontuxizumab 2–12 mg/kg weekly) and part 2 (cohort-expansion; 4 or 8 mg/kg weekly, or 12 mg/kg biweekly). Results Fifteen patients were treated in part 1, and 31 in part 2 (16 patients with GC and 15 with HCC). In part 1, the most common treatment-related, treatment-emergent adverse event (TEAE) was fatigue (20%); no patients had grade ≥ 3 treatment-related TEAEs. In part 2, the most common treatment-related TEAEs were constipation, malaise, hiccups, and increased bilirubin; treatment-related grade 3 TEAEs occurred in two patients with HCC. In part 1, no patients achieved a partial response, and 6/15 (40%) had stable disease (SD). In part 2, 2/15 patients (13.3%) with GC and 8/15 (53.3%) with HCC had SD. Tumor shrinkage was observed in 5/15 HCC patients (33.3%). Conclusions Ontuxizumab, up to a dosage of 12 mg/kg weekly, was generally safe and well tolerated in this population, with no dose-limiting toxicities. The maximum tolerated dose was not reached; 8 mg/kg weekly or 12 mg/kg biweekly were the recommended dosages. We observed long-term disease stabilization in GC and extraskeletal chondrosarcoma, and tumor shrinkage in gastrointestinal stromal tumor and HCC. Trial registration: NCT01773434 (ClinicalTrials.gov).
Genetische Ursachen und Therapie beim Alport-Syndrom
Authors: Gross Oliver , Hoefele Julia
Published: January 2019

Bei der Typ IV Kollagen-Erkrankung Alport-Syndrom (AS) handelt es sich um eine progressive hereditäre Nephropathie. Klinische Zeichen sind zunächst Hämaturie und Proteinurie, im weiteren Verlauf kommt es zu einem terminalen Nierenversagen. Zusätzlich werden extrarenale Manifestationen wie Innenohr-Schwerhörigkeit und Augenveränderungen beobachtet. Man unterscheidet drei Erbgänge: 85 % der Fälle sind X-chromosomal, ca. 10 % autosomal und weniger als 5 % digenisch. Ursächlich sind Varianten in den Kollagen Typ IV-Genen COL4A3, COL4A4 (beide autosomal) und COL4A5 (X-chromosomal). Die Symptomatik heterozygoter Anlageträger wurde früher als benigne familiäre Hämaturie bezeichnet. Da Anlageträger jedoch häufig keinen benignen Verlauf zeigen, werden sie inzwischen auch unter der Diagnose „Alport-Syndrom“ geführt.

Der Humangenetiker hat daher beim AS eine wichtige Lotsenfunktion: Bei früher Diagnose ist das AS inzwischen gut behandelbar, wodurch das terminale Nierenversagen um mehrere Jahre hinausgezögert und damit die Lebenserwartung verbessert werden kann. Aufgrund der Therapiemöglichkeiten sollte die (molekulargenetische) Diagnose bei Betroffenen, auch bei heterozygoten Anlageträgern, frühzeitig gestellt werden.

Mit diesem Artikel sollen die genetischen Ursachen des AS, mögliche genetische Einflussfaktoren auf den variablen Phänotyp, die unterschiedlichen Krankheitsstadien, Komplikationen sowie die derzeit zugelassene Behandlung aufgezeigt werden, um eine bestmögliche lebenslange Betreuung des Patienten zu gewährleisten.
In Situ Coupling Strategy for Anchoring Monodisperse Co9S8 Nanoparticles on S and N Dual-Doped Graphene as a Bifunctional Electrocatalyst for Rechargeable Zn–Air Battery
Authors: Shao Qi , Liu Jiaqi , Wu Qiong , Li Qiang , Wang Heng-guo , Li Yanhui , Duan Qian
Published: January 2019

An in situ coupling strategy to prepare Co9S8/S and N dual-doped graphene composite (Co9S8/NSG) has been proposed. The key point of this strategy is the function-oriented design of organic compounds. Herein, cobalt porphyrin derivatives with sulfo groups are employed as not only the coupling agents to form and anchor Co9S8 on the graphene in situ, but also the heteroatom-doped agent to generate S and N dual-doped graphene. The tight coupling of multiple active sites endows the composite materials with fast electrochemical kinetics and excellent stability for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The obtained electrocatalyst exhibits better activity parameter (ΔE = 0.82 V) and smaller Tafel slope (47.7 mV dec−1 for ORR and 69.2 mV dec−1 for OER) than commercially available Pt/C and RuO2. Most importantly, as electrocatalyst for rechargeable Zn–air battery, Co9S8/NSG displays low charge–discharge voltage gap and outstanding long-term cycle stability over 138 h compared to Pt/C–RuO2. To further broaden its application scope, a homemade all-solid-state Zn–air battery is also prepared, which displays good charge–discharge performance and cycle performance. The function-oriented design of N4-metallomacrocycle derivatives might open new avenues to strategic construction of high-performance and long-life multifunctional electrocatalysts for wider electrochemical energy applications.
Imaging of Post Transthoracic Needle Biopsy Complications
Authors: Dubé Jean-Philippe , Azzi Ziad , Semionov Alexandre , Sayegh Karl , Kosiuk John , Pressacco Josephine
Published: January 2019

When faced with characterization of a suspicious lung lesion, transthoracic needle biopsy (TTNB) is the standard technique used to retrieve a pathological specimen. Usual complications reported for this intervention are pneumothorax, hemorrhage, air embolism, and tumor seeding. This pictorial essay illustrates imaging of these complications.
Human Sacrifice
Authors: Recht Laerke
Published: January 2019

Sacrifice is not simply an expression of religious beliefs. Its highly symbolic nature lends itself to various kinds of manipulation by those carrying it out, who may use the ritual in maintaining and negotiating power and identity in carefully staged 'performances'. This Element will examine some of the many different types of sacrifice and ritual killing of human beings through history, from Bronze Age China and the Near East to Mesoamerica to Northern Europe. The focus is on the archaeology of human sacrifice, but where available, textual and iconographic sources provide valuable complements to the interpretation of the material.
Mollusks from the upper Shackleton Limestone (Cambrian Series 2), Central Transantarctic Mountains, East Antarctica
Authors: Claybourn Thomas M. , Jacquet Sarah M. , Skovsted Christian B. , Topper Timothy P. , Holmer Lars E. , Brock Glenn A.
Published: January 2019

An assemblage of Cambrian Series 2, Stages 3–4, conchiferan mollusks from the Shackleton Limestone, Transantarctic Mountains, East Antarctica, is formally described and illustrated. The fauna includes one bivalve, one macromollusk, and 10 micromollusks, including the first description of the speciesXinjispira simplexZhou and Xiao, 1984 outside North China. The new fauna shows some similarity to previously described micromollusks from lower Cambrian glacial erratics from the Antarctic Peninsula. The fauna, mainly composed of steinkerns, is relatively low diversity, but the presence of diagnostic taxa, including helcionelloidDavidonia rostrata(Zhou and Xiao, 1984), bivalvePojetaia runnegariJell, 1980, cambroclavidCambroclavus absonusConway Morris in Bengtson et al., 1990, and bradoriidSpinospitella coronataSkovsted et al., 2006, as well as the botsfordiid brachiopodSchizopholis yorkensis(Ushatinskaya and Holmer in Gravestock et al., 2001), in the overlying Holyoake Formation correlates the succession to theDailyatia odysseiZone (Cambrian Stages 3–4) in South Australia.
Regimes, Social Risks and the Welfare Mix: Unpacking Attitudes to Pensions and Childcare in Germany and the UK Through Deliberative Forums
Authors: TAYLOR-GOOBY PETER , HEUER JAN-OCKO , CHUNG HEEJUNG , LERUTH BENJAMIN , MAU STEFFEN , ZIMMERMANN KATHARINA
Published: January 2019

Modern welfare regimes rest on a range of actors – state, market, family/households, employers and charities – but austerity programmes diminish the contribution of the state. While changes in this ‘welfare mix’ require support from the population, attitude studies have focused mainly on people’s views on state responsibilities, using welfare regime theory to explain differences. This paper contributes to our understanding of the welfare mix by including other providers such as the market, the family or employers, and also introduces social risk theories, contrasting new and old risks. Regime theory implies differences will persist over time, but risk theory suggests that growing similarities in certain risks may tend to promote international convergence. This article examines attitudes to the roles of state, market, family, charity/community and employer for pension and childcare in Germany and the UK. We collected data using deliberative forums, a new method in social policy research that allows citizens space to pursue extended lightly moderated discussion and permits researchers to analyse people’s justifications for their attitudes. Our research indicated patterns of convergence especially in preferences for childcare, but that regime predominates in people’s justifications for their attitudes: regime differences in attitudes are resilient.
Long-term care system in Taiwan: the 2017 major reform and its challenges
Authors: Yeh Ming-Jui
Published: January 2019

This paper reviews the past development of the publicly funded long-term care (LTC) system and aims to advance further discussion of LTC in Taiwan. The Ten-year Long-Term Care Plan 2.0 introduced in 2017 calls for a major reform of a publicly funded LTC system in Taiwan. The reform expands on the previous universal tax-based LTC system, allowing for more comprehensive and accessible subsidies on LTC services. This paper provides a brief overview of the political context of the reform and an introduction to the legal basis, financing and delivery mechanisms of the reform plan. To this end, as a preliminary evaluation, this paper identifies major institutional and socio-cultural tensions that could challenge the implementation of the plan. Institutional tensions include the dominant foreign worker caring model, which relies on approximately 220,000 foreign workers to provide LTC services, and the discontinuity between health and social care governance, which leads to a discontinuity between curative and LTC care. Socio-cultural tensions focus on conflicting values in the allocation of responsibility of care and in the understanding of disability between universal social citizenship in the modern state and traditional Confucian ethics. Policy implications of these tensions for the LTC system are then discussed.
Proteins from male and female reproductive tracts involved in sperm function regulation
Authors: Hernández-Silva Gabriela , Chirinos Mayel
Published: January 2019

Spermatogenesis is a dynamic process that culminates in the production of mature spermatozoa in the seminiferous tubules of sexually mature animals. Although sperm leaving the testis are fully differentiated, they must further undergo two additional maturation steps before acquiring the capability to fertilize the egg. Such processes take place during the epididymal residency and transport in the seminal fluid during ejaculation and, after delivery into the female reproductive tract, during the journey aiming the encountering the egg in the oviduct. Throughout this trip, spermatozoa are exposed to different reproductive fluids whose molecular compositions regulate the progress towards obtaining a fertilized competent cell. This review summarizes the evidence obtained so far supporting the participation of male and female reproductive tract-derived proteins in the modulation of sperm fertilizing ability and discusses the mechanisms by which such regulation may be accomplished.
Cultural modifications of cognitive behavioural treatment of social anxiety among culturally diverse clients: a systematic literature review
Authors: Jankowska Maja
Published: January 2019

The aim of this study was to conduct a systematic literature review to ascertain whether cognitive behavioural therapy (CBT) for social anxiety disorder (SAD) can be successfully used in non-Western contexts and demonstrate sufficient effectiveness. This area is largely under-researched with conflicting evidence presented in quantitative studies, with virtually no qualitative studies published. This review utilized realist review methodology and focused on qualitative case studies presented by clinicians. A systematic search of EBSCO HOST, The Cochrane Library Database, Google, Google Scholar and reference mining, using various combinations of terms relating to: (1) CBT, (2) social anxiety and (3) cultural diversity were employed. Seven case studies of cultural adaptations of CBT treatment for culturally diverse SAD sufferers were included. The treatment outcomes were generally promising in all cases (reporting significant decrease of SAD symptoms, maintained over time) and the success of therapy was often attributed to culturally specific modifications introduced. CBT can be an acceptable and effective treatment for culturally diverse SAD sufferers with ‘modest’ modifications, without major diversions from the original CBT models and protocols, but this finding must be treated with caution and more methodologically rigorous research (qualitative and quantitative) is needed to more fully understand what works, for whom and in what circumstances.
An evidence-based framework to culturally adapt cognitive behaviour therapy
Authors: Rathod Shanaya , Phiri Peter , Naeem Farooq
Published: January 2019

Cognitive behaviour therapy (CBT) in its current form might not be applicable in non-Western cultures. Differences between Western and non-Western cultures have been reported widely. Most psychotherapeutic interventions have been developed in the West and are underpinned by the values that might be specific only to Western culture. To adapt CBT, we need to understand whether the concepts associated with CBT may conflict with cultural beliefs, identifying barriers to the success of the therapy using the views of experts by experience, public and practitioners. This paper discusses the process, foci and framework of cultural adaptation of CBT. We describe an evidence-based framework for adapting CBT for individuals from non-Western cultures that will benefit clinicians who practise CBT and individuals from different cultural backgrounds.
Working with unaccompanied asylum-seeking young people: cultural considerations and acceptability of a cognitive behavioural group approach
Authors: King Dorothy , Said Glorianne
Published: January 2019

This paper outlines a psychological skills group for unaccompanied asylum-seeking young people with a focus on cultural adaptations in the context of a UK mental health service. Unaccompanied asylum-seeking young people have typically experienced multiple losses, traumatic experiences, significant disruption and psychosocial stressors. These experiences occur during a key developmental period and outside of the context of a supportive family environment. Mental health difficulties are estimated to be present in 41–69% of this population. Prevalence rates are higher than among children seeking asylum with their families or children who are not from refugee or asylum-seeking backgrounds. Cognitive behavioural approaches were considered to be applicable and useful when working with this client group. Group approaches may offer unique benefits for this population through peer support and normalization. The group described was planned around three key themes: physical health needs, emotional wellbeing and resilience-building. A number of adaptations were made to meet the needs of this population which included engagement, considering physical health needs, sleep, language needs, issues related to power, race and status, and thinking about the needs of the group as young people. Attendance ratings, session rating scale outcomes, preliminary effectiveness data and qualitative feedback from young people identified that this is an acceptable approach for these young people. Unaccompanied asylum-seeking young people require a broad package of care; however, making adaptations to routine practice allowed access to evidence-based interventions to support mental health and wellbeing.
Combined effects of rainfall regime and plot length on runoff and soil loss in the Loess Plateau of China
Authors: LIU Jianbo , GAO Guangyao , WANG Shuai , FU Bojie
Published: January 2019

The purpose of this paper was to study the interaction effects of rainfall regime and slope length on runoff and soil loss under different land uses. Event runoff and soil loss in forest, shrub and grass were measured in plots with lengths of 5, 9 and 13m in the Loess Plateau from 2008 to 2016. A total of 59 erosive rainfall events were recorded and classified into three rainfall regimes. Firstly, the results showed that the runoff coefficient was grass>shrub>forest, and soil loss was grass>forest>shrub, but the differences between forest and shrub in runoff and between grass and forest in soil loss did not reach significant levels. Secondly, rainfall regimes had an important effect on runoff and soil loss under different land uses. The lowest runoff coefficients and the highest soil loss in regime 2 were found in shrub and forest land, respectively, which differed from that of regime 1. In total, rainfall regime 1 had the highest runoff coefficient of 0.84–2.06%, followed by regime 3 with 0.33–0.88% and regime 2 with 0.04–0.06%. Soil loss in forest and grass land had a different order of regime 3>regime 1>regime 2. Thirdly, both the runoff coefficient and soil loss decreased with increasing plot length, while the effect of slope length on runoff/soil loss were influenced by land use type and rainfall regimes.
Relative importance of urban and non-urban land-use types for potential denitrification derived N2O: insights from a regional study
Authors: XU Hui-Juan , DELGADO-BAQUERIZO Manuel , PAN Fu-Xia , AN Xin-Li , SINGH Brajesh K. , KHAN Sardar , LI Gang , TANG Jian-Feng , ZHAO Xiao-Feng , YAO Huai-Ying , ZHU Yong-Guan
Published: January 2019

Identifying the relative importance of urban and non-urban land-use types for potential denitrification derived N2O at a regional scale is critical for quantifying the impacts of human activities on nitrous oxide (N2O) emission under changing environments. In this study we used a regional dataset from China including 197 soil samples and six land-use types to evaluate the main predictors (land use, heavy metals, soil pH, soil moisture, substrate availability, functional and broad microbial abundances) of potential denitrification using multivariate and pathway analysis. Our results provide empirical evidence that soils on farms have the greatest potential denitrifying ability (PDA) (10.92±6.08ng N2O-N·g–1 dry soil·min–1) followed by urban soil (6.80±5.35ng N2O-N·g–1 dry soil·min–1). Our models indicate that land use (low vs. high human activity), followed by total nitrogen (TN) and heavy metals (Cu, Zn, Pb, Cd) was the most important driver of PDA. In addition, our path analysis suggests that at least part of the impacts of land use on potential denitrification were mediated via microbial abundance, soil pH and substrates including TN, dissolved organic carbon and nitrate. This study identifies the main predictors of denitrification at a regional scale which is needed to quantify the impact of human activities on ecosystem functionality under changing conditions.
Birth weight and adolescent blood pressure measured at age 12 years in the Gateshead Millennium Study
Authors: Mann K. D. , Basterfield L. , Wright C. , Parkinson K. , Reilly J. K. , Reilly J. J. , Adamson A. J. , Pearce M. S. ,   on behalf of the GMS core team
Published: January 2019

Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999–2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.
Genetik der amyotrophen Lateralsklerose
Authors: Czell David
Published: January 2019

Zusammenfassung. In den letzten Jahren hat sich mit Hilfe der Hochdurchsatzsequenzierung (Next Generation Sequencing, NGS) das Wissen über Genmutationen, die zu einer amyotrophen Lateralsklerose (ALS), zu einer frontotemporalen Demenz (FTD) oder einem FTD-ALS-Komplex führen können, drastisch verbessert werden. So konnten viele neue Gene und deren molekulargenetische Mechanismen und Krankheitsbilder beschrieben und untersucht werden. Unter anderem konnte festgestellt werden, dass in der gleichen Familie mit der gleichen Genmutation Patienten mit einer ALS, einer FTD oder einer anderen neurodegenerativen Erkrankung vorkommen können. Das Wissen über die Gene trägt aber nicht nur zum Verständnis bei, sondern soll helfen, entsprechende Therapieansätze zu entwickeln.
Ein nicht alltägliches Hemisyndrom
Authors: Barandun Silvio , Wyss André , Stucki Armin
Published: January 2019

Zusammenfassung. Ein Patient mit bekannter hereditärer hämorrhagischer Telangiektasie stellt sich aufgrund einer transienten rechtsseitigen Armschwäche und Schwindel vor. Aufgrund der Klinik und der Risikofaktoren wird die Diagnose einer transienten ischämischen Attacke gestellt. Im Verlauf erleidet der Patient ein Krampfereignis und fiebert zweimalig auf, ohne dass sich ein klarer Infektfokus zeigt. Die initiale Schädel-MRT zeigt eine zentroparietale Läsion links mit Zeichen eines Begleitödems. Aufgrund dieses ungewöhnlichen Begleitödems muss differenzialdiagnostisch auch an ein neoplastisches Geschehen gedacht werden. Die weiteren Untersuchungen zeigen jedoch keine Hinweise auf eine Neoplasie, die Verlaufs-MRT des Schädels dann jedoch das Bild septischer Embolien mit einem Hirnabszess. Nach neurochirurgischer Sanierung und entsprechender antibiotischer Behandlung zeigt sich ein erfreulicher klinischer Verlauf. Als Ursache der septischen Embolien fand sich eine pulmonale arteriovenöse Malformation im Rahmen der hereditären hämorrhagischen Teleangiektasie, die komplikationsfrei gecoilt werden konnte.
When Do Those High in Trait Self-Control Suffer From	Strain?
Authors: Externbrink Kai , Diestel Stefan , Krings Martina
Published: January 2019

Abstract. We explore the limits of the protective function of trait self-control in coping with sources of stress. Inspired by integrative self-control theory (ISCT) we predict that trait self-control only buffers the relationship between self-control demands and irritation when individuals have to cope with one source of stress, whereas in cases of two stressors, trait self-control fails to attenuate adverse effects. Samples consisted of occupational students ( N = 163) and partly or fully or not formally employed students ( N = 135). Job-related self-control demands (SCDs) did not predict strain when trait self-control was high and the other stressor (academic SCDs or weekly study time) was low, whereas strain was disproportionally higher and predicted by SCDs when trait self-control was low or the other stressor was high.
Dynamical Malaria Forecasts Are Skillful at Regional and Local Scales in Uganda up to 4 Months Ahead
Authors: Tompkins Adrian M. , Colón‐González Felipe J. , Di Giuseppe Francesca , Namanya Didacus B.
Published: January 2019

Malaria forecasts from dynamical systems have never been attempted at the health district or local clinic catchment scale, and so their usefulness for public health preparedness and response at the local level is fundamentally unknown. A pilot preoperational forecasting system is introduced in which the European Centre for Medium Range Weather Forecasts ensemble prediction system and seasonal climate forecasts of temperature and rainfall are used to drive the uncalibrated dynamical malaria model VECTRI to predict anomalies in transmission intensity 4 months ahead. It is demonstrated that the system has statistically significant skill at a number of sentinel sites in Uganda with high‐quality data. Skill is also found at approximately 50% of the Ugandan health districts despite inherent uncertainties of unconfirmed health reports. A cost‐loss economic analysis at three example sentinel sites indicates that the forecast system can have a positive economic benefit across a broad range of intermediate cost‐loss ratios and frequency of transmission anomalies. We argue that such an analysis is a necessary first step in the attempt to translate climate‐driven malaria information to policy‐relevant decisions.
Thermohaline‐Shear Instability
Authors: Radko Timour
Published: January 2019

This study presents the linear theory of thermohaline‐shear instability, which is realized in oceanic flows that are dynamically and diffusively stable. The framework is based on the unbounded Couette model, which makes it possible to decouple the destabilizing effects of spatially uniform shear from instabilities caused by the presence of inflection points in velocity profiles. The basic state is assumed to be time dependent, which reflects the role of internal waves in controlling fine‐scale shear. Linear stability analysis suggests that conditions for thermohaline‐shear instability are met in most ocean regions where temperature and salinity concurrently increase downward. We conclude that thermohaline‐shear instability represents a plausible mechanism for the initiation of active diffusive convection, which, in turn, is essential for the formation of thermohaline staircases and maintenance of double‐diffusive interleaving.
Nitric Oxide in Climatological Global Energy Budget During 1982–2013
Authors: Lin Cissi Y. , Deng Yue
Published: January 2019

Over the past decades, temperature and density of the upper atmosphere show negative trends and this decrease of the upper atmospheric temperature is attributed to the declining neutral density. Specifically, nitric oxide (NO) and carbon dioxide (CO2) govern thermospheric cooling at 5.3 and 15 μm, respectively. While a lot of efforts have focused on the CO2 effects on the long‐term trends, relatively less attention has been paid to the impacts by NO, which responds to solar and geomagnetic activities dynamically. In this study, we investigate the role of NO in climatological global energy budget for the recent three solar cycles using the Global Ionosphere‐Thermosphere Model. From 1982 to 2013, the F10.7 and Ap indices showed a decadal decrease of ~8% and ~20%, respectively. By imposing temporal‐varying F10.7 and Ap values in the simulations, we find a decadal change of −0.28 × 1011 W or −17.3% in total NO cooling power, which agrees well with that (−0.34 × 1011 W or −17.2%) from the empirical Thermosphere Climate Index derived from the Thermosphere Ionosphere Mesosphere Energetics and Dynamics/Sounding of the Atmosphere using Broadband Emission Radiometry data. Neutral density decreases by 10–20% at 200–450 km and Tex decreases by 25.3 K per decade. The deduced‐decadal change of NO cooling reaches ~25% of that of total heating at ~130 km and its significance decreases with altitude.
First MMS Observation of Energetic Particles Trapped in High‐Latitude Magnetic Field Depressions
Authors: Nykyri Katariina , Chu Christina , Ma Xuanye , Fuselier Stephen A. , Rice Rachel
Published: January 2019

We present a case study of the Magnetospheric Multiscale (MMS) observations of the Southern Hemispheric dayside magnetospheric boundaries under southward interplanetary magnetic field direction with strong By component. During this event MMS encountered several magnetic field depressions characterized by enhanced plasma beta and high fluxes of high‐energy electrons and ions at the dusk sector of the southern cusp region that resemble previous Cluster and Polar observations of cusp diamagnetic cavities. Based on the expected maximum magnetic shear model and magnetohydrodynamic simulations, we show that for the present event the diamagnetic cavity‐like structures were formed in an unusual location. Analysis of the composition measurements of ion velocity distribution functions and magnetohydrodynamics simulations show clear evidence of the creation of a new kind of magnetic bottle structures by component reconnection occurring at lower latitudes. We propose that the high‐energy particles trapped in these cavities can sometimes end up in the loss cone and leak out, providing a likely explanation for recent high‐energy particle leakage events observed in the magnetosheath.
On the Development of Shear Surface Roughness
Authors: Mukhopadhyay Manaska , Biswas Uddalak , Mandal Nibir , Misra Santanu
Published: January 2019

From deformed quartzites in the Singhbhum Shear Zone, eastern India, we report shear fractures of varying surface roughness: very smooth, containing no lineation to strongly rough with prominent slickenlines. We reproduced them in analogue laboratory experiments, which suggest that the modes of shear failure (brittle versus ductile) and the fracture orientation are potential factors to control the fracture roughness. The experiments were conducted on cohesive sand‐talc models with varying sand:talc volume ratio. Pure sand models underwent Coulomb failure in the brittle regime; this failure mode switched to plastic yielding in the ductile regime with increasing talc content. Such a transition in failure behavior resulted in a remarkable variation in the fracture roughness characteristics. Shear fractures produced by Coulomb failure are smooth, and devoid of any slickenlines, whereas those produced by plastic yielding display strongly linear roughness, defined by cylindrical ridges along the slip direction. Such linear irregularities become more prominent with increasing fracture orientation (θ) to the compression direction (θ = 30 to 60°). We develop a new computational technique, based on controlled optical images to map the shear surface geometry from field casts and laboratory samples. Binarization of the irregular surface images (cantor set) provides 1‐D fractal dimension (D), which is used to quantify the roughness variability, and the degree of their anisotropy in terms of ΔD (difference in D across and along the slip direction). From numerical models, we finally show onset of wave instability in the mechanically distinct rupture zone as an alternative mechanism for slickenline formation.
Dissimilarity Between Dust, Heat, and Momentum Turbulent Transports During Aeolian Soil Erosion
Authors: Dupont S. , Rajot J.‐L. , Labiadh M. , Bergametti G. , Lamaud E. , Irvine M. R. , Alfaro S. C. , Bouet C. , Fernandes R. , Khalfallah B. , Marticorena B. , Bonnefond J. M. , Chevaillier S. , Garrigou D. , Henry‐des‐Tureaux T. , Sekrafi S. , Zapf P.
Published: January 2019

Measuring accurately size‐resolved dust flux near the surface is crucial for better quantifying dust losses by semiarid soils. Dust fluxes have been usually estimated from the flux‐gradient approach, assuming similarity between dust and momentum turbulent transport. This similarity has, however, never been verified. Here we investigate the similarity between dust (0.3 to 6.0 μm in diameter), momentum, and heat fluxes during aeolian erosion events. These three fluxes were measured by the Eddy Covariance technique during the WIND‐O‐V (WIND erOsion in presence of sparse Vegetation's) 2017 field experiment over an isolated erodible bare plot in South Tunisia. Our measurements confirm the prevalence of ejection and sweep motions in transporting dust as for heat and momentum. However, our measurements also reveal a different partition of the dust flux between ejection and sweep motions and between eddy time scales compared to that of momentum and heat fluxes. This dissimilarity results from the intermittency of the dust emission compared to the more continuous emission (absorption) of heat (momentum) at the surface. Unlike heat emission and momentum absorption, dust release is conditioned by the wind intensity to initiate sandblasting. Consequently, ejection motions do not carry dust as often as heat and low momentum from the surface. This dissimilarity diminishes with increasing wind intensity as saltation patterns, and thus dust emission through sandblasting, become spatially more frequent. Overall, these findings may have implications on the evaluation of dust flux from techniques based on similarity with momentum or heat turbulent transport.
Weak Stratospheric Polar Vortex Events Modulated by the Arctic Sea‐Ice Loss
Authors: Hoshi Kazuhira , Ukita Jinro , Honda Meiji , Nakamura Tetsu , Yamazaki Koji , Miyoshi Yasunobu , Jaiser Ralf
Published: January 2019

We characterize the differences in the upward planetary‐scale wave propagation during observed weak polar vortex (WPV) events between heavy‐ and light‐sea‐ice years in the Barents‐Kara Sea based on a composite analysis for the period of 1979–2015. Upward wave propagation during WPV events in heavy‐ice years is dominated by the wavenumber 1 component. In contrast, WPV events occurring in light‐ice years are characterized by stronger wavenumber 2 propagation, which is caused by the tropospheric wavenumber 2 response to sea‐ice reduction in the Barents‐Kara Sea. The above observed features are supported by an Atmospheric General Circulation Model experiment. Thus, under present climate conditions, Arctic sea‐ice loss is a possible factor modulating the wave propagation during the WPV events. We also find that the WPV events in light‐ice years have stronger stratosphere‐troposphere coupling, followed by colder midlatitude surface conditions particularly over Eurasia.
Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes
Authors: Limbocker Ryan , Chia Sean , Ruggeri Francesco S. , Perni Michele , Cascella Roberta , Heller Gabriella T. , Meisl Georg , Mannini Benedetta , Habchi Johnny , Michaels Thomas C. T. , Challa Pavan K. , Ahn Minkoo , Casford Samuel T. , Fernando Nilumi , Xu Catherine K. , Kloss Nina D. , Cohen Samuel I. A. , Kumita Janet R. , Cecchi Cristina , Zasloff Michael , Linse Sara , Knowles Tuomas P. J. , Chiti Fabrizio , Vendruscolo Michele , Dobson Christopher M.
Published: January 2019

Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-β peptide (Aβ42) are key pathogenic agents in Alzheimer’s disease (AD). To investigate the relationship between Aβ42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aβ42-induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.
Breakdown of adaptive immunotolerance induces hepatocellular carcinoma in HBsAg-tg mice
Authors: Zong Lu , Peng Hui , Sun Cheng , Li Fenglei , Zheng Meijuan , Chen Yongyan , Wei Haiming , Sun Rui , Tian Zhigang
Published: January 2019

Hepatitis B virus (HBV) can induce chronic inflammation, cirrhosis, and eventually hepatocellular carcinoma (HCC). Despite evidence suggesting a link between adaptive immunity and HBV-related diseases in humans, the immunopathogenic mechanisms involved are seldom described. Here we show that expression of TIGIT, a promising immune checkpoint in tumor immunotherapy, increases with age on hepatic CD8+ T cells in HBsAg-transgenic (HBs-tg) mice whose adaptive immune system is tolerant to HBsAg. TIGIT blockade or deficiency leads to chronic hepatitis and fibrosis, along with the emergence of functional HBsAg-specific cytotoxic T lymphocytes (CTLs), suggesting adaptive immune tolerance could be broken by TIGIT blockade or deficiency. Importantly, HBsAg vaccination further induces nonresolving inflammation and HCC in a CD8+ T cell-dependent manner in TIGIT-blocked or -deficient HBs-tg mice. Therefore, CD8+ T cells play an important role in adaptive immunity-mediated tumor progression and TIGIT is critical in maintenance of liver tolerance by keeping CTLs in homeostatic balance.
A nanophotonic laser on a graph
Authors: Gaio Michele , Saxena Dhruv , Bertolotti Jacopo , Pisignano Dario , Camposeo Andrea , Sapienza Riccardo
Published: January 2019

Conventional nanophotonic schemes minimise multiple scattering to realise a miniaturised version of beam-splitters, interferometers and optical cavities for light propagation and lasing. Here instead, we introduce a nanophotonic network built from multiple paths and interference, to control and enhance light-matter interaction via light localisation. The network is built from a mesh of subwavelength waveguides, and can sustain localised modes and mirror-less light trapping stemming from interference over hundreds of nodes. With optical gain, these modes can easily lase, reaching ~100 pm linewidths. We introduce a graph solution to the Maxwell’s equation which describes light on the network, and predicts lasing action. In this framework, the network optical modes can be designed via the network connectivity and topology, and lasing can be tailored and enhanced by the network shape. Nanophotonic networks pave the way for new laser device architectures, which can be used for sensitive biosensing and on-chip optical information processing.
An orderly single-trial organization of population dynamics in premotor cortex predicts behavioral variability
Authors: Wei Ziqiang , Inagaki Hidehiko , Li Nuo , Svoboda Karel , Druckmann Shaul
Published: January 2019

Animals are not simple input-output machines. Their responses to even very similar stimuli are variable. A key, long-standing question in neuroscience is to understand the neural correlates of such behavioral variability. To reveal these correlates, behavior and neural population activity must be related to one another on single trials. Such analysis is challenging due to the dynamical nature of brain function (e.g., in decision making), heterogeneity across neurons and limited sampling of the relevant neural population. By analyzing population recordings from mouse frontal cortex in perceptual decision-making tasks, we show that an analysis approach tailored to the coarse grain features of the dynamics is able to reveal previously unrecognized structure in the organization of population activity. This structure is similar on error and correct trials, suggesting dynamics that may be constrained by the underlying circuitry, is able to predict multiple aspects of behavioral variability and reveals long time-scale modulation of population activity.
Magnetic-field-dependent quantum emission in hexagonal boron nitride at room temperature
Authors: Exarhos Annemarie L. , Hopper David A. , Patel Raj N. , Doherty Marcus W. , Bassett Lee C.
Published: January 2019

Optically addressable spins associated with defects in wide-bandgap semiconductors are versatile platforms for quantum information processing and nanoscale sensing, where spin-dependent inter-system crossing transitions facilitate optical spin initialization and readout. Recently, the van der Waals material hexagonal boron nitride (h-BN) has emerged as a robust host for quantum emitters, promising efficient photon extraction and atom-scale engineering, but observations of spin-related effects have remained thus far elusive. Here, we report room-temperature observations of strongly anisotropic photoluminescence patterns as a function of applied magnetic field for select quantum emitters in h-BN. Field-dependent variations in the steady-state photoluminescence and photon emission statistics are consistent with an electronic model featuring a spin-dependent inter-system crossing between triplet and singlet manifolds, indicating that optically-addressable spin defects are present in h-BN.
A welding phenomenon of dissimilar nanoparticles in dispersion
Authors: Huang Zhiqi , Zhao Zhi-Jian , Zhang Qian , Han Lili , Jiang Xiumei , Li Chao , Cardenas Maria T. Perez , Huang Peng , Yin Jun-Jie , Luo Jun , Gong Jinlong , Nie Zhihong
Published: January 2019

The oriented attachment of small nanoparticles (NPs) is recognized as an important mechanism involved in the growth of inorganic nanocrystals. However, non-oriented attachment of dissimilar NPs has been rarely observed in dispersion. This communication reports a welding phenomenon occurred directly between as-synthesized dispersions of single-component Au and chalcogenide NPs, which leads to the formation of asymmetric Au-chalcogenide hybrid NPs (HNPs). The welding of dissimilar NPs in dispersion is mainly driven by the ligand desorption-induced conformal contact between NPs and the diffusion of Au into chalcogenide NPs. The welding process can occur between NPs with distinct shapes or different capping agents or in different solvent media. A two-step assembly-welding mechanism is proposed for this process, based on our in situ electron spin resonance measurements and ab initio molecular dynamics simulation. The understanding of NP welding in dispersion may lead to the development of unconventional synthetic tools for the fabrication of hybrid nanostructures with diverse applications.
Structure of tRNA splicing enzyme Tpt1 illuminates the mechanism of RNA 2′-PO4 recognition and ADP-ribosylation
Authors: Banerjee Ankan , Munir Annum , Abdullahu Leonora , Damha Masad J. , Goldgur Yehuda , Shuman Stewart
Published: January 2019

Tpt1 is an essential agent of fungal tRNA splicing that removes the 2′-PO4 at the splice junction generated by fungal tRNA ligase. Tpt1 catalyzes a unique two-step reaction whereby the 2′-PO4 attacks NAD+ to form an RNA-2′-phospho-ADP-ribosyl intermediate that undergoes transesterification to yield 2′-OH RNA and ADP-ribose-1″,2″-cyclic phosphate products. Because Tpt1 is inessential in exemplary bacterial and mammalian taxa, Tpt1 is seen as an attractive antifungal target. Here we report a 1.4 Å crystal structure of Tpt1 in a product-mimetic complex with ADP-ribose-1″-phosphate in the NAD+ site and pAp in the RNA site. The structure reveals how Tpt1 recognizes a 2′-PO4 RNA splice junction and the mechanism of RNA phospho-ADP-ribosylation. This study also provides evidence that a bacterium has an endogenous phosphorylated substrate with which Tpt1 reacts.
Engineering of CRISPR-Cas12b for human genome editing
Authors: Strecker Jonathan , Jones Sara , Koopal Balwina , Schmid-Burgk Jonathan , Zetsche Bernd , Gao Linyi , Makarova Kira S. , Koonin Eugene V. , Zhang Feng
Published: January 2019

The type-V CRISPR effector Cas12b (formerly known as C2c1) has been challenging to develop for genome editing in human cells, at least in part due to the high temperature requirement of the characterized family members. Here we explore the diversity of the Cas12b family and identify a promising candidate for human gene editing from Bacillus hisashii, BhCas12b. However, at 37 °C, wild-type BhCas12b preferentially nicks the non-target DNA strand instead of forming a double strand break, leading to lower editing efficiency. Using a combination of approaches, we identify gain-of-function mutations for BhCas12b that overcome this limitation. Mutant BhCas12b facilitates robust genome editing in human cell lines and ex vivo in primary human T cells, and exhibits greater specificity compared to S. pyogenes Cas9. This work establishes a third RNA-guided nuclease platform, in addition to Cas9 and Cpf1/Cas12a, for genome editing in human cells.