bluuebunny/crossref_metadata_2025 huggingface dataset:
A Computationally Efficient, Time-Dependent Model of the Solar Wind for Use as a Surrogate to Three-Dimensional Numerical Magnetohydrodynamic Simulations
Authors: Owens Mathew , Lang Matthew , Barnard Luke , Riley Pete , Ben-Nun Michal , Scott Chris J. , Lockwood Mike , Reiss Martin A. , Arge Charles N. , Gonzi Siegfried
Published: March 2020

Near-Earth solar-wind conditions, including disturbances generated by coronal mass ejections (CMEs), are routinely forecast using three-dimensional, numerical magnetohydrodynamic (MHD) models of the heliosphere. The resulting forecast errors are largely the result of uncertainty in the near-Sun boundary conditions, rather than heliospheric model physics or numerics. Thus ensembles of heliospheric model runs with perturbed initial conditions are used to estimate forecast uncertainty. MHD heliospheric models are relatively cheap in computational terms, requiring tens of minutes to an hour to simulate CME propagation from the Sun to Earth. Thus such ensembles can be run operationally. However, ensemble size is typically limited to $10^{1}$101 to $10^{2}$102 members, which may be inadequate to sample the relevant high-dimensional parameter space. Here, we describe a simplified solar-wind model that can estimate CME arrival time in approximately 0.01 seconds on a modest desktop computer and thus enables significantly larger ensembles. It is a one-dimensional, incompressible, hydrodynamic model, which has previously been used for the steady-state solar wind, but it is here used in time-dependent form. This approach is shown to adequately emulate the MHD solutions to the same boundary conditions for both steady-state solar wind and CME-like disturbances. We suggest it could serve as a “surrogate” model for the full three-dimensional MHD models. For example, ensembles of $10^{5}$105 to $10^{6}$106 members can be used to identify regions of parameter space for more detailed investigation by the MHD models. Similarly, the simplicity of the model means it can be rewritten as an adjoint model, enabling variational data assimilation with MHD models without the need to alter their code. The model code is available as an Open Source download in the Python language.
The Situational Mental File Account of the False Belief Tasks: A New Solution of the Paradox of False Belief Understanding
Authors: Newen Albert , Wolf Julia
Published: March 2020

How can we solve the paradox of false-belief understanding:if infants pass the implicit false belief task (FBT) by nonverbal behavioural responses why do they nonetheless typically fail the explicit FBT till they are 4 years old? Starting with the divide between situational and cognitive accounts of the development of false-belief understanding, we argue that we need to consider both situational and internal cognitive factors together and describe their interaction to adequately explain the development of children’s Theory of Mind (ToM) ability. We then argue that a further challenge is raised for existing accounts by helping behaviour versions of the FBT. We argue that the common two-stage accounts are inadequate: we need to allow forthree central stagesin a continuous development. Furthermore, drawing on Perner et al.’s (Cognition145: 77–88, 2015) and Perner and Leahy’s (Review of Philosophy and Psychology7 (2): 491–508, 2016) recent mental files account, we provide a new account of the development of these three stages of ToM ability by describing the changes of the structure and organisation of mental files including the systematic triggering role of types of situations. Thereby we aim to establish asituational mental file (SMF) accountas a new and adequate solution to the paradox of false-belief understanding.
The identification of probable sarcopenia in early old age based on the SARC-F tool and clinical suspicion: findings from the 1946 British birth cohort
Authors: Dodds R. M. , Murray J. C. , Robinson S. M. , Sayer A. A.
Published: March 2020

Purpose

The European Working Group on Sarcopenia in Older People 2 (EWGSOP2) consensus definition introduced the concept of probable sarcopenia as a basis on which to begin treatment. Our aims were to describe the prevalence of probable sarcopenia in older adults and to investigate the utility of (1) the SARC-F tool and (2) clinical risk factors for the identification of those likely to have probable sarcopenia.

Methods

We used data from the 1946 British birth cohort at age 69, with 1686 participants included in the analyses. We used the EWGSOP2 cut points for weak grip strength and slow chair rise time, with the presence of one or both indicating probable sarcopenia. We examined the sensitivity and specificity of the SARC-F tool for probable sarcopenia. We also examined associations between clinical risk factors and probable sarcopenia.

Results

The prevalence of probable sarcopenia was 19%. A SARC-F score of ≥ 4 had low sensitivity (15%) and high specificity (99%) for probable sarcopenia, whereas a score of ≥ 1 had higher sensitivity (65%) and reasonable specificity (72%). Three clinical risk factors were independently associated with probable sarcopenia: polypharmacy [OR 2.7 (95% CI 1.7, 4.2)], lower body osteoarthritis [OR 1.8 (95% CI 1.3, 2.6)] and physical inactivity [OR of 2.1 (95% CI 1.5, 2.8)].

Conclusion

We have shown that EWGSOP2 probable sarcopenia is common in community-dwelling adults in early old age. Those with any positive responses to the questions in the SARC-F tool, a history of polypharmacy, lower body osteoarthritis or physical inactivity should be prioritised for the assessment of muscle strength.
Comparing multidimensional sensor data from vehicle fleets with methods of sequential data mining
Authors: Hartung Julia , Gühring Gabriele , Licht Valentin , Warta Alexander
Published: March 2020

Reading and understanding large amounts of sensor data from vehicle test drives becomes more and more important. In order to test vehicle components or analyze exhaust emissions in real test drives, the sensor data obtained from these test drives have to be comparable. Otherwise components or exhaust emissions are tested and analyzed under false conditions. The sensor data obtained during test drives are highly multidimensional which makes it even more complicated to identify recurring patterns. We present a process model to compare different test drives according to their sensor data and so give an answer to the question whether or not test drives in different cities, locations and environments are representative to real driving scenarios. The algorithms we use focus on segmentation of the individual multivariate test drive data and on clustering of the segments according to different methods. We present several segmentation and cluster methods and compare which of them is best suited for comparing test drives. The segmentation method we identified as best suited is based on principal component analysis. As cluster methods we examine hierarchical, partitioning and density-based clustering in detail.
Mechanisms of UV-induced mutations and skin cancer
Authors: Pfeifer Gerd P.
Published: March 2020

Ultraviolet (UV) irradiation causes various types of DNA damage, which leads to specific mutations and the emergence of skin cancer in humans, often decades after initial exposure. Different UV wavelengths cause the formation of prominent UV-induced DNA lesions. Most of these lesions are removed by the nucleotide excision repair pathway, which is defective in rare genetic skin disorders referred to as xeroderma pigmentosum. A major role in inducing sunlight-dependent skin cancer mutations is assigned to the cyclobutane pyrimidine dimers (CPDs). In this review, we discuss the mechanisms of UV damage induction, the genomic distribution of this damage, relevant DNA repair mechanisms, the proposed mechanisms of how UV-induced CPDs bring about DNA replication-dependent mutagenicity in mammalian cells, and the strong signature of UV damage and mutagenesis found in skin cancer genomes.
Commitment and communication: Are we committed to what we mean, or what we say?
Authors: BONALUMI FRANCESCA , SCOTT-PHILLIPS THOM , TACHA JULIUS , HEINTZ CHRISTOPHE
Published: March 2020

Are communicators perceived as committed to what they actually say (what is explicit), or to what they mean (including what is implicit)? Some research claims that explicit communication leads to a higher attribution of commitment and more accountability than implicit communication. Here we present theoretical arguments and experimental data to the contrary. We present three studies exploring whether the saying–meaning distinction affects commitment attribution in promises, and, crucially, whether commitment attribution is further modulated by the degree to which the hearer will actually rely on the promise. Our results support the conclusion that people perceive communicators to be committed to ‘what is meant’, and not simply to ‘what is said’. Our findings add to the experimental literature showing that the saying–meaning distinction is not as pivotal to social relations as often assumed, and that its role in commitment attribution might be overestimated. The attribution of commitment is strongly dependent on the (mutually known) relevance of ‘what is meant’.
Ketamine and neuroticism: a double-hit hypothesis of internalizing disorders
Authors: McNaughton N. , Glue P.
Published: March 2020

Psychiatric disorders can often be viewed as extremes of personality traits. The primary action of drugs that ameliorate these disorders may, thus, be to alter the patient’s position on a relevant trait dimension. Here, we suggest that interactions between such trait dimensions may also be important for disorder. Internalizing disorders show important differences in terms of range of activity and speed of response of medications. Established antidepressant and anxiolytic medications are slow in onset and have differing effects across different internalizing disorders. In contrast, low-dose ketamine is rapidly effective and improves symptom ratings in all internalizing disorders. To account for this, we propose a “double hit” model for internalizing disorders: generation (and maintenance) require two distinct forms of neural dysfunction to coincide. One hit, sensitive to ketamine, is disorder-general: dysfunction of a neural system linked to high levels of the personality trait of neuroticism. The other hit is disorder-specific: dysfunction of one of a set of disorder-specific neural modules, each with its own particular pattern of sensitivity to conventional drugs. Our hypothesis applies only to internalizing disorders. So, we predict that ketamine will be effective in simple phobia and (perhaps partially) in anorexia nervosa, but would make no such prediction about other disorders where neuroticism might also be important secondarily (e.g. attention deficit hyperactivity disorder and schizophrenia).
Palaeoecological and palaeoclimatic conditions on the Karelian Isthmus (northwestern Russia) during the Holocene
Authors: Nazarova Larisa , Syrykh Liudmila S. , Mayfield Roseanna J. , Frolova Larisa A. , Ibragimova Aisylu G. , Grekov Ivan M. , Subetto Dmitry A.
Published: March 2020

The Holocene evolution of climate in easternmost Fennoscandia and adjoining regions is poorly known, compared with regions to the west. To address this, a 224-cm-long sediment core from Lake Medvedevskoe, situated on the Central Upland of the Karelian Isthmus, northwestern Russia, was examined to investigate variations in the Holocene climate. Analyses indicate that the dry and cold late Pleistocene climate was replaced by the warmer and more humid early Holocene climate after ca. 10.5 cal ka BP. During the early Holocene, the lake transitioned from an oligotrophic to a mesotrophic state, characterized by a “Corynocera ambigua/Microtendipes pedellus-type” phase, which has been found in other lakes across Fennoscandia. Taxonomic shifts in the chironomid and cladoceran communities associated with climatic amelioration were identified at ca. 10.6 and 9.17 cal ka BP using breakpoint analysis. Reconstructed July temperatures indicate climatic patterns comparable to those seen in eastern Fennoscandia. The warm period between ca. 9.5 and 5.5 cal ka BP (T July 14.5–15°C) was interrupted by a slight cooling between ca. 8.5 and 8.1 cal ka BP, possibly relating to the 8.2 event, with peak temperature reached at ca. 7.8 cal ka BP. Neoglacial cooling started after ca. 5.5 cal ka BP, the median reconstructed July temperature dropped to 2–3°C cooler than present (mean T July 13.5°C) before recovering in recent time.
Identification and verification of differentially expressed genes in yak mammary tissue during the lactation cycle
Authors: Yuan Mao , Xia Wei , Zhang Xiaolei , Liu Yongtao , Jiang Mingfeng
Published: March 2020

Yaks (Bos grunniens) live primarily in the Qinghai-Tibetan plateau (altitude: 2000–5000 m). Their milk presents unusual characteristics, containing large amounts of solids including fat and protein, and it is, therefore, important to understand the genetic makeup of the yak. To identify potentially critical genes playing a role in yak mammary tissue from colostrum to mature milk phase of lactogenesis, the early lactation (colostrum) stage (ELS; day 1 after parturition) and mature lactation (milk) stage (MLS; day 15) were chosen for comparison. An ELS-specific cDNA library was established by suppression subtractive hybridization and 25 expressed sequence tags at ELS were identified by sequencing and alignment. To further confirm our results the expression levels of 21 genes during the lactation cycle were measured using quantitative real-time RT-PCR (qRT-PCR). The qRT-PCR results confirmed 9 significantly up-regulated genes at ELS vs. MLS in yak mammary tissue, in which thel-amino acid oxidase 1 (LAO1) and collagen, type I, alpha I (COL1A1) were the most significantly up-regulated. During the lactation cycle, the highest expression of some milk fat genes (i.e.,XDHandFABP3) in yak mammary tissue appears earlier than that in dairy cow. Our data also indicateMYCpotentially playing a central role through putative regulation ofCOL1A1,CD44,SPARC,FASNandGPAM.
Europe on the Sava: Austrian Encounters with “Turks” in Bosnia
Authors: Healy Maureen
Published: March 2020

This article examines Austrian perceptions of the people and landscape of Bosnia-Herzegovina from 1878 to 1908. It traces Austrians’ fantasies about and encounters with Bosnian Muslims, whom they often categorized as “Turks.” Following the Congress of Berlin, Austrians claimed to be doing the civilizing work of “Europe” in Bosnia. The article investigates the meanings of border and borderlands between the Habsburg Empire and Ottoman Bosnia, focusing in particular on crossings of the Sava River. Drawing on the writings of soldiers, administrators, journalists and travel writers, the essay considers a number of mental maps, imagined geographies of what Habsburg authors thought they knew about the land and people they occupied. It contributes to a growing scholarship on the Habsburg-Ottoman borderlands.
CAN CAPTIONED VIDEO BENEFIT SECOND LANGUAGE PRONUNCIATION?
Authors: Wisniewska Natalia , Mora Joan C.
Published: March 2020

The present study investigated the potential benefits of extended exposure to captioned videos for second language pronunciation. We tested 90 L2 adult learners of English on speech processing skills (segmentation, speed of lexical access, and sentence processing) and phonological accuracy in perception (ABX discrimination) and production (accentedness ratings) before and after an 8-week treatment consisting of regular exposure to audiovisual materials. Participants were randomly assigned to four experimental conditions involving two viewing modes (captioned or uncaptioned) and two task focus conditions (focus on phonetic form or focus on meaning). Results showed benefits in speech segmentation and speech processing skills irrespective of viewing mode. No significant benefits were found for phonological accuracy in perception. In production, a focus on phonetic form improved pronunciation only in the absence of captions, whereas captioned viewing led to pronunciation gains as long as there was no focus on phonetic form. These findings suggest that pronunciation improvement can take place with the help of captions or, in the absence of captions, when learners’ attention is directed to pronunciation. Cognitive overload might explain why no benefits were obtained when attention was directed to pronunciation in a captioned viewing mode.
Methods for prioritizing protected areas using individual and aggregate rankings
Authors: Carvalho Fabio , Brown Kerry A , Gordon Adam D , Yesuf Gabriel U , Raherilalao Marie Jeanne , Raselimanana Achille P , Soarimalala Voahangy , Goodman Steven M
Published: March 2020

Despite their legal protection status, protected areas (PAs) can benefit from priority ranks when ongoing threats to their biodiversity and habitats outpace the financial resources available for their conservation. It is essential to develop methods to prioritize PAs that are not computationally demanding in order to suit stakeholders in developing countries where technical and financial resources are limited. We used expert knowledge-derived biodiversity measures to generate individual and aggregate priority ranks of 98 mostly terrestrial PAs on Madagascar. The five variables used were state of knowledge (SoK), forest loss, forest loss acceleration, PA size and relative species diversity, estimated by using standardized residuals from negative binomial models of SoK regressed onto species diversity. We compared our aggregate ranks generated using unweighted averages and principal component analysis (PCA) applied to each individual variable with those generated via Markov chain (MC) and PageRank algorithms. SoK significantly affected the measure of species diversity and highlighted areas where more research effort was needed. The unweighted- and PCA-derived ranks were strongly correlated, as were the MC and PageRank ranks. However, the former two were weakly correlated with the latter two. We recommend using these methods simultaneously in order to provide decision-makers with the flexibility to prioritize those PAs in need of additional research and conservation efforts.
Infective endocarditis developing early after percutaneous closure of a patent ductus arteriosus in a child using the Amplatzer Duct Occluder II
Authors: Yilmazer Murat M. , Meşe Timur
Published: March 2020

A 10-month-old girl underwent patent ductus arteriosus closure with an Amplatzer Duct Occluder II. After 1 week, she was admitted to our emergency room with tachypnoea, fatigue, and fever. Consecutive blood cultures yielded vancomycin-sensitive Staphylococcus aureus. The patient was already receiving vancomycin, but the fever did not respond to this treatment. The device was successfully removed via left lateral thoracotomy.
The relationship between joining a US free trade agreement and processed food sales, 2002–2016: a comparative interrupted time-series analysis
Authors: Cowling Krycia , Stuart Elizabeth A , Neff Roni A , Vernick Jon , Magraw Daniel , Pollack Porter Keshia
Published: March 2020

Objective:

To examine changes in sales of highly processed foods, including infant formulas, in countries joining free trade agreements (FTAs) with the US.

Design:

Annual country-level data for food and beverage sales come from Euromonitor International. Analyses are conducted in a comparative interrupted time-series (CITS) framework using multivariate random-effects linear models, adjusted for key confounders: gross domestic product (GDP) per capita, percent of the population living in urban areas and female labor force participation rate. Memberships in other FTAs and investment treaties are also explored as possible confounders.

Setting:

Changes are assessed between 2002 and 2016.

Participants:

Ten countries joining US FTAs are compared with eleven countries without US FTAs in force; countries are matched on national income level, world region and World Trade Organization membership.

Results:

After countries join a US FTA, sales are estimated to increase by: 0·89 (95 % CI 0·16, 1·6;P= 0·016) kg per capita per annum for ultra-processed products, 0·81 (95 % CI 0·47, 1·1;P< 0·001) kg per capita per annum for processed culinary ingredients and 0·17 (95 % CI 0·052, 0·29;P= 0·005) kg per capita under age 5 per annum for baby food. No significant change is estimated for minimally processed foods. In statistical models, large unexplained variations in country-specific trends suggest additional unmeasured country-level factors also impact sales trends following entry into US FTAs.

Conclusions:

These findings strongly support the conclusion that joining US FTAs can contribute to detrimental changes in national dietary consumption that increase population risk of non-communicable diseases.
Serum 25-hydroxyvitamin D concentrations in 16-year-old Icelandic adolescent and its association with bone mineral density
Authors: Gudmundsdottir SL , Hrafnkelsson H , Sigurdsson EL , Johannsson E
Published: March 2020

Objective:

The aim of the study was to assess the potential association between serum 25-hydroxyvitamin D (25(OH)D) and whole-body bone mineral density (BMD) among 16-year-old adolescents and to study the prevalence of 25(OH)D insufficiency, defined as concentration under 50 nmol/l.

Design:

A cross-sectional study.

Setting:

Reykjavik, Iceland, latitude 64°08′N. Measurements took place in the Icelandic Heart Association's research lab during April–June 2015.

Participants:

In total, 411 students in Reykjavik, Iceland, were invited to participate, 315 accepted the invitation (76·6 %) and 289 had valid data (mainly Caucasian).

Results:

25(OH)D < 50 nmol/l was observed in 70 % of girls and 66·7 % of boys. 25(OH)D ≥ 50 nmol/l was significantly associated with higher whole-body BMD after adjusting for the influence of sex, height, fat mass and lean mass. A linear relationship between 25(OH)D and whole-body BMD was significant for 25(OH)D < 50 nmol/l (n 199, P < 0·05) but NS for 25(OH)D ≥ 50 nmol/l (n 86, P = 0·48).

Conclusions:

Our results are in line with some but not all previous studies on the relationship between BMD and 25(OH)D in adolescents. The observed difference in BMD between those with above v. below a 25(OH)D concentration of 50 nmol/l was of about a fifth of one SD, which may have a clinical relevance as one SD decrease in volumetric BMD has been associated with a 89 % increase in 2 years risk of fracture. Icelandic adolescents should be encouraged to increase their vitamin D intake as it is possible that their current intake is insufficient to achieve optimal peak bone mass.
Prevalence and determinants of vitamin D deficiency and insufficiency among three immigrant groups in Finland: evidence from a population-based study using standardised 25-hydroxyvitamin D data
Authors: Adebayo Folasade A , Itkonen Suvi T , Lilja Eero , Jääskeläinen Tuija , Lundqvist Annamari , Laatikainen Tiina , Koponen Päivikki , Cashman Kevin D , Erkkola Maijaliisa , Lamberg-Allardt Christel
Published: March 2020

Objective:

We investigated the determinants of serum 25-hydroxyvitamin D [S-25(OH)D] and dietary vitamin D sources among three immigrant groups in Finland and compared their S-25(OH)D to the general Finnish population.

Design:

Cross-sectional population-based Migrant Health and Wellbeing Study and the nationally representative Finnish Health 2011 Survey. S-25(OH)D was standardised according to the Vitamin D Standardisation Program. Vitamin D sources were assessed by interview.

Setting:

Six different municipalities in Finland (60°–63°N).

Participants:

Immigrants aged 18–64 years (446 Russians, 346 Somalis, 500 Kurds), 798 Finns aged 30–64 years.

Results:

The mean of S-25(OH)D was 64 (95 % CI 62, 66), 44 (95 % CI 41, 46), 35 (95 % CI 34, 37) and 64 (95 % CI 62, 66) nmol/l for Russians, Somalis, Kurds and Finns, respectively. S-25(OH)D among Somalis and Kurds was lower compared with Finns (P< 0·001). The prevalence of vitamin D deficiency (S-25(OH)D <30 nmol/l) and insufficiency (S-25(OH)D <50 nmol/l) was higher among immigrants than Finns (P< 0·001). Vitamin D-rich foods differed between the groups; vitamin D-fortified fat spread consumption was higher among Somalis (91 %) than among Russians (73 %) and Kurds (60 %); fish was less consumed among Kurds (17 %) than among Russians (43 %) and Somalis (38 %); and 57 % Russians, 56 % Kurds and 36 % Somalis consumed vitamin D-fortified dairy daily (P< 0·001 for all). Daily smoking, alcohol consumption and winter blood sampling were determinants of vitamin D insufficiency (P≤ 0·03). Older age, physical activity, fish and vitamin D-fortified dairy consumption were associated with lower odds of insufficiency (P≤ 0·04).

Conclusions:

Vitamin D status differed among immigrant groups and the determinants are, to some degree, associated with learned or existing cultural behaviours.
Tillage based, site-specific weed control for conservation cropping systems
Authors: Walsh Michael J. , Squires Caleb C. , Coleman Guy R. Y. , Widderick Michael J. , McKiernan Adam B. , Chauhan Bhagirath S. , Peressini Carlo , Guzzomi Andrew L.
Published: March 2020

Australian conservation cropping systems are practiced on very large farms (approximately 3,000 ha) where herbicides are relied on for effective and timely weed control. In many fields, though, there are low weed densities (e.g., <1.0 plant 10 m−2) and whole-field herbicide treatments are wasteful. For fallow weed control, commercially available weed detection systems provide the opportunity for site-specific herbicide treatments, removing the need for whole-field treatment of fallow fields with low weed densities. Concern about the sustainability of herbicide-reliant weed management systems remain and there has not been interest in the use of weed detection systems for alternative weed control technologies, such as targeted tillage. In this paper, we discuss the use of a targeted tillage technique for site-specific weed control in large-scale crop production systems. Three small-scale prototypes were used for engineering and weed control efficacy testing across a range of species and growth stages. With confidence established in the design approach and a demonstrated 100% weed-control potential, a 6-m wide pre-commercial prototype, the “Weed Chipper,” was built incorporating commercially available weed-detection cameras for practical field-scale evaluation. This testing confirmed very high (90%) weed control efficacies and associated low levels (1.8%) of soil disturbance where the weed density was fewer than 1.0 plant 10 m−2 in a commercial fallow. These data established the suitability of this mechanical approach to weed control for conservation cropping systems. The development of targeted tillage for fallow weed control represents the introduction of site-specific, nonchemical weed control for conservation cropping systems.
Climate Extreme Versus Carbon Extreme: Responses of Terrestrial Carbon Fluxes to Temperature and Precipitation
Authors: Pan Shufen , Yang Jia , Tian Hanqin , Shi Hao , Chang Jinfeng , Ciais Philippe , Francois Louis , Frieler Katja , Fu Bojie , Hickler Thomas , Ito Akihiko , Nishina Kazuya , Ostberg Sebastian , Reyer Christopher P.O. , Schaphoff Sibyll , Steinkamp Jörg , Zhao Fang
Published: March 2020

Carbon fluxes at the land‐atmosphere interface are strongly influenced by weather and climate conditions. Yet what is usually known as “climate extremes” does not always translate into very high or low carbon fluxes or so‐called “carbon extremes.” To reveal the patterns of how climate extremes influence terrestrial carbon fluxes, we analyzed the interannual variations in ecosystem carbon fluxes simulated by the Terrestrial Biosphere Models (TBMs) in the Inter‐Sectoral Impact Model Intercomparison Project. At the global level, TBMs simulated reduced ecosystem net primary productivity (NPP; 18.5 ± 9.3 g C m−2 yr−1), but enhanced heterotrophic respiration (Rh; 7 ± 4.6 g C m−2 yr−1) during extremely hot events. TBMs also simulated reduced NPP (60.9 ± 24.4 g C m−2 yr−1) and reduced Rh (16.5 ± 11.4 g C m−2 yr−1) during extreme dry events. Influences of precipitation extremes on terrestrial carbon uptake were larger in the arid/semiarid zones than other regions. During hot extremes, ecosystems in the low latitudes experienced a larger reduction in carbon uptake. However, a large fraction of carbon extremes did not occur in concert with either temperature or precipitation extremes. Rather these carbon extremes are likely to be caused by the interactive effects of the concurrent temperature and precipitation anomalies. The interactive effects showed considerable spatial variations with the largest effects on NPP in South America and Africa. Additionally, TBMs simulated a stronger sensitivity of ecosystem productivity to precipitation than satellite estimates. This study provides new insights into the complex ecosystem responses to climate extremes, especially the emergent properties of carbon dynamics resulting from compound climate extremes.
How Do Gaining and Losing Streams React to the Combined Effects of Climate Change and Pumping in the Gharehsoo River Basin, Iran?
Authors: Taie Semiromi M. , Koch M.
Published: March 2020

Projections of potential impacts of climate change and groundwater abstraction on gaining and losing streams, particularly in ephemeral river basins exhibiting sporadic and intricate flux exchanges, have remained largely unexplored. To fill this gap, we propose a promising modeling scheme based on the new fully integrated hydrological model SWAT‐MODFLOW‐NWT, calibrated and validated for 1978–2012, to quantify the intertwined surface‐groundwater interactions under a conjuncture of three climatic emission scenarios (RCP 2.6, 4.5 and 8.5) and two groundwater pumping variants: “pumping” (extending current groundwater utilization into the future) and “nonpumping” (assuming a complete cease of pumping in the future). By forcing the integrated model with future downscaled climate predictors of CanESM2 under the aforementioned RCPs for three time slices up to year 2100, projections of various water resources components for the Gharehsoo River Basin (GRB), in northwestern Iran were made. Results demonstrate that because of a general decrease of future precipitation, though with ups and downs across the total projection period, most of the surface and ‐subsurface budget quantities and fluxes are substantially affected. In particular, future groundwater discharge (baseflow) to the gaining streams will be more influenced by the “pumping” variant (increasing and decreasing for “nonpumping” and “pumping”, respectively) than the concentrated groundwater recharge from the losing streams (decreasing and increasing for “nonpumping” and “pumping”, respectively). Future water yield and groundwater storage will also diminish and, surprisingly, this cannot be alleviated by future “nonpumping”, indicating the groundwater overutilization is the compelling reason for the future water scarcity in the GRB, rather than climate change alone.
A Model Analysis of the Tidal Engine That Drives Nitrogen Cycling in Coastal Riparian Aquifers
Authors: Wallace Corey D. , Sawyer Audrey H. , Barnes Rebecca T. , Soltanian Mohamad Reza , Gabor Rachel S. , Wilkins Michael J. , Moore Myles T.
Published: March 2020

In coastal rivers, tides facilitate surface water‐groundwater exchange and strongly coupled nitrification‐denitrification near the fluctuating water table. We used numerical fluid flow and reactive transport models to explore hydrogeologic and biogeochemical controls on nitrogen transport along an idealized tidal freshwater zone based on field observations from White Clay Creek, Delaware, USA. The capacity of the riparian aquifer to remove nitrate depends largely on nitrate transport rates, which initially increase with increasing tidal range but then decline as sediments become muddier and permeability decreases. Over the entire model reach, local nitrification provides a similar amount of nitrate as surface and groundwater contributions combined. More than half (~66%) of nitrate removed via denitrification is produced in situ, while the vast majority of remaining nitrate removed comes from groundwater sources. In contrast, average nitrate removal from surface water due to tidal pumping amounts to only ~1% of the average daily in‐channel riverine nitrate load or 1.77 kg of nitrate along the reach each day. As a result, tidal bank storage zones may not be major sinks for nitrate in coastal rivers but can act as effective sinks for groundwater nitrate. By extension, tidal bank storage zones provide a critical ecosystem service, reducing contributions of groundwater nitrate, which is often derived from septic tanks and fertilizers, to coastal rivers.
Global analysis of human glycosyltransferases reveals novel targets for pancreatic cancer pathogenesis
Authors: Gupta Rohitesh , Leon Frank , Thompson Christopher M. , Nimmakayala Ramakrishna , Karmakar Saswati , Nallasamy Palanisamy , Chugh Seema , Prajapati Dipakkumar R. , Rachagani Satyanarayana , Kumar Sushil , Ponnusamy Moorthy P.
Published: March 2020

Background

Several reports have shown the role of glycosylation in pancreatic cancer (PC), but a global systematic screening of specific glycosyltransferases (glycoTs) in its progression remains unknown.

Methods

We demonstrate a rigorous top-down approach using TCGA-based RNA-Seq analysis, multi-step validation using RT-qPCR, immunoblots and immunohistochemistry. We identified six unique glycoTs (B3GNT3, B4GALNT3, FUT3, FUT6, GCNT3 and MGAT3) in PC pathogenesis and studied their function using CRISPR/Cas9-based KD systems.

Results

Serial metastatic in vitro models using T3M4 and HPAF/CD18, generated in house, exhibited decreases in B3GNT3, FUT3 and GCNT3 expression on increasing metastatic potential. Immunohistochemistry identified clinical significance for GCNT3, B4GALNT3 and MGAT3 in PC. Furthermore, the effects of B3GNT3, FUT3, GCNT3 and MGAT3 were shown on proliferation, migration, EMT and stem cell markers in CD18 cell line. Talniflumate, GCNT3 inhibitor, reduced colony formation and migration in T3M4 and CD18 cells. Moreover, we found that loss of GCNT3 suppresses PC progression and metastasis by downregulating cell cycle genes and β-catenin/MUC4 axis. For GCNT3, proteomics revealed downregulation of MUC5AC, MUC1, MUC5B including many other proteins.

Conclusions

Collectively, we demonstrate a critical role of O- and N-linked glycoTs in PC progression and delineate the mechanism encompassing the role of GCNT3 in PC.
Inhibition of topoisomerase IIA (Top2α) induces telomeric DNA damage and T cell dysfunction during chronic viral infection
Authors: Dang Xindi , Ogbu Stella C. , Zhao Juan , Nguyen Lam Ngoc Thao , Cao Dechao , Nguyen Lam Nhat , Khanal Sushant , Schank Madison , Thakuri Bal Krishna Chand , Wu Xiao Y. , Morrison Zheng D. , Zhang Jinyu , Li Zhengke , El Gazzar Mohamed , Ning Shunbin , Wang Ling , Wang Zhengqiang , Moorman Jonathan P. , Yao Zhi Q.
Published: March 2020

T cells play a critical role in controlling viral infection; however, the mechanisms regulating their responses remain incompletely understood. Here, we investigated the role of topoisomerase IIA (Top2α, an enzyme that is essential in resolving entangled DNA strands during replication) in telomeric DNA damage and T cell dysfunction during viral infection. We demonstrated that T cells derived from patients with chronic viral (HBV, HCV, and HIV) infection had lower Top2α protein levels and enzymatic activity, along with an accumulation of the Top2α cleavage complex (Top2cc) in genomic DNA. In addition, T cells from virally infected subjects with lower Top2α levels were vulnerable to Top2α inhibitor-induced cell apoptosis, indicating an important role for Top2α in preventing DNA topological disruption and cell death. Using Top2α inhibitor (ICRF193 or Etoposide)-treated primary T cells as a model, we demonstrated that disrupting the DNA topology promoted DNA damage and T cell apoptosis via Top2cc accumulation that is associated with protein-DNA breaks (PDB) at genomic DNA. Disruption of the DNA topology was likely due to diminished expression of tyrosyl-DNA phosphodiesterase 2 (TDP2), which was inhibited in T cells in vitro by Top2α inhibitor and in vivo by chronic viral infection. These results suggest that immune-evasive viruses (HBV, HCV, and HIV) can disrupt T cell DNA topology as a mechanism of dysregulating host immunity and establishing chronic infection. Thus, restoring the DNA topologic machinery may serve as a novel strategy to protect T cells from unwanted DNA damage and to maintain immune competence.
Comprehensive genomic analysis of dietary habits in UK Biobank identifies hundreds of genetic associations
Authors: Cole Joanne B. , Florez Jose C. , Hirschhorn Joel N.
Published: March 2020

Unhealthful dietary habits are leading risk factors for life-altering diseases and mortality. Large-scale biobanks now enable genetic analysis of traits with modest heritability, such as diet. We perform a genomewide association on 85 single food intake and 85 principal component-derived dietary patterns from food frequency questionnaires in UK Biobank. We identify 814 associated loci, including olfactory receptor associations with fruit and tea intake; 136 associations are only identified using dietary patterns. Mendelian randomization suggests our top healthful dietary pattern driven by wholemeal vs. white bread consumption is causally influenced by factors correlated with education but is not strongly causal for coronary artery disease or type 2 diabetes. Overall, we demonstrate the value in complementary phenotyping approaches to complex dietary datasets, and the utility of genomic analysis to understand the relationships between diet and human health.
Nonlinear plasmon-exciton coupling enhances sum-frequency generation from a hybrid metal/semiconductor nanostructure
Authors: Zhong Jin-Hui , Vogelsang Jan , Yi Jue-Min , Wang Dong , Wittenbecher Lukas , Mikaelsson Sara , Korte Anke , Chimeh Abbas , Arnold Cord L. , Schaaf Peter , Runge Erich , Huillier Anne L’ , Mikkelsen Anders , Lienau Christoph
Published: March 2020

The integration of metallic plasmonic nanoantennas with quantum emitters can dramatically enhance coherent harmonic generation, often resulting from the coupling of fundamental plasmonic fields to higher-energy, electronic or excitonic transitions of quantum emitters. The ultrafast optical dynamics of such hybrid plasmon–emitter systems have rarely been explored. Here, we study those dynamics by interferometrically probing nonlinear optical emission from individual porous gold nanosponges infiltrated with zinc oxide (ZnO) emitters. Few-femtosecond time-resolved photoelectron emission microscopy reveals multiple long-lived localized plasmonic hot spot modes, at the surface of the randomly disordered nanosponges, that are resonant in a broad spectral range. The locally enhanced plasmonic near-field couples to the ZnO excitons, enhancing sum-frequency generation from individual hot spots and boosting resonant excitonic emission. The quantum pathways of the coupling are uncovered from a two-dimensional spectrum correlating fundamental plasmonic excitations to nonlinearly driven excitonic emissions. Our results offer new opportunities for enhancing and coherently controlling optical nonlinearities by exploiting nonlinear plasmon-quantum emitter coupling.
Output from VIP cells of the mammalian central clock regulates daily physiological rhythms
Authors: Paul Sarika , Hanna Lydia , Harding Court , Hayter Edward A. , Walmsley Lauren , Bechtold David A. , Brown Timothy M.
Published: March 2020

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing.
FAM13A affects body fat distribution and adipocyte function
Authors: Fathzadeh Mohsen , Li Jiehan , Rao Abhiram , Cook Naomi , Chennamsetty Indumathi , Seldin Marcus , Zhou Xiang , Sangwung Panjamaporn , Gloudemans Michael J. , Keller Mark , Attie Allan , Yang Jing , Wabitsch Martin , Carcamo-Orive Ivan , Tada Yuko , Lusis Aldons J. , Shin Myung Kyun , Molony Cliona M. , McLaughlin Tracey , Reaven Gerald , Montgomery Stephen B. , Reilly Dermot , Quertermous Thomas , Ingelsson Erik , Knowles Joshua W.
Published: March 2020

Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcutaneous adipose tissue (SAT) and an insulin resistance-related phenotype (e.g. higher waist-to-hip ratio and fasting insulin levels, but lower body fat). In human adipocyte models, knockdown of FAM13A in preadipocytes accelerates adipocyte differentiation. In mice, Fam13a knockout (KO) have a lower visceral to subcutaneous fat (VAT/SAT) ratio after high-fat diet challenge, in comparison to their wild-type counterparts. Subcutaneous adipocytes in KO mice show a size distribution shift toward an increased number of smaller adipocytes, along with an improved adipogenic potential. Our results indicate that GWAS-associated variants within the FAM13A locus alter adipose FAM13A expression, which in turn, regulates adipocyte differentiation and contribute to changes in body fat distribution.
Rac1 activates non-oxidative pentose phosphate pathway to induce chemoresistance of breast cancer
Authors: Li Qingjian , Qin Tao , Bi Zhuofei , Hong Huangming , Ding Lin , Chen Jiewen , Wu Wei , Lin Xiaorong , Fu Wenkui , Zheng Fang , Yao Yandan , Luo Man-Li , Saw Phei Er , Wulf Gerburg M. , Xu Xiaoding , Song Erwei , Yao Herui , Hu Hai
Published: March 2020

Resistance development to one chemotherapeutic reagent leads frequently to acquired tolerance to other compounds, limiting the therapeutic options for cancer treatment. Herein, we find that overexpression of Rac1 is associated with multi-drug resistance to the neoadjuvant chemotherapy (NAC). Mechanistically, Rac1 activates aldolase A and ERK signaling which up-regulates glycolysis and especially the non-oxidative pentose phosphate pathway (PPP). This leads to increased nucleotides metabolism which protects breast cancer cells from chemotherapeutic-induced DNA damage. To translate this finding, we develop endosomal pH-responsive nanoparticles (NPs) which deliver Rac1-targeting siRNA together with cisplatin and effectively reverses NAC-chemoresistance in PDXs from NAC-resistant breast cancer patients. Altogether, our findings demonstrate that targeting Rac1 is a potential strategy to overcome acquired chemoresistance in breast cancer.
Publisher Correction: MEMOTE for standardized genome-scale metabolic model testing
Authors: Lieven Christian , Beber Moritz E. , Olivier Brett G. , Bergmann Frank T. , Ataman Meric , Babaei Parizad , Bartell Jennifer A. , Blank Lars M. , Chauhan Siddharth , Correia Kevin , Diener Christian , Dräger Andreas , Ebert Birgitta E. , Edirisinghe Janaka N. , Faria José P. , Feist Adam M. , Fengos Georgios , Fleming Ronan M. T. , García-Jiménez Beatriz , Hatzimanikatis Vassily , van Helvoirt Wout , Henry Christopher S. , Hermjakob Henning , Herrgård Markus J. , Kaafarani Ali , Kim Hyun Uk , King Zachary , Klamt Steffen , Klipp Edda , Koehorst Jasper J. , König Matthias , Lakshmanan Meiyappan , Lee Dong-Yup , Lee Sang Yup , Lee Sunjae , Lewis Nathan E. , Liu Filipe , Ma Hongwu , Machado Daniel , Mahadevan Radhakrishnan , Maia Paulo , Mardinoglu Adil , Medlock Gregory L. , Monk Jonathan M. , Nielsen Jens , Nielsen Lars Keld , Nogales Juan , Nookaew Intawat , Palsson Bernhard O. , Papin Jason A. , Patil Kiran R. , Poolman Mark , Price Nathan D. , Resendis-Antonio Osbaldo , Richelle Anne , Rocha Isabel , Sánchez Benjamín J. , Schaap Peter J. , Sheriff Rahuman S. Malik , Shoaie Saeed , Sonnenschein Nikolaus , Teusink Bas , Vilaça Paulo , Vik Jon Olav , Wodke Judith A. H. , Xavier Joana C. , Yuan Qianqian , Zakhartsev Maksim , Zhang Cheng
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Using already-solved cases of a mass disaster event for prioritizing the search among remaining victims: a Bayesian approach
Authors: Caridi Inés , Alvarez Enrique E. , Somigliana Carlos , Puerto Mercedes Salado
Published: March 2020

This work presents a new method for assisting in the identification process of missing persons in several contexts, such as enforced disappearances. We apply a Bayesian technique to incorporate non-genetic variables in the construction of prior information. In that way, we can learn from the already-solved cases of a particular mass event of death, and use that information to guide the search among remaining victims. This paper describes a particular application to the proposed method to the identification of human remains of the so-called disappeared during the last dictatorship in Argentina, which lasted from 1976 until 1983. Potential applications of the techniques presented hereby, however, are much wider. The central idea of our work is to take advantage of the already-solved cases within a certain event to use the gathered knowledge to assist in the investigation process, enabling the construction of prioritized rankings of victims that could correspond to each certain unidentified human remains.
Replication of FTO Gene associated with lean mass in a Meta-Analysis of Genome-Wide Association Studies
Authors: Ran Shu , Jiang Zi-Xuan , He Xiao , Liu Yu , Zhang Yu-Xue , Zhang Lei , Pei Yu-Fang , Zhang Meng , Hai Rong , Gu Gui-Shan , Liu Bao-Lin , Tian Qing , Zhang Yong-Hong , Wang Jing-Yu , Deng Hong-Wen
Published: March 2020

Sarcopenia is characterized by low skeletal muscle, a complex trait with high heritability. With the dramatically increasing prevalence of obesity, obesity and sarcopenia occur simultaneously, a condition known as sarcopenic obesity. Fat mass and obesity-associated (FTO) gene is a candidate gene of obesity. To identify associations between lean mass and FTO gene, we performed a genome-wide association study (GWAS) of lean mass index (LMI) in 2207 unrelated Caucasian subjects and replicated major findings in two replication samples including 6,004 unrelated Caucasian and 38,292 unrelated Caucasian. We found 29 single nucleotide polymorphisms (SNPs) in FTO significantly associated with sarcopenia (combined p-values ranging from 5.92 × 10−12 to 1.69 × 10−9). Potential biological functions of SNPs were analyzed by HaploReg v4.1, RegulomeDB, GTEx, IMPC and STRING. Our results provide suggestive evidence that FTO gene is associated with lean mass.