bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale and methods of the IDOMENEO health outcomes of the peripheral arterial disease revascularisation study in the GermanVasc registry
Authors: Debus Eike Sebastian , Kriston Levente , Schwaneberg Thea , Hischke Sandra , Rieß Henrik Christian , Härter Martin , Marschall Ursula , Federrath Hannes , Behrendt Christian-Alexander
Published: August 2018

Abstract. Background: Atherosclerotic disease of the lower extremity arteries (PAD) remains a significant burden on global healthcare systems with increasing prevalence. Various guidelines on the diagnosis and treatment of patients with PAD are available but they often lack a sufficient evidence base for high-grade recommendations since randomized and controlled trials (RCT) remain rare or are frequently subject to conflicts of interest. This registry trial aims to evaluate the outcomes of catheter-based endovascular revascularisations vs. open-surgical endarterectomy vs. bypass surgery for symptomatic PAD on medical and patient-reported outcomes. Methods and design: The study is a prospective non-randomized multicentre registry trial including invasive revascularisations performed in 10 000 patients treated for symptomatic PAD at 30 to 40 German vascular centres. All patients matching the inclusion criteria are consecutively included for a recruitment period of six months (between May and December 2018) or until 10 000 patients have been included in the study registry. There are three follow-up measures at three, six, and 12 months. Automated completeness and plausibility checks as well as independent site visit monitoring will be performed to assure high internal and external validity of the study data. Study endpoints include relevant major cardiovascular and limb events and patient-reported outcomes from two Delphi studies with experts in vascular medicine and registry-based research. Discussion: It remains unclear if results from RCT can reflect daily treatment practice. Furthermore, great costs and complexity make it challenging to accomplish high quality randomized trials in PAD treatment. Prospective registry-based studies to collect real-world evidence can help to overcome these limitations.
Developing Behavior Change Interventions for Self-Management in	Chronic Illness
Authors: Araújo-Soares Vera , Hankonen Nelli , Presseau Justin , Rodrigues Angela , Sniehotta Falko F.
Published: August 2018

Abstract. More people than ever are living longer with chronic conditions such as obesity, type 2 diabetes, and heart disease. Behavior change for effective self-management can improve health outcomes and quality of life in people living with such chronic illnesses. The science of developing behavior change interventions with impact for patients aims to optimize the reach, effectiveness, adoption, implementation, and maintenance of interventions and rigorous evaluation of outcomes and processes of behavior change. The development of new services and technologies offers opportunities to enhance the scope of delivery of interventions to support behavior change and self-management at scale. Herein, we review key contemporary approaches to intervention development, provide a critical overview, and integrate these approaches into a pragmatic, user-friendly framework to rigorously guide decision-making in behavior change intervention development. Moreover, we highlight novel emerging methods for rapid and agile intervention development. On-going progress in the science of intervention development is needed to remain in step with such new developments and to continue to leverage behavioral science’s capacity to contribute to optimizing interventions, modify behavior, and facilitate self-management in individuals living with chronic illness.
Three Paradoxical Effects on Academic Self-Concept Across Countries,	Schools, and Students
Authors: Marsh Herbert W. , Parker Philip D. , Pekrun Reinhard
Published: August 2018

Abstract. We simultaneously resolve three paradoxes in academic self-concept research with a single unifying meta-theoretical model based on frame-of-reference effects across 68 countries, 18,292 schools, and 485,490 15-year-old students. Paradoxically, but consistent with predictions, effects on math self-concepts were negative for: • being from countries where country-average achievement was high; explaining the paradoxical cross-cultural self-concept effect; • attending schools where school-average achievement was high; demonstrating big-fish-little-pond-effects (BFLPE) that generalized over 68 countries, Organisation for Economic Co-operation and Development (OECD)/non-OECD countries, high/low achieving schools, and high/low achieving students; • year-in-school relative to age; unifying different research literatures for associated negative effects for starting school at a younger age and acceleration/skipping grades, and positive effects for starting school at an older age (“academic red shirting”) and, paradoxically, even for repeating a grade.

Contextual effects matter, resulting in significant and meaningful effects on self-beliefs, not only at the student (year in school) and local school level (BFLPE), but remarkably even at the macro-contextual country-level. Finally, we juxtapose cross-cultural generalizability based on Programme for International Student Assessment (PISA) data used here with generalizability based on meta-analyses, arguing that although the two approaches are similar in many ways, the generalizability shown here is stronger in terms of support for the universality of the frame-of-reference effects.
How Much Land Surface Is Under Water at Any Given Time?
Authors: Pavelsky Tamlin , Minear J.
Published: August 2018

NASA Workshop on Remote Sensing of Inundation Extent; Boulder, Colorado, 21–22 May 2018
Global Responses of the Coupled Thermosphere and Ionosphere System to the August 2017 Great American Solar Eclipse
Authors: Dang Tong , Lei Jiuhou , Wang Wenbin , Zhang Binzheng , Burns Alan , Le Huijun , Wu Qian , Ruan Haibing , Dou Xiankang , Wan Weixing
Published: August 2018

It is commonly believed that solar eclipses have a great impact on the ionosphere‐thermosphere (I‐T) system within the eclipse shadow, but little attention has been paid to the global response to these events. In this study, we investigate the global upper atmospheric responses to the recent Great American Solar Eclipse that occurred on 21 August 2017 using a high‐resolution coupled ionosphere‐thermosphere‐electrodynamics model. The simulation results show that the ionosphere and thermosphere response to the eclipse is not just local but global. Large‐scale traveling atmospheric disturbances (TADs), seen in the thermospheric temperature and winds, were triggered from the eclipse region and propagated in a southeast direction when the eclipse ended. A large total electron content (TEC) enhancement occurred over South America after the eclipse was over. The TEC enhancement was primarily the result of transport by the thermospheric wind perturbations associated with the eclipse‐induced TADs. The perturbations of TEC, neutral temperature, and winds exhibited asymmetric distributions with respect to the totality path during the solar eclipse. Furthermore, ionospheric electrodynamic processes also play an important role in the global responses of the I‐T system to the solar eclipse. Unlike the case of large‐scale TADs propagating from the eclipse region to other locations in the globe, the ionospheric electric fields and plasma drifts began to show significant perturbations even during the local pre‐eclipse period when local wind and temperature had not been perturbed. This is related to the instantaneous global response of the ionospheric current system to changes in the ionospheric conductivity and winds in the eclipse region.
Deposition and Fate of Mercury in Litterfall, Litter, and Soil in Coniferous and Broad‐Leaved Forests
Authors: Zhou Jun , Wang Zhangwei , Zhang Xiaoshan
Published: August 2018

Mercury dynamics in the process of litter decomposition is crucial to understanding the atmospheric mercury deposition to soils in the forest catchments. This work aimed to quantify mercury internal biogeochemical cycling and the fractionation process in a coniferous forest and a broad‐leaved forest in southwest China. Annual deposition fluxes of total mercury (THg) and methylmercury (MeHg) via litterfall were 40.5 and 0.10 μg/m2 in the coniferous forest and were 90.9 and 0.34 μg/m2 in the broad‐leaved forest, respectively. The litterfall biomass was the most influential factor resulting in the higher mercury input in the broad‐leaved forest. During the one‐year incubation, THg and MeHg mass in the decomposing litter increased 49 and 444% in the coniferous forest compared to those in the broad‐leaved forest, respectively. Methylation has increased the risk of MeHg mobilization to aquatic and soil ecosystems during litter decomposition. Additionally, higher mercury deposition flux but lower accumulation in the broad‐leaved forest resulted in similar mercury content in the coniferous forest soils. Six mercury fractions were determined by sequential extraction for the decomposing litter, while MeHg concentrations were statistically significantly correlated to water soluble and salt soluble fractions. The residual mercury fraction accounted for over 90% of the THg and increased with litter decomposition. During the last half of the litter decomposition, the ratio of residual fraction significantly increased, while the sum of the other ratios reduced, which indicated that litter dynamics in the internal forests stabilized the mercury in organic soils during litter decomposition.
Biphasic cellular adaptations and ecological implications of Alteromonas macleodii degrading a mixture of algal polysaccharides
Authors: Koch Hanna , Dürwald Alexandra , Schweder Thomas , Noriega-Ortega Beatriz , Vidal-Melgosa Silvia , Hehemann Jan-Hendrik , Dittmar Thorsten , Freese Heike M , Becher Dörte , Simon Meinhard , Wietz Matthias
Published: August 2018

Algal polysaccharides are an important bacterial nutrient source and central component of marine food webs. However, cellular and ecological aspects concerning the bacterial degradation of polysaccharide mixtures, as presumably abundant in natural habitats, are poorly understood. Here, we contextualize marine polysaccharide mixtures and their bacterial utilization in several ways using the model bacterium Alteromonas macleodii 83-1, which can degrade multiple algal polysaccharides and contributes to polysaccharide degradation in the oceans. Transcriptomic, proteomic and exometabolomic profiling revealed cellular adaptations of A. macleodii 83-1 when degrading a mix of laminarin, alginate and pectin. Strain 83-1 exhibited substrate prioritization driven by catabolite repression, with initial laminarin utilization followed by simultaneous alginate/pectin utilization. This biphasic phenotype coincided with pronounced shifts in gene expression, protein abundance and metabolite secretion, mainly involving CAZymes/polysaccharide utilization loci but also other functional traits. Distinct temporal changes in exometabolome composition, including the alginate/pectin-specific secretion of pyrroloquinoline quinone, suggest that substrate-dependent adaptations influence chemical interactions within the community. The ecological relevance of cellular adaptations was underlined by molecular evidence that common marine macroalgae, in particular Saccharina and Fucus, release mixtures of alginate and pectin-like rhamnogalacturonan. Moreover, CAZyme microdiversity and the genomic predisposition towards polysaccharide mixtures among Alteromonas spp. suggest polysaccharide-related traits as an ecophysiological factor, potentially relating to distinct ‘carbohydrate utilization types’ with different ecological strategies. Considering the substantial primary productivity of algae on global scales, these insights contribute to the understanding of bacteria–algae interactions and the remineralization of chemically diverse polysaccharide pools, a key step in marine carbon cycling.
Diverse diazotrophs are present on sinking particles in the North Pacific Subtropical Gyre
Authors: Farnelid Hanna , Turk-Kubo Kendra , Ploug Helle , Ossolinski Justin E , Collins James R , Van Mooy Benjamin A S , Zehr Jonathan P
Published: August 2018

Sinking particles transport carbon and nutrients from the surface ocean into the deep sea and are considered hot spots for bacterial diversity and activity. In the oligotrophic oceans, nitrogen (N2)-fixing organisms (diazotrophs) are an important source of new N but the extent to which these organisms are present and exported on sinking particles is not well known. Sinking particles were collected every 6 h over a 2-day period using net traps deployed at 150 m in the North Pacific Subtropical Gyre. The bacterial community and composition of diazotrophs associated with individual and bulk sinking particles was assessed using 16S rRNA and nifH gene amplicon sequencing. The bacterial community composition in bulk particles remained remarkably consistent throughout time and space while large variations of individually picked particles were observed. This difference suggests that unique biogeochemical conditions within individual particles may offer distinct ecological niches for specialized bacterial taxa. Compared to surrounding seawater, particle samples were enriched in different size classes of globally significant N2-fixing cyanobacteria including Trichodesmium, symbionts of diatoms, and the unicellular cyanobacteria Crocosphaera and UCYN-A. The particles also contained nifH gene sequences of diverse non-cyanobacterial diazotrophs suggesting that particles could be loci for N2 fixation by heterotrophic bacteria. The results demonstrate that diverse diazotrophs were present on particles and that new N may thereby be directly exported from surface waters on sinking particles.
Genetic diversity and phenotypic plasticity of AHL-mediated Quorum sensing in environmental strains of Vibrio mediterranei
Authors: Girard Léa , Lantoine François , Lami Raphaël , Vouvé Florence , Suzuki Marcelino T , Baudart Julia
Published: August 2018

N-Acyl homoserine lactone (AHL)-mediated Quorum sensing (QS) is one of the most studied social behavior among Proteobacteria. However, despite the current knowledge on QS-associated phenotypes such as bioluminescence, biofilm formation, or pathogenesis, the characterization of environmental factors driving QS in realistic ecological settings remains scarce. We investigated the dynamics of AHL and AHL-producing Vibrio among 840 isolates  collected fortnightly from the Salses-Leucate Mediterranean lagoon in spring and summer 2015 and 2016. Vibrio isolates were characterized by gyrB gene sequencing, Enterobacterial repetitive intergenic consensus polymerase chain reaction, and genome sequencing, and AHL production was investigated by a biosensors-based UHPLC–HRMS/MS approach. Our results revealed, for the first time, a succession of V. mediterranei isolates with different AHL production phenotypes over time and this dynamics was observed in a single genotype (average genomic nucleotide identity >99.9). A multivariate DistLM analysis revealed that 83.4% of the temporal variation of V. mediterranei QS phenotypes was explained by environmental variables. Overall, our results suggest that isolates of a single genotype are able to change their QS phenotypes in response to environmental conditions, highlighting the phenotypic plasticity of bacterial communication in the environment.
Effect of valproate and pregabalin on human anxiety-like behaviour in a randomised controlled trial
Authors: Bach Dominik R. , Korn Christoph W. , Vunder Johanna , Bantel Antonia
Published: August 2018

Valproate is an anticonvulsant drug with strong preclinical evidence for reducing anxiety behaviour in rodents but no clear clinical evidence. To motivate clinical trials, we here investigate the use of valproate in a translational human model of anxiety behaviour. In a double-blind, randomised, placebo-controlled trial, n = 118 healthy participants played a previously validated approach/avoidance conflict computer game to measure anxiety-like behaviour, while under 400 mg valproate, under 200 mg of the established anxiolytic/anticonvulsant pregabalin, or under placebo. Saccadic peak velocity and subjective ratings were assessed to control for drug-induced sedation. Compared to placebo, valproate and pregabaline were anxiolytic in the primary outcome, and several secondary outcomes. Bayesian model comparison decisively demonstrated no differences between the two drugs. Subjective and objective sedation was significantly more pronounced under pregabalin than valproate, but did not explain anxiolytic effects. We demonstrate acute anxiolytic properties of valproate in healthy humans. Both drugs have similar anxiolytic properties at the doses used. Valproate is less sedative than pregabalin. Our results suggest clinical trials on the use of valproate in anxiolytic treatment. More generally, we propose a strategy of screening drugs in human preclinical models that can directly be compared across species, such as the approach/avoidance conflict computer game used here. This approach could thus facilitate translational anxiety research.
Neural hypersensitivity to pleasant touch in women remitted from anorexia nervosa
Authors: Bischoff-Grethe Amanda , Wierenga Christina E. , Berner Laura A. , Simmons Alan N. , Bailer Ursula , Paulus Martin P. , Kaye Walter H.
Published: August 2018

Interoception, or the sensing and integration of bodily state signals, has been implicated in anorexia nervosa (AN), given that the hallmark symptoms involve food restriction and body image disturbance. Here we focus on brain response to the anticipation and experience of affective interoceptive stimuli. Women remitted from AN (RAN;N = 18) and healthy comparison women (CW;N = 26) underwent a pleasant affective touch paradigm consisting of gentle strokes with a soft brush administered to the forearm or palm during functional neuroimaging. RAN had a lower brain response relative to CW during anticipation of touch, but a greater response when experiencing touch in the right ventral mid-insula. In RAN, this reduced anticipatory response was associated with higher levels of harm avoidance. Exploratory analyses in RAN also suggested that lower response during touch anticipation was associated with greater body dissatisfaction and higher perceived touch intensity ratings. This reduced responsivity to the anticipation of pleasant affective interoceptive stimuli in association with higher harm avoidance, along with an elevated response to the experience of touch, suggests an impaired ability in AN to predict and interpret incoming physiological stimuli. Impaired interoception may thus impact one’s sense of self, thereby supporting observations of disturbed body image and avoidance of affective and social stimuli. Therapeutic approaches that help AN to better anticipate and interpret salient affective stimuli or improve tolerance of interoceptive experiences may be an important addition to current interventions.
Genomic patterns of progression in smoldering multiple myeloma
Authors: Bolli Niccolò , Maura Francesco , Minvielle Stephane , Gloznik Dominik , Szalat Raphael , Fullam Anthony , Martincorena Inigo , Dawson Kevin J. , Samur Mehmet Kemal , Zamora Jorge , Tarpey Patrick , Davies Helen , Fulciniti Mariateresa , Shammas Masood A. , Tai Yu Tzu , Magrangeas Florence , Moreau Philippe , Corradini Paolo , Anderson Kenneth , Alexandrov Ludmil , Wedge David C. , Avet-Loiseau Herve , Campbell Peter , Munshi Nikhil
Published: August 2018

We analyzed whole genomes of unique paired samples from smoldering multiple myeloma (SMM) patients progressing to multiple myeloma (MM). We report that the genomic landscape, including mutational profile and structural rearrangements at the smoldering stage is very similar to MM. Paired sample analysis shows two different patterns of progression: a “static progression model”, where the subclonal architecture is retained as the disease progressed to MM suggesting that progression solely reflects the time needed to accumulate a sufficient disease burden; and a “spontaneous evolution model”, where a change in the subclonal composition is observed. We also observe that activation-induced cytidine deaminase plays a major role in shaping the mutational landscape of early subclinical phases, while progression is driven by APOBEC cytidine deaminases. These results provide a unique insight into myelomagenesis with potential implications for the definition of smoldering disease and timing of treatment initiation.
Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies
Authors: Pardi Norbert , Parkhouse Kaela , Kirkpatrick Ericka , McMahon Meagan , Zost Seth J. , Mui Barbara L. , Tam Ying K. , Karikó Katalin , Barbosa Christopher J. , Madden Thomas D. , Hope Michael J. , Krammer Florian , Hensley Scott E. , Weissman Drew
Published: August 2018

Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.
Hapten-mediated recruitment of polyclonal antibodies to tumors engenders antitumor immunity
Authors: Schrand Brett , Clark Emily , Levay Agata , Capote Ailem Rabasa , Martinez Olivier , Brenneman Randall , Castro Iris , Gilboa Eli
Published: August 2018

Uptake of tumor antigens by tumor-infiltrating dendritic cells is limiting step in the induction of tumor immunity, which can be mediated through Fc receptor (FcR) triggering by antibody-coated tumor cells. Here we describe an approach to potentiate tumor immunity whereby hapten-specific polyclonal antibodies are recruited to tumors by coating tumor cells with the hapten. Vaccination of mice against dinitrophenol (DNP) followed by systemic administration of DNP targeted to tumors by conjugation to a VEGF or osteopontin aptamer elicits potent FcR dependent, T cell mediated, antitumor immunity. Recruitment of αGal-specific antibodies, the most abundant naturally occurring antibodies in human serum, inhibits tumor growth in mice treated with a VEGF aptamer–αGal hapten conjugate, and recruits antibodies from human serum to human tumor biopsies of distinct origin. Thus, treatment with αGal hapten conjugated to broad-spectrum tumor targeting ligands could enhance the susceptibility of a broad range of tumors to immune elimination.
One-pot aminobenzylation of aldehydes with toluenes
Authors: Wang Zhiting , Zheng Zhipeng , Xu Xinyu , Mao Jianyou , Walsh Patrick J.
Published: August 2018

Amines are fundamental motifs in bioactive natural products and pharmaceuticals. Using simple toluene derivatives, a one-pot aminobenzylation of aldehydes is introduced that provides rapid access to amines. Simply combining benzaldehydes, toluenes, NaN(SiMe3)2, and additive Cs(O2CCF3) (0.35 equiv.) generates a diverse array of 1,2-diarylethylamine derivatives (36 examples, 56–98% yield). Furthermore, suitably functionalized 1,2-diarylethylamines were transformed into 2-aryl-substituted indoline derivatives via Buchwald–Hartwig amination. It is proposed that the successful deprotonation of toluene by MN(SiMe3)2 is facilitated by cation–π interactions between the arene and the group(I) cation that acidify the benzylic C–Hs.
Precession-band variance missing from East Asian monsoon runoff
Authors: Clemens S. C. , Holbourn A. , Kubota Y. , Lee K. E. , Liu Z. , Chen G. , Nelson A. , Fox-Kemper B.
Published: August 2018

Speleothem CaCO3 δ18O is a commonly employed paleomonsoon proxy. However, inferring local rainfall amount from speleothem δ18O can be complicated due to changing source water δ18O, temperature effects, and rainout over the moisture transport path. These complications are addressed using δ18O of planktonic foraminiferal CaCO3, offshore from the Yangtze River Valley (YRV). The advantage is that the effects of global seawater δ18O and local temperature changes can be quantitatively removed, yielding a record of local seawater δ18O, a proxy that responds primarily to dilution by local precipitation and runoff. Whereas YRV speleothem δ18O is dominated by precession-band (23 ky) cyclicity, local seawater δ18O is dominated by eccentricity (100 ky) and obliquity (41 ky) cycles, with almost no precession-scale variance. These results, consistent with records outside the YRV, suggest that East Asian monsoon rainfall is more sensitive to greenhouse gas and high-latitude ice sheet forcing than to direct insolation forcing.
V2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements
Authors: Song Jianren , Dahlberg Elin , El Manira Abdeljabbar
Published: August 2018

Locomotion is a complex motor task generated by spinal circuits driving motoneurons in a precise sequence to control the timing and vigor of movements, but the underlying circuit logic remains to be understood. Here we reveal, in adult zebrafish, how the diversity and selective distribution of two V2a interneuron types within the locomotor network transform commands into an appropriate, task-dependent circuit organization. Bursting-type V2a interneurons with unidirectional axons predominantly target distal dendrites of slow motoneurons to provide potent, non-linear excitation involving NMDA-dependent potentiation. A second type, non-bursting V2a interneurons with bidirectional axons, predominantly target somata of fast motoneurons, providing weaker, non-potentiating excitation. Together, this ensures the rapid, first-order recruitment of the slow circuit, while reserving the fast circuit for highly salient stimuli involving synchronous inputs. Our results thus identify how interneuron diversity is captured and transformed into a parsimonious task-specific circuit design controlling the vigor of locomotion.
Experience-dependent structural plasticity targets dynamic filopodia in regulating dendrite maturation and synaptogenesis
Authors: Sheng Chengyu , Javed Uzma , Gibbs Mary , Long Caixia , Yin Jun , Qin Bo , Yuan Quan
Published: August 2018

Highly motile dendritic protrusions are hallmarks of developing neurons. These exploratory filopodia sample the environment and initiate contacts with potential synaptic partners. To understand the role for dynamic filopodia in dendrite morphogenesis and experience-dependent structural plasticity, we analyzed dendrite dynamics, synapse formation, and dendrite volume expansion in developing ventral lateral neurons (LNvs) of the Drosophila larval visual circuit. Our findings reveal the temporal coordination between heightened dendrite dynamics with synaptogenesis in LNvs and illustrate the strong influence imposed by sensory experience on the prevalence of dendritic filopodia, which regulate the formation of synapses and the expansion of dendritic arbors. Using genetic analyses, we further identified Amphiphysin (Amph), a BAR (Bin/Amphiphysin/Rvs) domain-containing protein as a required component for tuning the dynamic state of LNv dendrites and promoting dendrite maturation. Taken together, our study establishes dynamic filopodia as the key cellular target for experience-dependent regulation of dendrite development.
Entropy contributions to phase stability in binary random solid solutions
Authors: Manzoor Anus , Pandey Shubham , Chakraborty Debajit , Phillpot Simon R. , Aidhy Dilpuneet S.
Published: August 2018

High entropy alloys contain multiple elements in large proportions that make them prone to phase separation. These alloys generally have shallow enthalpy of mixing which makes the entropy contributions of similar magnitude. As a result, the phase stability of these alloys is equally dependent on enthalpy and entropy of mixing and understanding the individual contribution of thermodynamic properties is critical. In the overall vision of designing high entropy alloys, in this work, using density functional theory calculations, we elucidate the contributions of various entropies, i.e., vibrational, electronic and configurational towards the phase stability of binary alloys. We show that the contribution of electronic entropy is very small compared to the vibrational and configurational entropies, and does not play a significant role in the phase stability of alloys. The configurational and vibrational entropies can either destabilize or can collectively contribute to stabilize the solid solutions. As a result, even those systems that have negative mixing enthalpy can show phase instability, revealed as a miscibility gap; conversely, systems with positive mixing enthalpy can be phase stable due to entropic contributions. We suggest that including entropic contributions are critical in the development of theoretical framework for the computational prediction of stable, single-phase high entropy alloys that have shallow mixing enthalpies, unlike ordered intermetallics.
1q21.1 microduplication: large verbal–nonverbal performance discrepancy and ddPCR assays of HYDIN/HYDIN2 copy number
Authors: Xavier Jean , Zhou Bo , Bilan Frédéric , Zhang Xianglong , Gilbert-Dussardier Brigitte , Viaux-Savelon Sylvie , Pattni Reenal , Ho Steve S. , Cohen David , Levinson Douglas F. , Urban Alexander E. , Laurent-Levinson Claudine
Published: August 2018

Microduplication of chromosome 1q21.1 is observed in ~0.03% of adults. It has a highly variable, incompletely penetrant phenotype that can include intellectual disability, global developmental delay, specific learning disabilities, autism, schizophrenia, heart anomalies and dysmorphic features. We evaluated a 10-year-old-male with a 1q21.1 duplication by CGH microarray. He presented with major attention deficits, phonological dysphasia, poor fine motor skills, dysmorphia and mild autistic features, but not the typical macrocephaly. Neuropsychiatric evaluation demonstrated a novel phenotype: an unusually large discrepancy between non-verbal capacities (borderline-impaired WISC-IV index scores of 70 for Working Memory and 68 for Processing Speed) vs. strong verbal skills – scores of 126 for Verbal Comprehension (superior) and 111 for Perceptual Reasoning (normal). HYDIN2 has been hypothesized to underlie macrocephaly and perhaps cognitive deficits in this syndrome, but assessment of HYDIN2 copy number by microarray is difficult because of extensive segmental duplications. We performed whole-genome sequencing which supported HYDIN2 duplication (chr1:146,370,001-148,590,000, 2.22 Mb, hg38). To evaluate copy number more rigorously we developed droplet digital PCR assays of HYDIN2 (targeting unique 1 kb and 6 kb insertions) and its paralog HYDIN (targeting a unique 154 bp segment outside the HYDIN2 overlap). In an independent cohort, ddPCR was concordant with previous microarray data. Duplication of HYDIN2 was confirmed in the patient by ddPCR. This case demonstrates that a large discrepancy of verbal and non-verbal abilities can occur in 1q21.1 duplication syndrome, but it remains unclear whether this has a specific genomic basis. These ddPCR assays may be useful for future research on HYDIN2 copy number.
Compliant plant wearables for localized microclimate and plant growth monitoring
Authors: Nassar Joanna M. , Khan Sherjeel M. , Villalva Diego Rosas , Nour Maha M. , Almuslem Amani S. , Hussain Muhammad M.
Published: August 2018

The microclimate surrounding a plant has major effect on its health and photosynthesis process, where certain plants struggle in suboptimal environmental conditions and unbalanced levels of humidity and temperature. The ability to remotely track and correlate the effect of local environmental conditions on the healthy growth of plants can have great impact for increasing survival rate of plants and augmenting agriculture output. This necessitates the widespread distribution of lightweight sensory devices on the surface of each plant. Using flexible and biocompatible materials coupled with a smart compact design for a low power and lightweight system, we develop widely deployed, autonomous, and compliant wearables for plants. The demonstrated wearables integrate temperature, humidity and strain sensors, and can be intimately deployed on the soft surface of any plant to remotely and continuously evaluate optimal growth settings. This is enabled through simultaneous detection of environmental conditions while quantitatively tracking the growth rate (viz. elongation). Finally, we establish a nature-inspired origami-assembled 3D-printed “PlantCopter”, used as a launching platform for our plant wearable to enable widespread microclimate monitoring in large fields.
Subtle left-right asymmetry of gene expression profiles in embryonic and foetal human brains
Authors: de Kovel Carolien G. F. , Lisgo Steven N. , Fisher Simon E. , Francks Clyde
Published: August 2018

Left-right laterality is an important aspect of human –and in fact all vertebrate– brain organization for which the genetic basis is poorly understood. Using RNA sequencing data we contrasted gene expression in left- and right-sided samples from several structures of the anterior central nervous systems of post mortem human embryos and foetuses. While few individual genes stood out as significantly lateralized, most structures showed evidence of laterality of their overall transcriptomic profiles. These left-right differences showed overlap with age-dependent changes in expression, indicating lateralized maturation rates, but not consistently in left-right orientation over all structures. Brain asymmetry may therefore originate in multiple locations, or if there is a single origin, it is earlier than 5 weeks post conception, with structure-specific lateralized processes already underway by this age. This pattern is broadly consistent with the weak correlations reported between various aspects of adult brain laterality, such as language dominance and handedness.
Targeting protein-protein interactions for therapeutic discovery via FRET-based high-throughput screening in living cells
Authors: Stroik Daniel R. , Yuen Samantha L. , Janicek Kevyn A. , Schaaf Tory M. , Li Ji , Ceholski Delaine K. , Hajjar Roger J. , Cornea Razvan L. , Thomas David D.
Published: August 2018

We have developed a structure-based high-throughput screening (HTS) method, using time-resolved fluorescence resonance energy transfer (TR-FRET) that is sensitive to protein-protein interactions in living cells. The membrane protein complex between the cardiac sarcoplasmic reticulum Ca-ATPase (SERCA2a) and phospholamban (PLB), its Ca-dependent regulator, is a validated therapeutic target for reversing cardiac contractile dysfunction caused by aberrant calcium handling. However, efforts to develop compounds with SERCA2a-PLB specificity have yet to yield an effective drug. We co-expressed GFP-SERCA2a (donor) in the endoplasmic reticulum membrane of HEK293 cells with RFP-PLB (acceptor), and measured FRET using a fluorescence lifetime microplate reader. We screened a small-molecule library and identified 21 compounds (Hits) that changed FRET by >3SD. 10 of these Hits reproducibly alter SERCA2a-PLB structure and function. One compound increases SERCA2a calcium affinity in cardiac membranes but not in skeletal, suggesting that the compound is acting specifically on the SERCA2a-PLB complex, as needed for a drug to mitigate deficient calcium transport in heart failure. The excellent assay quality and correlation between structural and functional assays validate this method for large-scale HTS campaigns. This approach offers a powerful pathway to drug discovery for a wide range of protein-protein interaction targets that were previously considered “undruggable”.
Flood inundation assessment for the Hanoi Central Area, Vietnam under historical and extreme rainfall conditions
Authors: Luo Pingping , Mu Dengrui , Xue Han , Ngo-Duc Thanh , Dang-Dinh Kha , Takara Kaoru , Nover Daniel , Schladow Geoffrey
Published: August 2018

Flash floods have long been common in Asian cities, with recent increases in urbanization and extreme rainfall driving increasingly severe and frequent events. Floods in urban areas cause significant damage to infrastructure, communities and the environment. Numerical modelling of flood inundation offers detailed information necessary for managing flood risk in such contexts. This study presents a calibrated flood inundation model using referenced photos, an assessment of the influence of four extreme rainfall events on water depth and inundation area in the Hanoi central area. Four types of historical and extreme rainfall were input into the inundation model. The modeled results for a 2008 flood event with 9 referenced stations resulted in an R2 of 0.6 compared to observations. The water depth at the different locations was simulated under the four extreme rainfall types. The flood inundation under the Probable Maximum Precipitation presents the highest risk in terms of water depth and inundation area. These results provide insights into managing flood risk, designing flood prevention measures, and appropriately locating pump stations.
Genomic and molecular analysis of conserved and unique features of soybean PIF4
Authors: Arya Hina , Singh Mohan B. , Bhalla Prem L.
Published: August 2018

Phytochrome-interacting factor 4 (PIF4) participates in light signaling by interacting with photoreceptors, phytochromes, and cryptochromes. Although well characterized in Arabidopsis, PIF4′s role in crop plants is unknown. Here we performed the first integrated genomics, transcriptomics, and molecular characterization of PIF4 in soybean (Glycine max) plants. Fifteen identified Glycine max PIFs (GmPIFs) grouped into PIF3, PIF4, and PIF8 subfamilies based on their phylogenetic relationships. The GmPIF4 subfamily formed two distinct clades (GmPIF4 I and GmPIF4 II) with different amino acid sequences in the conserved bHLH region. Quantitative transcriptional analysis of soybean plants exposed to different photoperiods and temperatures indicated that all PIF4 I clade GmPIF4s conserved PIF4-like expression. Three out of four GmPIF4 transcripts of the GmPIF4 I clade increased at 35 °C compared to 25 °C under short day conditions. RNA sequencing of soybeans undergoing floral transition showed differential regulation of GmPIF4b, and ectopic GmPIF4b expression in wild type Arabidopsis resulted in an early flowering phenotype. Complementation of GmPIF4b in Arabidopsis pif4-101 mutants partially rescued the mutant phenotype. PIF4 protein levels peaked before dawn, and a GmPIF4b protein variant was observed in soybean plants treated at high temperatures.
Optical Characterization of Neurosurgical Operating Microscopes: Quantitative Fluorescence and Assessment of PpIX Photobleaching
Authors: Belykh Evgenii , Miller Eric J. , Patel Arpan A. , Bozkurt Baran , Yağmurlu Kaan , Robinson Timothy R. , Nakaji Peter , Spetzler Robert F. , Lawton Michael T. , Nelson Leonard Y. , Seibel Eric J. , Preul Mark C.
Published: August 2018

Protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (5-ALA) is increasingly used as a fluorescent marker for fluorescence-guided resection of malignant gliomas. Understanding how the properties of the excitation light source and PpIX fluorescence interact with the surgical microscope is critical for effective use of the fluorescence-guided tumor resection technique. In this study, we performed a detailed assessment of the intensity of the emitted blue light and white light and the light beam profile of clinical grade operating microscopes used for PpIX visualization. These measurements revealed both recognized fluorescence photobleaching limitations and unrecognized limitations that may alter quantitative observations of PpIX fluorescence obtained with the operating microscope with potential impact on research and clinical uses. We also evaluated the optical properties of a photostable fluorescent standard with an excitation-emission profile similar to PpIX. In addition, we measured the time-dependent dynamics of 5-ALA-induced PpIX fluorescence in an animal glioma model. Finally, we developed a ratiometric method for quantification of the PpIX fluorescence that uses the photostable fluorescent standard to normalize PpIX fluorescence intensity. This method increases accuracy and allows reproducible and direct comparability of the measurements from multiple samples.
Impact of iterative model reconstruction combined with dose reduction on the image quality of head and neck CTA in children
Authors: Cheng Bochao , Xing Haoyang , Lei Du , Guo Yingkun , Ning Gang , Gong Qiyong , Cai Wu
Published: August 2018

This study aimed to evaluate the imaging quality of head and neck computed tomographic angiography (CTA) in pediatric patients at a lowered radiation dose by combining an iterative model reconstruction (IMR) with low voltage scanning. Eighty-three pediatric patients were randomized into two groups as follows: Group A (n = 42), 100 kV/50 ml contrast media (CM), using filtered back projection (FBP); and Group B (n = 41), 80 kV/30 ml CM, using IMR. The enhanced CT value of the arteries, the image noise, the signal-to-noise ratio (SNR)/contrast-to-noise ratio (CNR), the image quality, the effective radiation dose (ED) and the iodine intake were compared between the two groups. The mean ED and iodine intake of group B were reduced by 69.8% and 40.0%, respectively, compared to those of group A. The mean CT values of the arteries in group B were higher than those in group A (p < 0.01), whereas the image noise of group B was lower than that of group A (p < 0.01). Group B exhibited a better image quality and a higher mean CNR/SNR than that of group A (p < 0.01). Compared to FBP, IMR in head and neck CTA enables a significant reduction in the radiation dose while preserving the diagnostic image quality. Thus, IMR, combined with low tube voltage scanning, provided an excellent solution for improving the image quality of craniocervical vessels in children.
Modelling electron-phonon interactions in graphene with curved space hydrodynamics
Authors: Giordanelli Ilario , Mendoza Miller , Herrmann Hans Jürgen
Published: August 2018

We introduce a different perspective describing electron-phonon interactions in graphene based on curved space hydrodynamics. Interactions of phonons with charge carriers increase the electrical resistivity of the material. Our approach captures the lattice vibrations as curvature changes in the space through which electrons move following hydrodynamic equations. In this picture, inertial corrections to the electronic flow arise naturally effectively producing electron-phonon interactions. The strength of the interaction is controlled by a coupling constant, which is temperature independent. We apply this model to graphene and recover satisfactorily the linear scaling law for the resistivity that is expected at high temperatures. Our findings open up a new perspective of treating electron-phonon interactions in graphene, and also in other materials where electrons can be described by the Fermi liquid theory.
Assessment of Corneal Stromal Remodeling and Regeneration after Photorefractive Keratectomy
Authors: Kivanany Pouriska B. , Grose Kyle C. , Tippani Madhavi , Su Shan , Petroll W. Matthew
Published: August 2018

This study utilizes high resolution multi-dimensional imaging to identify temporal and spatial changes in cell/extracellular matrix (ECM) patterning mediating cell migration, fibrosis, remodeling and regeneration during wound healing. Photorefractive keratectomy (PRK) was performed on rabbits. In some cases, 5([4,6-dichlorotriazin-2yl]-amino)fluorescein (DTAF) was applied immediately after surgery to differentiate native vs. cell-secreted collagen. Corneas were assessed 3–180 days postoperatively using in vivo confocal microscopy, and cell/ECM patterning was evaluated in situ using multiphoton and second harmonic generation (SHG) imaging. 7 days post-PRK, migrating fibroblasts below the ablation site were co-aligned with the stromal lamellae. At day 21, randomly patterned myofibroblasts developed on top of the ablation site; whereas cells underneath were elongated, co-aligned with collagen, and lacked stress fibers. Over time, fibrotic tissue was remodeled into more transparent stromal lamellae. By day 180, stromal thickness was almost completely restored. Stromal regrowth occurred primarily below the ablation interface, and was characterized by co-localization of gaps in DTAF labeling with elongated cells and SHG collagen signaling. Punctate F-actin labeling was detected along cells co-aligned with DTAF and non-DTAF labeled collagen, suggesting cell-ECM interactions. Overall, collagen lamellae appear to provide a template for fibroblast patterning during wound healing that mediates stromal repopulation, regeneration and remodeling.
Improvement of vascular dysfunction by argirein through inhibiting endothelial cell apoptosis associated with ET-1/Nox4 signal pathway in diabetic rats
Authors: Su Jie , An Xing-Rong , Li Qing , Li Xiao-Xue , Cong Xiao-dong , Xu Ming
Published: August 2018

Endothelial cell apoptosis plays an important role in the pathophysiological mechanism of vascular complications in type 2 diabetes mellitus (T2DM). Argirein, a new synthetic compound was demonstrated to inactivate NADPH oxidase to alleviate cardiac dysfunction in T2DM. Here, we investigated whether argirein medication attenuated the vascular dysfunction in T2DM by inhibiting endothelial cell apoptosis which was associated with NADPH oxidase. The rat aortic endothelial cells (RAECs) were incubated with glucose (30 mM) for 48 hour in vitro. It was shown that high glucose significantly increased the protein expression of BAX (Bcl-2 Associated X protein) and Caspase-3 and decreased Bcl2 (B-Cell Leukemia/Lymphoma 2) protein level in RAECs, which was normalized by argirein medication. The annexin V-FITC bound cell percentage and DNA fragments in agarose electrophoresis were markedly suppressed by argirein to confirm the anti-apoptotic property of argirein in RAECs. Furthermore, we found that argirein blocked the endothelin (ET)-1/Nox4 signal-dependent superoxide (O2−.) generation, which regulated endothelial cell apoptosis in RAECs. In vivo, argirein intervention relieved the vasodilatory response to acetylcholine and restored the expressions of Nox4 and BAX in the aorta endothelium of high-fat diet (HFD)-fed rats following streptozocin (STZ) injection. For the first time, we demonstrated that argirein could inhibit vascular endothelial cell apoptosis, which was attributed to blocking ET-1/Nox4 signal-dependent O2− generation in RAECs. This current study revealed the therapeutic effects of argirein to prevent the vascular complication in T2DM through inhibiting endothelial cell apoptosis which was associated with the anti-oxidative property of argirein.