bluuebunny/crossref_metadata_2025 huggingface dataset:
Frasnian (Upper Devonian) integrated facies analysis, magnetic susceptibility and sea-level fluctuations in the NW Algerian Sahara
Authors: Mahboubi Abdessamed , Cornée Jean-Jacques , Feist Raimund , Camps Pierre , Girard Catherine
Published: October 2018

Changes in the palaeoenvironment are investigated in two representative Frasnian sections of the NW Algerian Sahara, integrating sedimentology and magnetic susceptibility (MS). The Ben Zireg section is characterized by condensed and ferruginous calcareous deposits; in the South Marhouma section the sedimentation rate is high, dominated by muddy nodular limestones with several hypoxic shale intervals. In both sections, sediments were mostly emplaced on pelagic outer ramps below the limit of storm wave-base, evolving through time from proximal to distal setting. Investigations of the temporal evolution of facies and MS data permit a first estimate of the local sea-level trends in NW Algeria. These trends match the overall long-term rise of sea level recognized worldwide from Frasnian Zone 5 upwards. Noteable positive excursions of the sea-level curve related to the semichatovae transgression, as well as to the late Frasnian transgression prior to the late Kellwasser event, can be established in this area. Although the sharp regression of sea level at the upper Kellwasser level can be confirmed from our data, no particular trend is depicted at the transition of conodont zones (Frasnian Zones 12–13) where the presence of the lower Kellwasser level has not yet been clearly recognized.
IS THE EUNETHTA HTA CORE MODEL® FIT FOR PURPOSE? EVALUATION FROM AN INDUSTRY PERSPECTIVE
Authors: Gyldmark Marlene , Lampe Kristian , Ruof Jörg , Pöhlmann Johannes , Hebborn Ansgar , Kristensen Finn Børlum
Published: October 2018

Objectives:

The HTA Core Model® was developed to improve the transferability of health technology assessment (HTA) between settings. The model has been used by HTA agencies but is also of interest to manufacturers, for improving internal evidence generation and communicating with other HTA stakeholders. To establish if the model is fit for purpose from an industry perspective, the pharmaceutical company Roche, collaborating with the European Network for HTA (EUnetHTA), conducted an assessment of the model.

Methods:

A questionnaire was developed to evaluate all assessment elements in the HTA Core Model v2.0 for their usefulness in meeting payers’ evidence needs and demonstrating value. The questionnaire was completed by country affiliate teams working in evidence generation and reimbursement submissions for pharmaceuticals. Survey results were discussed in workshops to ensure consistency and alignment between teams.

Results:

The questionnaire was completed by six teams. An additional team from global pricing and market access participated in workshops. Model domains pertaining to the health problem and current technology use, technology description, clinical effectiveness, and economic value were considered most important because they meet payers’ evidence needs. Overall, the model was considered useful to improve the efficiency of HTA evidence generation, share evidence internally, and communicate value to payers and HTA agencies.

Conclusions:

From an industry perspective, the HTA Core Model provides a useful framework and common terminology for efficient generation of transferable HTA evidence. The timeliness, efficiency, and transparency of HTA processes could be improved by a more standardized approach to HTA across settings.
Une succession d'empires: Les historicités d'une société maghrébine (1860-1930)
Authors: Oualdi M'hamed
Published: October 2018

En étudiant un conflit juridique transméditerranéen autour de la succession d'un ancien ministre tunisien mort à Florence en 1887, cet article appelle à une écriture de l'histoire du Maghreb contemporain qui ne soit pas seulement conçue à partir de l’étude des sources coloniales européennes ou selon une temporalité coloniale mais qui puisse emprunter d'autres cadres d'analyse. Il s'agit aussi de prendre en compte le chevauchement des temporalités impériales française et ottomane en Méditerranée jusqu'aux années 1920, ainsi que la multiplication des litiges nés avant la colonisation de la Tunisie, des dissensions qui continuaient à fournir des raisons d'agir durant la période coloniale. Reconsidérer ces conflits non pas à l'aune de la colonisation mais selon leurs multiples temporalités et en diversifiant les sources nuancerait largement l'idée d'une absence de sources dites « locales » souvent avancée dans les études d'histoire coloniale du Maghreb. Tout autant que les parties prenantes européennes, les acteurs maghrébins impliqués dans des litiges juridiques furent à l'origine d'une profusion documentaire. Ils n'ont cessé de produire des preuves écrites et des justifications – y compris littéraires – en langue arabe pour appuyer leurs argumentaires. Les archives coloniales n'ont capté qu'une partie de ces écrits et donc des sources disponibles pour raconter une autre histoire contemporaine du Maghreb.
Simulation of Legionnaires’ disease prospective spatiotemporal cluster detection, Allegheny County, Pennsylvania, USA
Authors: Orkis L. T. , Peterson E. R. , Brooks M. M. , Mertz K. J. , Harrison L. H. , Stout J. E. , Greene S. K.
Published: October 2018

Legionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.
Effects of Bilingualism on Verbal and Nonverbal Memory Measures in Mild Cognitive Impairment
Authors: Rosselli Mónica , Loewenstein David A. , Curiel Rosie E. , Penate Ailyn , Torres Valeria L. , Lang Merike , Greig Maria T. , Barker William W. , Duara Ranjan
Published: October 2018

Objectives:Maintaining two active languages may increase cognitive and brain reserve among bilingual individuals. We explored whether such a neuroprotective effect was manifested in the performance of memory tests for participants with amnestic mild cognitive impairment (aMCI).Methods:We compared 42 bilinguals to 25 monolinguals on verbal and nonverbal memory tests. We used: (a) the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive test that taps into proactive, retroactive, and recovery from proactive semantic interference (verbal memory), and (b) the Benson Figure delayed recall (nonverbal memory). A subsample had volumetric MRI scans.Results:The bilingual group significantly outperformed the monolingual group on two LASSI-L cued recall measures (Cued A2 and Cued B2). A measure of maximum learning (Cued A2) showed a correlation with the volume of the left hippocampus in the bilingual group only. Cued B2 recall (sensitive to recovery from proactive semantic interference) was correlated with the volume of the hippocampus and the entorhinal cortex of both cerebral hemispheres in the bilingual group, as well as with the left and right hippocampus in the monolingual group. The memory advantage in bilinguals on these measures was associated with higher inhibitory control as measured by the Stroop Color-Word test.Conclusions:Our results demonstrated a superior performance of aMCI bilinguals over aMCI monolinguals on selected verbal memory tasks. This advantage was not observed in nonverbal memory. Superior memory performance of bilinguals over monolinguals suggests that bilinguals develop a different and perhaps more efficient semantic association system that influences verbal recall. (JINS, 2019, 25, 15–28)
Association between dietary intake and inflammatory markers: results from the CoLaus study
Authors: Piccand Eva , Vollenweider Peter , Guessous Idris , Marques-Vidal Pedro
Published: October 2018

Objective

To assess the associations between single foods, nutrients, dietary patterns and dietary scores, and inflammatory markers (C-reactive protein (CRP), IL-6, TNF-α and leucocyte count).

Design

Cross-sectional, population-based study.

Setting

City of Lausanne, Switzerland, years 2009–2012.

Subjects

Adults (n4027; 46·5 % men), mean age 57·2 (sd10·2) years. Dietary intake was collected using a semi-quantitative FFQ. Single foods and nutrients, three dietary patterns (‘Meat & fries’; ‘Fruits & vegetables’; ‘Fatty & sugary’) and three dietary scores (two Mediterranean; Alternative Healthy Eating Index (AHEI)) were used. Associations were assessed using correlation and multivariable linear regression.

Results

After adjusting for total energy intake, gender and other sociodemographic factors, no individual macro- or micronutrient was associated with inflammatory markers. Among single foods, only fruit intake was negatively associated with CRP levels (standardized regression score=−0·043,P<0·01). The ‘Fruits & vegetables’ pattern, the Mediterranean and the AHEI scores were negatively associated with CRP levels (standardized regression score=−0·079, −0·043 and −0·067, respectively, allP<0·01). When entered simultaneously with fruit intake, the ‘Fruits & vegetables’ pattern, the Mediterranean and the AHEI scores tended to remain significantly and negatively associated with CRP levels, while the association with fruit intake was no longer significant. No association between all dietary markers and IL-6, TNF-α or leucocyte count was found.

Conclusions

Dietary scores, but not individual foods, are associated with inflammatory markers in the general population.
Weight estimation among multi-racial/ethnic infants and children aged 0–5·9 years in the USA: simple tools for a critical measure
Authors: Zhu Yeyi , Hernandez Ladia M , Dong Yongquan , Himes John H , Caulfield Laura E , Kerver Jean M , Arab Lenore , Voss Paula , Hirschfeld Steven , Forman Michele R
Published: October 2018

Objective

In resource-constrained facilities or during resuscitation, immediate paediatric weight estimation remains a fundamental challenge. We aimed to develop and validate weight estimation models based on ulna length and forearm width and circumference measured by simple and portable tools; and to compare them against previous methods (advanced paediatric life support (APLS), Theron and Traub–Johnson formulas).

Design

Cross-sectional analysis of anthropometric measurements. Four ulna- and forearm-based weight estimation models were developed in the training set (n 1016). Assessment of bias, precision and accuracy was examined in the validation set (n 457).

Setting

National Children’s Study-Formative Research in Anthropometry (2011–2012).

Subjects

Multi-racial/ethnic infants and children aged <6 years (n 1473).

Results

Developed Models 1–4 had high predictive precision (R2=0·91–0·97). Mean percentage errors between predicted and measured weight were significantly smaller across the developed models (0·1–0·7 %) v. the APLS, Theron and Traub–Johnson formulas (−1·7, 9·2 and −4·9 %, respectively). Root-mean-squared percentage error was overall smaller among Models 1–4 v. the three existing methods (range=7·5–8·7 v. 9·8–13·3 %). Further, Models 1–4 were within 10 and 20 % of actual weight in 72–87 and 95–99 % of the weight estimations, respectively, which outperformed any of the three existing methods.

Conclusions

Ulna length, forearm width and forearm circumference by simple and portable tools could serve as valid and reliable surrogate measures of weight among infants and children aged <6 years with improved precision over the existing age- or length-based methods. Further validation of these models in physically impaired or non-ambulatory children is warranted.
Ultrastructural Analysis of Vesicular Transport in Electrotransfection
Authors: Wang Liangli , Miller Sara E. , Yuan Fan
Published: October 2018

Emerging evidence from various studies indicates that plasmid DNA (pDNA) is internalized by cells through an endocytosis-like process when it is used for electrotransfection. To provide morphological evidence of the process, we investigated ultrastructures in cells that were associated with the electrotransfected pDNA, using immunoelectron microscopy. The results demonstrate that four endocytic pathways are involved in the uptake of the pDNA, including caveolae- and clathrin-mediated endocytosis, macropinocytosis, and the clathrin-independent carrier/glycosylphosphatidylinositol-anchored protein-enriched early endosomal compartment (CLIC/GEEC) pathway. Among them, macropinocytosis is the most common pathway utilized by cells having various pDNA uptake capacities, and the CLIC/GEEC pathway is observed primarily in human umbilical vein endothelial cells. Quantitatively, the endocytic pathways are more active in easy-to-transfect cells than in hard-to-transfect ones. Taken together, our data provide ultrastructural evidence showing that endocytosis plays an important role in cellular uptake and intracellular transport of electrotransfected pDNA.
Biomass Pretreatment and Enzymatic Hydrolysis Dynamics Analysis Based on Particle Size Imaging
Authors: Kapsokalyvas Dimitrios , Wilbers Arnold , Boogers Ilco A.L.A. , Appeldoorn Maaike M. , Kabel Mirjam A. , Loos Joachim , Van Zandvoort Marc A.M.J.
Published: October 2018

Parameters such as pretreatment method, enzyme type and concentration, determine the conversion efficiency of biomass’ cellulose and hemicellulose to glucose and mainly xylose in biomass-based fuel production. Chemical quantification of these processes offers no information on the effect of enzymatic hydrolysis (EH) on particle morphology. We report on the development of a microscopy method for imaging pretreated biomass particles at different EH stages. The method was based on acquiring large field of view images, typically 20×10 mm2 containing thousands of particles. Morphology of particles with lengths between 2 μm and 5 mm could be visualized and analyzed. The particle length distribution of corn stover samples, pretreated with increasing amounts of sulfuric acid at different EH stages, was measured. Particle size was shown to be dependent on pretreatment severity and EH time. The methodology developed could offer an alternative method for characterization of EH of biomass for second generation biofuels and visualization of recalcitrant structures.
The mass impacts on chemosynthetic primary producers: potential implications on anammox communities and their consequences
Authors: Pérez Noel , Velazco-Vargas Jorge Luis , Martin Osmel , Cardenas Rolando , Martínez-Frías Jesús
Published: October 2018

The potential of a mass asteroid impact on Earth to disturb the chemosynthetic communities at global scale is discussed. Special emphasis is made on the potential influence on anammox communities and their implications in the nitrogen biogeochemical cycle. According to our preliminary estimates, anammox communities could be seriously affected as a consequence of global cooling and the large process of acidification usually associated with the occurrence of this kind of event. The scale of affectations could vary in a scenario like the Chicxulub as a function of the amount of soot, depth of the water column and the deposition rate for sulphates assumed in each case. The most severe affectations take place where the amount of soot and sulphates produced during the event is higher and the scale of time of settlements for sulphates is short, of the order of 10 h. In this extreme case, the activity of anammox is considerably reduced, a condition that may persist for several years after the impact. Furthermore, the impact of high levels of other chemical compounds like sulphates and nitrates associated with the occurrence of this kind of event are also discussed.
Gravitational Potential Energy in Iberia: A Driver of Active Deformation in High‐Topography Regions
Authors: Neres M. , Neves M. C. , Custódio S. , Palano M. , Fernandes R. , Matias L. , Carafa M. , Terrinha P.
Published: October 2018

In this study, we present a new estimation of the gravitational potential energy (GPE) in Iberia and use numerical modeling to evaluate its relative contribution to the present‐day stress field and deformation. We also present an improved (larger time span and denser coverage) compilation of Global Navigation Satellite System velocities, which we use to compute the strain rate field of Iberia. We take advantage of recent neotectonic modeling developed for Iberia and northwest Africa to study the isolated dynamic contribution of GPE‐related stresses. We present two models—one including only the stress generated by GPE and another reproducing the net stress field—and compare their predictions with the most up‐to‐date compilations of stress indicators, hypocenter clusters, and geodetic strain rates. The main effect of GPE is to induce second‐order spatial variations in the stress field. GPE appears to play an important role in high‐topography regions, where it explains deviatoric stress patterns mainly associated with extensional regimes. In north Iberia, especially in the Pyrenees and Cantabria, GPE causes an extensional regime over the highest peaks. In the Iberian Chain and eastern Betics, GPE is in agreement with the observed extensional deformation. Normal focal mechanisms of shallow earthquake clusters appear to be related with GPE maxima and GPE‐induced extensional regimes. Wavelength analysis suggests that both GPE and the long‐wavelength topography of intraplate Iberia record the plate boundary forces that acted in Iberia during the Alpine orogeny at Eocene to lower Miocene times.
Electron Reconnection in the Magnetopause Current Layer
Authors: Norgren C. , Graham D. B. , Khotyaintsev Yu. V. , André M. , Vaivads A. , Hesse M. , Eriksson E. , Lindqvist P.‐A. , Lavraud B. , Burch J. , Fuselier S. , Magnes W. , Gershman D. J. , Russell C. T.
Published: October 2018

The electron dynamics within thin current sheets plays a key role both for the process of magnetic reconnection and other energy transfer mechanisms but, from an observational point of view, is not well understood. In this paper we report observations of a reconnecting current sheet with intermediate guide field BG=0.5Bin, where Bin is the magnetic field amplitude in the inflow regions. The current sheet width is comparable to electron spatial scales. It shows a bifurcated structure and is embedded within the magnetopause current layer with thickness of several ion scales. The electron scale current sheet has strong out‐of‐plane and in‐plane currents, Hall electric and magnetic fields, a finite magnetic field component normal to the current sheet, and nongyrotropic electron distributions formed due to finite gyroradius effects at the boundary of the current sheet. Comparison between test particle simulations and electron data shows that electrons approaching from the edge of the largest magnetic curvature are scattered to perpendicular pitch angles in the center of the current sheet while electrons entering from the opposite side remain close to field aligned. The comparison also shows that an observed depletion in phase space at antiparallel pitch angles can be explained if an out‐of‐plane electric field, which due to the guide field is close to antiparallel to the magnetic field, is present in the center of the current sheet. This electric field would be consistent with the reconnection electric field, and we therefore interpret the depletion of electron phase space density as a manifestation of ongoing reconnection.
Coseismic Throw Variation Across Along‐Strike Bends on Active Normal Faults: Implications for Displacement Versus Length Scaling of Earthquake Ruptures
Authors: Iezzi Francesco , Mildon Zoë , Walker Joanna Faure , Roberts Gerald , Goodall Huw , Wilkinson Maxwell , Robertson Jennifer
Published: October 2018

Fault bends, and associated changes in fault dip, play a key role in explaining the scatter in maximum offset versus surface rupture length fault scaling relationships. Detailed field measurements of the fault geometry and magnitude of slip in the 2016–2017 Central Italy earthquake sequence, alongside three examples from large historical normal‐faulting earthquakes in different tectonic settings, provide multiple examples in which coseismic throw increases across bends in fault strike where dip also increases beyond what is necessary to accommodate a uniform slip vector. Coseismic surface ruptures produced by two mainshocks of the 2016–2017 Central Italy earthquake sequence (24 August 2016 Mw6.0 and 30 October 2016 Mw6.5) cross a ~0.83‐km amplitude along‐strike bend, and the coseismic throws for both earthquakes increase by a factor of 2–3, where the strike of the fault changes by ~28oand the dip increases by 20–25o. We present similar examples from historical normal faulting earthquakes (1887, Sonora earthquake, Mw7.5; 1981, Corinth earthquakes, Mw6.7–6.4; and 1983, Borah Peak earthquake, Mw7.3). We demonstrate that it is possible to estimate the expected change in throw across a bend by applying equations that relate strike, dip, and slip vector to horizontal strain conservation along a nonplanar fault for a single earthquake rupture. The calculated slip enhancement in bends can explain much of the scatter in maximum displacement (Dmax) versus surface rupture length scaling relationships. If fault bends are unrecognized, they can introduce variation inDmaxthat may lead to erroneous inferences of stress drop variability for earthquakes, and exaggerate maximum earthquake magnitudes derived from vertical offsets in paleoseismic data sets.
Xenos peckii vision inspires an ultrathin digital camera
Authors: Keum Dongmin , Jang Kyung-Won , Jeon Daniel S. , Hwang Charles S. H. , Buschbeck Elke K. , Kim Min H. , Jeong Ki-Hun
Published: October 2018

Increased demand for compact devices leads to rapid development of miniaturized digital cameras. However, conventional camera modules contain multiple lenses along the optical axis to compensate for optical aberrations that introduce technical challenges in reducing the total thickness of the camera module. Here, we report an ultrathin digital camera inspired by the vision principle of Xenos peckii, an endoparasite of paper wasps. The male Xenos peckii has an unusual visual system that exhibits distinct benefits for high resolution and high sensitivity, unlike the compound eyes found in most insects and some crustaceans. The biologically inspired camera features a sandwiched configuration of concave microprisms, microlenses, and pinhole arrays on a flat image sensor. The camera shows a field-of-view (FOV) of 68 degrees with a diameter of 3.4 mm and a total track length of 1.4 mm. The biologically inspired camera offers a new opportunity for developing ultrathin cameras in medical, industrial, and military fields.
Global long non-coding RNA expression in the rostral anterior cingulate cortex of depressed suicides
Authors: Zhou Yi , Lutz Pierre-Eric , Wang Yu Chang , Ragoussis Jiannis , Turecki Gustavo
Published: October 2018

Long non-coding RNAs (lncRNAs) are an emerging class of regulatory RNA that may be implicated in psychiatric disorders. Here we performed RNA-sequencing in the rostral anterior cingulate cortex of 26 depressed suicides and 24 matched controls. We first performed differential lncRNA expression analysis, and then conducted Weighted Gene Co-expression Network Analysis (WGCNA) to identify co-expression modules associating with depression and suicide. We identified 23 differentially expressed lncRNAs (FDR < 0.1) as well as their differentially expressed overlapping and antisense protein-coding genes. Several of these overlapping or antisense genes were associated with interferon signaling, which is a component of the innate immune response. Using WGCNA, we identified modules of highly co-expressed genes associated with depression and suicide and found protein-coding genes highly connected to differentially expressed lncRNAs within these modules. These protein-coding genes were located distal to their associated lncRNAs and were found to be part of several GO terms enriched in the significant modules, which include: cytoskeleton organization, plasma membrane, cell adhesion, nucleus, DNA-binding, and regulation of dendrite development and morphology. Altogether, we report that lncRNAs are differentially expressed in the brains of depressed individuals who died by suicide and may represent regulators of important molecular functions and biological processes.
SOX17 regulates uterine epithelial–stromal cross-talk acting via a distal enhancer upstream of Ihh
Authors: Wang Xiaoqiu , Li Xilong , Wang Tianyuan , Wu San-Pin , Jeong Jae-Wook , Kim Tae Hoon , Young Steven L. , Lessey Bruce A. , Lanz Rainer B. , Lydon John P. , DeMayo Francesco J.
Published: October 2018

Mammalian pregnancy depends on the ability of the uterus to support embryo implantation. Previous studies reveal the Sox17 gene as a downstream target of the Pgr-Gata2-dependent transcription network that directs genomic actions in the uterine endometrium receptive for embryo implantation. Here, we report that ablating Sox17 in the uterine epithelium impairs leukemia inhibitory factor (LIF) and Indian hedgehog homolog (IHH) signaling, leading to failure of embryo implantation. In vivo deletion of the SOX17-binding region 19 kb upstream of the Ihh locus by CRISPR-Cas technology reduces Ihh expression specifically in the uterus and alters proper endometrial epithelial–stromal interactions, thereby impairing pregnancy. This SOX17-binding interval is also bound by GATA2, FOXA2, and PGR. This cluster of transcription factor binding is common in 737 uterine genes and may represent a key regulatory element essential for uterine epithelial gene expression.
Late Bayesian inference in mental transformations
Authors: Remington Evan D. , Parks Tiffany V. , Jazayeri Mehrdad
Published: October 2018

Many skills rely on performing noisy mental computations on noisy sensory measurements. Bayesian models suggest that humans compensate for measurement noise and reduce behavioral variability by biasing perception toward prior expectations. Whether a similar strategy is employed to compensate for noise in downstream mental and sensorimotor computations is not known. We tested humans in a battery of tasks and found that tasks which involved more complex mental transformations resulted in increased bias, suggesting that humans are able to mitigate the effect of noise in both sensorimotor and mental transformations. These results indicate that humans delay inference in order to account for both measurement noise and noise in downstream computations.
A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection
Authors: Fourati Slim , Talla Aarthi , Mahmoudian Mehrad , Burkhart Joshua G. , Klén Riku , Henao Ricardo , Yu Thomas , Aydın Zafer , Yeung Ka Yee , Ahsen Mehmet Eren , Almugbel Reem , Jahandideh Samad , Liang Xiao , Nordling Torbjörn E. M. , Shiga Motoki , Stanescu Ana , Vogel Robert ,   The Respiratory Viral DREAM Challenge Consortium, Abdallah Emna Ben , Aghababazadeh Farnoosh Abbas , Amadoz Alicia , Bhalla Sherry , Bleakley Kevin , Bongen Erika , Borzacchielo Domenico , Bucher Philipp , Carbonell-Caballero Jose , Chaudhary Kumardeep , Chinesta Francisco , Chodavarapu Prasad , Chow Ryan D , Cokelaer Thomas , Cubuk Cankut , Dhanda Sandeep Kumar , Dopazo Joaquin , Faux Thomas , Feng Yang , Flinta Christofer , Guziolowski Carito , He Di , Hidalgo Marta R. , Hou Jiayi , Inoue Katsumi , Jaakkola Maria K , Ji Jiadong , Kumar Ritesh , Kumar Sunil , Kursa Miron Bartosz , Li Qian , Łopuszyński Michał , Lu Pengcheng , Magnin Morgan , Mao Weiguang , Miannay Bertrand , Nikolayeva Iryna , Obradovic Zoran , Pak Chi , Rahman Mohammad M. , Razzaq Misbah , Ribeiro Tony , Roux Olivier , Saghapour Ehsan , Saini Harsh , Sarhadi Shamim , Sato Hiroki , Schwikowski Benno , Sharma Alok , Sharma Ronesh , Singla Deepak , Stojkovic Ivan , Suomi Tomi , Suprun Maria , Tian Chengzhe , Tomalin Lewis E. , Xie Lei , Yu Xiang , Pandey Gaurav , Chiu Christopher , McClain Micah T. , Woods Christopher W. , Ginsburg Geoffrey S. , Elo Laura L. , Tsalik Ephraim L. , Mangravite Lara M. , Sieberts Solveig K.
Published: October 2018

The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure. Analysis of predictive gene features reveal little overlap among models; however, in aggregate, these genes are enriched for common pathways. Heme metabolism, the most significantly enriched pathway, is associated with a higher risk of developing symptoms following viral exposure. This study demonstrates that pre-exposure molecular predictors can be identified and improves our understanding of the mechanisms of response to respiratory viruses.
Gene synthesis allows biologists to source genes from farther away in the tree of life
Authors: Kunjapur Aditya M. , Pfingstag Philipp , Thompson Neil C.
Published: October 2018

Gene synthesis enables creation and modification of genetic sequences at an unprecedented pace, offering enormous potential for new biological functionality but also increasing the need for biosurveillance. In this paper, we introduce a bioinformatics technique for determining whether a gene is natural or synthetic based solely on nucleotide sequence. This technique, grounded in codon theory and machine learning, can correctly classify genes with 97.7% accuracy on a novel data set. We then classify ∼19,000 unique genes from the Addgene non-profit plasmid repository to investigate whether natural and synthetic genes have differential use in heterologous expression. Phylogenetic analysis of distance between source and expression organisms reveals that researchers are using synthesis to source genes from more genetically-distant organisms, particularly for longer genes. We provide empirical evidence that gene synthesis is leading biologists to sample more broadly across the diversity of life, and we provide a foundational tool for the biosurveillance community.
Nuclear lactate dehydrogenase A senses ROS to produce α-hydroxybutyrate for HPV-induced cervical tumor growth
Authors: Liu Yuan , Guo Ji-Zheng , Liu Ying , Wang Kui , Ding Wencheng , Wang Hui , Liu Xiang , Zhou Shengtao , Lu Xiao-Chen , Yang Hong-Bin , Xu Chenyue , Gao Wei , Zhou Li , Wang Yi-Ping , Hu Weiguo , Wei Yuquan , Huang Canhua , Lei Qun-Ying
Published: October 2018

It is well known that high-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and E7 was identified as one of the key initiators in HPV-mediated carcinogenesis. Here we show that lactate dehydrogenase A (LDHA) preferably locates in the nucleus in HPV16-positive cervical tumors due to E7-induced intracellular reactive oxygen species (ROS) accumulation. Surprisingly, nuclear LDHA gains a non-canonical enzyme activity to produce α-hydroxybutyrate and triggers DOT1L (disruptor of telomeric silencing 1-like)-mediated histone H3K79 hypermethylation, resulting in the activation of antioxidant responses and Wnt signaling pathway. Furthermore, HPV16 E7 knocking-out reduces LDHA nuclear translocation and H3K79 tri-methylation in K14-HPV16 transgenic mouse model. HPV16 E7 level is significantly positively correlated with nuclear LDHA and H3K79 tri-methylation in cervical cancer. Collectively, our findings uncover a non-canonical enzyme activity of nuclear LDHA to epigenetically control cellular redox balance and cell proliferation facilitating HPV-induced cervical cancer development.
Multi-hierarchical profiling the structure-activity relationships of engineered nanomaterials at nano-bio interfaces
Authors: Cai Xiaoming , Dong Jun , Liu Jing , Zheng Huizhen , Kaweeteerawat Chitrada , Wang Fangjun , Ji Zhaoxia , Li Ruibin
Published: October 2018

Increasing concerns over the possible risks of nanotechnology necessitates breakthroughs in structure–activity relationship (SAR) analyses of engineered nanomaterials (ENMs) at nano-bio interfaces. However, current nano-SARs are often based on univariate assessments and fail to provide tiered views on ENM-induced bio-effects. Here we report a multi-hierarchical nano-SAR assessment for a representative ENM, Fe2O3, by metabolomics and proteomics analyses. The established nano-SAR profile allows the visualizing of the contributions of seven basic properties of Fe2O3 to its diverse bio-effects. For instance, although surface reactivity is responsible for Fe2O3-induced cell migration, the inflammatory effects of Fe2O3 are determined by aspect ratio (nanorods) or surface reactivity (nanoplates). These nano-SARs are examined in THP-1 cells and animal lungs, which allow us to decipher the detailed mechanisms including NLRP3 inflammasome pathway and monocyte chemoattractant protein-1-dependent signaling. This study provides more insights for nano-SARs, and may facilitate the tailored design of ENMs to render them desired bio-effects.
Shear-band affected zone revealed by magnetic domains in a ferromagnetic metallic glass
Authors: Shen L. Q. , Luo P. , Hu Y. C. , Bai H. Y. , Sun Y. H. , Sun B. A. , Liu Y. H. , Wang W. H.
Published: October 2018

Plastic deformation of metallic glasses (MGs) has long been considered to be confined to nanoscale shear bands, but recently an affected zone around the shear band was found. Yet, due to technical limitations, the shear-band affected zone (SBAZ), which is critical for understanding shear banding and design of ductile MGs, has yet to be precisely identified. Here, by using magnetic domains as a probe with sufficiently high sensitivity and spatial resolution, we unveil the structure of SBAZs in detail. We demonstrate that shear banding is accompanied by a micrometer-scale SBAZ with a gradient in the strain field, and multiple shear bands interact through the superimposition of SBAZs. There also exists an ultra-long-range gradual elastic stress field extending hundreds of micrometers away from the shear band. Our findings provide a comprehensive picture on shear banding and are important for elucidating the micro-mechanisms of plastic deformation in glasses.
Structural insights into cGAMP degradation by Ecto-nucleotide pyrophosphatase phosphodiesterase 1
Authors: Kato Kazuki , Nishimasu Hiroshi , Oikawa Daisuke , Hirano Seiichi , Hirano Hisato , Kasuya Go , Ishitani Ryuichiro , Tokunaga Fuminori , Nureki Osamu
Published: October 2018

ENPP1 (Ecto-nucleotide pyrophosphatase phosphodiesterase 1), a type II transmembrane glycoprotein, hydrolyzes ATP to produce AMP and diphosphate, thereby inhibiting bone mineralization. A recent study showed that ENPP1 also preferentially hydrolyzes 2′3′-cGAMP (cyclic GMP-AMP) but not its linkage isomer 3′3′-cGAMP, and negatively regulates the cGAS-STING pathway in the innate immune system. Here, we present the high-resolution crystal structures of ENPP1 in complex with 3′3′-cGAMP and the reaction intermediate pA(3′,5′)pG. The structures revealed that the adenine and guanine bases of the dinucleotides are recognized by nucleotide- and guanine-pockets, respectively. Furthermore, the structures indicate that 2′3′-cGAMP, but not 3′3′-cGAMP, binds to the active site in a conformation suitable for catalysis, thereby explaining the specific degradation of 2′3′-cGAMP by ENPP1. Our findings provide insights into how ENPP1 hydrolyzes both ATP and cGAMP to participate in the two distinct biological processes.
Angular-momentum nanometrology in an ultrathin plasmonic topological insulator film
Authors: Yue Zengji , Ren Haoran , Wei Shibiao , Lin Jiao , Gu Min
Published: October 2018

Complementary metal–oxide–semiconductor (CMOS) technology has provided a highly sensitive detection platform for high-resolution optical imaging, sensing and metrology. Although the detection of optical beams carrying angular momentum have been explored with nanophotonic methods, the metrology of optical angular momentum has been limited to bulk optics. We demonstrate angular-momentum nanometrology through the spatial displacement engineering of plasmonic angular momentum modes in a CMOS-compatible plasmonic topological insulator material. The generation and propagation of surface plasmon polaritons on the surface of an ultrathin topological insulator Sb2Te3 film with a thickness of 100 nm is confirmed, exhibiting plasmonic figures of merit superior to noble metal plasmonics in the ultraviolet-visible frequency range. Angular-momentum nanometrology with a low crosstalk of less than −20 dB is achieved. This compact high-precision angular-momentum nanometrology opens an unprecedented opportunity for on-chip manipulation of optical angular momentum for high-capacity information processing, ultrasensitive molecular sensing, and ultracompact multi-functional optoelectronic devices.
Compound tool construction by New Caledonian crows
Authors: Bayern A. M. P. von , Danel S. , Auersperg A. M. I. , Mioduszewska B. , Kacelnik A.
Published: October 2018

The construction of novel compound tools through assemblage of otherwise non-functional elements involves anticipation of the affordances of the tools to be built. Except for few observations in captive great apes, compound tool construction is unknown outside humans, and tool innovation appears late in human ontogeny. We report that habitually tool-using New Caledonian crows (Corvus moneduloides) can combine objects to construct novel compound tools. We presented 8 naïve crows with combinable elements too short to retrieve food targets. Four crows spontaneously combined elements to make functional tools, and did so conditionally on the position of food. One of them made 3- and 4-piece tools when required. In humans, individual innovation in compound tool construction is often claimed to be evolutionarily and mechanistically related to planning, complex task coordination, executive control, and even language. Our results are not accountable by direct reinforcement learning but corroborate that these crows possess highly flexible abilities that allow them to solve novel problems rapidly. The underlying cognitive processes however remain opaque for now. They probably include the species’ typical propensity to use tools, their ability to judge affordances that make some objects usable as tools, and an ability to innovate perhaps through virtual, cognitive simulations.
Acupuncture reduces the time from extubation to ‘ready for discharge’ from the post anaesthesia care unit: results from the randomised controlled AcuARP trial
Authors: Fleckenstein J. , Baeumler P. , Gurschler C. , Weissenbacher T. , Annecke T. , Geisenberger T. , Irnich D.
Published: October 2018

Acupuncture may improve peri-operative care as it reduces post-operative symptoms, such as pain, nausea and vomiting, or sedation. This patient-assessor blinded, randomised trial in 75 women undergoing gynaecologic laparoscopy evaluated the effects of acupuncture combined with a standardised anaesthetic regimen (ACU) on post-anaesthetic recovery, when compared to acupressure (APU) or standard anaesthesia alone (CON). Main outcome measure was the time from extubation to ‘ready for discharge’ from recovery as assessed by validated questionnaires. The main outcome differed significantly between groups (p = 0.013). Median time to ready for discharge in the ACU group (30 (IQR: 24–41) min) was 16 minutes (35%) shorter than in the CON group (46 (36–64) min; p = 0.015) and tended to be shorter than in the APU group (43 (31–58) min; p = 0.08). Compared to CON (p = 0.029), median time to extubation was approximately 7 minutes shorter in both, the ACU and the APU group. No acupuncture or acupressure-related side-effects could be observed. A difference in time to recovery of 16 minutes compared to standard alone can be considered clinically relevant. Thus, results of this study encourage the application of acupuncture in gynaecological laparoscopy as it improves post-anaesthetic recovery.
Dose-compatible grating-based phase-contrast mammography on mastectomy specimens using a compact synchrotron source
Authors: Eggl Elena , Grandl Susanne , Sztrόkay-Gaul Anikό , Dierolf Martin , Jud Christoph , Heck Lisa , Burger Karin , Günther Benedikt , Achterhold Klaus , Mayr Doris , Wilkens Jan J. , Auweter Sigrid D. , Gleich Bernhard , Hellerhoff Karin , Reiser Maximilian F. , Pfeiffer Franz , Herzen Julia
Published: October 2018

With the introduction of screening mammography, the mortality rate of breast cancer has been reduced throughout the last decades. However, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses from mammography. Two pathways appear especially promising to reduce the number of false-positive diagnoses. In a clinical study, mammography using synchrotron radiation was able to clarify the diagnosis in the majority of inconclusive cases. The second highly valued approach focuses on the application of phase-sensitive techniques such as grating-based phase-contrast and dark-field imaging. Feasibility studies have demonstrated a promising enhancement of diagnostic content, but suffer from dose concerns. Here we present dose-compatible grating-based phase-contrast and dark-field images as well as conventional absorption images acquired with monochromatic x-rays from a compact synchrotron source based on inverse Compton scattering. Images of freshly dissected mastectomy specimens show improved diagnostic content over ex-vivo clinical mammography images at lower or equal dose. We demonstrate increased contrast-to-noise ratio for monochromatic over clinical images for a well-defined phantom. Compact synchrotron sources could potentially serve as a clinical second level examination.
Nonequilibrium Magnetic Oscillation with Cylindrical Vector Beams
Authors: Fujita Hiroyuki , Sato Masahiro
Published: October 2018

Magnetic oscillation is a generic property of electronic conductors under magnetic fields and widely appreciated as a useful probe of their electronic band structure, i.e. the Fermi surface geometry. However, the usage of the strong static magnetic field makes the measurement insensitive to the magnetic order of the target material. That is, the magnetic order is anyhow turned into a forced ferrromagnetic one. Here we theoretically propose an experimental method of measuring the magnetic oscillation in a magnetic-order-resolved way by using the azimuthal cylindrical vector (CV) beam, an example of topological lightwaves. The azimuthal CV beam is unique in that, when focused tightly, it develops a pure longitudinal magnetic field. We argue that this characteristic focusing property and the discrepancy in the relaxation timescale between conduction electrons and localized magnetic moments allow us to develop the nonequilibrium analogue of the magnetic oscillation measurement. Our optical method would be also applicable to metals under the ultra-high pressure of diamond anvil cells.
Ultra-fast artificial neuron: generation of picosecond-duration spikes in a current-driven antiferromagnetic auto-oscillator
Authors: Khymyn Roman , Lisenkov Ivan , Voorheis James , Sulymenko Olga , Prokopenko Oleksandr , Tiberkevich Vasil , Akerman Johan , Slavin Andrei
Published: October 2018

We demonstrate analytically and numerically, that a thin film of an antiferromagnetic (AFM) material, having biaxial magnetic anisotropy and being driven by an external spin-transfer torque signal, can be used for the generation of ultra-short “Dirac-delta-like” spikes. The duration of the generated spikes is several picoseconds for typical AFM materials and is determined by the inplane magnetic anisotropy and the effective damping of the AFM material. The generated output signal can consist of a single spike or a discrete group of spikes (“bursting”), which depends on the repetition (clock) rate, amplitude, and shape of the external control signal. The spike generation occurs only when the amplitude of the control signal exceeds a certain threshold, similar to the action of a biological neuron in response to an external stimulus. The “threshold” behavior of the proposed AFM spike generator makes possible its application not only in the traditional microwave signal processing but also in the future neuromorphic signal processing circuits working at clock frequencies of tens of gigahertz.
Understanding the mismatch between behaviour and development in a novel host-parasitoid association
Authors: Konopka Joanna K. , Poinapen Danny , Gariepy Tara , McNeil Jeremy N.
Published: October 2018

Foraging parasitoid females should preferentially oviposit on hosts most suitable for progeny development to maximize their fitness. However, the introduction of a new host species may disrupt the link between the reliability of the cues and the expected adaptive outcome of female choice, leading to an evolutionary trap. This mismatch between behavioural acceptance and lack of development exists for North American and European egg parasitoids (Scelionidae) that encounter invasive Halyomorpha halys in areas where this exotic host has recently established. To explain this mismatch, we utilized an L9 orthogonal array design to assess and rank the influence of several critical factors characterizing host resource (host species, egg age, egg status, and surface wash) on behaviour (acceptance, patch residence and patch exploitation) and development of North American native Trissolcus euschisti egg parasitoid. Our results indicate that the host egg age is most important for behaviour, but is least influential for development of the progeny. This study suggests that the maladaptive decision to oviposit in an unsuitable host is due to a mismatch between the cues that females use, and the subsequent expected outcome of this choice. Therefore, it is the relative importance of individual factors when assessed simultaneously that influences the decision-making of female parasitoids.