bluuebunny/crossref_metadata_2025 huggingface dataset:
The Structure of the Rivermead Post-Concussion Symptoms Questionnaire in Australian Adults with Traumatic Brain Injury
Authors: Thomas Matt , Skilbeck Clive , Cannan Phillipa , Slatyer Mark
Published: December 2017

Background and aims: Many sustaining traumatic brain injury (TBI) suffer ongoing post-concussion symptoms (PCS). The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is widely used, although there is disagreement about its structure. This study compared the fit of published RPQ structures with a four-factor structure derived from a large adult sample with TBI in Tasmania.

Method: 661 adults with TBI completed the RPQ at approximately one month post injury. Exploratory factor analysis (EFA), using the first half of the sample (n = 330), suggested a four-factor solution. This was compared with models reported in the literature with the second half of the sample (n = 331), using structural equation modelling. Trajectory of recovery across these factors was examined within subsamples at 1, 3, 6 and 12 months following TBI.

Results: Inter-correlations between items were strongest for somatic, cognitive and emotional functioning items and the EFA identified a four-factor model. Fit was examined utilising bootstrapping for model comparison. The data at 1 month following TBI best fitted the four-factor model (CFI = .95, RMSEA = .060 (.049–.071) and factors had adequate internal consistency (r = .61–.89). This model appeared a good fit and clinically useful across time points to 12 months post injury.

Conclusions: Data best fitted a four-factor model, identified using a rigorous statistical approach. Clinicians and clinical researchers may use this preferred model to provide more specific measurement of the severity of PCS. Future research could attempt replication within international samples.
Topological classification of Morse–Smale diffeomorphisms without heteroclinic curves on 3-manifolds
Authors: BONATTI CH. , GRINES V. , LAUDENBACH F. , POCHINKA O.
Published: December 2017

We show that, up to topological conjugation, the equivalence class of a Morse–Smale diffeomorphism without heteroclinic curves on a $3$-manifold is completely defined by an embedding of two-dimensional stable and unstable heteroclinic laminations to a characteristic space.
Experimental investigation of torque hysteresis behaviour of Taylor–Couette Flow
Authors: Gul M. , Elsinga G. E. , Westerweel J.
Published: December 2017

This paper describes the hysteresis in the torque for Taylor–Couette flow in the turbulent flow regime for different shear Reynolds numbers, aspect ratios and boundary conditions. The hysteresis increases with decreasing shear Reynolds number and becomes more pronounced as the aspect ratio is increased from 22 to 88. Measurements conducted in two different Taylor–Couette set-ups depict the effect of the flow conditions at the ends of the cylinders on the flow hysteresis by showing reversed hysteresis behaviour. In addition, the flow structure in the different branches of the hysteresis loop was investigated by means of stereoscopic particle image velocimetry. The results show that the dominant flow structures differ in shape and magnitude depending on the branch of the hysteresis loop. Hence, it can be concluded that the geometry could have an effect on the hysteresis behaviour of turbulent Taylor–Couette flow, but its occurrence is related to a genuine change in the flow dynamics.
The effect of core size on the speed of compressible hollow vortex streets
Authors: Crowdy Darren G. , Krishnamurthy Vikas S.
Published: December 2017

The effect of weak compressibility on the speed of steadily translating staggered vortex streets of hollow vortices in isentropic subsonic flow is studied. A small-Mach-number perturbation expansion about the incompressible solutions for staggered streets of hollow vortices found recently by Crowdy & Green (Phys. Fluids, 2011, vol. 23, 126602) is carried out; the latter solutions provide a desingularization of the classical point vortex streets of von Kármán. The first-order compressible flow correction is calculated. We employ a novel scheme based on a complex variable formulation of the compressible flow equations (the Imai–Lamla method) combined with conformal mapping theory to track the vortex shape in this free boundary problem. The analysis to find the perturbed streamfunction and compressible vortex shapes is greatly facilitated by exploiting a calculus based on use of the Schottky–Klein prime function of a conformally equivalent parametric annulus. It is found that, for a vortex street of specified aspect ratio comprising vortices of specified circulation, the vortex core size is a key determinant of whether compressibility increases or decreases the steady propagation speed (relative to the incompressible street with the same parameters) and that both eventualities are possible. We focus attention on streets with aspect ratios around 0.28, which is close to the neutrally stable case for incompressible flow, and find that a critical vortex core size exists at which compressibility does not affect the speed of the street at first order in the (squared) Mach number. Streets comprising vortices with core size below the critical value speed up due to compressibility; larger vortices slow down.
A minimalist macroparasite diversity in the round goby of the Upper Rhine reduced to an exotic acanthocephalan lineage
Authors: David Gwendoline M. , Staentzel Cybill , Schlumberger Olivier , Perrot-Minnot Marie-Jeanne , Beisel Jean-Nicolas , Hardion Laurent
Published: December 2017

The round goby, Neogobius melanostomus, is a Ponto-Caspian fish considered as an invasive species in a wide range of aquatic ecosystems. To understand the role that parasites may play in its successful invasion across Western Europe, we investigated the parasitic diversity of the round goby along its invasion corridor, from the Danube to the Upper Rhine rivers, using data from literature and a molecular barcoding approach, respectively. Among 1666 parasites extracted from 179 gobies of the Upper Rhine, all of the 248 parasites barcoded on the c oxidase subunit I gene were identified as Pomphorhynchus laevis. This lack of macroparasite diversity was interpreted as a loss of parasites along its invasion corridor without spillback compensation. The genetic diversity of P. laevis was represented by 33 haplotypes corresponding to a haplotype diversity of 0·65 ± 0·032, but a weak nucleotide diversity of 0·0018 ± 0·00015. Eight of these haplotypes were found in 88·4% of the 248 parasites. These haplotypes belong to a single lineage so far restricted to the Danube, Vistula and Volga rivers (Eastern Europe). This result underlines the exotic status of this Ponto-Caspian lineage in the Upper Rhine, putatively disseminated by the round goby along its invasion corridor.
Timor and Colonial Conquest: Voices and Claims about the End of the Sonba’i Realm in 1906
Authors: Hägerdal Hans
Published: December 2017

In 1905–1906 the Dutch colonial state ended the autonomy of the inland of West Timor, hitherto home to the prestigious but crumbling Sonba’i Dynasty. The article addresses the problems and possibilities of writing the history of this traumatic event, which is described in several colonial reports and memorandums, while the Timorese did not leave written texts. A number of oral accounts were recorded in the 1960s by local historian F. H. Fobia, some six decades after the event. The article discusses the possibilities of an oral history approach against a backdrop of recent research about such methods. The contemporary and near-contemporary Dutch reports are systematically compared with the recordings of oral versions. It is argued that the latter destabilize the colonial version in a number of ways regarding the causes of the conflict, the conduct of the colonial troops, and the circumstances of the capture of the Sonba’i lord. At the same time, the oral versions are likely to have been processed over the decades into a meaningful set of decisive events that make sense to “traditional” Timorese discourses as well as modern Indonesian ones.
Weakly relativistic self-focusing of Gaussian laser beam in magnetized cold quantum plasma
Authors: Aggarwal M. , Goyal V. , Richa  , Kumar H. , Gill T.S.
Published: December 2017

In the present paper, we have studied self-focusing of Gaussian laser beam in weakly relativistic magnetized cold quantum plasma. When interparticle distance is comparable to the de Broglie wavelength of charged particles, we cannot neglect the quantum contribution of plasma constituents. Therefore, propagation characteristics are studied by taking in to account quantum contribution in the presence of static magnetic field applied along the beam propagation. Our results show that the magnetic field plays a key role in achieving additional focusing, it modifies the quiver motion of electrons by adding cyclotron frequency to the natural frequency of oscillating electrons during laser beam propagation. The results are compared with those of weakly relativistic quantum plasma and weakly relativistic magnetized plasma. The self-focusing is found to be more pronounced when axial magnetic field is increased in the present model. We have setup the non-linear differential equation for the evolution of beam-width parameter by well-known paraxial ray approximation and solved it with the help of computational technique.
DOES HAVING GOOD ARTICULATORY SKILLS LEAD TO MORE FLUENT SPEECH IN FIRST AND SECOND LANGUAGES?
Authors: De Jong Nivja H. , Mora Joan C.
Published: December 2017

Speaking fluently requires three main processes to run smoothly: conceptualization, formulation, and articulation. This study investigates to what extent fluency in spontaneous speech in both first (L1) and second (L2) languages can be explained by individual differences in articulatory skills. A group of L2 English learners (n = 51) performed three semispontaneous speaking tasks in their L1 Spanish and in their L2 English. In addition, participants performed articulatory skill tasks that measured the speed at which their articulatory speech plans could be initiated (delayed picture naming) and the rate and accuracy at which their articulatory gestures could be executed (diadochokinetic production). The results showed that fluency in spontaneous L2 speech can be predicted by L1 fluency, replicating earlier studies and showing that L2 fluency measures are, to a large degree, measures of personal speaking style. Articulatory skills were found to contribute modestly to explaining variance in both L1 and L2 fluency.
Capability-based localization of distributed and heterogeneous queries
Authors: SECO JOÃO COSTA , FERREIRA PAULO , LOURENÇO HUGO
Published: December 2017

One key aspect of data-centric applications is the manipulation of data stored in persistent repositories, which is moving fast from querying a centralized relational database to the ad-hoc combination of constellations of data sources. The extension of general purpose languages with query operations is increasingly popular, as a tool to improve reasoning and optimizing capabilities of interpreters and compilers. However, not much is being done to integrate and orchestrate different and separate sources of data. We present a data manipulation language that abstracts the nature and location of data-sources. We define its semantics and a type directed query localization mechanism to be used in development tools for heterogeneous environments to efficiently compile them into native queries. We introduce a localization procedure based on rewriting of query expressions that is confluent, terminating and provides the maximum mapping between site capabilities and the structure of the query. We provide formal type safety results that support the sound distribution of query fragments over remote sites. Our approach is also suitable for an interactive query construction environment by rich user interfaces that provide immediate feedback on data manipulation operations. This approach is currently the base for the data layer of a development platform for mobile and web applications.
NEW RECORDS IN THE FLORA CHECKLISTS OF LAOS, RESULTING FROM A SURVEY OF PHOU HIN POUN NATIONAL BIODIVERSITY CONSERVATION AREA
Authors: Prosperi J. , Lamxay V. , Hallé F. , Bompard J.-M. , Blanc P. , Ramesh B. R. , Ayyappan N. , Cardinal S.
Published: December 2017

The flora of Laos remains one of the least known within the Indo-Burma biodiversity hotspot. A floristic inventory was carried out in Phou Hin Poun National Biodiversity Conservation Area, an under-explored area of the Khammouane Limestone. This study provides a list of 27 taxa that are additions to the most recent country checklists. The Ebenaceae, Euphorbiaceae and Myrtaceae are the families with the highest species number. In this list, four species are endemic to Indochina (Cambodia, Laos and Vietnam): Cynometra dongnaiensis Pierre, Jasminum vidalii P.S.Green, Memecylon chevalieri Guillaumin and Pothos gigantipes Buchet ex P.C.Boyce. These results illustrate the paucity of our knowledge of the region surveyed and of the flora of Laos in general.
Relative importance of phosphatidylinositol-3 kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK3/1) signaling during maturational steroid-induced meiotic G2–M1 transition in zebrafish oocytes
Authors: Das Debabrata , Nath Poulomi , Pal Soumojit , Hajra Sudip , Ghosh Pritha , Maitra Sudipta
Published: December 2017

Participation and relative importance of phosphatidylinositol-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) signalling, either alone or in combination, have been investigated during 17α,20β-dihydroxy-4-pregnen-3-one (DHP)-induced meiotic G2−M1 transition in denuded zebrafish oocyte. Results demonstrate that concomitant with rapid phosphorylation (activation) of Akt (Ser473) and MAPK (ERK1/2) at as early as 15 min of incubation, DHP stimulation promotes enhanced an GVBD response and histone H1 kinase activation between 1 and 5 h in full-grown oocytesin vitro. While p-Akt reaches its peak at 60 to 90 min and undergoes downregulation to the basal level by 240 min, ERK1/2 phosphorylation (activation) increases gradually until 120 min and remains high thereafter. Although, priming with MEK1/2 inhibitor U0126 is without effect, PI3K inhibitors, wortmannin or LY294002, delay the GVBD response significantly (P <0.001) until 3 h but not at 5 h of incubation. Interestingly, blocking PI3K and MEK function together could abrogate steroid-induced oocyte maturation at all time points tested. While DHP stimulation promotes phospho-PKA catalytic (p-PKAc) dephosphorylation (inactivation) between 30–120 min of incubation, simultaneous inhibition of PI3K and MEK1/2 kinases abrogates DHP action. Conversely, elevated intra-oocyte cAMP, through priming with either adenylyl cyclase (AC) activator forskolin (FK) or dibutyryl cAMP (db-cAMP), abrogates steroid-induced Akt and ERK1/2 phosphorylation. Taken together, these results suggest that DHP-induced Akt and ERK activation precedes the onset of meiosis (GVBD response) in a cAMP-sensitive manner and PI3K/Akt and MEK/MAPK pathways together have a pivotal influence in the downregulation of PKA and resumption of meiotic maturation in zebrafish oocytesin vitro.
Can auctions help reduce mandatory pension fund fees?
Authors: KURACH RADOSŁAW , KUŚMIERCZYK PAWEŁ , PAPLA DANIEL
Published: December 2017

Companies that manage mandatory pension funds are frequently accused of excessive fee taking. International analyses have found that in countries with legal caps, commissions remain within these caps; hence, market competition does not function. Surprisingly, there are few international cases where local regulators implement mechanisms to facilitate competition. The variety of auction mechanisms available raises the question of whether an optimal solution exists for this purpose. Therefore, in this study, we present evidence, based on a controlled regulatory experiment, on the fee-reduction potential of reverse auctions.
Psychometric Properties of a French Version of the Narcissistic Personality Inventory in Young Adults
Authors: Potard Catherine , Lignier Baptiste , Henry Audrey
Published: December 2017

Abstract. The Narcissistic Personality Inventory (NPI) is widely used in social and personality psychology. The present study validates a French version of the NPI (NPI-Fr) for use with young adults. Respondents (N = 1275, Mage = 21.83, SD = 4.97) completed the NPI and two other convergent measures (Rosenberg Self-Esteem Scale and French version of the Big Five Inventory) for three validation steps. Exploratory factor analyses yielded evidence for a structure with either two (Power/Authority, Exhibitionism/Self-Admiration) or four (Leadership/Authority, Grandiosity/Exhibitionism, Special Person, Exploitativeness/Entitlement) first-order factors for the NPI. Confirmatory factor analyses supported the 33-item four-factor model, with moderate model fit indices (χ2/df = 2.04, RMSEA = .058, CFI = .90, GFI = .85). We found significant positive correlations (r = .11 to .44) with self-esteem, Extraversion, and Openness, and a negative correlation with Neuroticism (r = –.09 to –.21). There was high internal consistency, with a reliability coefficient of α = .73 to .93, while test–retest reliability at 4 weeks was satisfactory. Our results confirm the psychometric quality of the questionnaire for French young adults.
Validation of an Adapted French Form of the Structured Interview for the Five-Factor Model (SIFFM) in a Swiss Sample
Authors: Pocnet Cornelia , Antonietti Jean-Philippe , von Gunten Armin , Rossier Jérôme
Published: December 2017

Abstract. We analyzed the psychometric properties of the Structured Interview for the Five-Factor Model (SIFFM) in a French-speaking Swiss sample and compared the French version to the original English version. A community-based sample of 260 participants (183 women and 77 men, aged 20 to 88 years, Mage = 46.23, SDage = 16.37) were assessed using the SIFFM and the NEO-FFI-R. Forty of the participants agreed to be filmed or to be assessed by two investigators simultaneously. The internal consistency coefficients of the five dimensions of SIFFM ranged from .63 to .84. An exploratory factor analysis within the confirmatory factor analysis framework showed that the structure of the French version of the SIFFM was in line with the structure suggested by the Five-Factor Model. Except for the modesty and dutifulness subscales, each facet scale had its highest factor loading on the factor representing the targeted domain. Moreover, a principal axis joint factor analysis of the SIFFM and NEO-FFI-R domains suggested that the convergent validity between the two instruments was adequate. Furthermore, the interrater reliability coefficients for the SIFFM scores were high. The French version of the SIFFM shows acceptable psychometric properties, comparable to those of the English version, and may be an informative assessment method and an alternative to self-report measures.
Wie sinnvoll sind Tumormarker im klinischen Alltag?
Authors: Gassmann Désirée , Schmid Sandra , Hofer Silvia
Published: December 2017

Zusammenfassung. Konventionelle Tumormarker sind Proteine, Peptide oder andere biologische Substanzen, die von Tumorzellen selber oder vom Körper als Reaktion auf einen Tumor gebildet werden. Einflussfaktoren, die zu falsch positiven oder falsch negativen Werten führen sind häufig wenig bekannt. Der klinische Nutzen eines Tumormarkes hängt von seiner Spezifität und Sensitivität ab. Beide Parameter sind in der Regel zu wenig hoch, weshalb sich Tumormarker für ein Tumorscreening nicht eignen. Der Hauptnutzen von Tumormarkern liegt in Therapieverlaufskontrollen oder in der Nachsorge von Tumoren. In Zukunft werden präzisere, DNA-basierte Marker die Tumorbehandlung unterstützen.
Science at the Border Between Ice and Ocean
Authors: Wendel JoAnna
Published: December 2017

A suite of instruments, including drones, remotely operated boats, and multibeam sonar, is helping scientists understand a little-studied area at the front of a calving glacier.
Structural basis for nucleotide-modulated p97 association with the ER membrane
Authors: Tang Wai Kwan , Zhang Ting , Ye Yihong , Xia Di
Published: December 2017

Association of the cytosolic AAA (ATPases associated with various cellular activities) protein p97 to membranes is essential for various cellular processes including endoplasmic reticulum (ER)-associated degradation. The p97 consists of two ATPase domains and an N domain that interacts with numerous cofactors. The N domain of p97 is known to undergo a large nucleotide-dependent conformation switch, but its physiological relevance is unclear. Here we show p97 is recruited to canine ER membranes predominantly by interacting with VCP-interacting membrane protein (VIMP), an ER-resident protein. We found that the recruitment is modulated through a nucleotide-dependent conformation switch of the N domain in wild-type p97, but this modulation is absent in pathogenic mutants. We demonstrate the molecular mechanism of the modulation by a series of structures of p97, VIMP and their complexes and suggest a physiological role of the nucleotide-dependent N domain conformation switch. The lack of modulation in pathogenic mutants is caused by changes in interactions between the N and D1 domain, as demonstrated by multiple intermediate positions adopted by N domains of mutant p97. Our findings suggest the nucleotide-modulated membrane association may also have a role in other p97-dependent processes.
ANGPTL8 negatively regulates NF-κB activation by facilitating selective autophagic degradation of IKKγ
Authors: Zhang Yu , Guo Xian , Yan Wanyao , Chen Yan , Ke Mengxiang , Cheng Cheng , Zhu Xiuqin , Xue Weili , Zhou Qiaoqiao , Zheng Ling , Wang Shun , Wu Bin , Liu Xinran , Ma Liang , Huang Lianqi , Huang Kun
Published: December 2017

Excessive nuclear factor-κB (NF-κB) activation mediated by tumor necrosis factor α (TNFα) plays a critical role in inflammation. Here we demonstrate that angiopoietin-like 8 (ANGPTL8) functions as a negative feedback regulator in TNFα-triggered NF-κB activation intracellularly. Inflammatory stimuli induce ANGPTL8 expression, and knockdown or knockout of ANGPTL8 potentiates TNFα-induced NF-κB activation in vitro. Mechanistically, upon TNFα stimulation, ANGPTL8 facilitates the interaction of IKKγ with p62 via forming a complex, thus promoting the selective autophagic degradation of IKKγ. Furthermore, the N-terminal domain mediated self-oligomerization of ANGPTL8 is essential for IKKγ degradation and NF-κB activation. In vivo, circulating ANGPTL8 level is high in patients diagnosed with infectious diseases, and the ANGPTL8/p62-IKKγ axis is responsive to inflammatory stimuli in the liver of LPS-injected mice. Altogether, our study suggests the ANGPTL8/p62-IKKγ axis as a negative feedback loop that regulates NF-κB activation, and extends the role of selective autophagy in fine-tuned inflammatory responses.
A flexible ontology for inference of emergent whole cell function from relationships between subcellular processes
Authors: Hansen Jens , Meretzky David , Woldesenbet Simeneh , Stolovitzky Gustavo , Iyengar Ravi
Published: December 2017

Whole cell responses arise from coordinated interactions between diverse human gene products functioning within various pathways underlying sub-cellular processes (SCP). Lower level SCPs interact to form higher level SCPs, often in a context specific manner to give rise to whole cell function. We sought to determine if capturing such relationships enables us to describe the emergence of whole cell functions from interacting SCPs. We developed the Molecular Biology of the Cell Ontology based on standard cell biology and biochemistry textbooks and review articles. Currently, our ontology contains 5,384 genes, 753 SCPs and 19,180 expertly curated gene-SCP associations. Our algorithm to populate the SCPs with genes enables extension of the ontology on demand and the adaption of the ontology to the continuously growing cell biological knowledge. Since whole cell responses most often arise from the coordinated activity of multiple SCPs, we developed a dynamic enrichment algorithm that flexibly predicts SCP-SCP relationships beyond the current taxonomy. This algorithm enables us to identify interactions between SCPs as a basis for higher order function in a context dependent manner, allowing us to provide a detailed description of how SCPs together can give rise to whole cell functions. We conclude that this ontology can, from omics data sets, enable the development of detailed SCP networks for predictive modeling of emergent whole cell functions.
A novel mode of cytokinesis without cell-substratum adhesion
Authors: Taira Risa , Yumura Shigehiko
Published: December 2017

Cytokinesis is a final step in cell division. Dictyostelium cells, a model organism for the study of cytokinesis, have multiple modes, denoted cytokinesis A, B, C, and D. All these modes have been mainly investigated using cells adhering to the substratum although they can grow in shaking suspension culture. Here, we observed how cells divide without adhering to the substratum using a new non-adhesive material. These detached cells formed the cleavage furrow but eventually failed in the final abscission. Thus, the cells cannot divide without adhesion, suggesting that they cannot divide only through the conventional cytokinesis A. However, in a long-term culture, the detached cells adhered each other to form multicellular aggregates and divided properly in these aggregates. Myosin II-null cells also formed such aggregates but could not divide in the aggregates. Several lines of experiments using mutant cells showed that the process of cytokinesis in multicellular aggregates is a novel mode utilizing a confined space in the aggregate in a myosin II-dependent manner. These results shed light on a poorly characterized mechanism of cytokinesis in multicellular spheroids or tissues. We propose to redefine and classify multiple modes of cytokinesis.
Comprehensive Expression Analysis of microRNAs and mRNAs in Synovial Tissue from a Mouse Model of Early Post-Traumatic Osteoarthritis
Authors: Kung Louise H. W. , Ravi Varshini , Rowley Lynn , Bell Katrina M. , Little Christopher B. , Bateman John F.
Published: December 2017

To better understand the molecular processes involved in driving osteoarthritis disease progression we characterized expression profiles of microRNAs (miRNA) and mRNAs in synovial tissue from a post-traumatic OA mouse model. OA was induced in 10–12 week old male C57BL6 mice by bilateral surgical destabilization of the medial meniscus (DMM). RNA isolated from the anterior synovium of mice at 1 and 6 weeks post-surgery was subject to expression profiling using Agilent microarrays and qPCR. OA severity was determined histologically. Anterior and posterior synovitis decreased with post-operative time after sham and DMM. No differences in synovitis parameters were evident between sham and DMM in the anterior synovium at either time. While expression profiling revealed 394 miRNAs were dysregulated between 1 and 6 week time-points in the anterior synovium, there were no significant changes in miRNA or mRNA expression between DMM and sham mice at both time-points. Bioinformatic analysis of the miRNAs and mRNAs differentially expressed in tandem with the resolution of anterior synovial inflammation revealed similar biological processes and functions, including organismal injury, connective tissue disorder and inflammatory responses. Our data demonstrates that early OA-specific patterns of synovial miRNAs or mRNAs dysregulation could not be identified in this model of post-traumatic OA.
Estimating the occurrence of primary ubiquinone deficiency by analysis of large-scale sequencing data
Authors: Hughes Bryan G. , Harrison Paul M. , Hekimi Siegfried
Published: December 2017

Primary ubiquinone (UQ) deficiency is an important subset of mitochondrial disease that is caused by mutations in UQ biosynthesis genes. To guide therapeutic efforts we sought to estimate the number of individuals who are born with pathogenic variants likely to cause this disorder. We used the NCBI ClinVar database and literature reviews to identify pathogenic genetic variants that have been shown to cause primary UQ deficiency, and used the gnomAD database of full genome or exome sequences to estimate the frequency of both homozygous and compound heterozygotes within seven genetically-defined populations. We used known population sizes to estimate the number of afflicted individuals in these populations and in the mixed population of the USA. We then performed the same analysis on predicted pathogenic loss-of-function and missense variants that we identified in gnomAD. When including only known pathogenic variants, our analysis predicts 1,665 affected individuals worldwide and 192 in the USA. Adding predicted pathogenic variants, our estimate grows to 123,789 worldwide and 1,462 in the USA. This analysis predicts that there are many undiagnosed cases of primary UQ deficiency, and that a large proportion of these will be in developing regions of the world.
Heritability of the melatonin synthesis variability in autism spectrum disorders
Authors: Benabou Marion , Rolland Thomas , Leblond Claire S. , Millot Gaël A. , Huguet Guillaume , Delorme Richard , Leboyer Marion , Pagan Cécile , Callebert Jacques , Maronde Erik , Bourgeron Thomas
Published: December 2017

Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with a complex genetic architecture. They are characterized by impaired social communication, stereotyped behaviors and restricted interests and are frequently associated with comorbidities such as intellectual disability, epilepsy and severe sleep disorders. Hyperserotonemia and low melatonin levels are among the most replicated endophenotypes reported in ASD, but their genetic causes remain largely unknown. Based on the biochemical profile of 717 individuals including 213 children with ASD, 128 unaffected siblings and 376 parents and other relatives, we estimated the heritability of whole-blood serotonin, platelet N-acetylserotonin (NAS) and plasma melatonin levels, as well as the two enzymes arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT) activities measured in platelets. Overall, heritability was higher for NAS (0.72 ± 0.091) and ASMT (0.59 ± 0.097) compared with serotonin (0.31 ± 0.078), AANAT (0.34 ± 0.077) and melatonin (0.22 ± 0.071). Bivariate analyses showed high phenotypic and genetic correlations between traits of the second step of the metabolic pathway (NAS, ASMT and melatonin) indicating the contribution of shared genetic factors. A better knowledge of the heritability of the melatonin synthesis variability constitutes an important step to identify the factors that perturb this pathway in individuals with ASD.
Dual direction CRISPR transcriptional regulation screening uncovers gene networks driving drug resistance
Authors: le Sage Carlos , Lawo Steffen , Panicker Prince , Scales Tim M. E. , Rahman Syed Asad , Little Annette S. , McCarthy Nicola J. , Moore Jonathan D. , Cross Benedict C. S.
Published: December 2017

Pooled CRISPR–Cas9 knock out screens provide a valuable addition to the methods available for novel drug target identification and validation. However, where gene editing is targeted to amplified loci, the resulting multiple DNA cleavage events can be a cause of false positive hit identification. The generation of nuclease deficient versions of Cas9 has enabled the development of two additional techniques – CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) – that enable the repression or overexpression, respectively, of target genes. Here we report the first direct combination of all three approaches (CRISPRko, CRISPRi and CRISPRa) in the context of genome-wide screens to identify components that influence resistance and sensitivity to the BRAF inhibitor, vemurafenib. The pairing of both loss- and gain-of-function datasets reveals complex gene networks which control drug response and illustrates how such data can add substantial confidence to target identification and validation analyses.
Preparation and reactivity of a square-planar PNP cobalt(ii)–hydrido complex: isolation of the first {Co–NO}8–hydride
Authors: Krishnan V. Mahesh , Arman Hadi D. , Tonzetich Zachary J.
Published: December 2017

The synthesis of a square-planar cobalt(ii) hydrido complex supported by a pyrrole-based PNP ligand has been reinvestigated and its reactivity with various small molecules examined.
Stereocontrolled glycoside synthesis by activation of glycosyl sulfone donors with scandium(iii) triflate
Authors: Xolin Amandine , Losa Romain , Kaid Aicha , Tresse Cédric , Beau Jean-Marie , Boyer François-Didier , Norsikian Stéphanie
Published: December 2017

Activation of armed glycosyl sulfone donors, using scandium(iii) triflate under microwave irradiation, provides a selective preparation of α-mannosides.
Structural revision of two unusual rhamnofolane diterpenes, curcusones I and J, by means of DFT calculations of NMR shifts and coupling constants
Authors: Sarotti Ariel M.
Published: December 2017

The structures of two unusual rhamnofolane diterpenes, curcusones I and J, have been revised using quantum calculations of NMR shifts.
Assaying kinase activity of the TPL-2/NF-κB1 p105/ABIN-2 complex using an optimal peptide substrate
Authors: Kümper Sandra , Gantke Thorsten , Chen Chao-Sheng , Soneji Yasmina , Pattison Michael J. , Chakravarty Probir , Kjær Svend , Thomas Daniel , Haslam Carl , Leavens Bill J. , House David , Powell David J. , Ley Steven C.
Published: December 2017

The MKK1/2 kinase tumour progression locus 2 (TPL-2) is critical for the production of tumour necrosis factor alpha (TNFα) in innate immune responses and a potential anti-inflammatory drug target. Several earlier pharmaceutical company screens with the isolated TPL-2 kinase domain have identified small-molecule inhibitors that specifically block TPL-2 signalling in cells, but none of these have progressed to clinical development. We have previously shown that TPL-2 catalytic activity regulates TNF production by macrophages while associated with NF-κB1 p105 and ABIN-2, independently of MKK1/2 phosphorylation via an unknown downstream substrate. In the present study, we used a positional scanning peptide library to determine the optimal substrate specificity of a complex of TPL-2, NF-κB1 p105 and ABIN-2. Using an optimal peptide substrate based on this screen and a high-throughput mass spectrometry assay to monitor kinase activity, we found that the TPL-2 complex has significantly altered sensitivities versus existing ATP-competitive TPL-2 inhibitors than the isolated TPL-2 kinase domain. These results imply that screens with the more physiologically relevant TPL-2/NF-κB1 p105/ABIN-2 complex have the potential to deliver novel TPL-2 chemical series; both ATP-competitive and allosteric inhibitors could emerge with significantly improved prospects for development as anti-inflammatory drugs.
Efficacy and safety of linezolid compared with other treatments for skin and soft tissue infections: a meta-analysis
Authors: Li Yan , Xu Wei
Published: December 2017

Linezolid with other treatments for skin and soft tissue infections (SSTIs) has been evaluated in several studies. However, the conclusions remain controversial. By searching PubMed, EMBASE, and Cochrane library databases, we conducted a meta-analysis to evaluate linezolid and other treatments for skin and soft tissue infections. The study was summarized, and the risk ratio (RR) and its 95% confidence interval (CI) were calculated. Eleven related articles were included in the meta-analysis. Our results revealed that linezolid was associated with a significantly better clinical (RR = 1.09, 95% CI: 1.02–1.16, Pheterogeneity = 0.326, I2 = 13.0%) and microbiological cure rates (RR = 1.08, 95% CI: 1.01–1.16, Pheterogeneity = 0.089, I2 = 41.7%) when comparing with vancomycin. There was no significant difference in the incidence of anemia, nausea, and mortality; however, the incidence of vomiting, diarrhea, and thrombocytopenia in patients treated with linezolid is significantly higher than that with other treatments. Our study confirmed that linezolid seems to be more effective than vancomycin for treating people with SSTIs. It is recommended that linezolid be monitored for thrombocytopenia, vomiting, and diarrhea. Further studies with larger dataset and well-designed models are required to validate our findings.
Molecular control of chaperone-mediated autophagy
Authors: Catarino Steve , Pereira Paulo , Girão Henrique
Published: December 2017

Chaperone-mediated autophagy (CMA) is a selective form of autophagy in which cytosolic proteins bearing a pentapeptide motif biochemically related to the KFERQ sequence, are recognized by the heat shock protein family A member 8 (HSPA8) chaperone, delivered to the lysomal membrane, and directly translocated across the lysosomal membrane by a protein complex containing lysosomal associated membrane protein 2a (Lamp2a). Since its discovery over two decades ago, the importance of this pathway in cell proteostasis has been made increasingly apparent. Deregulation of this pathway has been implicated in a variety of diseases and conditions, including lysosomal storage diseases, cancer, neurodegeneration and even aging. Here, we describe the main molecular features of the pathway, its regulation, cross-talk with other degradation pathways and importance in disease.
The non-T-cell-inflamed tumor microenvironment: contributing factors and therapeutic solutions
Authors: Horton Brendan L. , Spranger Stefani
Published: December 2017

The recent successes of cancer immunotherapy, first and foremost checkpoint blockade therapy, illustrate the power of the immune system to control cancer. As the number of patients receiving this therapy is increasing, the number of patients being resistant or establishing resistance toward immunotherapy is also increasing. We, therefore, need to further understand the mechanisms mediate resistance in order to prevent or overcome those mechanisms. Increasing evidence is being reported that alterations in tumor cell-intrinsic signaling pathways, including the activation of the WNT/β-catenin pathway, are associated with blunted T-cell infiltration. Infiltration of tumor by CD8 T cells is one of the most predictive biomarkers for the response toward immunotherapy and therefore the notion that alterations of certain tumor cell-intrinsic signaling pathways might mediate resistance should be considered. Understanding the molecular and immunological mechanisms mediating resistance will ultimately facilitate the development of effective treatment strategies counteracting immune evasion.
Newborn Screening of Genetic Mutations in Common Deafness Genes With Bloodspot-Based Gene Chip Array
Authors: He Xuehu , Li Xiuzhong , Guo Yaqi , Zhao Yue , Dong Hui , Dong Jie , Zhong Li , Shi Zhiyun , Zhang Yuying , Soliman Mario , Song Chunhua , Zhao Zhijun
Published: December 2017

Purpose

This study screens for deafness gene mutations in newborns in the Northwest China population.

Method

The 9 sites of 4 common deafness genes (
GJB2, GJB3, SLC26A
4,
and
mt 12S rRNA
) were detected by bloodspot-based gene chip array in 2,500 newborns.

Results

We detected mutations of the 4 genes in 101 (4.04%) newborns; particularly, 0.20% detected the double mutations. In the Hui population, 4.58% of the newborns tested positive for mutations, whereas 4.01% of Han newborns tested positive for mutations. The detective rates are as follows: 1.44% for
GJB2
235delC, 1.08% for
SLC26A4
IVS7-2A>G, 0.48% for
GJB2 299
_300delAT, 0.28% for
SLC26A4
2168A>G, 0.2% for
mt 12S rRNA
1555A>G, and 0.16% for
GJB3
538C>T. The 31.25% (5/16) of infants with
GJB2
235delC, 50% (3/6) with
GJB2
299_300delAT, and 25% (3/12) with
SLC26A4
IVS7-2A>G showed abnormal hearing when tested; only 1 double mutation case received the hearing test, and this infant showed abnormality in both ears on the hearing test.

Conclusions

High mutation rates in the common deafness genes were detected in newborns in Northwest China. Our study is helpful in understanding the deafness genomic epidemiology and also provides evidence for prenatal and postnatal care as well as policy making on population health in the region.
Integrated printing stereo antenna with dual materials 3D printing technology
Authors: Lou Qun , Wu Rui‐xin
Published: December 2017

A three‐dimensional printing technology that can be applied to stereo antennas fabrication is presented. The main steps of the fabrication include printing antenna model by dual materials fused deposition modelling and the following selective chemical plating. As a demonstration of this powerful technology, a typical stereo antenna, the Yagi‐Uda antenna, is designed and fabricated. Measured results show the printed antenna has good performances and agree well with simulated results. The technology provides a simple, straightforward way for antenna fabrication, and is especially suitable for the fabrication of stereo structure antennas.
X‐band negative group‐delay lossy stub line
Authors: Ravelo Blaise
Published: December 2017

This study investigates the negative group delay (NGD) passive circuit constituted by a fully distributed parallel stub line. The proposed S‐parameter modelling is developed. The transmission parameter band‐pass NGD function identification is described. The NGD characterisation is established by determination of the NGD level and bandwidth in function of the stub line parameters. It was analytically found that with a basic cell consisted of single stub line, the insertion loss is usually degraded to reach significant figure‐of‐merit which is obtained with the NGD level‐bandwidth product. As a solution, it is shown that this insertion loss can be improved with the consideration of matching network. As proof‐of‐concept (POC), microstrip distributed circuits printed on the flexible Kapton substrate without lumped element were synthesised, designed and fabricated. The theoretical, simulated and measured results are in good correlation. As expected, band‐pass NGD behaviours centred beyond 10 GHz were observed. The POC generates NGD level of about −1.5 ns over the NGD bandwidth 0.65 GHz. In the future, thanks to the theoretical approach simplicity and the topology integrability, the NGD principle can be potentially useful for the improvement of RF/microwave circuits.
Monte Carlo simulation of biological shielding parameters in PGNAA
Authors: Yang Jianbo , Peng Kexin , Qiao Yujie , Zhang Can , Li Rui , Li Zhe
Published: December 2017

A prompt γ neutron activation analysis (PGNAA) facility based on a 252 Cf spontaneous fission neutron was performed with the final goal of obtaining various optimised radiation protection design parameters. MCNP Monte Carlo code was used to simulate the lead (Pb) shield thickness on two sides of the sample chamber, and B4 C, B2O3, LiOH, LiF, and borax were selected as neutron‐absorbing materials that were simulated to determine optimal parameters for the optimal design of a biological multilayer composite shield. A series of calculations performed with the MCNP code indicated that the 5 cm thick Pb innermost layer of a biological shield rapidly reduced fast neutrons, and a moderation layer of 25 cm thick paraffin, 20 mm thick borax, and 2 mm thick B4 C were selected as neutron‐absorbing materials. The calculated biological shield protection parameters satisfied the requirements of the PGNAA facility used in the experiment.
Shifting of the resonance location for planets embedded in circumstellar disks
Authors: Marzari F.
Published: December 2017

Context. In the early evolution of a planetary system, a pair of planets may be captured in a mean motion resonance while still embedded in their nesting circumstellar disk.

Aims. The goal is to estimate the direction and amount of shift in the semimajor axis of the resonance location due to the disk gravity as a function of the gas density and mass of the planets. The stability of the resonance lock when the disk dissipates is also tested.

Methods. The orbital evolution of a large number of systems is numerically integrated within a three-body problem in which the disk potential is computed as a series of expansion. This is a good approximation, at least over a limited amount of time.

Results. Two different resonances are studied: the 2:1 and the 3:2. In both cases the shift is inwards, even if by a different amount, when the planets are massive and carve a gap in the disk. For super-Earths, the shift is instead outwards. Different disk densities, Σ, are considered and the resonance shift depends almost linearly on Σ. The gas dissipation leads to destabilization of a significant number of resonant systems, in particular if it is fast.

Conclusions. The presence of a massive circumstellar disk may significantly affect the resonant behavior of a pair of planets by shifting the resonant location and by decreasing the size of the stability region. The disk dissipation may explain some systems found close to a resonance but not locked in it.
Atlas of new and revised high-resolution spectroscopy of six CO isotopologues in the 101–115 nm range
Authors: Lemaire J. L. , Heays A. N. , Eidelsberg M. , Gavilan L. , Stark G. , Federman S. R. , Lyons J. R. , de Oliveira N.
Published: December 2017

Our knowledge of astronomical environments containing CO depends on accurate molecular data to reproduce and interpret observed spectra. The recent and future improvements of ultraviolet space instrumentation, both in sensitivity and resolution, require increasingly detailed laboratory molecular spectroscopy as a reference. As part of a long-term experimental campaign at the SOLEIL Synchrotron facility, we have acquired gas-phase absorption spectra of six CO isotopologues in the vacuum ultraviolet. These spectra are recorded using the Fourier-transform spectrometer installed on the DESIRS beamline, providing a unique resolving power up to 106 in the 8–13 eV range. We have used resolutions in the 300 000–450 000 range for this campaign, which enable the analysis of individual line positions. We report new measurements on neighboring Rydberg states in the 101–115 nm range that could also be used as f-value calibrators, namely B1Σ+, C1Σ+, and E1Π, for six CO isotopologues. This range encompasses the absorption transitions B(v′ = 0, 1, and 2), C(v′ = 0, 1, 2, and 3), and E(v′ = 0, 1, 2, and 3) from X1Σ+(v′′ = 0). Higher resolution laser-based measurements of CO isotopologues from the literature are used to improve the absolute calibration and accuracy of our data. The overall uncertainty of the great majority of the line positions presented in this atlas is estimated to be 0.01 cm−1. In addition, some of the data derived from transition energies measurements, such as term values and molecular constants, are obtained for the first time, and others are improvements on previous sparser or lower spectral resolution datasets.