bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical analysis of financial data with many zeros
Authors: Song Kai‐Sheng , Kieschnick Robert
Published: June 2017

One of the core issues in finance is to understand why firms finance themselves as they do. This issue has become increasingly important because how firms are financed influences their performance and value. Since the 1950s, the capital structure literature has addressed this fundamental issue by focusing on a firm's mix of debt and equity. However, firms often use more than one type of debt claim. Furthermore, some firms use certain types of debt claim that others do not use. The financing choices of various forms of debt claim and different amounts of debt issued lead to financial data with multiple continuous proportions and many zeros implied by debt structures. We propose a novel method for addressing such choice‐implied statistical issues. Our method is based on choice probability‐driven submodels and is empirically implementable even in large dimensions. Its performance is demonstrated by simulations. Its application to the analysis of debt structures of U.S. corporations reveals that the determinants of the choice to use a particular form of debt and how much of that type of debt to use are not identical: a valuable insight missing from prior financial research. Our methodology is applicable not only to firm financing decisions in corporate finance, but also to choices in other critical areas of finance such as household investment decisions in household finance. WIREs Comput Stat 2017, 9:e1399. doi: 10.1002/wics.1399

This article is categorized under:

Applications of Computational Statistics > Computational Finance

Statistical and Graphical Methods of Data Analysis > Multivariate Analysis
Numerical simulation of circulation control turbine cascade with Coanda jet and counter-flow blowing at high Mach numbers
Authors: Feng Y. , Song Y. , Chen F.
Published: June 2017

The performance of a circulation-control inlet guide vane that makes use of the Coanda effect was studied numerically in a high Mach number turbine cascade. The effect of different shapes (elliptic and circular) of the Coanda surface at the blade trailing edge was investigated by implementing both a Coanda jet and a counter-flow blowing. Under high subsonic flow conditions, with a total blowing ratio of 3% of the mainstream, the circulation control cascade can reach the same performance as the reference stator with a 13.5% reduction in the axial chord length, with minimal increase of the energy loss coefficient. The Coanda surfaces with small curvature are more efficient in entraining the mainstream flow, and they achieve better aerodynamic performance. The wall attachment of the Coanda jet is improved by employing counter-flow blowing, resulting in a slight increase of both the exit flow angle and the expansion ratio. Under supersonic flow conditions at the cascade exit, it is more difficult for the circulation control cascade to reach the appropriate flow turning due to a premature shock wave, which is absent in the original cascade until the very end of the suction surface.
The core emergency ultrasound curriculum project: A report from the Curriculum Working Group of the CAEP Emergency Ultrasound Committee
Authors: Olszynski Paul , Kim Dan , Chenkin Jordan , Rang Louise
Published: June 2017

Emergency ultrasound (EUS) is now widely considered to be a “skill integral to the practice of emergency medicine.”1The Canadian Association of Emergency Physicians (CAEP) initially issued a position statement in 1999 supporting the availability of focused ultrasound 24 hours per day in the emergency department (ED).2
Personality Goes a Long Way
Authors: Lobo Marina Costa
Published: June 2017

This article reviews books which test the personalization of politics, looking at different dimensions of the growing importance of leaders over time, namely for political parties, in electoral behaviour and in the media. Only recently have wide-ranging comparative longitudinal studies on leaders been carried out. The personalization thesis is not equally demonstrated across all dimensions. Indeed, we find something of a puzzle: There is no strong trend towards personalization of party organizations, whereas in electoral behaviour the evidence points to the increasing use by voters of leaders as heuristics. This attests to the decline of the importance of parties. The personalization of media may be the mechanism which explains the change in voting behaviour, and the third and final section of the review looks into that arena. We conclude with some suggestions on further research on the personalization of politics.
Indirect Versus Direct Standardization Methods for Reporting Healthcare-Associated Infections: An Analysis of Central Line–Associated Bloodstream Infections in Maryland
Authors: O’Hara Lyndsay M. , Masnick Max , Leekha Surbhi , Jackson Sarah S. , Blanco Natalia , Harris Anthony D.
Published: June 2017

Whether healthcare-associated infection data should be presented using indirect (current CMS/CDC methodology) or direct standardization remains controversial. We applied both methods to central-line–associated bloodstream infection data from 45 acute-care hospitals in Maryland from 2012 to 2014. We found that the 2 methods generate different hospital rankings with payment implications.

Infect Control Hosp Epidemiol 2017;38:989–992
Estimation of present-day glacial isostatic adjustment, ice mass change and elastic vertical crustal deformation over the Antarctic ice sheet
Authors: ZHANG BAOJUN , WANG ZEMIN , LI FEI , AN JIACHUN , YANG YUANDE , LIU JINGBIN
Published: June 2017

This study explores an iterative method for simultaneously estimating the present-day glacial isostatic adjustment (GIA), ice mass change and elastic vertical crustal deformation of the Antarctic ice sheet (AIS) for the period October 2003–October 2009. The estimations are derived by combining mass measurements of the GRACE mission and surface height observations of the ICESat mission under the constraint of GPS vertical crustal deformation rates in the spatial domain. The influence of active subglacial lakes on GIA estimates are mitigated for the first time through additional processing of ICESat data. The inferred GIA shows that the strongest uplift is found in the Amundsen Sea Embayment (ASE) sector and subsidence mostly occurs in Adelie Terre and the East Antarctica inland. The total GIA-related mass change estimates for the entire AIS, West Antarctica Ice Sheet (WAIS), East Antarctica Ice Sheet (EAIS), and Antarctic Peninsula Ice Sheet (APIS) are 43 ± 38, 53 ± 24, −23 ± 29 and 13 ± 6 Gt a−1, respectively. The overall ice mass change of the AIS is −46 ± 43 Gt a−1 (WAIS: −104 ± 25, EAIS: 77 ± 35, APIS: −20 ± 6). The most significant ice mass loss and most significant elastic vertical crustal deformations are concentrated in the ASE and northern Antarctic Peninsula.
CALIBRATING DETERMINACY STRENGTH IN LEVELS OF THE BOREL HIERARCHY
Authors: HACHTMAN SHERWOOD
Published: June 2017

We analyze the set-theoretic strength of determinacy for levels of the Borel hierarchy of the form$\Sigma _{1 + \alpha + 3}^0 $, forα<ω1. Well-known results of H. Friedman and D.A. Martin have shown this determinacy to requireα+ 1 iterations of the Power Set Axiom, but we ask what additional ambient set theory is strictly necessary. To this end, we isolate a family of weak reflection principles, Π1-RAPα, whose consistency strength corresponds exactly to the logical strength of${\rm{\Sigma }}_{1 + \alpha + 3}^0 $determinacy, for$\alpha < \omega _1^{CK} $. This yields a characterization of the levels ofLby or at which winning strategies in these games must be constructed. Whenα= 0, we have the following concise result: The leastθso that all winning strategies in${\rm{\Sigma }}_4^0 $games belong toLθ+1is the least so that$L_\theta \models {\rm{``}}{\cal P}\left( \omega \right)$exists, and all wellfounded trees are ranked”.
THE HERBRAND FUNCTIONAL INTERPRETATION OF THE DOUBLE NEGATION SHIFT
Authors: ESCARDÓ MARTÍN , OLIVA PAULO
Published: June 2017

This paper considers a generalisation of selection functions over an arbitrary strong monad T, as functionals of type $J_R^T X = (X \to R) \to TX$. It is assumed throughout that R is a T-algebra. We show that $J_R^T$ is also a strong monad, and that it embeds into the continuation monad $K_R X = (X \to R) \to R$. We use this to derive that the explicitly controlled product of T-selection functions is definable from the explicitly controlled product of quantifiers, and hence from Spector’s bar recursion. We then prove several properties of this product in the special case when T is the finite powerset monad ${\cal P}_{\rm{f}} \left( \cdot \right)$. These are used to show that when $TX = {\cal P}_{\rm{f}} \left( X \right)$ the explicitly controlled product of T-selection functions calculates a witness to the Herbrand functional interpretation of the double negation shift.
Between Means and Ends: Reconstructing Coercion in Dewey's Democratic Theory
Authors: LIVINGSTON ALEXANDER
Published: June 2017

John Dewey's democratic theory is celebrated as a classic statement of the theory of deliberative democracy. This article challenges deliberative appropriations of Dewey's political thought by situating his democratic theory within the contentious history of American labor politics. In his writings on direct action, strikes, and class struggle, Dewey advocated coercive and nondeliberative modes of political action as democratic means for democratic ends. Examining Dewey's writings on democracy, action, and the use of force reveals how a means-oriented pragmatism circumvents the problematic dichotomy of ideal ends and non-ideal means framing contemporary debates about idealism and realism in democratic theory. Pragmatism's account of the interdependence of means and ends in political action, as a process of creative and collaborative experimentation, combines a robust defense of coercive tactics with a consequentialist critique of violence.
Morphological assessment of the earliest paradoxidid trilobites (Cambrian Series 3) from Morocco and Spain
Authors: ÁLVARO J. JAVIER , ESTEVE JORGE , ZAMORA SAMUEL
Published: June 2017

A Cambrian immigration event of paradoxidid trilobites has traditionally marked some regional lower–middle Cambrian boundaries in the Acado-Baltic subprovince (including Baltica and the Mediterranean and Avalonian margins of West Gondwana). The earliest paradoxidine species in Morocco and the Iberian Peninsula have been used as a chronostratigraphic link to support the definition of a common base for the Cambrian Series 3, but recent studies have proposed new species without revising previously established ones. This paper offers a morphological statistical analysis based on both linear measurement and landmark-based geometric morphometric approaches performed on the earliest paradoxinine trilobites sampled in the Anti-Atlas (Morocco) and the Iberian Chains (Spain). As a result, the diagnosis ofAcadoparadoxides mureroensisis emended and several species recently erected in Morocco (A.cf.mureroensis,A. levisettii,A. ovatopygeandA. pampalius) are suggested as synonyms ofA. mureroensisuntil 3D statistical analyses are available based on material preserved on carbonate or silica nodules. The first appearance ofA. mureroensisin both areas can be provisionally used for regional correlation until homotaxic tests are checked.
Bovine intra-mammary challenge withStreptococcus dysgalactiaespp.Dysgalactiaeto explore the effect on the response of Complement activity
Authors: Maye Susan , Flynn James , Stanton Catherine , Fitzgerald Gerald F. , Kelly Philip M.
Published: June 2017

Recently published work as described by the authors highlighted the extent of Complement activity in bovine milk. Localised mastitis infection occurring in the mammary glands of dairy cows is readily detectable by the levels of somatic cells in milk. Thus, it is opportune to monitor Complement activity in milks in association with the animal's innate immune response to mammary infection. Preliminary screening of milk samples taken randomly showed that milk with a high somatic cell count (SCC) reduced growth of the Complement-sensitive strainE. coliO111 to a greater extent (P< 0·05) than when the marker microorganism was grown in milk heated for the purpose of inactivating Complement. A follow-up study set out to determine the effect on Complement activity when a sub-clinical mastitis infection was induced in the mammary gland of four lactating dairy cows. The effect ofStr. dysgalactiaespp.dysgalactiaeinoculation into selected individual udder quarters of the mammary glands of each animal was followed by monitoring of SCC levels in the milks from the segregated udder samples during subsequent milking. At 72 and 96 h post inoculation (PI), the SCCs for the challenged quarter were increased compared to normal values. At the same time, the bactericidal sequestration assay identified increasedE. coliO111 inhibition that can be directly linked to greater Complement activity in those quarter milks affected by induced inflammation. Thus, it can be identified that the high SCC milks were more effective in limitingE. coliO111 growth. Milks from the unchallenged quarters in all four cows were significantly less effective at reducing growth of the assay strain (P< 0·05).

An ELISA assay targeting specific activation components of the Complement pathways confirmed that greater bacterial inhibition observed during the bactericidal sequestration assay was attributable to higher Complement activity in the milk samples from the affected quarters, i.e., with higher SCC. The induced infection was confirmed as self-limiting in three of the affected animals and their SCC returned to normal levels within 14 d PI, while the fourth cow required brief antibiotic intervention.
Endoscopic electrocautery and fibrin obliteration of an acutely complicated pyriform fossa sinus tract in a septuagenarian
Authors: Heyes R , Aulakh A G , Lingam R K , Tatla T
Published: June 2017

Background:

Pyriform fossa sinus tracts classically present with neck abscess, recurrent infections and suppurative thyroiditis in children; acute presentation in a geriatric patient is rare.

Methods:

Case report and Medline literature review.

Case report:

A 79-year-old female presented with a left-sided neck mass and severe odynophagia of 3 days’ duration. Magnetic resonance imaging revealed a large-volume, loculated fluid collection extending throughout the deep spaces of the neck on the left, within and around the thyroid gland capsule. There was radiological evidence of internal jugular vein thrombophlebitis. Abscess incision and drainage, and endoscopic evaluation, were performed. A deeply penetrating sinus was seen in the left pyriform apex, the entrance of which was circumferentially cauterised and the lumen obliterated with fibrin glue. Following post-operative intravenous antibiotics, the patient made a complete recovery.

Conclusion:

This paper describes the first use of fibrin glue to obliterate a pyriform fossa sinus tract in an adult.
You'll feel better in the morning: slow wave activity and overnight mood regulation in interepisode bipolar disorder
Authors: Soehner A. M. , Kaplan K. A. , Saletin J. M. , Talbot L. S. , Hairston I. S. , Gruber J. , Eidelman P. , Walker M. P. , Harvey A. G.
Published: June 2017

Background

Sleep disturbances are prominent correlates of acute mood episodes and inadequate recovery in bipolar disorder (BD), yet the mechanistic relationship between sleep physiology and mood remains poorly understood. Using a series of pre-sleep mood inductions and overnight sleep recording, this study examined the relationship between overnight mood regulation and a marker of sleep intensity (non-rapid eye movement sleep slow wave activity; NREM SWA) during the interepisode phase of BD.

Methods

Adults with interepisode BD type 1 (BD;n= 20) and healthy adult controls (CTL;n= 23) slept in the laboratory for a screening night, a neutral mood induction night (baseline), a happy mood induction night, and a sad mood induction night. NREM SWA (0.75–4.75 Hz) was derived from overnight sleep EEG recordings. Overnight mood regulation was evaluated using an affect grid pleasantness rating post-mood induction (pre-sleep) and the next morning.

Results

Overnight mood regulation did not differ between groups following the sad or happy inductions. SWA did not significantly change for either group on the sad induction night compared with baseline. In BD only, SWA on the sad night was related to impaired overnight negative mood regulation. On the happy induction night, SWA increased relative to baseline in both groups, though SWA was not related to overnight mood regulation for either group.

Conclusions

These findings indicate that SWA disruption may play a role in sustaining negative mood state from the previous night in interepisode BD. However, positive mood state could enhance SWA in bipolar patients and healthy adults.
Is penal substitution incoherent? An examination of Mark Murphy's criticisms
Authors: CRAIG WILLIAM LANE
Published: June 2017

Some critics of the doctrine of penal substitution have alleged that the doctrine is incoherent because punishment entails an attitude of condemnation or censure towards the person punished, which is impossible in the case of Christ. It is shown that this objection is multiply flawed and that a number of viable ways of avoiding the alleged incoherence are available to the penal substitution theorist.
A MARKOV-MODULATED DIFFUSION MODEL FOR ENERGY HARVESTING SENSOR NODES
Authors: Abdelrahman Omer H.
Published: June 2017

This paper presents a probability model of an energy-harvesting wireless sensor node, with the objective of linking quality of sensed data to energy consumption and self-sustainability. The model departs from the common energy discretization framework used in the literature, and instead uses a diffusion process modulated by discrete packet arrival and transmission processes for the detailed representation of renewable energy supply, consumption and storage. An analytical–numerical method is developed to compute the average time until the node experiences an outage, due to lack of energy, for a given workload and ambient energy characteristics, battery capacity and initial charge. The results are illustrated with numerical examples.
Ultra-processed foods and added sugars in the Chilean diet (2010)
Authors: Cediel Gustavo , Reyes Marcela , da Costa Louzada Maria Laura , Martinez Steele Euridice , Monteiro Carlos A , Corvalán Camila , Uauy Ricardo
Published: June 2017

Objective

To assess the consumption of ultra-processed foods and analyse its association with the content of added sugars in the Chilean diet.

Design

Cross-sectional study of national dietary data obtained through 24 h recalls and classified into food groups according to the extent and purpose of food processing (NOVA classification).

Setting

Chile.

Subjects

A probabilistic sample of 4920 individuals (aged 2 years or above) studied in 2010 by a national dietary survey (Encuesta Nacional de Consumo Alimentario).

Results

Ultra-processed foods represented 28·6 (se0·5) % of total energy intake and 58·6 (se0·9) % of added sugars intake. The mean percentage of energy from added sugars increased from 7·7 (se0·3) to 19·7 (se0·5) % across quintiles of the dietary share of ultra-processed foods. After adjusting for several potential sociodemographic confounders, a 5 percentage point increase in the dietary share of ultra-processed foods determined a 1 percentage point increase in the dietary content of added sugars. Individuals in the highest quintile were three times more likely (OR=2·9; 95 % CI 2·4, 3·4) to exceed the 10 % upper limit for added sugars recommended by the WHO compared with those in the lowest quintile, after adjusting for sociodemographic variables. This association was strongest among individuals aged 2–19 years (OR=3·9; 95 % CI 2·7, 5·9).

Conclusions

In Chile, ultra-processed foods are important contributors to total energy intake and to the consumption of added sugars. Actions aimed at limiting consumption of ultra-processed foods are being implemented as effective ways to achieve WHO dietary recommendations to limit added sugars and processed foods, especially for children and adolescents.
Breast-feeding duration for the prevention of excess body weight of mother–child pairs concurrently: a 2-year cohort study
Authors: Mastroeni Marco Fabio , Mastroeni Silmara Salete de Barros Silva , Czarnobay Sandra Ana , Ekwaru John Paul , Loehr Sarah A , Veugelers Paul J
Published: June 2017

Objective

To examine the association between breast-feeding duration and the risk of excess body weight (children >85th percentile, mothers BMI≥25·0 kg/m2) concurrently in mother–child pairs two years after delivery.

Design

Prospective cohort study in Joinville, Brazil. Multivariable logistic regression was used to examine the independent relationship between breast-feeding duration and risk of excess body weight.

Setting

Brazilian public maternity hospital.

Subjects

Three hundred and five mother–child pairs.

Results

At 2-year follow-up, 23·6 % of mother–child pairs had excess body weight. Children breast-fed for <2 months were more likely to have excess body weight than children breast-fed for ≥6 months (OR=2·4; 95 % CI 1·1, 5·1). Breast-feeding for <2 months was also associated with a greater likelihood of maternal excess body weight compared with those who breast-fed for ≥6 months (OR=2·9; 95 % CI 1·1, 8·1). There was a progressive increase in the likelihood of mother–child pairs having excess body weight as breast-feeding duration decreased. In addition to breast-feeding duration, other independent determinants of excess body weight were pre-pregnancy weight, gestational weight gain and number of pregnancies in mothers, and birth weight in children.

Conclusions

Breast-feeding for a longer duration has a parallel protective effect on the risk of excess body weight in mother–child pairs two years after birth. Since members of the same family could be influenced by the same risk factors, continued promotion and support of breast-feeding may help to attenuate the rising prevalence of overweight in mother–child pairs.
Aspect-dependent efficient multipath ghost suppression in TWRI with sparse reconstruction
Authors: Muqaibel Ali Hussein , Abdalla Abdi Talib , Alkhodary Mohammad Tamim , Al-Dharrab Suhail
Published: June 2017

In through-the-wall radar imaging, multipath propagation can create ghost targets, which can adversely affect the image reconstruction process. However, unlike genuine targets, ghost positions are aspect-dependent, which means their position changes with the transceiver location. This paper proposes efficient ghost suppression methods exploiting aspect dependence feature under compressive sensing framework. This paper proposes a generalized signal model that accommodates for the reflections of the front-wall and target-to-target interactions, making the scheme more practical, yet the knowledge of the location of reflecting geometry is not a requirement as in most of the recent literatures. In addition, the sensing matrix is greatly reduced making the methods more attractive. Moreover, this paper investigates the influence of array configurations by examining two antenna array configurations: multimonostatic, and single-view bistatic configurations. Results based on synthesized data and real experiment show that the proposed method can greatly suppress multipath ghosts and hence increase signal-to-clutter ratio.
Mental health service use and need for care of Australians without diagnoses of mental disorders: findings from a large epidemiological survey
Authors: Bobevski I. , Rosen A. , Meadows G.
Published: June 2017

Aims.

While epidemiological surveys worldwide have found a considerable proportion of people using mental health services not to have a diagnosis of a mental disorder, with possible implications of service overuse, other work has suggested that most people without a current diagnosis who used services exhibited other indicators of need. The aims of the present study were, using somewhat different categorisations than previous work, to investigate whether: (1) Australians without a diagnosis of a mental disorder who used mental health services had other indicators of need; and (2) how rate and frequency of service use in Australia related to level of need, then to discuss the findings in light of recent developments in Australian Mental Health Policy and other epidemiological and services research findings.

Methods.

Data from the Australian National Survey of Mental Health and Wellbeing (NSMHWB) 2007 was analysed.

Results.

Most people using mental health services had evident indicators of need for mental health care (MHC), and most of those with lower evident levels of need did not make heavy use of services. Only a small proportion of individuals without any disorders or need indicators received MHC (4%). Although this latter group comprises a fair proportion of service users when extrapolating to the Australian population (16%), the vast majority of these individuals only sought brief primary-care or counselling treatment rather than consultations with psychiatrists. Access and frequency of MHC consultations were highest for people with diagnosed lifetime disorders, followed by people with no diagnosed disorders but other need indicators, and least for people with no identified need indicators. Limitations include some disorders not assessed in interview and constraints based on survey size to investigate subgroups defined, for instance, by socioeconomic advantage and disadvantage individually or by characteristics of area.

Conclusions.

MHC for individuals with no recognised disorders or other reasonable need for such care may be occurring but if so is likely to be an area-specific phenomenon. Rather than revealing a large national pool of treatment resources being expended on the so-called ‘worried well’, the findings suggested a generally appropriate dose–response relationship between need indicators and service use. Definitive ascertainment of area-specific disparities in this national pattern would require a different survey approach. Government proposals for widespread introduction of stepped-care models that may seek to divert patients from existing treatment pathways need to be implemented with care and well informed by local data.
Lübecker Memorandum zur Zukunft der Suchtkrankenversorgung
Authors: Rumpf Hans-Jürgen , Bischof Gallus , Bischof Anja , Hoch Eva , Teilnehmerinnen die , der Lübecker Zukunftswerkstatt Teilnehmer
Published: June 2017

Zusammenfassung. Hintergrund: Suchterkrankungen verursachen hohe Kosten für die Gesellschaft und beträchtliches Leid bei Betroffenen und deren Familien. Das Suchthilfesystem leistet eine hervorragende Arbeit und erreicht diejenigen, die Behandlung aufsuchen, gut und effizient. Die Mehrheit der Suchtkranken – je nach konsumiertem Suchtstoff in unterschiedlichem Ausmaß – sucht jedoch von sich aus keine Hilfe auf und ist somit für das Suchthilfesystem derzeit nicht erreichbar. Methode: Eine Expertinnen- und Expertengruppe hat eine Zukunftsvision für die Suchtkrankenversorgung erarbeitet, die folgende vier Arbeitsfelder umfasst. Ergebnisse: 1) Nahtlose und zugeschnittene Hilfen: Menschen mit Suchterkrankungen werden in allen wichtigen Bereichen des Lebens erkannt und erhalten die für sie geeignete Hilfe, die von Frühintervention über Beratung und Therapie bis hin zu kontinuierlicher Betreuung reicht und Angebote der Selbsthilfe einschließt. Bereiche der medizinischen und psychosozialen Versorgung sind mit der Suchthilfe vernetzt und bieten gemeinschaftlich nahtlose Hilfe an. Die Finanzierung ist vereinfacht und gesichert. 2) Frühzeitige, umfassende und wirksame Prävention: Präventionsstrategien beinhalten eine frühzeitige und lebensweltorientierte Berücksichtigung von problematischen Gesundheits-Verhaltensweisen. Sucht, schädlicher und riskanter Konsum haben hier eine Schlüsselstellung. Es werden über den gesamten Lebensverlauf Hilfen zur Verbesserung des Gesundheitsverhaltens angeboten. 3) Vorurteilfreies Klima und fördernde Grundhaltung: Die Stigmatisierung ist wirksam reduziert. Sucht, schädlicher und riskanter Konsum werden wertfrei als optimier- und veränderbare Verhaltensweisen angesehen. Der Umgang mit Betroffenen ist geprägt von Partnerschaftlichkeit, Akzeptanz, Mitgefühl und motivierender Förderung. 4) Freier Zugang zu einem Spektrum wirksamer Hilfen: Es ist gesichert, dass die bestwirksamen Behandlungsformen qualifiziert angeboten werden. Die Betroffenen werden durch eine unabhängige Beratung darin unterstützt, selbstbestimmt daraus die für ihre spezifische Problematik passende Wahl zu treffen. Schlussfolgerung: Die entwickelten Ideen sollen nun in einem fortlaufenden Prozess umgesetzt werden. Hierzu wird eine Kommission mit verschiedenen Arbeitsgruppen gegründet. Es wird eine Zusammenarbeit mit Politik, Verbänden, Praxis und Forschung erfolgen.
Measurement of copy number variation in single cancer cells using rapid-emulsification digital droplet MDA
Authors: Kim Samuel C. , Premasekharan Gayatri , Clark Iain C. , Gemeda Hawi B. , Paris Pamela L. , Abate Adam R.
Published: June 2017

Uniform amplification of low-input DNA is important for applications across biology, including single-cell genomics, forensic science, and microbial and viral sequencing. However, the requisite biochemical amplification methods are prone to bias, skewing sequence proportions and obscuring signals relating to copy number. Digital droplet multiple displacement amplification enables uniform amplification but requires expert knowledge of microfluidics to generate monodisperse emulsions. In addition, existing microfluidic methods are tedious and labor intensive for preparing many samples. Here, we introduce rapid-emulsification multiple displacement amplification, a method to generate monodisperse droplets with a hand-held syringe and hierarchical droplet splitter. Although conventional microfluidic devices require >10 min to emulsify a sample, our system requires tens of seconds and yields data of equivalent quality. We demonstrate the approach by using it to accurately measure copy number variation (CNV) in single cancer cells.
A bioinspired and biocompatible ortho-sulfiliminyl phenol synthesis
Authors: Xiong Feng , Lu Liang , Sun Tian-Yu , Wu Qian , Yan Dingyuan , Chen Ying , Zhang Xinhao , Wei Wei , Lu Yi , Sun Wei-Yin , Li Jie Jack , Zhao Jing
Published: June 2017

Synthetic methods inspired by Nature often offer unique advantages including mild conditions and biocompatibility with aqueous media. Inspired by an ergothioneine biosynthesis protein EgtB, a mononuclear non-haem iron enzyme capable of catalysing the C–S bond formation and sulfoxidation, herein, we discovered a mild and metal-free C–H sulfenylation/intramolecular rearrangement cascade reaction employing an internally oxidizing O–N bond as a directing group. Our strategy accommodates a variety of oxyamines with good site selectivity and intrinsic oxidative properties. Combining an O–N bond with an X–S bond generates a C–S bond and an S=N bond rapidly. The newly discovered cascade reaction showed excellent chemoselectivity and a wide substrate scope for both oxyamines and sulfenylation reagents. We demonstrated the biocompatibility of the C–S bond coupling reaction by applying a coumarin-based fluorogenic probe in bacterial lysates. Finally, the C–S bond coupling reaction enabled the first fluorogenic formation of phospholipids, which self-assembled to fluorescent vesicles in situ.
Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression
Authors: Kar Gozde , Kim Jong Kyoung , Kolodziejczyk Aleksandra A. , Natarajan Kedar Nath , Torlai Triglia Elena , Mifsud Borbala , Elderkin Sarah , Marioni John C. , Pombo Ana , Teichmann Sarah A.
Published: June 2017

Polycomb repressive complexes (PRCs) are important histone modifiers, which silence gene expression; yet, there exists a subset of PRC-bound genes actively transcribed by RNA polymerase II (RNAPII). It is likely that the role of Polycomb repressive complex is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcription. Here, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data. We find that Polycomb repressive complex-active genes have greater cell-to-cell variation in expression than active genes, and these results are validated by knockout experiments. We also show that PRC-active genes are clustered on chromosomes in both two and three dimensions, and interactions with active enhancers promote a stabilization of gene expression noise. These findings provide new insights into how chromatin regulation modulates stochastic gene expression and transcriptional bursting, with implications for regulation of pluripotency and development.
Prognostic value of CD146 in solid tumor: A Systematic Review and Meta-analysis
Authors: Zeng Ping , Li Hai , Lu Pei-Hua , Zhou Li-Na , Tang Min , Liu Chao-Ying , Chen Min-Bin
Published: June 2017

CD146, also known as melanoma cell adhesion molecule, was initially identified as a marker of melanoma progression and metastasis. Recently many clinical studies investigated overexpression of CD146 predict poor prognosis of solid tumor, however, the results was inconclusive, partly due to small numbers of patients included. This present meta-analysis was therefore performed utilizing the results of all clinical studies concerned to determine the prognostic value of CD146 expression in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. In this meta-analysis, 12 studies involving 2,694 participants were included, and we drew the conclusion that strong significant associations between CD146 expression and all endpoints: overall survival (OS) [hazard ratio (HR) = 2.496, 95% confidence interval (95% CI) 2.115–2.946], time to progression (TTP) (HR = 2.445, 95% CI 1.975–3.027). Furthermore, the subgroup analysis revealed that the associations between CD146 overexpression and the outcome endpoints (OS or TTP) were significant in Mongoloid patients and Caucasian patients, as well in patients with lung cancer and digestive system cancer. In conclusion, these results showed that high CD146 was associated with poor survival in human solid tumors. CD146 may be a valuable prognosis predictive biomarker; nevertheless, whether CD146 could be a potential therapeutic target in human solid tumors needs to be further studied.
Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples
Authors: Manso Carmen F. , Bibby David F. , Mbisa Jean L.
Published: June 2017

RNA viruses cause significant human pathology and are responsible for the majority of emerging zoonoses. Mainstream diagnostic assays are challenged by their intrinsic diversity, leading to false negatives and incomplete characterisation. New sequencing techniques are expanding our ability to agnostically interrogate nucleic acids within diverse sample types, but in the clinical setting are limited by overwhelming host material and ultra-low target frequency. Through selective host RNA depletion and compensatory protocol adjustments for ultra-low RNA inputs, we are able to detect three major blood-borne RNA viruses – HIV, HCV and HEV. We recovered complete genomes and up to 43% of the genome from samples with viral loads of 104 and 103 IU/ml respectively. Additionally, we demonstrated the utility of this method in detecting and characterising members of diverse RNA virus families within a human plasma background, some present at very low levels. By applying this method to a patient sample series, we have simultaneously determined the full genome of both a novel subtype of HCV genotype 6, and a co-infecting human pegivirus. This method builds upon earlier RNA metagenomic techniques and can play an important role in the surveillance and diagnostics of blood-borne viruses.
Size-dependent validation of MODIS MCD64A1 burned area over six vegetation types in boreal Eurasia: Large underestimation in croplands
Authors: Zhu Chunmao , Kobayashi Hideki , Kanaya Yugo , Saito Masahiko
Published: June 2017

Pollutants emitted from wildfires in boreal Eurasia can be transported to the Arctic, and their subsequent deposition could accelerate global warming. The Moderate Resolution Imaging Spectroradiometer (MODIS) MCD64A1 burned area product is the basis of fire emission products. However, uncertainties due to the “moderate resolution” (500 m) characteristic of the MODIS sensor could be introduced. Here, we present a size-dependent validation of MCD64A1 with reference to higher resolution (better than 30 m) satellite products (Landsat 7 ETM+, RapidEye, WorldView-2, and GeoEye-1) for six ecotypes over 12 regions of boreal Eurasia. We considered the 2012 boreal Eurasia burning season when severe wildfires occurred and when Arctic sea ice extent was historically low. Among the six ecotypes, we found MCD64A1 burned areas comprised only 13% of the reference products in croplands because of inadequate detection of small fires (<100 ha). Our results indicate that over all ecotypes, the actual burned area in boreal Eurasia (15,256 km2) could have been ~16% greater than suggested by MCD64A1 (13,187 km2) when applying the correction factors proposed in this study. This implies the effects of wildfire emissions in boreal Eurasia on Arctic warming could be greater than currently estimated.
A comparison between sphere and rod nanoparticles regarding their in vivo biological behavior and pharmacokinetics
Authors: Zhao Yating , Wang Yu , Ran Fu , Cui Yu , Liu Chang , Zhao Qinfu , Gao Yikun , Wang Da , Wang Siling
Published: June 2017

In recent years, spherical nanoparticles has been studied extensively on biomedical applications including bioimaging and biosensing, diagnostics and theranostics, but the effect of the shape of nanoparticles has received little attention. In the present study, we designed three different shaped fluorescent mesoporous silica nanoparticles (MSNs), long rod nanoparticles (NLR), short rod nanoparticles (NSR), and spherical nanoparticles (NS) to systematically examine their behavior in vivo after oral administration. The results of the ex vivo optical imaging study in mice indicated that rod nanoparticles had a longer residence time in the gastrointestinal compared with spherical nanoparticles. The in vivo biodistribution showed that all the orally administered MSNs were mainly taken up by the liver, and kidney. NLR had a great capacity to overcoming rapid clearance by the RES and exhibited a longer circulation in the blood than NSR and NS. During renal excretion, the spherical nanoparticles were cleared faster than rod nanoparticles. In addition, it was also found that MSNs can be degraded in vivo and NSR were degraded faster than NLR and NS probably owing to their higher specific surface area. The pharmacokinetic results demonstrated that nifedipine(NI)-loaded NLR had a higher bioavailability than NI-loaded NSR and NS.
Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
Authors: Roy Saptarshi , Dutta Devawati , Satyavarapu Eswara M. , Yadav Pawan K. , Mandal Chhabinath , Kar Susanta , Mandal Chitra
Published: June 2017

Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress. Additionally, mahanine-treated Leishmania-infected macrophages exhibited anti-amastigote activity by nitric oxide (NO)/ROS generation along with suppression of uncoupling protein 2 and Th1-biased cytokines response through modulating STAT pathway. Moreover, we have demonstrated the interaction of a few antioxidant enzymes present in parasite with mahanine through molecular modeling. Reduced genetic and protein level expression of one such enzyme namely ascorbate peroxidase was also observed in mahanine-treated promastigotes. Furthermore, oral administration of mahanine in acute murine model exhibited almost complete reduction of parasite burden, upregulation of NO/iNOS/ROS/IL-12 and T cell proliferation. Taken together, we have established a new function of mahanine as a potent antileishmanial molecule, capable of inducing ROS and exploit antioxidant enzymes in parasite along with modulation of host’s immune response which could be developed as an inexpensive and nontoxic therapeutics either alone or in combination.
High-resolution 3D visualization of ductular proliferation of bile duct ligation-induced liver fibrosis in rats using x-ray phase contrast computed tomography
Authors: Qin Lili , Zhao Xinyan , Jian Jianbo , Zhao Yuqing , Sun Mengyu , Hu Chunhong
Published: June 2017

X-ray phase-contrast computed tomography (PCCT) can provide excellent image contrast for soft tissues with small density differences, and it is particularly appropriate for three-dimensional (3D) visualization of accurate microstructures inside biological samples. In this study, the morphological structures of proliferative bile ductules (BDs) were visualized without contrast agents via PCCT with liver fibrosis samples induced by bile duct ligation (BDL) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group, 2-week and 6-week post-BDL groups. All livers were removed after euthanasia for a subsequent imaging. The verification of the ductular structures captured by PCCT was achieved by a careful head-to-head comparison with their corresponding histological images. Our experimental results demonstrated that PCCT images corresponded very well to the proliferative BDs shown by histological staining using cytokeratin 19 (CK19). Furthermore, the 3D density of proliferative BDs increased with the progression of liver fibrosis. In addition, PCCT accurately revealed the architecture of proliferative BDs in a 3D fashion, including the ductular ramification, the elongation and tortuosity of the branches, and the corrugations of the luminal duct surface. Thus, the high-resolution PCCT technique can improve our understanding of the characteristics of ductular proliferation from a new 3D perspective.
Direct observation of a non-crystalline state of Li2S–P2S5 solid electrolytes
Authors: Tsukasaki Hirofumi , Mori Shigeo , Morimoto Hideyuki , Hayashi Akitoshi , Tatsumisago Masahiro
Published: June 2017

There are two types of solid electrolytes which has been recently expected to be applied to all-solid-state batteries. One is the glasses characterized by an amorphous state. The other is the glass ceramics containing crystalline in an amorphous matrix. However, the non-crystalline state of glasses and glass ceramics is still an open question. It has been anticipated that sea-island and core-shell structures including crystalline nanoparticles have been proposed as candidate models for glass ceramics. Nevertheless, no direct observation has been conducted so far. Here we report the non-crystalline state of Li2S–P2S5 glasses and glass ceramics, and the crystallization behavior of the glasses during heating via direct transmission electron microscopy (TEM) observation. High resolution TEM images clearly revealed the presence of crystalline nanoparticles in an amorphous region. Eventually we suggest that the precipitation and connection of crystalline nanoparticles in an amorphous matrix are key to achieving high ionic conductivity.
High-intensity Interval Training Improves Mitochondrial Function and Suppresses Thrombin Generation in Platelets undergoing Hypoxic Stress
Authors: Wu Li-Hua , Chang Shao-Chiang , Fu Tieh-Cheng , Huang Ching-Hui , Wang Jong-Shyan
Published: June 2017

This study elucidates how high-intensity interval training (HIT) and moderate-intensity continuous training (MCT) affect mitochondrial functionality and thrombin generation (TG) in platelets following hypoxic exercise (HE, 100 W under 12% O2 for 30 min). Forty-five healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n = 15) or MCT (sustained 60%VO2max, n = 15) for 30 minutes/day, 5 days/week for 6 weeks, or to a control group (CTL, n = 15) that did not received exercise intervention. Before the intervention, HE (i) reduced the ATP-linked O2 consumption rate (OCR), the reserve capacity of OCR, and the activities of citrate synthase (CS) and succinate dehydrogenase (SDH), (ii) lowered mitochondrial membrane potential (MP) and elevated matrix oxidant burden (MOB) in platelets, and (iii) enhanced dynamic TG in platelet-rich plasma (PRP), which responses were attenuated by pretreating PRP with oligomycin or rotenone/antimycin A. However, 6-week HIT (i) increased mitochondrial OCR capacity with enhancing the CS and SDH activities and (ii) heightened mitochondrial MP with depressing MOB in platelets following HE, compared to those of MCT and CTL. Moreover, the HIT suppressed the HE-promoted dynamic TG in PRP. Hence, we conclude that the HIT simultaneously improves mitochondrial bioenergetics and suppresses dynamic TG in platelets undergoing hypoxia.
YvcK, a protein required for cell wall integrity and optimal carbon source utilization, binds uridine diphosphate-sugars
Authors: Foulquier Elodie , Galinier Anne
Published: June 2017

In Bacillus subtilis, Listeria monocytogenes and in two Mycobacteria, it was previously shown that yvcK is a gene required for normal cell shape, for optimal carbon source utilization and for virulence of pathogenic bacteria. Here we report that the B. subtilis protein YvcK binds to Uridine diphosphate-sugars like Uridine diphosphate-Glucose (UDP-Glc) and Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) in vitro. Using the crystal structure of Bacillus halodurans YvcK, we identified residues involved in this interaction. We tested the effect of point mutations affecting the ability of YvcK to bind UDP-sugars on B. subtilis physiology and on cell size. Indeed, it was shown that UDP-Glc serves as a metabolic signal to regulate B. subtilis cell size. Interestingly, we observed that, whereas a yvcK deletion results in the formation of unusually large cells, inactivation of YvcK UDP-sugar binding site does not affect cell length. However, these point mutations result in an increased sensitivity to bacitracin, an antibiotic which targets peptidoglycan synthesis. We thus propose that UDP-GlcNAc, a precursor of peptidoglycan, could be a good physiological ligand candidate of YvcK.