bluuebunny/crossref_metadata_2025 huggingface dataset:
Du corps et des origines dans l’institution : l’empreinte incestuelle
Authors: Le Clef Bruno
Published: October 2015

L’atmosphère incestuelle peut-elle infiltrer l’institution de soins ? Ce thème est interrogé à partir de l’existence d’une asymétrie anthropologique adulte-enfant issue d’une unité psychosomatique originaire et pourvoyeuse de mouvements de séduction. L’institution sera appréhendée comme une métaphore d’un organisme vivant accueillant, telle une matrice, les constructions narcissiques des intervenants professionnels et des usagers, lesquelles sont invitées à un travail de transformation. Selon un gradient variable, les défenses que recouvrent les divers mouvements de séduction peuvent mener vers un dévoiement des asymétries structurantes et entraver la capacité de penser par divers agirs. Ces propos sont éclairés par une clinique centrée sur la question des origines, celle de l’IVG.
Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis
Authors: Hainzl Eva , Stockinger Silvia , Rauch Isabella , Heider Susanne , Berry David , Lassnig Caroline , Schwab Clarissa , Rosebrock Felix , Milinovich Gabriel , Schlederer Michaela , Wagner Michael , Schleper Christa , Loy Alexander , Urich Tim , Kenner Lukas , Han Xiaonan , Decker Thomas , Strobl Birgit , Müller Mathias
Published: October 2015

In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2−/− mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22–STAT3 target genes is reduced in IECs from healthy and colitic Tyk2−/− mice. Experiments with conditional Tyk2−/− mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22–Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22–dependent colitis was confirmed in Citrobacter rodentium–induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3.
Cutting Edge: Inhibiting TBK1 by Compound II Ameliorates Autoimmune Disease in Mice
Authors: Hasan Maroof , Dobbs Nicole , Khan Shaheen , White Michael A. , Wakeland Edward K. , Li Quan-Zhen , Yan Nan
Published: October 2015

TANK-binding kinase 1 (TBK1) is a serine/threonine protein kinase that plays a crucial role in innate immunity. Enhanced TBK1 function is associated with autoimmune diseases and cancer, implicating the potential benefit of therapeutically targeting TBK1. In this article, we examined a recently identified TBK1 inhibitor Compound II on treating autoimmune diseases. We found that Compound II is a potent and specific inhibitor of TBK1-mediated IFN response. Compound II inhibited polyinosinic-polycytidylic acid–induced immune activation in vitro and in vivo. Compound II treatment also ameliorated autoimmune disease phenotypes of Trex1−/− mice, increased mouse survival, and dampened the IFN gene signature in TREX1 mutant patient lymphoblasts. In addition, we found that TBK1 gene expression is elevated in systemic lupus erythematosus patient cells, and systemic lupus erythematosus cells with high IFN signature responded well to Compound II treatment. Together, our findings provided critical experimental evidence for inhibiting TBK1 with Compound II as an effective treatment for TREX1-associated autoimmune diseases and potentially other interferonopathies.
Novel Role of TRPML2 in the Regulation of the Innate Immune Response
Authors: Sun Lu , Hua Yinan , Vergarajauregui Silvia , Diab Heba I. , Puertollano Rosa
Published: October 2015

TRPMLs (or mucolipins) constitute a family of endosomal cation channels with homology to the transient receptor potential superfamily. In mammals, the TRPML family includes three members: TRPML1–3. Although TRPML1 and TRPML3 have been well characterized, the cellular function of TRPML2 has remained elusive. To address TRPML2 function in a physiologically relevant cell type, we first analyzed TRPML2 expression in different mouse tissues and organs and found that it was predominantly expressed in lymphoid organs and kidney. Quantitative RT-PCR revealed tight regulation of TRPML2 at the transcriptional level. Although TRPML2 expression was negligible in resting macrophages, TRPML2 mRNA and protein levels dramatically increased in response to TLR activation both in vitro and in vivo. Conversely, TRPML1 and TRPML3 levels did not change upon TLR activation. Immunofluorescence analysis demonstrated that endogenous TRPML2 primarily localized to recycling endosomes both in culture and primary cells, in contrast with TRPML1 and TRPML3, which distribute to the late and early endosomal pathway, respectively. To better understand the in vivo function of TRPML2, we generated a TRPML2-knockout mouse. We found that the production of several chemokines, in particular CCL2, was severely reduced in TRPML2-knockout mice. Furthermore, TRPML2-knockout mice displayed impaired recruitment of peripheral macrophages in response to i.p. injections of LPS or live bacteria, suggesting a potential defect in the immune response. Overall, our study reveals interesting differences in the regulation and distribution of the members of the TRPML family and identifies a novel role for TRPML2 in the innate immune response.
Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing Granzyme B Transfer Allograft Tolerance in Rodents
Authors: Durand Justine , Huchet Virginie , Merieau Emmanuel , Usal Claire , Chesneau Melanie , Remy Severine , Heslan Michele , Anegon Ignacio , Cuturi Maria-Cristina , Brouard Sophie , Chiffoleau Elise
Published: October 2015

Emerging knowledge regarding B cells in organ transplantation has demonstrated that these cells can no longer be taken as mere generators of deleterious Abs but can also act as beneficial players. We previously demonstrated in a rat model of cardiac allograft tolerance induced by short-term immunosuppression an accumulation in the blood of B cells overexpressing inhibitory molecules, a phenotype also observed in the blood of patients that spontaneously develop graft tolerance. In this study, we demonstrated the presence in the spleen of regulatory B cells enriched in the CD24intCD38+CD27+IgD−IgM+/low subpopulation, which are able to transfer donor-specific tolerance via IL-10 and TGF-β1–dependent mechanisms and to suppress in vitro TNF-α secretion. Following anti-CD40 stimulation, IgD−IgM+/low B cells were blocked in their plasma cell differentiation pathway, maintained high expression of the inhibitory molecules CD23 and Bank1, and upregulated Granzyme B and Irf4, two molecules described as highly expressed by regulatory B cells. Interestingly, these B cells recognized specifically a dominant donor Ag, suggesting restricted specificity that could lead to a particular B cell response. Regulatory B cells were not required for induction of tolerance and appeared following Foxp3+CD4+CD25+ regulatory T cells, suggesting cooperation with regulatory T cells for their expansion. Nevertheless, following transfer to new recipients, these B cells migrated to the allograft, kept their regulatory profile, and promoted local accumulation of Foxp3+CD4+CD25+ regulatory T cells. Mechanisms of regulatory B cells and their cell therapy potential are important to decipher in experimental models to pave the way for future developments in the clinic.
Targeting Anti-Insulin B Cell Receptors Improves Receptor Editing in Type 1 Diabetes–Prone Mice
Authors: Bonami Rachel H. , Thomas James W.
Published: October 2015

Autoreactive B lymphocytes that commonly arise in the developing repertoire can be salvaged by receptor editing, a central tolerance mechanism that alters BCR specificity through continued L chain rearrangement. It is unknown whether autoantigens with weak cross-linking potential, such as insulin, elicit receptor editing, or whether this process is dysregulated in related autoimmunity. To resolve these issues, we developed an editing-competent model in which anti-insulin Vκ125 was targeted to the Igκ locus and paired with anti-insulin VH125Tg. Physiologic, circulating insulin increased RAG-2 expression and was associated with BCR replacement that eliminated autoantigen recognition in a proportion of developing anti-insulin B lymphocytes. The proportion of anti-insulin B cells that underwent receptor editing was reduced in the type 1 diabetes–prone NOD strain relative to a nonautoimmune strain. Resistance to editing was associated with increased surface IgM expression on immature (but not transitional or mature) anti-insulin B cells in the NOD strain. The actions of mAb123 on central tolerance were also investigated, because selective targeting of insulin-occupied BCR by mAb123 eliminates anti-insulin B lymphocytes and prevents type 1 diabetes. Autoantigen targeting by mAb123 increased RAG-2 expression and dramatically enhanced BCR replacement in newly developed B lymphocytes. Administering F(ab′)2123 induced IgM downregulation and reduced the frequency of anti-insulin B lymphocytes within the polyclonal repertoire of VH125Tg/NOD mice, suggesting enhanced central tolerance by direct BCR interaction. These findings indicate that weak or faulty checkpoints for central tolerance can be overcome by autoantigen-specific immunomodulatory therapy.
A Cost-Effectiveness Analysis of Plasmodium falciparum Malaria Elimination in Hainan Province, 2002–2012
Authors: Sun Ding-Wei , Du Jian-Wei , Wang Guang-Ze , Li Yu-Chun , He Chang-Hua , Xue Rui-De , Wang Shan-Qing , Hu Xi-Min
Published: October 2015

In Hainan Province, China, great achievements in elimination of falciparum malaria have been made since 2010. There have been no locally acquired falciparum malaria cases since that time. The cost-effectiveness of elimination of falciparum malaria has been analyzed in Hainan Province. There were 4,422 falciparum malaria cases reported from 2002 to 2012, more cases occurred in males than in females. From 2002 to 2012, a total of 98.5 disability-adjusted life years (DALYs) were reported because of falciparum malaria. Populations in the age ranges of 15–25 and 30–44 years had higher incidences and DALYs than other age groups. From 2002 to 2012, malaria-related costs for salaries of staff, funds from the provincial government, national government, and the GFATM were US$3.02, US$2.24, US$1.44, and US$5.08 million, respectively. An estimated 9,504 falciparum malaria cases were averted during the period 2003–2012. The estimated cost per falciparum malaria case averted was US$116.5. The falciparum malaria elimination program in Hainan was highly effective and successful. However, funding for maintenance is still needed because of imported cases.
Microbiological Contamination of Drinking Water Associated with Subsequent Child Diarrhea
Authors: Luby Stephen P. , Halder Amal K. , Huda Tarique Md. , Unicomb Leanne , Islam M. Sirajul , Arnold Benjamin F. , Johnston Richard B.
Published: October 2015

We used a prospective, longitudinal cohort enrolled as part of a program evaluation to assess the relationship between drinking water microbiological quality and child diarrhea. We included 50 villages across rural Bangladesh. Within each village field-workers enrolled a systematic random sample of 10 households with a child under the age of 3 years. Community monitors visited households monthly and recorded whether children under the age of 5 years had diarrhea in the preceding 2 days. Every 3 months, a research assistant visited the household and requested a water sample from the source or container used to provide drinking water to the child. Laboratory technicians measured the concentration of Escherichia coli in the water samples using membrane filtration. Of drinking water samples, 59% (2,273/3,833) were contaminated with E. coli. Of 12,192 monthly follow-up visits over 2 years, mothers reported that their child had diarrhea in the preceding 2 days in 1,156 (9.5%) visits. In a multivariable general linear model, the log10 of E. coli contamination of the preceding drinking water sample was associated with an increased prevalence of child diarrhea (prevalence ratio = 1.14, 95% CI = 1.05, 1.23). These data provide further evidence of the health benefits of improved microbiological quality of drinking water.
Hepatitis E Virus Exposure is Increased in Pork Butchers from Burkina Faso
Authors: Traoré Kuan Abdoulaye , Ouoba Jean Bienvenue , Huot Nicolas , Rogée Sophie , Dumarest Marine , Traoré Alfred S. , Pavio Nicole , Barro Nicolas , Roques Pierre
Published: October 2015

We conducted the first survey of zoonotic risk of Hepatitis E virus (HEV) transmissions in Ouagadougou, Burkina Faso, through the direct contact with pork meat during professional activity. Anti-HEV antibodies were more prevalent in pork butchers, 76% than in the general population, which was 47.8% in 2013 (odds ratio = 3.46, 95% CI = 2.85–4.21, P < 0.001). Among slaughter-aged swine, HEV seroprevalence was of 80%, and HEV RNA was detected in 1% of pork livers. Phylogenetic analysis pointed out HEV genotype 3. Thus, in addition to possible HEV contamination through the water source, as in endemic region, zoonotic transmissions of HEV probably occur in west Africa.
U.S. and Swedish Student Learning Through Online Synchronous International Interactions
Authors: Aldrich Rebecca M. , Johansson Karin E.
Published: October 2015

There is a continued need to communicate global perspectives in occupational therapy education, but the literature addressing how to incorporate firsthand global experiences into campus learning environments is scant. This article describes how course-based synchronous interactions between U.S. undergraduate occupational science students and Swedish undergraduate occupational therapy students occur via online technology. In a 2014 pilot study, we thematically analyzed students’ open-ended survey responses to discern what students learned through the interactive sessions. We also performed a content analysis of four audio-recorded interactive sessions to understand the content and nature of students’ learning. Our findings suggest that course-based online synchronous interactions provide a positive way for students to learn about other cultures and global differences in occupational therapy practice. The findings also highlight needs for improvement relative to the structure and aims of the interactive sessions. We relate these findings to the global availability of technology and occupational therapists’ cultural competence.
On reconstruction of time series in climatology
Authors: Privalsky V. , Gluhovsky A.
Published: October 2015

Abstract. The approach to time series reconstruction in climatology based upon cross-correlation coefficients and regression equations is mathematically incorrect because it ignores the dependence of time series upon their past. The proper method described here for the bivariate case requires the autoregressive time- and frequency domains modeling of the time series which contains simultaneous observations of both scalar series with subsequent application of the model to restore the shorter one into the past. The method presents further development of previous efforts taken by a number of authors starting from A. Douglass who introduced some concepts of time series analysis into paleoclimatology. The method is applied to the monthly data of total solar irradiance (TSI), 1979–2014, and sunspot numbers (SSN), 1749–2014, to restore the TSI data over 1749–1978. The results of the reconstruction are in statistical agreement with observations.
Systematic liquidity: commonality and inter-temporal variation in the Portuguese stock market
Authors:   Faculty of Economics and Business, Department of Financial Economics, Av. Elvas s/n 06071, Badajoz (Spain). jlmiralles@unex.es, Miralles Marcelo José Luis , Miralles Quirós María Del Mar ,   Faculty of Economics and Business, Department of Financial Economics, Av. Elvas s/n 06071, Badajoz (Spain). marmiralles@unex.es, Oliveira Célia ,   School of Technology and Management, Morro do Lena - Alto Vieiro, P.O. Box 4163 2411-901 Leiria (Portugal). celia.oliveira@ipleiria.pt
Published: October 2015

The aim of this paper is to study systematic liquidity at the Euronext Lisbon Stock Exchange. The motivation for this research is provided by the growing interest in financial literature about stock liquidity and the implications of commonality in liquidity for asset pricing since it could represent a source of non-diversifiable risk. Namely, it is analysed whether there exist common factors that drive the variation in individual stock liquidity and the causes of the inter-temporal variation of aggregate liquidity. Monthly data for the period between January 1988 and December 2011 is used to compute some of the most used proxies for liquidity: bid-ask spreads, turnover rate, trading volume, proportion of zero returns and the illiquidity ratio. Following Chordia et al. (2000) methodology, some evidence of commonality in liquidity is found in the Portuguese stock market when the proportion of zero returns is used as a measure of liquidity. In relation to the factors that drive the inter-temporal variation of the Portuguese stock market liquidity, the results obtained within a VAR framework suggest that changes in real economy activity, monetary policy (proxied by changes in monetary aggregate M1) and stock market returns play an important role as determinants of commonality in liquidity.
Retinal Vessel Segmentation: A Comparative Study of Fuzzy C-Means and Sum Entropy Information on Phase Congruency
Authors: Mapayi Temitope , Tapamo Jules-Raymond , Viriri Serestina
Published: October 2015

As the use of robotic-assisted surgery systems continue to increase, highly accurate and timely efficient automatic vasculature detection techniques for large and thin vessels in the retinal images are needed. Vascular segmentation has however been challenging due to uneven illumination in retinal images. The use of efficient pre-processing techniques as well as good segmentation techniques are highly needed to produce good vessel segmentation results. This paper presents an investigatory study on the combination of phase congruence with fuzzy c-means and the combination of phase congruence with gray level co-occurrence (GLCM) matrix sum entropy for the segmentation of retinal vessels. Fuzzy C-Means combined with phase congruence yields a higher accuracy rate but a longer running time while compared to GLCM sum entropy combined with phase congruence. While compared with the widely previously used techniques on DRIVE and STARE databases, the techniques investigated yield high average accuracy rates.
Comparative Study of Effect of Fin Arrangement on Propulsion Performance of Bio-Inspired Underwater Vehicles with Multiple SMA Fins
Authors: He Jian-hui , Zhang Yong-hua , Low Kin-huat
Published: October 2015

A biologically inspired underwater vehicle (BIUV) was built using multiple lightweight bio-inspired shape memory alloy (SMA) fins. An unsteady 3D computational fluid dynamics (CFD) method using an unstructured, grid-based, and unsteady Navier-Stokes solver with automatic adaptive re-meshing was adopted to compute unsteady flow. The hydrodynamics of multiple fins at a certain Reynolds number (Re = Uc/v, where U is the upstream flow velocity, c is the chord length, and v is the kinematic viscosity) was studied and simulated using CFD to estimate hydrodynamic forces and characterize flow and vortex patterns created by the fins. Two common arrangements of multiple fins on the BIUV were considered: a posterior fin that is parallel to the anterior fins (case 1) and a posterior fin that is perpendicular to the anterior fins (case 2). First, the influence of the distance between two anterior undulating fins on the propulsion performance of both arrangements of multiple fins on the BIUV was investigated. The effect of the distance between the anterior undulating fins and the posterior oscillating fin was also analysed. The length of the posterior oscillating fin was varied and the fin surface area was held constant (24 mm2) to illustrate the influence of this parameter. Finally, the effect of frequency, amplitude, and wave number of anterior undulating fins on the non-dimensional drag coefficient of the posterior oscillating fin was investigated. Based on the flow structures, the reasons for the different performances of the BIUV are discussed. BIUV performances largely depend on the arrangements of multiple fins and the gap between the fins. Dimension and kinematic parameters also affect the performance of the BIUV. The results provide a physical insight into the understanding of fin interaction in fish or BIUVs that are propelled by multiple fins.
“Ahí me aguanté mi dolor”. Contexto sociocultural y económico de mujeres con síndrome con coronario residentes en Cali y otros municipios del Valle del Cauca
Authors: Valencia Micolta Susana Genith , Rodríguez Torres Estela
Published: October 2015

La investigación forma parte  del “Estudio Multicéntrico, Comparación de la caracterización de los síntomas de angina en la mujer en ocho ciudades de Colombia”. Aborda las condiciones de desigualdad en empleo, educación, género y etnia, situaciones de violencia y desplazamiento forzoso, factores fisiológicos que desencadenan una serie de síntomas y aparición del síndrome coronario, angina e infarto agudo de miocardio.

Objetivo: Determinar  aspectos socioculturales y económicos que influyen en  la aparición de síntomas de angina en mujeres de Cali y  municipios del Valle del Cauca

Material y método. Estudio descriptivo con abordaje cualitativo, en  23 mujeres. Con criterios de haber experimentado molestia, dolor o sensación de disconfort torácico, hemodinámicamente estables, arteriografía coronaria con lesión de vasos mayor de 70%, y postsíndrome coronario agudo. Las entrevistas son analizadas con técnica de análisis de contenido de Klipendorf y Teoría de Síntomas Desagradables de Lenz y colaboradores

Resultados. Los síntomas desagradables, tienen relación con antecedentes fisiológicos y factores influyentes del ambiente físico, familiar y social. Emergen categorías acerca de responsabilidades laborales y domésticas, asumir roles, apoyo a la familia y conviviendo con sus dificultades, viviendo con incertidumbre e inseguridad, relaciones con el entorno, cumpliendo con el tratamiento.

Conclusión. El modo de vida  en las mujeres que padecen de  síndrome coronario agudo  es un factor influyente en el agravamiento de los síntomas. Las mujeres están  expuestas a experiencias y entornos desventajosos en condiciones de vulnerabilidad e inequidad.
Rendre audible la voix d’une rescapée tutsie : le rôle du paratexte dans Le Livre d’Élise
Authors: MacLeod George
Published: October 2015

This article uses trauma theory to show the unique paratextual framing of Tutsi genocide survivor Élise Rida Musomandera’s memoir, Le Livre d’Élise (Les Belles Lettres, 2014). While dozens of survivor accounts from the Tutsi diaspora have been published in the last two decades, Musomandera’s is the first eye-witness memoir written by a Tutsi survivor still living in Rwanda. The vast majority of these testimonial memoirs contain introductions and postfaces which present the text for a Western reader. These paratexts have tended to privilege one of two discourses, comparing the Tutsi survivor’s story either to a moral lesson or to Holocaust testimonies. In contrast, the introduction to Le Livre d’Élise emphasizes the encounter between Musomandera’s authorial voice and the reader. The introduction’s European co-authors suggest that in reading Musomandera’s text, the reader joins a community of attentive interlocutors who are participating in the ongoing process of helping her find agency and social recognition following the devastating impact of genocide.
A quantitative framework for whole-body coordination reveals specific deficits in freely walking ataxic mice
Authors: Machado Ana S , Darmohray Dana M , Fayad João , Marques Hugo G , Carey Megan R
Published: October 2015

The coordination of movement across the body is a fundamental, yet poorly understood aspect of motor control. Mutant mice with cerebellar circuit defects exhibit characteristic impairments in locomotor coordination; however, the fundamental features of this gait ataxia have not been effectively isolated. Here we describe a novel system (LocoMouse) for analyzing limb, head, and tail kinematics of freely walking mice. Analysis of visibly ataxic Purkinje cell degeneration (pcd) mice reveals that while differences in the forward motion of individual paws are fully accounted for by changes in walking speed and body size, more complex 3D trajectories and, especially, inter-limb and whole-body coordination are specifically impaired. Moreover, the coordination deficits in pcd are consistent with a failure to predict and compensate for the consequences of movement across the body. These results isolate specific impairments in whole-body coordination in mice and provide a quantitative framework for understanding cerebellar contributions to coordinated locomotion.
Metacarpal torsion in apes, humans, and earlyAustralopithecus:implications for manipulatory abilities
Authors: Drapeau Michelle S.M.
Published: October 2015

Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown thatAustralopithecus afarensisandAu. africanusdisplay some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals ofAu. afarensisare very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon.Au. africanuspresent a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than inAu. afarensis. Overall, this study supports previous studies onAu. afarensisandAu. africanusthat these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predatedHomo.
Interpreting de novo Variation in Human Disease Using denovolyzeR
Authors: Ware James S. , Samocha Kaitlin E. , Homsy Jason , Daly Mark J.
Published: October 2015

Spontaneously arising (de novo) genetic variants are important in human disease, yet every individual carries many such variants, with a median of 1 de novo variant affecting the protein‐coding portion of the genome. A recently described mutational model provides a powerful framework for the robust statistical evaluation of such coding variants, enabling the interpretation of de novo variation in human disease. Here we describe a new open‐source software package, denovolyzeR, that implements this model and provides tools for the analysis of de novo coding sequence variants. © 2015 by John Wiley & Sons, Inc.
Huntington Disease: Molecular Diagnostics Approach
Authors: Bastepe Murat , Xin Winnie
Published: October 2015

Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at‐risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed. © 2015 by John Wiley & Sons, Inc.
Magnetostratigraphic constraints on the age of the lower Beaufort Group, western Karoo basin, South Africa, and a critical analysis of existing U‐Pb geochronological data
Authors: Tohver E. , Lanci L. , Wilson A. , Hansma J. , Flint S.
Published: October 2015

We studied three partially overlapping sections with a composite thickness of ∼600 m in the upper Permian fluvial siltstones and fine‐grained sandstones of the Abrahamskraal Formation, the basal unit of the Beaufort Group, in the Karoo Basin of Western Cape Province, South Africa. Paleomagnetic analysis reveals three components of Natural Remanent Magnetization (NRM). Heating to ∼180°C removes a remanent magnetization parallel to the present‐day field, which is interpreted as a viscous overprint. An intermediate unblocking temperature component is removed by heating to 450°C; this direction is always of normal polarity and is identical to a regional overprint imparted during the Early Jurassic emplacement of the Karoo Large Igneous Province. A high‐temperature component isolated above 450°C is of dual polarity and is interpreted as primary on the basis of a positive reversals test. The virtual geomagnetic pole position for the Abrahamskraal Formation computed from the average high‐temperature characteristic remanent magnetization direction is in agreement with the late Permian directions for stable Gondwana and with previous results from the lowermost Abrahamskraal Formation and Waterford Formation at the Ouberg Pass section. The predominantly normal polarity of this magnetization is in agreement with either a middle‐late Lopingian age (ca. 254–256 Ma) or a late Guadalupian age (ca. 262 Ma) according to the global geomagnetic polarity time scale. We integrate these new results with existing magnetostratigraphic, biostratigraphic, and geochronological results from the Karoo Basin, with particular emphasis on the controversy over zircon age data reported from the underlying Ecca Group.
Receiver function imaging of the mantle transition zone beneath the South China Block
Authors: Huang Haibo , Tosi Nicola , Chang Sung‐Joon , Xia Shaohong , Qiu Xuelin
Published: October 2015

Upper mantle discontinuities are influenced by convection‐related thermal heterogeneities arising in complex geodynamic settings. Slab rollback of the Pacific plate and mantle upwelling in the Meso‐Cenozoic caused the extension and spreading of continental segments in the South China Block leading to profound variations of the local temperature conditions. We processed 201 teleseismic events beneath 87 stations in the Hainan, Guangdong, and Fujian provinces in the South China Block, and extracted 4172 high‐quality receiver functions. We imaged the topography of the local mantle discontinuities by using phase‐weighted common conversion point stacking of the receiver functions, which effectively improves the P‐to‐S‐converted phases. We found that the average depths of the discontinuities at 410 and 660 km depth are 414 and 657 km, respectively, while no clearly defined discontinuity at 520 km depth was detected. We mapped the thickness of the mantle transition zone (MTZ), which can reflect temperature and/or compositional heterogeneities as well as the presence of water, and discussed possible geodynamic implications. In particular, we found that the MTZ beneath the Leizhou Peninsula in the Hainan province is 42 km thinner than average. This scenario suggests that the Hainan plume is responsible for positive temperature anomalies between ∼270 and 380 K and between ∼200 and 240 K at the 660 and 410 km discontinuities, respectively. We also observed a prominent uplifting of the 660 km boundary beneath the coast regions that may be indicative of lateral flow of the Hainan plume.
Nucleation and dynamic rupture on weakly stressed faults sustained by thermal pressurization
Authors: Schmitt Stuart V. , Segall Paul , Dunham Eric M.
Published: October 2015

Earthquake nucleation requires that the shear stress τ locally reaches a fault's static strength, fσeff, the product of the friction coefficient and effective normal stress. Once rupture initiates, shear heating‐induced thermal pressurization can sustain rupture at much lower τ/σeff ratios, a stress condition believed to be the case during most earthquakes. This requires that earthquakes nucleate at heterogeneities. We model nucleation and dynamic rupture on faults in a 2‐D elastic medium with rate/state friction and thermal pressurization, subjected to globally low τ but with local stress heterogeneities that permit nucleation. We examine end‐member cases of either high‐τ or low‐σeff heterogeneities. We find that thermal pressurization can sustain slip at τ/σeff values as low as 0.13, compared to static friction of ∼0.7. Background τ (and, to lesser extent, heterogeneity width) controls whether ruptures arrest or are sustained, with extremely low values resulting in arrest. For a small range of background τ, sustained slip is pulse‐like. Cessation of slip in a pulse tail can result from either diffusive restrengthening of σeff or a wave‐mediated stopping phase that follows the rupture tip. Slightly larger background τ leads to sustained crack‐like rupture. Thermal pressurization is stronger at high‐τ heterogeneities, resulting in a lower background τ threshold for sustained rupture and potentially larger arresting ruptures. High‐stress events also initiate with higher moment rate, although this may be difficult to observe in nature. For arresting ruptures, stress drops and the dependence of fracture energy on mean slip are both consistent with values inferred for small earthquakes.
Backscattering by very small particles in coastal waters
Authors: Zhang Xiaodong , Gray Deric J.
Published: October 2015

The volume scattering and backscattering by very small particles (VSPs) of sizes <0.2 µm in four coastal waters in U.S. (Chesapeake Bay, Monterey Bay, Mobile Bay, and the LEO‐15 site) were estimated by inverting the measured volume scattering functions (VSFs) at 532 nm. The measured VSFs are consistent with concurrent measurements of total scattering coefficients by the ac‐meters and angular scattering at 100, 125, and 150° by the ECO‐VSF sensor and at 140° by the HydroScat‐6 sensor. The inferred backscattering coefficients by the VSPs correlate strongly with the absorption coefficients measured for the colored dissolved organic matter, indicating that the dissolved portion of particles do scatter light. In the coastal waters that we studied, the backscattering by VSPs dominate over larger particles (of sizes >0.2 µm), accounting for 40–80% of total backscattering at 532 nm, while only account for <5% of total scattering.
Downward lee wave radiation from tropical instability waves in the central equatorial Pacific Ocean: A possible energy pathway to turbulent mixing
Authors: Tanaka Yuki , Hibiya Toshiyuki , Sasaki Hideharu
Published: October 2015

Turbulent mixing in the equatorial Pacific Ocean is an important process that controls diapycnal heat transport and hence affects the air‐sea interactions and global climate. It is recently shown that, in the eastern equatorial Pacific, strong mixing is induced in the thermocline by enhanced vertical shear associated with tropical instability waves (TIWs), which propagate westward along the equator at a speed of
with a wavelength of
. In this study, using a high‐resolution ocean general circulation model, we show that the TIWs can play an important role in inducing turbulent mixing in the thermocline also in the central equatorial Pacific, although the thermocline is too deep to be directly affected by the vertical shear of the TIWs. The front of the TIW is clearly manifested as a narrow strip of strong convergence of horizontal surface flow, from which area downward and westward propagating internal waves are intermittently emanated. These internal waves can be interpreted as lee waves generated by the surface‐flow convergence zone, which acts like an inverted obstacle moving along the stratified ocean surface by inducing downward flow. The associated downward energy flux below the surface mixed layer increases as the TIW structure becomes deeper toward the central equatorial Pacific, so that the energy pathway to turbulent mixing in the thermocline can be created. The downward energy flux integrated over the entire equatorial Pacific and averaged during January 2011 amounts to ∼8.1 GW, occupying a significant fraction of the energy input to the TIWs.
The Role of Heteroatoms Leading to Hydrogen Bonds in View of Extended Chemical Stability of Organic Semiconductors
Authors: Enengl Christina , Enengl Sandra , Havlicek Marek , Stadler Philipp , Glowacki Eric D. , Scharber Markus C. , White Matthew , Hingerl Kurt , Ehrenfreund Eitan , Neugebauer Helmut , Sariciftci Niyazi Serdar
Published: October 2015

The major challenge in organic electronics concerns the stability of organic semiconductor materials which affects the operational lifetime of devices. Recent reports have shown that hydrogen‐bonded pigments of the indigoid family are air‐ and moisture resistant. The magenta pigment quinacridone, a hydrogen‐bonded molecule in the solid state with a pentacene like frame, is a perfect example for extraordinary chemical stability. Here, studies using in situ spectroscopic methods comparing quinacridone and pentacene are presented. A different spectral response of their radical cations is observed upon chemical doping. While in pentacene the barrier between doping and irreversible overoxidation is small, this stability toward overoxidation is increased by the heteroatomic structure, leading to hydrogen‐bonded quinacridone. This work provides insight into molecular design principles that may lead to next‐generation organic semiconductors with enhanced stability and performance.
Halloysite Clay Nanotubes for Loading and Sustained Release of Functional Compounds
Authors: Lvov Yuri , Wang Wencai , Zhang Liqun , Fakhrullin Rawil
Published: October 2015

Halloysite is an alumosilicate tubular clay with a diameter of 50 nm, an inner lumen of 15 nm and a length of 600–900 nm. It is a natural biocompatible nanomaterial available in thousands of tons at low price, which makes it a good candidate for nanoarchitectural composites. The inner lumen of halloysite may be adjusted by etching to 20–30% of the tube volume and loading with functional agents (antioxidants, anticorrosion agents, flame‐retardant agents, drugs, or proteins) allowing for formulations with sustained release tuned by the tube end‐stoppers for hours and days. Clogging the tube ends in polymeric composites allows further extension of the release time. Thus, antioxidant‐loaded halloysite doped into rubber enhances anti‐aging properties for at least 12 months. The addition of 3–5 wt% of halloysite increases the strength of polymeric materials, and the possibility of the tube's orientation promises a gradient of properties. Halloysite nanotubes are a promising mesoporous media for catalytic nanoparticles that may be seeded on the tube surface or synthesized exclusively in the lumens, providing enhanced catalytic properties, especially at high temperatures. In vitro and in vivo studies on biological cells and worms indicate the safety of halloysite, and tests for efficient adsorption of mycotoxins in animals' stomachs are also carried out.
Octonary Resistance States in La0.7Sr0.3MnO3/BaTiO3/La0.7Sr0.3MnO3 Multiferroic Tunnel Junctions
Authors: Yin Yue‐Wei , Huang Wei‐Chuan , Liu Yu‐Kuai , Yang Sheng‐Wei , Dong Si‐Ning , Tao Jing , Zhu Yi‐Mei , Li Qi , Li Xiao‐Guang
Published: October 2015

General drawbacks of current electronic/spintronic devices are high power consumption and low density storage. A multiferroic tunnel junction (MFTJ), employing a ferroelectric barrier layer sandwiched between two ferromagnetic layers, presents four resistance states in a single device and therefore provides an alternative way to achieve high density memories. Here, an MFTJ device with eight nonvolatile resistance states by further integrating the design of noncollinear magnetization alignments between the ferromagnetic layers is demonstrated. Through the angle‐resolved tunneling magnetoresistance investigations on La0.7Sr0.3MnO3/BaTiO3/La0.7Sr0.3MnO3 junctions, it is found that, besides collinear parallel/antiparallel magnetic configurations, the MFTJ shows at least two other stable noncollinear (45° and 90°) magnetic configurations. Combining the tunneling electroresistance effect caused by the ferroelectricity reversal of the BaTiO3 barrier, an octonary memory device is obtained, representing potential applications in high density nonvolatile storage in the future.
Prediction of gas–liquid interfacial area in valve trays
Authors: Wang Jun , Leng Yixin , Shao Hui , Li Weiming , Huang Chunxiang
Published: October 2015

An accurate prediction of gas–liquid interfacial area is very important for the design and optimization of column trays. However, the difference of the gas–liquid flow regimes operating at different scale trays significantly affect the interfacial area calculation. Therefore, in this study, an interfacial area model operating at small column was established using the Kolmogorov's isotropic turbulence hypothesis. According to the analyzes of the gas–liquid flow phenomena of different scale columns, an assumption that the similarity principle of flow characteristics of gas–liquid in full contact was proposed. Moreover, a new model that can be used to predict the gas–liquid interfacial area of a large column with exiting the nonideal flow was obtained through the extension of the small tray interfacial area model based on this principle. Finally, the new model was tested by comparisons with the experimental results of references. The prediction accuracy significantly improved with the maximum deviation of approximately 40%. © 2015 American Institute of Chemical Engineers AIChE J, 62: 905–915, 2016
Laboratory tests for disorders of complement and complement regulatory proteins
Authors: Shih Angela R. , Murali Mandakolathur R.
Published: October 2015

The complement pathway is a cascade of proteases that is involved in immune surveillance and innate immunity, as well as adaptive immunity. Dysfunction of the complement cascade may be mediated by aberrations in the pathways of activation, complement regulatory proteins, or complement deficiencies, and has been linked to a number of hematologic disorders, including paroxysmal noctural hemoglobinuria (PNH), hereditary angioedema (HAE), and atypical hemolytic‐uremic syndrome (aHUS). Here, current laboratory tests for disorders of the complement pathway are reviewed, and their utility and limitations in hematologic disorders and systemic diseases are discussed. Current therapeutic advances targeting the complement pathway in treatment of complement‐mediated hematologic disorders are also reviewed. Am. J. Hematol. 90:1180–1186, 2015. © 2015 Wiley Periodicals, Inc.
Luminescent (N^C^C) Gold(III) Complexes: Stabilized Gold(III) Fluorides
Authors: Kumar Roopender , Linden Anthony , Nevado Cristina
Published: October 2015

We report the design, synthesis, and application of a (N^C^C)‐ligand framework able to stabilize highly electron‐deprived gold(III) species. This novel platform enabled the preparation of C(sp2)‐gold(III) fluorides for the first time in monomeric, easy‐to‐handle, bench‐stable form by a Cl/F ligand‐exchange reaction. Devoid of oxidative conditions or stoichiometric use of toxic Hg salts, this method was applied to the preparation of multiple [C(sp2)‐AuIII‐F] complexes, which were used as mechanistic probes for the study of the unique properties and intrinsic reactivity of AuF bonds. The improved photophysical properties of [(N^C^C)AuIII] complexes compared to classical pincer (C^N^C)‐Au systems paves the way for the design of new late‐transition‐metal‐based OLEDs.
Polymerkäfige als universelles Hilfsmittel für die präzise Bottom‐up‐Synthese metallischer Nanopartikel
Authors: Fan Ziyin , Chen Xuelian , Köhn Serrano Melissa , Schmalz Holger , Rosenfeldt Sabine , Förster Stephan , Agarwal Seema , Greiner Andreas
Published: October 2015

Eine neue, Templat‐gestützte Synthese monodisperser Nanopartikel stellt keine Anforderungen an die Selbstorganisation und ist hoch reproduzierbar. Hierzu werden maßgeschneiderte Polymerkäfige für die Synthese von Nanopartikeln verwendet, die aus vernetzten Makromolekülen mit Thiolendgruppen bestehen. Goldnanopartikel (AuNPs) wurden in verschiedenen Verhältnissen von Polymerkäfig zu Gold in situ in den Polymerkäfigen synthetisiert. Die Polymerkäfige zeichneten sich dabei durch eine definierte Beladungskapazität aus, mit exzellenter Kontrolle über Form und Größe. Dagegen zeigten Kontrollversuche mit linearen Diblockcopolymeren einen linearen Anstieg der Partikelgrößen mit steigendem Goldanteil. Das unterschiedliche Wachstumsverhalten der AuNPs wird durch die Vernetzungsgrad‐abhängige Flexibilität der Polymerketten erklärt. Des Weiteren wird die Polymerkäfig‐gesteuerte In‐situ‐Synthese auf Silber‐ (AgNPs), Palladium‐ (PdNPs) und Platinnanopartikel (PtNPs) übertragen.
Unusual Aggregation‐Induced Emission of a Coumarin Derivative as a Result of the Restriction of an Intramolecular Twisting Motion
Authors: Bu Fan , Duan Ruihong , Xie Yujun , Yi Yuanping , Peng Qian , Hu Rongrong , Qin Anjun , Zhao Zujin , Tang Ben Zhong
Published: October 2015

Aggregation‐induced emission (AIE) is commonly observed for propeller‐like luminogens with aromatic rotors and stators. Herein, we report that a coumarin derivative containing a seven‐membered aliphatic ring (CD‐7) but no rotors showed typical AIE characteristics, whereas its analogue with a five‐membered aliphatic ring (CD‐5) exhibited an opposite aggregation‐caused quenching (ACQ) effect. Experimental and theoretical results revealed that a large aliphatic ring in CD‐7 weakens structural rigidity and promotes out‐of‐plane twisting of the molecular backbone to drastically accelerate nonradiative excited‐state decay, thus resulting in poor emission in solution. The restriction of twisting motion in aggregates blocks the nonradiative decay channels and enables CD‐7 to fluoresce strongly. The results also show that AIE is a general phenomenon and not peculiar to propeller‐like molecules. The AIE and ACQ effects can be switched readily by the modulation of molecular rigidity.