bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward an Informal Account of Legal Interpretation
Authors: Hutchinson Allan C.
Published: October 2016

Toward an Informal Account of Legal Interpretation offers a viable account of law, judicial decision-making, and legal interpretation that is as fresh as it is familiar. The author expertly challenges the dominant mode of formalist theorizing and proposes an explanatory account of legal interpretation that can profitably be understood as an 'informal' intervention. Such an informal approach has no truck with either the claims of the formalists (i.e., that law is something separate from ideology) or those of the anti-formalists (i.e., that law is nothing other than ideological posturing). Hutchinson insists that, when understood properly, legal interpretation is an applied exercise in law-and-ideology; it is both constrained and unconstrained in equal measure. In developing this informalist account through a sustained application of the 'no vehicles in the park' rule, this book is wide-ranging in theoretical scope and substance, but also accessible and practical in style.
Mathematical Explorations
Authors: Beardon Alan F.
Published: October 2016

Mathematical Explorations follows on from the author's previous book, Creative Mathematics, in the same series, and gives the reader experience in working on problems requiring a little more mathematical maturity. The author's main aim is to show that problems are often solved by using mathematics that is not obviously connected to the problem, and readers are encouraged to consider as wide a variety of mathematical ideas as possible. In each case, the emphasis is placed on the important underlying ideas rather than on the solutions for their own sake. To enhance understanding of how mathematical research is conducted, each problem has been chosen not for its mathematical importance, but because it provides a good illustration of how arguments can be developed. While the reader does not require a deep mathematical background to tackle these problems, they will find their mathematical understanding is enriched by attempting to solve them.
MOVING FRAMES AND NOETHER’S CONSERVATION LAWS—THE GENERAL CASE
Authors: GONÇALVES TÂNIA M. N. , MANSFIELD ELIZABETH L.
Published: October 2016

In recent works [Gonçalves and Mansfield, Stud. Appl. Math., 128 (2012), 1–29; Mansfield, A Practical Guide to the Invariant Calculus (Cambridge University Press, Cambridge, 2010)], the authors considered various Lagrangians, which are invariant under a Lie group action, in the case where the independent variables are themselves invariant. Using a moving frame for the Lie group action, they showed how to obtain the invariantized Euler–Lagrange equations and the space of conservation laws in terms of vectors of invariants and the Adjoint representation of a moving frame. In this paper, we show how these calculations extend to the general case where the independent variables may participate in the action. We take for our main expository example the standard linear action of SL(2) on the two independent variables. This choice is motivated by applications to variational fluid problems which conserve potential vorticity. We also give the results for Lagrangians invariant under the standard linear action of SL(3) on the three independent variables.
Effect of the Orientation of Hexagonal Fibers on the Effective Elastic Properties of Unidirectional Composites
Authors: Wang H. , Kang Y.-X. , Liu B. , Qin Q.-H.
Published: October 2016

Existing studies reveal that the shape corners of hexagonal fiber affect the degree of constraint on the matrix material. However, none of these studies included the effect of orientation of hexagonal fibers. In this study, a computational micromechanics model of oriented hexagonal fibers in periodic unidirectional composite materials is established for the determination of effective orthotropic elastic properties of the composite. In the present numerical modeling, the representative unit composite cell including the matrix material and the single oriented hexagonal fiber or random oriented hexagonal fibers is solved by micro-scale finite element analysis with different stress loads and periodic displacement boundary conditions, which are applied along the cell boundary to meet the requirement of straight-line constraint during deformation of the cell. Subsequently, the effective elastic properties of the composite are evaluated for periodic regular packing and random packing using the homogenization approach for investigating the influence of unified orientation and random orientation of the hexagonal fibers on the overall elastic properties of the fiber-reinforced composites. The numerical results are verified by comparing with other available results.
Numerical Analysis of the Sulcus Vocalis Disorder on the Function of the Vocal Folds
Authors: Vazifehdoostsaleh A. , Fatouraee N. , Navidbakhsh M. , Izadi F.
Published: October 2016

Speaking is a very complex process resulting from the interaction between the air flow along the larynx and the vibrating structure of the vocal folds. Sulcus is a disease missing layers in the vocal folds result in cracks resulting in some disorders in producing sounds. Sulcus and its effects on the vocal cord vibrations are numerically studied for the first time in this paper. An ideal model of healthy vocal folds and Sulcus vocalis has been two-dimensionally defined and the finite element model of vocal folds is solved in a fully coupled form. The proposed calculative model was used in a fluid range of the computational fluid dynamics, arbitrary Lagrangian-Eulerian (ALE), incompressible continuity and Navier-Stokes equations and in a structure range of a three-layer elastic linear model. Self-excited oscillations were presented for vocal folds among type II patients and compared with healthy models. Responses were qualitatively and quantitatively studied. The healthy model was compared with numerical and empirical results. In addition, the effects of the disease on the flow parameters and the vibration frequency of the vocal folds were studied. According to the simulated model, the oscillation frequency decreased 25% and the average and instantaneous volume flux significantly increased compared to healthy samples. Results may help present a guideline for surgery and subsequently evaluate patients’ improvement.
Vitamin E and the risk of pneumonia: using the I2 statistic to quantify heterogeneity within a controlled trial
Authors: Hemilä Harri
Published: October 2016

Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50–69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I2 statistic. The I2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.
Morse Theory and the Lusternik–Schnirelmann Category of Quaternionic Grassmannians
Authors: Macías-Virgós Enrique , Pereira-sáez María José , Tanré Daniel
Published: October 2016

The Lusternik–Schnirelmann category of the quaternionic Grassmannian

is known to bek(n − k). In this paper we show that this result can be deduced from Morse theory.
Extremal Beltrami Differentials of Non-Landslide Type
Authors: Yao Guowu
Published: October 2016

In this paper it is shown that there are infinitely many extremal Beltrami differentials of non-landside type and non-constant modulus in a Teichmüller equivalence class if the class contains a landslide extremal. The result answers, affirmatively in a stronger sense, a problem posed by Li.
Morphological and molecular characterization of cucullanid nematodes including Cucullanus opisthoporus n. sp. in freshwater fish from the Brazilian Amazon
Authors: Pereira F.B. , Luque J.L.
Published: October 2016

Molecular and morphological characterization of two species of Cucullanidae from freshwater fish in Brazil are provided, one of which represented an undescribed taxon. Cucullanus opisthoporus n. sp. was collected in Cichla melaniae from River Xingu, State of Pará, and in C. pinima from River Jamarí, State of Rondônia. Nematodes referable to Cucullanus grandistomis were collected in Oxydoras niger from River Xingu. The new species has an appendage in the tail tip, ventrally covered by small spines, which is an exclusive feature of Cucullanus tucunarensis. However, C. tucunarensis differs from C. opisthoporus n. sp. based upon the relative position of deirids and the excretory pore, which are more posterior from the oesophageal end in the new species. Observations of C. tucunarensis type specimens also revealed features that were wrongly or not reported in the original description. Type specimens of C. grandistomis were observed, although they were poorly preserved. After evaluation of newly collected specimens of C. grandistomis, features unreported in the original description were observed for the first time, including the presence of an intestinal caecum. Thus, C. grandistomis was transferred to Dichelyne. Sequences of the 18S and 28S rRNA genes revealed high genetic similarity between the specimens of C. opisthoporus n. sp. from the two different hosts as well as their genetic distance from Dichelyne grandistomis n. comb. Phylogenetic reconstructions using representatives of Cucullanidae suggested the artificiality of the current morphological system adopted to separate the genera, since most genera were not monophyletic, although the availability of genetic data is still fragmented.
East-west spatial groupings in intertidal communities, environmental drivers and key species
Authors: Merder Julian , Freund Jan A. , Meysick Lukas , Simkanin Christina , O'Riordan Ruth M. , Power Anne Marie
Published: October 2016

The rocky intertidal communities of Ireland contain a mix of cold- and warm-adapted species, however the spatial distribution of these communities has not been investigated in a systematic way. Based on a benthic community dataset collected in 2003 at 63 sites, several statistical analyses were combined with the aims of (i) detecting groups of similar communities and their spatial arrangement, (ii) relating these groups to environmental factors and (iii) identifying the species that drive the different community groups. Sørensen's index suggested two marine community groups, one of the east and south-east (termed ‘east’) and the other in the west, south-west and north (termed ‘west’). A second partition based on combined wave exposure and sea surface chlorophyll comprised four groups, as did a further partition based on combined sea surface and air temperatures. The spatial arrangement of wave height plus chlorophyll conditions agreed reasonably well with the binary marine community partition, but the temperature partition did not. The ‘east’ community appeared to be associated with low wave height and chlorophyll conditions. The species that were most influential to the ‘east’ community wereBalanus crenatus, Austrominius modestusandFucus vesiculosus. The ‘west’ sites were associated with high wave height/low chlorophyll (with some variation in this due to local shelter) and the speciesParacentrotus lividus, Chthamalus stellatus, Alaria esculentaandHimanthalia elongata. A longitudinal pattern rather than one associated with latitude was evident in this marine community and local drivers rather than temperature clines appeared most important for the dominant community patterns.
Empathy and aversion: the neural signature of mentalizing in Tourette syndrome
Authors: Eddy C. M. , Cavanna A. E. , Hansen P. C.
Published: October 2016

Background

Previous studies suggest that adults with Tourette syndrome (TS) can respond unconventionally on tasks involving social cognition. We therefore hypothesized that these patients would exhibit different neural responses to healthy controls in response to emotionally salient expressions of human eyes.

Method

Twenty-five adults with TS and 25 matched healthy controls were scanned using fMRI during the standard version of the Reading the Mind in the Eyes Task which requires mental state judgements, and a novel comparison version requiring judgements about age.

Results

During prompted mental state recognition, greater activity was apparent in TS within left orbitofrontal cortex, posterior cingulate, right amygdala and right temporo-parietal junction (TPJ), while reduced activity was apparent in regions including left inferior parietal cortex. Age judgement elicited greater activity in TS within precuneus, medial prefrontal and temporal regions involved in mentalizing. The interaction between group and task revealed differential activity in areas including right inferior frontal gyrus. Task-related activity in the TPJ covaried with global ratings of the urge to tic.

Conclusions

While recognizing mental states, adults with TS exhibit greater activity than controls in brain areas involved in the processing of negative emotion, in addition to reduced activity in regions associated with the attribution of agency. In addition, increased recruitment of areas involved in mental state reasoning is apparent in these patients when mentalizing is not a task requirement. Our findings highlight differential neural reactivity in response to emotive social cues in TS, which may interact with tic expression.
Choral possible selves: The interaction of Australian males’ past, present and future identities in shaping decisions about participation in choir
Authors: Powell Sarah J.
Published: October 2016

This paper reports on the findings related to the possible selves of males who participate in choir. It focuses on the perceptions of participants’ past, present and future identities and the way these interact to influence decisions about choir. The paper is derived from a larger study, set in Australia, which investigated the perceptions of success, notions of masculinity and the impact of possible selves on male choral participation. Four choirs of different age groups were involved: junior school, secondary school, university and community. Data were collected through interviews, focus groups, surveys and observational video analysis. Findings demonstrated that the strength of possible selves was influenced by past experience and present self-perception, which impacted future projections of self and subsequent decisions about choir. The research points to the importance of providing positive and fulfilling experiences of choir in school because of its positive impact on individual well being and the active pursuit of desired goals.
A Novel Examination of Successful Aging Trajectories at the End of Life
Authors: Cosco Theodore D. , Stephan Blossom C.M. , Muniz Graciela , Brayne Carol ,   the CC75C Study Collaboration
Published: October 2016

Un indice de vieillissement réussi (SA) a été capturé dans une étude de cohorte longitudinale basée sur la population des personnes de 75 ans et plus, qui a été examiné longitudinalement en utilisant la modélisation d’un mélange de croissance (MMC) pour identifier les groupes ayant des trajectoires similaires utilisant la dernière interview complète de personnes décédées et jusqu’à quatre collections de données précédentes avant la mort. MMC a identifié un modèle avec trois classes. Les classes étaient : haut fonctionnement, pas de déclin (HPD); fonctionnement élevé, baisse progressive (HBP); et un faible fonctionnement, fort baisse (FB). Les individus de la classe HPD étaient significativement plus jeunes à la mort, et à la fin de l’examen, se composait de plus d’hommes, et plus susceptibles d’être mariées, comparativement aux individus HBP et FB. Ces résultats démontrent différentes façons dont les individus peuvent éprouver un vieillissement réussi à la fin de vie. Cette étude fournit le cadre pour la recherche future en ce qui concerne les processus du vieillissement pendant toute la vie, avec des implications importantes pour la politique et la pratique.
Pupillary and affective responses to maternal feedback and the development of borderline personality disorder symptoms
Authors: Scott Lori N. , Zalewski Maureen , Beeney Joseph E. , Jones Neil P. , Stepp Stephanie D.
Published: October 2016

Etiological models propose that a biological vulnerability to emotional reactivity plays an important role in the development of borderline personality disorder (BPD). However, the physiological and phenomenological components of emotional reactivity that predict the course of BPD symptoms in adolescence are poorly understood. This prospective study examines pupillary and affective responses to maternal feedback as predictors of BPD symptom development in adolescent girls over 18 months. Fifty-seven 16-year-old girls completed a laboratory task in which they heard recorded clips of their own mothers making critical or praising statements about them, as well as neutral statements that did not pertain to them. Changes in girls’ pupil dilation and subjective affect were assessed throughout the task. The results demonstrated that greater pupillary response to maternal criticism predicted increases in BPD symptoms over time. In addition, greater pupillary and positive affective responses to maternal praise were associated with higher BPD symptoms at age 16 and faster decreases in BPD symptoms over time, but only among girls who heard clips that were rated by independent observers as less praising. The results suggest that emotional reactivity can serve as either a risk or a protective factor depending on context, with differential effects of reactivity to criticism versus praise.
Exploring Ceremony: The Archaeology of a Men's Meeting House (‘Kod’) on Mabuyag, Western Torres Strait
Authors: Wright Duncan , Stephenson Birgitta , Taçon Paul S.C. , Williams Robert N. , Fogel Aaron , Sutton Shannon , Ulm Sean ,   the Goemulgal of Mabuyag
Published: October 2016

The materiality of ritual performance is a growing focus for archaeologists. In Europe, collective ritual performance is expected to be highly structured and to leave behind a loud archaeological signature. In Australia and Papua New Guinea, ritual is highly structured; however, material signatures for performance are not always apparent, with ritual frequently bound up in the surrounding natural and cultural landscape. One way of assessing long-term ritual in this context is by using archaeology to historicize ethno-historical and ethnographic accounts. Examples of this in the Torres Strait region, islands between Papua New Guinea and mainland Australia, suggest that ritual activities were materially inscribed at kod sites (ceremonial men's meeting places) through distribution of clan fireplaces, mounds of stone/bone and shell. This paper examines the structure of Torres Strait ritual for a site ethnographically reputed to be the ancestral kod of the Mabuyag Islanders. Intra-site partitioning of ritual performance is interpreted using ethnography, rock art and the divergent distribution of surface and sub-surface materials (including microscopic analysis of dugong bone and lithic material) across the site. Finally, it discusses the materiality of ritual at a boundary zone between mainland Australia and Papua New Guinea and the extent to which archaeology provides evidence for Islander negotiation through ceremony of external incursions.
One, no one and one hundred thousand events: Defining and processing events in an inter-disciplinary perspective
Authors: SPRUGNOLI R. , TONELLI S.
Published: October 2016

We present an overview of event definition and processing spanning 25 years of research in NLP. We first provide linguistic background to the notion of event, and then present past attempts to formalize this concept in annotation standards to foster the development of benchmarks for event extraction systems. This ranges from MUC-3 in 1991 to the Time and Space Track challenge at SemEval 2015. Besides, we shed light on other disciplines in which the notion of event plays a crucial role, with a focus on the historical domain. Our goal is to provide a comprehensive study on event definitions and investigate which potential past efforts in the NLP community may have in a different research domain. We present the results of a questionnaire, where the notion of event for historians is put in relation to the NLP perspective.
Detransitivisation as a support strategy for causativebring
Authors: MONDORF BRITTA , SCHNEIDER ULRIKE
Published: October 2016

This article presents diachronic corpus analyses of causativebring(bringcaus) which provide new insights into a fairly novel research paradigm in language change: the role of ‘Moderate Transitivity Contexts’ (MTCs) as a refuge for waning verbs and as a breeding ground for waxing verbs (see Mondorf 2010, 2011, 2016; Rohdenburg 2014b; Schneider & Mondorf 2015). It argues that the modulation of transitivity serves as a support strategy for a formerly well-established verb that is leaving the language.

The potential of semantic transitivity for the development of explanatory principles in language change has been hinted at by Hopper & Thompson (1980: 279). Empirically investigating the diachronic stages of detransitivisation for a recessive English verb we gain first systematic, empirically validated insights into the link between transitivity and language change.

This article adduces support for the claim thatbringcaus+to-infinitive has (almost completely) lost its ability to take fully fledged direct objects. There are, however, at least three, partly overlapping contexts, in which this verb can stand its ground: with reflexives, modals and negation. What these contexts have in common is that they reduce the clause's transitivity, defined by Hopper & Thompson (1980: 251) as ‘the effectiveness with which the verbal action takes place’. Assuming that the higher the transitivity, the stronger the effect of the verbal action is on the object, these detransitivised contexts can be interpreted as alleviating the effect of the verbal action.
Testing two processing principles with respect to the extraction of elements out of complement clauses in English
Authors: ROHDENBURG GÜNTER
Published: October 2016

The present article contrasts two processing principles, the Domain Minimization Principle (e.g. Hawkins 1999, 2004) and the Complexity Principle (e.g. Rohdenburg 1996, 2007b) in structures involving the extraction of postverbal elements out of (competing) complement clauses. The Domain Minimization Principle may be described as a processing tendency which consists in minimizing the size and complexity of various domains including the filler–gap domain in cases like the following:This is a problem (that) they had promised (that) they would tackle. By contrast, the Complexity Principle represents a correlation between processing complexity and grammatical explicitness. It stipulates that more explicit (and typically more bulky) constructional options are favoured in cognitively more complex environments.

This article deals with two sets of rival complements. The behaviour of the first group of clausal alternatives is in line with Hawkins’ prediction, though incompatible with the Complexity Principle. However, there is an even larger group of complement pairs whose distribution inside and outside extraction contexts is predicted by the Complexity Principle but unaccounted for by Domain Minimization. Thus, in extraction contexts, the visible effects of the two antagonistic principles are found with virtually complementary ranges of complement types. The article concludes by attempting to account for the kind of division of labour observed between the two principles under scrutiny. It will be suggested among other things that, in English, the marked infinitive (on its own or with an associated NP) enjoys a privileged or target status in extraction contexts.
Using evolutionary tools to search for novel psychoactive plants
Authors: Halse-Gramkow Morten , Ernst Madeleine , Rønsted Nina , Dunn Robert R. , Saslis-Lagoudakis C. Haris
Published: October 2016

Bioprospecting is the search for valuable products from natural sources. Given that most species are poorly known, a key question is where to search. Ethnodirected bioprospecting approaches use traditional knowledge in the process of selecting plants to screen for desired properties. A complementary approach is to utilize phylogenetic analyses based on traditional uses or known chemistry to identify lineages in which desired properties are most likely to be found. Novel discoveries of plant bioactivity from these approaches can aid the development of treatments for diseases with unmet medical needs. For example, neurological disorders are a growing concern, and psychoactive plants used in traditional medicine may provide botanical sources for bioactivity relevant for treating diseases related to the brain and nervous system. However, no systematic study has explored the diversity and phylogenetic distribution of psychoactive plants. We compiled a database of 501 psychoactive plant species and their properties from published sources. We mapped these plant attributes on a phylogenetic tree of all land plant genera and showed that psychoactive properties are not randomly distributed on the phylogeny of land plants; instead certain plant lineages show overabundance of psychoactive properties. Furthermore, employing a ‘hot nodes’ approach to identify these lineages, we can narrow down our search for novel psychoactive plants to 8.5% of all plant genera for psychoactivity in general and 1–4% for specific categories of psychoactivity investigated. Our results showcase the potential of using a phylogenetic approach to bioprospect plants for psychoactivity and can serve as foundation for future investigations.
SCHOOL REFORM AS PROGRESSIVE STATECRAFT: EDUCATION POLICY IN NEW YORK UNDER GOVERNOR ALFRED E. SMITH, 1919–1928
Authors: Chiles Robert
Published: October 2016

Since the Progressive Era itself, scholars have exhibited strong interest in the connections between progressivism and education. Historical studies have elucidated countless ways that such reformist impulses as the settlement house movement, the country life movement, the progressive education movement, the “cult of efficiency,” and battles against social ills like child labor influenced early twentieth-century education policy.1Indeed, as historian Lawrence Cremin has contended, “the Progressive mind was ultimately an educator's mind, and … its characteristic contribution was that of a socially responsible reformist pedagogue.”2
A compact microstrip low-pass filter with ultra wide stopband using compact microstrip resonant cells
Authors: Roshani Saeed
Published: October 2016

In this paper, a novel compact microstrip low-pass filter (LPF) with ultra wide stop band and sharp roll off, is proposed. In the proposed structure, a high impedance transmission line is loaded by compact microstrip resonant cells, which results in ultra wide stopband. The −3 dB cut-off frequency of filter is 1.5 GHz and the maximum insertion loss is <0.1 dB in the passband. The proposed LPF presents extremely wide stopband from 1.68 to 44 GHz, with more than the −20 dB attenuation level, which suppresses the 2nd to 29th harmonics with high rejection levels. The size of the proposed LPF is only 0.1 λg × 0.19 λg, which shows excellent size reduction. There is a good agreement between the simulated and measured results.
Technological change and the evolution of the law of war
Authors: Liivoja Rain
Published: October 2016

Advances in military technology have led many, including the developers of such technology, to propose new regulation. International lawyers have extensively examined the adequacy of the existing law to address emerging technology, but they have devoted relatively little attention in these analyses to the prior development of the law as a result of, or despite, technological change. This essay highlights two challenges that those wishing to undertake such an exercise might encounter. The first of these is the general paucity of serious engagement with the history of international law applicable in armed conflicts and the perpetuation of a particular “origin myth” of international humanitarian law. The second challenge has to do with the controversies about the impact of technology on society in general, and the impact of military technology on warfare in particular. Nevertheless, the essay concludes by pointing towards some of the insight that might be gained from a more history-conscious analysis of the relationship between technology and law in the military context.
Chromatin proteins and RNA are associated with DNA during all phases of mitosis
Authors: L Black Kathryn , Petruk Svetlana , Fenstermaker Tyler K , Hodgson Jacob W , Caplan Jeffrey L , Brock Hugh W , Mazo Alexander
Published: October 2016

Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs inDrosophilaembryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of proximity ligation assay-based techniques and super-resolution microscopy, we found that the number of protein–DNA and RNA–DNA foci undergoes significant reduction during mitosis, suggesting that mitosis may be accompanied by structural re-arrangement or compaction of specific chromatin domains.
Elevated granzyme B+ B‐cell level in SIV‐infection correlate with viral load and low CD4 T‐cell count
Authors: Kotb Ahmad , Klippert Antonina , Daskalaki Maria , Sauermann Ulrike , Stahl‐Hennig Christiane , Neumann Berit
Published: October 2016

Granzyme B‐expressing (GrB+) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB+ B cells in SIV‐infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV‐infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T‐cell counts. When investigating GrB+ B cells in different compartments, levels were highest in blood, spleen and bone marrow, but considerably lower in lymph nodes and tonsils. Analysis of expression of various surface markers on this particular B‐cell subset in SIV‐infected macaques revealed differences between the phenotype in macaques and in humans. GrB+ B cells in SIV‐infected rhesus macaques exhibit an elevated expression of CD5, CD10, CD25 and CD27, while expression of CD19, CD185 and HLA‐DR is reduced. In contrast to human GrB+ B cells, we did not observe a significantly increased expression of CD43 and CD86. B‐cell receptor stimulation in combination with IL‐21 of purified B cells from healthy animals led to the induction of GrB expression. Furthermore, initial functional analyses indicated a regulatory role on T‐cell proliferation. Overall, our data pave the way for longitudinal analyses including studies on the functionality of GrB+ B cells in the nonhuman primate model for AIDS.
Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny
Authors: Davis Felicity M. , Lloyd-Lewis Bethan , Harris Olivia B. , Kozar Sarah , Winton Douglas J. , Muresan Leila , Watson Christine J.
Published: October 2016

The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progenyin situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium.
Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
Authors: Ölmezer Gizem , Levikova Maryna , Klein Dominique , Falquet Benoît , Fontana Gabriele Alessandro , Cejka Petr , Rass Ulrich
Published: October 2016

Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts parallel to homologous recombination (HR) in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling. Yen1, but not the HJ resolvases Slx1-Slx4 and Mus81-Mms4, safeguards chromosome segregation by removing replication intermediates that escape Dna2. Post-replicative DNA damage checkpoint activation in Dna2 helicase-defective cells causes terminal G2/M arrest by precluding Yen1-dependent repair, whose activation requires progression into anaphase. These findings explain the exquisite replication stress sensitivity of Dna2 helicase-defective cells, and identify a non-canonical role for Yen1 in the processing of replication intermediates that is distinct from HJ resolution. The involvement of Dna2 helicase activity in completing replication may have implications for DNA2-associated pathologies, including cancer and Seckel syndrome.
Simulating the exchange of Majorana zero modes with a photonic system
Authors: Xu Jin-Shi , Sun Kai , Han Yong-Jian , Li Chuan-Feng , Pachos Jiannis K. , Guo Guang-Can
Published: October 2016

The realization of Majorana zero modes is in the centre of intense theoretical and experimental investigations. Unfortunately, their exchange that can reveal their exotic statistics needs manipulations that are still beyond our experimental capabilities. Here we take an alternative approach. Through the Jordan–Wigner transformation, the Kitaev's chain supporting two Majorana zero modes is mapped to the spin-1/2 chain. We experimentally simulated the spin system and its evolution with a photonic quantum simulator. This allows us to probe the geometric phase, which corresponds to the exchange of two Majorana zero modes positioned at the ends of a three-site chain. Finally, we demonstrate the immunity of quantum information encoded in the Majorana zero modes against local errors through the simulator. Our photonic simulator opens the way for the efficient realization and manipulation of Majorana zero modes in complex architectures.
Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium
Authors: Ruiz-Narváez Edward A , Lunetta Kathryn L , Hong Chi-Chen , Haddad Stephen , Yao Song , Cheng Ting-Yuan David , Bensen Jeannette T , Bandera Elisa V , Haiman Christopher A , Troester Melissa A , Ambrosone Christine B , Rosenberg Lynn , Palmer Julie R
Published: October 2016

The insulin/insulin-like growth factor (IGF) system and related pathways such as growth hormone, and leptin signaling have a key role in cancer development. It is unclear how germline variation in these pathways affects breast cancer risk. We conducted gene-based analyses of 184 genes in the insulin/IGF, growth hormone, and leptin pathways to identify genetic variation associated with risk of breast cancer overall, and for estrogen receptor (ER) subtypes. Tag single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina SNP array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 91,627 SNPs genotyped or imputed in 3,663 breast cancer cases, (1,983 ER-positive and 1,098 ER-negative) and 4,687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African-American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint test to determine the association of each gene with overall breast cancer and ER subtypes. The most significant gene associations (P⩽0.01) were BAIAP2 and CALM2 for overall breast cancer; BAIAP2 and CSNK2A1 for ER+ breast cancer; and BRAF, BAD, and MAPK3 for ER− breast cancer. The association of BAD with ER− breast cancer was explained by a two-SNP risk model; all other associations were best explained by one-SNP risk models. In total, six genes and seven SNPs had suggestive associations with overall breast cancer or ER subtypes in African-American women.
Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway
Authors: Wang Gang , Cao Rui , Wang Yongzhi , Qian Guofeng , Dan Han C. , Jiang Wei , Ju Lingao , Wu Min , Xiao Yu , Wang Xinghuan
Published: October 2016

Simvastatin is currently one of the most common drugs for old patients with hyperlipidemia, hypercholesterolemia and atherosclerotic diseases by reducing cholesterol level and anti-lipid properties. Importantly, simvastatin has also been reported to have anti-tumor effect, but the underlying mechanism is largely unknown. We collected several human bladder samples and performed microarray. Data analysis suggested bladder cancer (BCa) was significantly associated with fatty acid/lipid metabolism via PPAR signalling pathway. We observed simvastatin did not trigger BCa cell apoptosis, but reduced cell proliferation in a dose- and time-dependent manner, accompanied by PPARγ-activation. Moreover, flow cytometry analysis indicated that simvastatin induced cell cycle arrest at G0/G1 phase, suggested by downregulation of CDK4/6 and Cyclin D1. Furthermore, simvastatin suppressed BCa cell metastasis by inhibiting EMT and affecting AKT/GSK3β. More importantly, we found that the cell cycle arrest at G0/G1 phase and the alterations of CDK4/6 and Cyclin D1 triggered by simvastatin could be recovered by PPARγ-antagonist (GW9662), whereas the treatment of PPARα-antagonist (GW6471) shown no significant effects on the BCa cells. Taken together, our study for the first time revealed that simvastatin inhibited bladder cancer cell proliferation and induced cell cycle arrest at G1/G0 phase via PPARγ signalling pathway.
Racial differences in microRNA and gene expression in hypertensive women
Authors: Dluzen Douglas F. , Noren Hooten Nicole , Zhang Yongqing , Kim Yoonseo , Glover Frank E. , Tajuddin Salman M. , Jacob Kimberly D. , Zonderman Alan B. , Evans Michele K.
Published: October 2016

Systemic arterial hypertension is an important cause of cardiovascular disease morbidity and mortality. African Americans are disproportionately affected by hypertension, in fact the incidence, prevalence, and severity of hypertension is highest among African American (AA) women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases and we hypothesized that this phenomena may affect health disparities in hypertension. Transcriptional profiling of peripheral blood mononuclear cells from AA or white, normotensive or hypertensive females identified thousands of mRNAs differentially-expressed by race and/or hypertension. Predominant gene expression differences were observed in AA hypertensive females compared to AA normotensives or white hypertensives. Since microRNAs play important roles in regulating gene expression, we profiled global microRNA expression and observed differentially-expressed microRNAs by race and/or hypertension. We identified novel mRNA-microRNA pairs potentially involved in hypertension-related pathways and differently-expressed, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, and PLD1/miR-4709-3p. We validated gene expression levels via RT-qPCR and microRNA target validation was performed in primary endothelial cells. Altogether, we identified significant gene expression differences between AA and white female hypertensives and pinpointed novel mRNA-microRNA pairs differentially-expressed by hypertension and race. These differences may contribute to the known disparities in hypertension and may be potential targets for intervention.
Responses of the summer Asian-Pacific zonal thermal contrast and the associated evolution of atmospheric circulation to transient orbital changes during the Holocene
Authors: Xiao Dong , Zhao Ping , Wang Yue , Zhou Xiuji
Published: October 2016

This study investigates the response of large-scale atmospheric circulation over the Asian-Pacific sector and precipitation over eastern China to transient orbital changes during the Holocene summer using an intermediate-complexity climate model. Corresponding to variations in the incoming solar radiation, the eddy sea level pressure (SLP) exhibited an out-of-phase relationship between the North Pacific and the Eurasian landmass that was similar to the present-day Asia-Pacific Oscillation (APO) pattern and was defined as the paleo-APO. Its index presented an increasing trend, which implies the enhancement of a zonal thermal contrast between Asia and the North Pacific. Associated with the strengthening of the paleo-APO was the westward shift in North Pacific high pressure. Accordingly, there was less/more summer precipitation over both the middle reach of the Yangtze River and Southwest China/over North China. The high-resolution stalagmite δ18O records further support this decrease in the model precipitation. Along with the strengthening of paleo-APO from the early Holocene to the present, the eddy SLP anomalies exhibited a decreasing/increasing trend over the Eurasian landmass/the North Pacific, with a phase change of approximately 4.5 ka BP, and they both moved westward. Meanwhile, a less rainfall belt over eastern China exhibited northward propagation from southern China.
Soluble P-selectin rescues viper venom–induced mortality through anti-inflammatory properties and PSGL-1 pathway-mediated correction of hemostasis
Authors: Sun Der-Shan , Ho Pei-Hsun , Chang Hsin-Hou
Published: October 2016

Venomous snakebites are lethal and occur frequently worldwide each year, and receiving the antivenom antibody is currently the most effective treatment. However, the specific antivenom might be unavailable in remote areas. Snakebites by Viperidae usually lead to hemorrhage and mortality if untreated. In the present study, challenges of rattlesnake (Crotalus atrox) venom markedly increased the circulating soluble P-selectin (sP-sel) level, but not P-selectin (P-sel, Selp−/−) mutants, in wild-type mice. Because sP-sel enhances coagulation through the P-selectin ligand 1 (PSGL-1, Selplg) pathway to produce tissue factor–positive microparticles, we hypothesized that increasing the plasma sP-sel level can be a self-rescue response in hosts against snake venom–mediated suppression of the coagulation system. Confirming our hypothesis, our results indicated that compared with wild-type mice, Selp−/− and Selplg−/− mice were more sensitive to rattlesnake venom. Additionally, administration of recombinant sP-sel could effectively reduce the mortality rate of mice challenged with venoms from three other Viperidae snakes. The antivenom property of sP-sel is associated with improved coagulation activity in vivo. Our data suggest that the elevation of endogenous sP-sel level is a self-protective response against venom-suppressed coagulation. The administration of recombinant sP-sel may be developed as a new strategy to treat Viperidae snakebites.
Dispersing upconversion nanocrystals in a single silicon microtube
Authors: Li Hanyang , Wang Yan , Li Hui , Zhang Yundong , Yang Jun
Published: October 2016

Nanocrystals of Ln3+ (Ln = Yb, Tm and Ho) doped β-NaLuF4 with average diameter about 200 nm are dispersed in silica-based microtube (MT) by a simple flame heating method. The fabricated microtube has a diameter range from 2 μm to 30 μm and lengths up to hundreds microns. The fluorescence of upconversion nanocrystals (UCNCs) can propagate along a single MT and couple into another MT through evanescent field. The guiding performance of the single UCNCs doped MT is measured to prove that it can be used as an active waveguide. Moreover, optical temperature sensing based on the single UCNCs-MT is also demonstrated, and the sensitivity of UCNCs-MT is significantly enough for thermometry applications in the range of 298–383 K.
Disabled-2 Determines Commitment of a Pre-adipocyte Population in Juvenile Mice
Authors: Tao Wensi , Moore Robert , Meng Yue , Yeasky Toni M. , Smith Elizabeth R. , Xu Xiang-Xi
Published: October 2016

Disabled-2 (Dab2) is a widely expressed clathrin binding endocytic adaptor protein and known for the endocytosis of the low-density lipoprotein (LDL) family receptors. Dab2 also modulates endosomal Ras/MAPK (Erk1/2) activity by regulating the disassembly of Grb2/Sos1 complexes associated with clathrin-coated vesicles. We found that the most prominent phenotype of Dab2 knockout mice was their striking lean body composition under a high fat and high caloric diet, although the weight of the mutant mice was indistinguishable from wild-type littermates on a regular chow. The remarkable difference in resistance to high caloric diet-induced weight gain of the dab2-deleted mice was presented only in juvenile but not in mature mice. Investigation using Dab2-deficient embryonic fibroblasts and mesenchymal stromal cells indicated that Dab2 promoted adipogenic differentiation by modulation of MAPK (Erk1/2) activity, which otherwise suppresses adipogenesis through the phosphorylation of PPARγ. The results suggest that Dab2 is required for the excessive calorie-induced differentiation of an adipocyte progenitor cell population that is present in juvenile but depleted in mature animals. The finding provides evidence for a limited pre-adipocyte population in juvenile mammals and the requirement of Dab2 in the regulation of Ras/MAPK signal in the commitment of the precursor cells to adipose tissues.