bluuebunny/crossref_metadata_2025 huggingface dataset:
Calibration and Stokes Imaging with Full Embedded Element Primary Beam Model for the Murchison Widefield Array
Authors: Sokolowski M. , Colegate T. , Sutinjo A. T. , Ung D. , Wayth R. , Hurley-Walker N. , Lenc E. , Pindor B. , Morgan J. , Kaplan D. L. , Bell M. E. , Callingham J. R. , Dwarakanath K. S. , For Bi-Qing , Gaensler B. M. , Hancock P. J. , Hindson L. , Johnston-Hollitt M. , Kapińska A. D. , McKinley B. , Offringa A. R. , Procopio P. , Staveley-Smith L. , Wu C. , Zheng Q.
Published: November 2017

The Murchison Widefield Array (MWA), located in Western Australia, is one of the low-frequency precursors of the international Square Kilometre Array (SKA) project. In addition to pursuing its own ambitious science programme, it is also a testbed for wide range of future SKA activities ranging from hardware, software to data analysis. The key science programmes for the MWA and SKA require very high dynamic ranges, which challenges calibration and imaging systems. Correct calibration of the instrument and accurate measurements of source flux densities and polarisations require precise characterisation of the telescope’s primary beam. Recent results from the MWA GaLactic Extragalactic All-sky Murchison Widefield Array (GLEAM) survey show that the previously implemented Average Embedded Element (AEE) model still leaves residual polarisations errors of up to 10–20% in Stokes Q. We present a new simulation-based Full Embedded Element (FEE) model which is the most rigorous realisation yet of the MWA’s primary beam model. It enables efficient calculation of the MWA beam response in arbitrary directions without necessity of spatial interpolation. In the new model, every dipole in the MWA tile (4 × 4 bow-tie dipoles) is simulated separately, taking into account all mutual coupling, ground screen, and soil effects, and therefore accounts for the different properties of the individual dipoles within a tile. We have applied the FEE beam model to GLEAM observations at 200–231 MHz and used false Stokes parameter leakage as a metric to compare the models. We have determined that the FEE model reduced the magnitude and declination-dependent behaviour of false polarisation in Stokes Q and V while retaining low levels of false polarisation in Stokes U.
World Literature and Literary Value: Is “Global” The New “Lowbrow?”
Authors: Watroba Karolina
Published: November 2017

This paper is about the critical debates surrounding contemporary novels with a global reach, especially those written by non-Western authors, but highly successful on the Western literary market, such as Haruki Murakami’s and Orhan Pamuk’s works. A close analysis of the evaluative terms used in these debates, epitomized by Tim Park’s coinage “the dull new global novel,” reveals that they conflate two distinct lines of argument. Fashioned as a materialist narrative about cultural hegemony in the globalized world, these critiques turn out to be motivated by a much older concern to preserve a literary elite. “The global” and its opposite, “the local,” start to sound like code words for “highbrow” and “lowbrow,” and, seen in this light, the whole critical debate about the new global novel appears as an attempt to sidestep a direct engagement with the ever-elusive question of literary value.
Supplemental psyllium fibre regulates the intestinal barrier and inflammation in normal and colitic mice
Authors: Ogata Miyuki , Ogita Tasuku , Tari Hiroyuki , Arakawa Teruaki , Suzuki Takuya
Published: November 2017

Our previous study demonstrated that supplemental psyllium fibre increased cytoprotective heat-shock protein (Hsp) 25 levels in the intestinal cells of mice. Here, we examined the effect of psyllium fibre on colonic gene and protein expression and faecal microbiota in normal and colitic mice to improve the understanding of the preventive role of the supplement. DNA microarray analysis revealed that a 10 % psyllium fibre diet administered for 5 d up-regulated eleven extracellular matrix (ECM)-associated genes, including collagens and fibronectins, in normal mice. Acute colitis was induced using dextran sodium sulphate (DSS) in mice that were administered a pre-feeding 5 to 10 % psyllium fibre diet for 5 d. Psyllium fibre partially ameliorated or resolved the DSS-induced colon damage and inflammation characterised by body weight loss, colon shortening, increased levels of pro-inflammatory cytokines and decreased tight junction protein expression in the colon. Analysis of faecal microbiota using denaturing gradient gel electrophoresis of the PCR-amplified 16S rRNA gene demonstrated that psyllium fibre affected the colonic microbiota. Intestinal permeability was evaluated by growing intestinal Caco-2 cell monolayers on membrane filter supports coated with or without fibronectin and collagen. Cells grown on collagen and fibronectin coating showed higher transepithelial electrical resistance, indicating a strengthening of barrier integrity. Therefore, increased Hsp25 levels and modification of colonic ECM contribute to the observed psyllium-mediated protection against DSS-induced colitis. Furthermore, ECM modification appears to play a role in the strengthening of the colon barrier. In conclusion, psyllium fibre may be useful in the prevention of intestinal inflammatory diseases.
Polygenic prediction of the phenome, across ancestry, in emerging adulthood
Authors: Docherty Anna R. , Moscati Arden , Dick Danielle , Savage Jeanne E. , Salvatore Jessica E. , Cooke Megan , Aliev Fazil , Moore Ashlee A. , Edwards Alexis C. , Riley Brien P. , Adkins Daniel E. , Peterson Roseann , Webb Bradley T. , Bacanu Silviu A. , Kendler Kenneth S.
Published: November 2017

Background

Identifying genetic relationships between complex traits in emerging adulthood can provide useful etiological insights into risk for psychopathology. College-age individuals are under-represented in genomic analyses thus far, and the majority of work has focused on the clinical disorder or cognitive abilities rather than normal-range behavioral outcomes.

Methods

This study examined a sample of emerging adults 18–22 years of age (N = 5947) to construct an atlas of polygenic risk for 33 traits predicting relevant phenotypic outcomes. Twenty-eight hypotheses were tested based on the previous literature on samples of European ancestry, and the availability of rich assessment data allowed for polygenic predictions across 55 psychological and medical phenotypes.

Results

Polygenic risk for schizophrenia (SZ) in emerging adults predicted anxiety, depression, nicotine use, trauma, and family history of psychological disorders. Polygenic risk for neuroticism predicted anxiety, depression, phobia, panic, neuroticism, and was correlated with polygenic risk for cardiovascular disease.

Conclusions

These results demonstrate the extensive impact of genetic risk for SZ, neuroticism, and major depression on a range of health outcomes in early adulthood. Minimal cross-ancestry replication of these phenomic patterns of polygenic influence underscores the need for more genome-wide association studies of non-European populations.
Psychosocial functioning among regular cannabis users with and without cannabis use disorder
Authors: Foster Katherine T. , Arterberry Brooke J. , Iacono William G. , McGue Matt , Hicks Brian M.
Published: November 2017

Background

In the United States, cannabis accessibility has continued to rise as the perception of its harmfulness has decreased. Only about 30% of regular cannabis users develop cannabis use disorder (CUD), but it is unclear if individuals who use cannabis regularly without ever developing CUD experience notable psychosocial impairment across the lifespan. Therefore, psychosocial functioning was compared across regular cannabis users with or without CUD and a non-user control group during adolescence (age 17; early risk) and young adulthood (ages 18–25; peak CUD prevalence).

Method

Weekly cannabis users with CUD (n = 311), weekly users without CUD (n = 111), and non-users (n = 996) were identified in the Minnesota Twin Family Study. Groups were compared on alcohol and illicit drug use, psychiatric problems, personality, and social functioning at age 17 and from ages 18 to 25. Self-reported cannabis use and problem use were independently verified using co-twin informant report.

Results

In both adolescence and young adulthood, non-CUD users reported significantly higher levels of substance use problems and externalizing behaviors than non-users, but lower levels than CUD users. High agreement between self- and co-twin informant reports confirmed the validity of self-reported cannabis use problems.

Conclusions

Even in the absence of CUD, regular cannabis use was associated with psychosocial impairment in adolescence and young adulthood. However, regular users with CUD endorsed especially high psychiatric comorbidity and psychosocial impairment. The need for early prevention and intervention – regardless of CUD status – was highlighted by the presence of these patterns in adolescence.
Considering the filmmaker: Intensified continuity, narrative structure, and the Distancing-Embracing model
Authors: Armstrong Kacie L. , Cutting James E.
Published: November 2017

Menninghaus et al. pose two open-ended questions: To what extent do formal elements of art elicit negative affect, and do artists try to elicit this response in a theory-based or intuitive manner? For popular movies, we argue that the consideration of their construction is prior to the consideration of the experience that they evoke.
The urge to judge: Why the judgmental attitude has anything to do with the aesthetic enjoyment of negative emotions
Authors: Brattico Elvira , Vuust Peter
Published: November 2017

Based on arguments from both philosophical and empirical aesthetics, we hereby propose that the enjoyment of negative emotions in art and fiction is distinct from the immediate pleasure deriving from sensory features, because it requires a conscious, intentional attitude toward the object. This attitude is linked with the compelling goal of providing a judgment of liking, beauty, perfection, or similar.
What is art and how does it differ from aesthetics?
Authors: Kreuzbauer Robert
Published: November 2017

Art objects differ from other objects because they are intentionally created to embody a producer's (i.e., artist's) expression. Hence, art objects are social objects whose appeal and value are determined largely by the strategic interaction between the artist and the audience. I discuss several aspects of how strategic interaction can affect an art object's perceived value and aesthetic appeal.
Examining lexical development in second language learners: An approximate replication of Salsbury, Crossley & McNamara (2011)
Authors: Crossley Scott A. , Skalicky Stephen
Published: November 2017

This paper reports on an approximate or partial replication of a study by Salsbury, Crossley & McNamara (2011) that examined the longitudinal developmental of a number of core lexical features related to word imageability, concreteness, familiarity, and meaningfulness in a spoken corpus of English second language (L2) learners. Salsbury et al. found no developmental growth patterns for word familiarity but strong growth patterns for word concreteness, imageability, and meaningfulness as a function of time such that L2 learners began to produce more sophisticated words. Salsbury et al. were the first to formally identify this relation between English proficiency and lexical sophistication, and a large number of studies investigating lexical proficiency have cited this article as a foundational study. There were, however, a number of limitations to the Salsbury et al. (2011) study that make it appropriate for replication. First, the sample size was relatively small (six learners sampled six times over the course of a year). In addition, the study did not control for a number of factors important in L2 acquisition studies (e.g., age, proficiency level, gender) and used a statistical technique that averaged group means and did not properly account for individual participant variation. This replication study addresses these areas and the findings from the replication reflect those reported by Salsbury et al., providing support for the notion that developing L2 lexicons move from the production of words with stronger links to core lexical items to words with weaker links to core lexical items over time. Implications for language learning and teaching are discussed.
Extraordinary Isolation? Woodrow Wilson and the Civil Rights Movement
Authors: Jacobs Nicholas F. , Milkis Sidney M.
Published: November 2017

This article explores the contentious and dynamic relationship between Woodrow Wilson and a nascent, diverse civil rights movement from 1912 to 1919. The pivotal relationship between Wilson and the early civil rights movement emerged out of two concurrent and related political developments: the increasing centrality of presidential administration in the constitutional order and the growing national aspirations of political strategies and goals among reform activists. Not only do we illustrate an early form of social movement politics that was largely antithetical to the administration's objectives, but we also trace how the strategies adopted by civil rights leaders were contingent on an early, still-to-be institutionalized administrative presidency. We highlight Wilson's involvement in the racial unrest that emerged from the debut of the filmThe Birth of a Nationand in the race riots that accompanied the Great Migration and World War I in his second term. These early twentieth-century episodes legitimized a form of collective action and helped to recast the modern presidency as an institution that both collaborated and competed with social movement organizations to control the timing and conditions of change.
Occupational therapy for functional neurological disorders: a scoping review and agenda for research
Authors: Gardiner Paula , MacGregor Lindsey , Carson Alan , Stone Jon
Published: November 2017

Functional neurological disorders (FND)—also called psychogenic, nonorganic, conversion, and dissociative disorders—constitute one of the commonest problems in neurological practice. An occupational therapist (OT) is commonly involved in management, but there is no specific literature or guidance for these professionals. Classification now emphasizes the importance of positive diagnosis of FND based on physical signs, more than psychological features. Studies of mechanism have produced new clinical and neurobiological ways of thinking about these disorders. Evidence has emerged to support the use of physiotherapy and occupational therapy as part of a multidisciplinary team for functional movement disorders (FMD) and psychotherapy for dissociative (nonepileptic) attacks. The diagnosis and management of FND has entered a new evidence-based era and deserves a standard place in the OT neurological curriculum. We discuss specific management areas relevant to occupational therapy and propose a research agenda.
Vitamin-D-Mangel in der Schweizer Sonnenstube?
Authors: Quarenghi Massimo Clay , Aubry Emilie , Aeberhard Carla , Ossola Nicola , Marone Claudio , Stanga Zeno
Published: November 2017

Zusammenfassung. In dieser Studie wurden die Prävalenz sowie saisonale Fluktuationen des VitD-Mangels bei Bewohnern des Tessins evaluiert. Klinische Indikatoren zur Erkennung eines VitD-Mangelzustands wurden untersucht (Alter, Geschlecht, Hauptdiagnose, Komorbiditäten, Medikamentenanzahl). Beim Eintreffen auf der Notfallstation des Regionalspitals Bellinzona wurde bei je einer Population älterer internistischer Patienten eine einmalige VitD-Serumspiegelbestimmung im Frühling (n = 58) und im Herbst (n = 49) durchgeführt. Die Prävalenz des VitD-Mangels im Frühling betrug 98 % (Serumspiegelmittelwert 21,4±12,2 nmol/l) versus 63 % im Herbst (Serumspiegelmittelwert 43,7±18,6 nmol/l). Auch nach dem Sommer litten 66 % der Patienten an einem VitD-Mangel. Es konnten keine verlässlichen Indikatoren eruiert werden. Angesichts dieser Ergebnisse und der BAG-Empfehlungen ist eine Prophylaxe mit 800 IE täglich bei allen älteren Schweizern, v.a. im Winter, sinnvoll. Diese Präventionsmassnahme ist kostengünstig, einfach, sicher und effektiv.
Wisdom and How to Cultivate It
Authors: Grossmann Igor
Published: November 2017

Abstract. Some folk beliefs characterize wisdom as an essence – a set of immutable characteristics, developing as a consequence of an innate potential and extraordinary life experiences. Emerging empirical scholarship involving experiments, diary, and cross-cultural studies contradicts such folk beliefs. Characteristics of wise thinking, which include intellectual humility, recognition of uncertainty and change, consideration of different perspectives, and integration of these perspectives, is highly variable across situations. Cumulatively, empirical research suggests that variability in wise thinking is systematic, with greater wisdom in ecological and experimentally-induced contexts promoting an ego-decentered (vs. egocentric) viewpoint. Moreover, teaching for wisdom benefits from appreciation of context-dependency of intentions and actions depicted in the narratives of wisdom exemplars’ lives. I conclude by advancing a constructivist model of wisdom, suggesting that cultural-historical, personal-motivational, and situational contexts play a critical role for wisdom, its development, and its application in daily life.
Erratum: Cooling a mechanical resonator with nitrogen-vacancy centres using a room temperature excited state spin–strain interaction
Authors: MacQuarrie E. R. , Otten M. , Gray S. K. , Fuchs G. D.
Published: November 2017

Nature Communications 8: Article number: 14358 (2017); Published 6 February 2017; Updated 29 November 2017. This Article contains a typographical error in the sentence preceding Eq. 4. This sentence should read, ‘Under the secular approximation and working in the limit , the dynamical equation for the phonon occupancy can be simplified to’; that is, with a much-less-than symbol rather than a much-greater-than symbol.
A new stem sarcopterygian illuminates patterns of character evolution in early bony fishes
Authors: Lu Jing , Giles Sam , Friedman Matt , Zhu Min
Published: November 2017

Discoveries of putative stem sarcopterygians from the late Silurian and Early Devonian of South China have increased our knowledge of the initial diversification of osteichthyans while also highlighting incongruities in character evolution in this major jawed vertebrate group. Character-rich endocrania are incompletely preserved for early bony fishes, limiting a detailed understanding of complex internal morphology and evolutionary changes in the cranium. Here we report a new sarcopterygian (Ptyctolepis brachynotus gen. et sp. nov.) from the Pragian (Early Devonian) of South China, which preserves a unique example of a completely ossified otoccipital division of the braincase in a stem lobe-finned fish. The hyomandibular facets are paired but lie dorsal to the jugular canal, representing a hitherto unobserved combination of derived and primitive character states. This new taxon prompts a reassessment of early osteichthyan interrelationships, including the phylogenetic placement of psarolepids, which might branch from the osteichthyan—rather than sarcopterygian—stem.
Existence of multi-radical and closed-shell semiconducting states in post-graphene organic Dirac materials
Authors: Alcón Isaac , Viñes Francesc , Moreira Iberio de P. R. , Bromley Stefan T.
Published: November 2017

Post-graphene organic Dirac (PGOD) materials are ordered two-dimensional networks of triply bonded sp2 carbon nodes spaced by π-conjugated linkers. PGOD materials are natural chemical extensions of graphene that promise to have an enhanced range of properties and applications. Experimentally realised molecules based on two PGOD nodes exhibit a bi-stable closed-shell/multi-radical character that can be understood through competing Lewis resonance forms. Here, following the same rationale, we predict that similar states should be accessible in PGOD materials, which we confirm using accurate density functional theory calculations. Although for graphene the semimetallic state is always dominant, for PGOD materials this state becomes marginally meta-stable relative to open-shell multi-radical and/or closed-shell states that are stabilised through symmetry breaking, in line with analogous molecular systems. These latter states are semiconducting, increasing the potential use of PGOD materials as highly tuneable platforms for future organic nano-electronics and spintronics.
Pandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic cell death
Authors: Hartmann Boris M. , Albrecht Randy A. , Zaslavsky Elena , Nudelman German , Pincas Hanna , Marjanovic Nada , Schotsaert Michael , Martínez-Romero Carles , Fenutria Rafael , Ingram Justin P. , Ramos Irene , Fernandez-Sesma Ana , Balachandran Siddharth , García-Sastre Adolfo , Sealfon Stuart C.
Published: November 2017

The risk of emerging pandemic influenza A viruses (IAVs) that approach the devastating 1918 strain motivates finding strain-specific host–pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA degradation. Here, we show that DC infection with seasonal IAV causes immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic DC cell death. Only DC infected with seasonal IAV, but not with pandemic IAV, enhance maturation of uninfected DC and T cell proliferation. In vivo, circulating T cell levels are reduced after pandemic, but not seasonal, IAV infection. Using recombinant viruses, we identify the HA genomic segment as the mediator of cell death inhibition. These results show how pandemic influenza viruses subvert the immune response.
Bacteriophage T5 tail tube structure suggests a trigger mechanism for Siphoviridae DNA ejection
Authors: Arnaud Charles-Adrien , Effantin Grégory , Vivès Corinne , Engilberge Sylvain , Bacia Maria , Boulanger Pascale , Girard Eric , Schoehn Guy , Breyton Cécile
Published: November 2017

The vast majority of phages, bacterial viruses, possess a tail ensuring host recognition, cell wall perforation and safe viral DNA transfer from the capsid to the host cytoplasm. Long flexible tails are formed from the tail tube protein (TTP) polymerised as hexameric rings around and stacked along the tape measure protein (TMP). Here, we report the crystal structure of T5 TTP pb6 at 2.2 Å resolution. Pb6 is unusual in forming a trimeric ring, although structure analysis reveals homology with all classical TTPs and related tube proteins of bacterial puncturing devices (type VI secretion system and R-pyocin). Structures of T5 tail tubes before and after interaction with the host receptor were determined by cryo-electron microscopy at 6 Å resolution. Comparison of these two structures reveals that host-binding information is not propagated to the capsid through conformational changes in the tail tube, suggesting a role of the TMP in this information transduction process.
A two-dimensional Fe-doped SnS2 magnetic semiconductor
Authors: Li Bo , Xing Tao , Zhong Mianzeng , Huang Le , Lei Na , Zhang Jun , Li Jingbo , Wei Zhongming
Published: November 2017

Magnetic two-dimensional materials have attracted considerable attention for their significant potential application in spintronics. In this study, we present a high-quality Fe-doped SnS2 monolayer exfoliated using a micromechanical cleavage method. Fe atoms were doped at the Sn atom sites, and the Fe contents are ∼2.1%, 1.5%, and 1.1%. The field-effect transistors based on the Fe0.021Sn0.979S2 monolayer show n-type behavior and exhibit high optoelectronic performance. Magnetic measurements show that pure SnS2 is diamagnetic, whereas Fe0.021Sn0.979S2 exhibits ferromagnetic behavior with a perpendicular anisotropy at 2 K and a Curie temperature of ~31 K. Density functional theory calculations show that long-range ferromagnetic ordering in the Fe-doped SnS2 monolayer is energetically stable, and the estimated Curie temperature agrees well with the results of our experiment. The results suggest that Fe-doped SnS2 has significant potential in future nanoelectronic, magnetic, and optoelectronic applications.
Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy
Authors: Zhu Guizhi , Lynn Geoffrey M. , Jacobson Orit , Chen Kai , Liu Yi , Zhang Huimin , Ma Ying , Zhang Fuwu , Tian Rui , Ni Qianqian , Cheng Siyuan , Wang Zhantong , Lu Nan , Yung Bryant C. , Wang Zhe , Lang Lixin , Fu Xiao , Jin Albert , Weiss Ido D. , Vishwasrao Harshad , Niu Gang , Shroff Hari , Klinman Dennis M. , Seder Robert A. , Chen Xiaoyuan
Published: November 2017

Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund’s adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent peripheral antigen-specific CD8+cytotoxic T lymphocytes with immune memory than IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for combination cancer immunotherapy.
Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
Authors: Shinoda Keiko , Fujitani Hideaki
Published: November 2017

Proline cis-trans isomerisation is a regulatory mechanism used in a range of biological processes, and is related to various diseases such as Alzheimers disease and cancer. However, the details of the exact molecular mechanism by which it occurs are not known. Using X-ray crystallography, proline isomerisation has been shown to occur following formation of an antigen-antibody complex between the target epiregulin (EPR) and the antibody 9E5, at proline (Pro103), located in the third complementarity-determining region (CDR) of the heavy chain of 9E5. To obtain an accurate description of the pathway involved in cis-trans isomerisation in this system, we performed ten independent long molecular dynamics (MD) simulations starting at a stable transient bound structure obtained from many short binding MD simulations. As a result, we were able to describe the process by which cis-trans isomerisation is initiated, and suggest a catalysis mechanism for cis-trans isomerization in this antigen-antibody system. We found that Asp102, which is immediately adjacent to Pro103, rotates while changing its interacting partner residues in the light chain of 9E5, and at the same time EPR polar residues help to stabilise the intermediate states in the isomerisation process by interacting strongly with Asp102.
Comprehensive statistical inference of the clonal structure of cancer from multiple biopsies
Authors: Liu Jie , Halloran John T. , Bilmes Jeffrey A. , Daza Riza M. , Lee Choli , Mahen Elisabeth M. , Prunkard Donna , Song Chaozhong , Blau Sibel , Dorschner Michael O. , Gadi Vijayakrishna K. , Shendure Jay , Blau C. Anthony , Noble William S.
Published: November 2017

A comprehensive characterization of tumor genetic heterogeneity is critical for understanding how cancers evolve and escape treatment. Although many algorithms have been developed for capturing tumor heterogeneity, they are designed for analyzing either a single type of genomic aberration or individual biopsies. Here we present THEMIS (Tumor Heterogeneity Extensible Modeling via an Integrative System), which allows for the joint analysis of different types of genomic aberrations from multiple biopsies taken from the same patient, using a dynamic graphical model. Simulation experiments demonstrate higher accuracy of THEMIS over its ancestor, TITAN. The heterogeneity analysis results from THEMIS are validated with single cell DNA sequencing from a clinical tumor biopsy. When THEMIS is used to analyze tumor heterogeneity among multiple biopsies from the same patient, it helps to reveal the mutation accumulation history, track cancer progression, and identify the mutations related to treatment resistance. We implement our model via an extensible modeling platform, which makes our approach open, reproducible, and easy for others to extend.
Deconvoluting the Photonic and Electronic Response of 2D Materials: The Case of MoS2
Authors: Zhang Kehao , Borys Nicholas J. , Bersch Brian M. , Bhimanapati Ganesh R. , Xu Ke , Wang Baoming , Wang Ke , Labella Michael , Williams Teague A. , Haque Md Amanul. , Barnard Edward S. , Fullerton-Shirey Susan , Schuck P. James , Robinson Joshua A.
Published: November 2017

Evaluating and tuning the properties of two-dimensional (2D) materials is a major focus of advancing 2D science and technology. While many claim that the photonic properties of a 2D layer provide evidence that the material is “high quality”, this may not be true for electronic performance. In this work, we deconvolute the photonic and electronic response of synthetic monolayer molybdenum disulfide. We demonstrate that enhanced photoluminescence can be robustly engineered via the proper choice of substrate, where growth of MoS2 on r-plane sapphire can yield >100x enhancement in PL and carrier lifetime due to increased molybdenum-oxygen bonding compared to that of traditionally grown MoS2 on c-plane sapphire. These dramatic enhancements in optical properties are similar to those of super-acid treated MoS2, and suggest that the electronic properties of the MoS2 are also superior. However, a direct comparison of the charge transport properties indicates that the enhanced PL due to increased Mo-O bonding leads to p-type compensation doping, and is accompanied by a 2x degradation in transport properties compared to MoS2 grown on c-plane sapphire. This work provides a foundation for understanding the link between photonic and electronic performance of 2D semiconducting layers, and demonstrates that they are not always correlated.
Network effects on coordination in asymmetric games
Authors: Broere Joris , Buskens Vincent , Weesie Jeroen , Stoof Henk
Published: November 2017

Network structure can have an important effect on the behavior of players in an iterated 2 × 2 game. We study the effect of network structure on global and local behavior in asymmetric coordination games using best response dynamics. We find that global behavior is highly dependent on network topology. Random (Erdös-Rényi) networks mostly converge to homogeneous behavior, but the higher the clustering in the network the more heterogeneous the behavior becomes. Behavior within the communities of the network is almost exclusively homogeneous. The findings suggest that clustering of networks facilitates self-organization of uniform behavior within clusters, but heterogeneous behavior between clusters. At the local level we find that some nodes are more important in determining the equilibrium behavior than other nodes. Degree centrality is for most networks the main predictor for the behavior and nodes with an even degree have an advantage over nodes with an uneven degree in dictating the behavior. We conclude that the behavior is difficult to predict for (Erdös-Rényi) networks and that the network imposes the behavior as a function of clustering and degree heterogeneity in other networks.
Establishment of a strain of haemophilia-A pigs by xenografting of foetal testicular tissue from neonatally moribund cloned pigs
Authors: Kaneko Hiroyuki , Kikuchi Kazuhiro , Nakai Michiko , Fuchimoto Daiichiro , Suzuki Shunichi , Sembon Shoichiro , Noguchi Junko , Onishi Akira
Published: November 2017

Grafting of testicular tissue into immunodeficient mice makes it possible to obtain functional sperm from immature donor animals that cannot be used for reproduction. We have developed a porcine model of human haemophilia A (haemophilia-A pigs) by nuclear transfer cloning from foetal fibroblasts after disruption of the X-linked coagulation factor VIII (F8) gene. Despite having a recessive condition, female F8+/− cloned pigs died of severe bleeding at an early age, as was the case for male F8−/Y cloned pigs, thus making it impossible to obtain progeny. In this study, therefore, we produced sperm from F8−/Y cloned pigs by grafting their foetal testicular tissue into nude mice. Two F8+/− female pigs were generated from oocytes injected with xenogeneic sperm. Unlike the F8+/− cloned pigs, they remained asymptomatic, and delivered five F8−/Y and four F8+/− pigs after being crossed with wild-type boars. The descendant F8−/Y pigs conserved the haemophilia phenotype. Thus, the present F8+/− pigs show resolution of the phenotypic abnormality, and will facilitate production of F8−/Y pigs as founders of a strain of haemophilia-A pigs for the development of new therapeutics for haemophilia A. This strategy will be applicable to other genetically modified pigs.
ATR-FTIR spectral discrimination between normal and tumorous mouse models of lymphoma and melanoma from serum samples
Authors: Ghimire Hemendra , Venkataramani Mahathi , Bian Zhen , Liu Yuan , Perera A. G. Unil
Published: November 2017

This study presents, attenuated total reflection Fourier transforms infrared spectroscopy of dried serum samples in an effort to assess biochemical changes induced by non-Hodgkin’s lymphoma and subcutaneous melanoma. An EL4 mouse model of non-Hodgkin lymphoma and a B16 mouse model of subcutaneous melanoma are used to extract a snapshot of tumor-associated alteration in the serum. The study of both cancer-bearing mouse models in wild types and their corresponding control types, emphasizes the diagnostic potential of this approach as a screening technique for non-Hodgkin lymphoma and melanoma skin cancer. Infrared absorbance values of the different spectral bands, hierarchical clustering and integral values of the component bands by curve fitting, show statistically significant differences (student’s t-test, two-tailed unequal variance p-value < 0.05) between spectra representing healthy and tumorous mouse. This technique may thus be useful for having individualized route maps for rapid evaluation of lymphoma and melanoma status and associated therapeutic modalities.
Coupling of sea level and tidal range changes, with implications for future water levels
Authors: Devlin Adam T. , Jay David A. , Talke Stefan A. , Zaron Edward D. , Pan Jiayi , Lin Hui
Published: November 2017

Are perturbations to ocean tides correlated with changing sea-level and climate, and how will this affect high water levels? Here, we survey 152 tide gauges in the Pacific Ocean and South China Sea and statistically evaluate how the sum of the four largest tidal constituents, a proxy for the highest astronomical tide (HAT), changes over seasonal and interannual time scales. We find that the variability in HAT is significantly correlated with sea-level variability; approximately 35% of stations exhibit a greater than ±50 mm tidal change per meter sea-level fluctuation. Focusing on a subset of three stations with long records, probability density function (PDF) analyses of the 95% percentile exceedance of total sea level (TSL) show long-term changes of this high-water metric. At Hong Kong, the increase in tides significantly amplifies the risk caused by sea-level rise. Regions of tidal decrease and/or amplification highlight the non-linear response to sea-level variations, with the potential to amplify or mitigate against the increased flood risk caused by sea-level rise. Overall, our analysis suggests that in many regions, local flood level determinations should consider the joint effects of non-stationary tides and mean sea level (MSL) at multiple time scales.
Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?
Authors: Magalhães Pedro , Pejchinovski Martin , Markoska Katerina , Banasik Miroslaw , Klinger Marian , Švec-Billá Dominika , Rychlík Ivan , Rroji Merita , Restivo Arianna , Capasso Giovambattista , Bob Flaviu , Schiller Adalbert , Ortiz Alberto , Perez-Gomez Maria Vanessa , Cannata Pablo , Sanchez-Niño Maria Dolores , Naumovic Radomir , Brkovic Voin , Polenakovic Momir , Mullen William , Vlahou Antonia , Zürbig Petra , Pape Lars , Ferrario Franco , Denis Colette , Spasovski Goce , Mischak Harald , Schanstra Joost P.
Published: November 2017

Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the urinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in Masson trichrome stained kidney tissues. The urinary proteome was analysed by capillary electrophoresis coupled to mass spectrometry. CKD273 displayed a significant and positive correlation with the degree of fibrosis (Rho = 0.430, P = 0.0044), while the routinely used parameters (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio) did not (Rho = −0.222; −0.137; −0.070 and P = 0.16; 0.39; 0.66, respectively). We identified seven fibrosis-associated peptides displaying a significant and negative correlation with the degree of fibrosis. All peptides were collagen fragments, suggesting that these may be causally related to the observed accumulation of ECM in the kidneys. CKD273 and specific peptides are significantly associated with kidney fibrosis; such an association could not be detected by other biomarkers for CKD. These non-invasive fibrosis-related biomarkers can potentially be implemented in future trials.
Plant-endophytes interaction influences the secondary metabolism in Echinacea purpurea (L.) Moench: an in vitro model
Authors: Maggini Valentina , De Leo Marinella , Mengoni Alessio , Gallo Eugenia Rosaria , Miceli Elisangela , Reidel Rose Vanessa Bandeira , Biffi Sauro , Pistelli Luisa , Fani Renato , Firenzuoli Fabio , Bogani Patrizia
Published: November 2017

The influence of the interaction(s) between the medicinal plant Echinacea purpurea (L.) Moench and its endophytic communities on the production of alkamides is investigated. To mimic the in vivo conditions, we have set up an infection model of axenic in vitro E. purpurea plants inoculated with a pool of bacterial strains isolated from the E. purpurea stems and leaves. Here we show different alkamide levels between control (not-inoculated) and inoculated plants, suggesting that the alkamide biosynthesis may be modulated by the bacterial infection. Then, we have analysed the branched-chain amino acids (BCCA) decarboxylase gene (GenBank Accession #LT593930; the enzymatic source for the amine moiety formation of the alkamides) expression patterns. The expression profile shows a higher expression level in the inoculated E. purpurea tissues than in the control ones. These results suggest that the plant-endophyte interaction can influence plant secondary metabolism affecting the therapeutic properties of E. purpurea.
Fe4S4 Cubane Type Cluster Immobilized on a Graphene Support: A High Performance H2 Evolution Catalysis in Acidic Water
Authors: Begum Ameerunisha , Sheikh Aasif Hassan , Moula Golam , Sarkar Sabyasachi
Published: November 2017

The development of alternate catalysts that utilize non-precious metal based electrode materials such as the first row transition metal complexes is an important goal for economic fuel cell design. In this direction, a new Fe4S4 cubane type cluster, [PPh4]2[Fe4S4(DMET)4] (1) (DMET = cis-1,2-dicarbomethoxyethylene dithiolate) and its composite with functionalized graphene, (1@graphene) have been synthesized and characterized. The presence of nanocrystalline structures on graphene matrix in TEM and SEM images of 1@graphene indicate that the cluster (1) has been immobilized. The composite, 1@graphene evolves H2 gas from p-toluene sulfonic acid (TsOH) in a mixture of H2O and CH3CN under ambient conditions with a significant turnover number of 3200. 1@graphene electro-catalyzes H2 evolution at Ep, −1.2 V with remarkable throughput, catalytic efficiency and stability in only H2O or in only CH3CN. The Fe4S4 cluster (1) alone electro-catalyzes hydrogen evolution at Ep, −0.75 V from TsOH in CH3CN. The X-ray crystal structure of the Fe4S4 cluster (1) (λmax, CH2Cl2, 823 nm; ε, 2200 mol−1 cm−1) shows that it is dianionic with a cumulative oxidation state of +2.5 for the iron centers and short C-S bond distances (ca., 1.712 Å & 1.727 Å) indicating the presence of sulfur based radicals.
Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer
Authors: Cheng An Ning , Fan Chi-Chen , Lo Yu-Kang , Kuo Cheng-Liang , Wang Hui-Chun , Lien I.-Hsin , Lin Shu-Yu , Chen Chung-Hsing , Jiang Shih Sheng , Chang I.-Shou , Juan Hsueh-Fen , Lyu Ping-Chiang , Lee Alan Yueh-Luen
Published: November 2017

Cdc7-Dbf4 kinase plays a key role in the initiation of DNA replication and contributes to the replication stress in cancer. The activity of human Cdc7-Dbf4 kinase remains active and acts as an effector of checkpoint under replication stress. However, the downstream targets of Cdc7-Dbf4 contributed to checkpoint regulation and replication stress-support function in cancer are not fully identified. In this work, we showed that aberrant Cdc7-Dbf4 induces DNA lesions that activate ATM/ATR-mediated checkpoint and homologous recombination (HR) DNA repair. Using a phosphoproteome approach, we identified HSP90-S164 as a target of Cdc7-Dbf4 in vitro and in vivo. The phosphorylation of HSP90-S164 by Cdc7-Dbf4 is required for the stability of HSP90-HCLK2-MRN complex and the function of ATM/ATR signaling cascade and HR DNA repair. In clinically, the phosphorylation of HSP90-S164 indeed is increased in oral cancer patients. Our results indicate that aberrant Cdc7-Dbf4 enhances replication stress tolerance by rewiring ATR/ATM mediated HR repair through HSP90-S164 phosphorylation and by promoting recovery from replication stress. We provide a new solution to a subtyping of cancer patients with dominant ATR/HSP90 expression by combining inhibitors of ATR-Chk1, HSP90, or Cdc7 in cancer combination therapy.
QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p53 signaling pathway
Authors: Chang Hong , Li Chun , Wang Qiyan , Lu Linghui , Zhang Qian , Zhang Yi , Zhang Na , Wang Yong , Wang Wei
Published: November 2017

The ancient traditional Chinese medicine Qishenkeli (QSKL) is widely used in the treatment of heart failure (HF) in China. Previous studies have shown that QSKL has definite effects on HF. The purpose of this study is to identify the regulation of QSKL on apoptosis and clarify the underlying mechanism. An apoptosis model of H9C2 cells was induced by oxygen-glucose deprivation/recovery (OGD/R). An animal model of HF was induced by ligation of left anterior descending (LAD) coronary artery in rat. We found that QSKL reduced intracellular ROS generation, increased mitochondrial membrane potential and protected H9C2 cells against OGD/R-induced apoptosis. In vivo results showed that QSKL administration could improve cardiac functions, decrease fibrotic area, infarct size and apoptotic rate in HF model. QSKL regulated the expressions of key apoptotic molecules, including increasing Bcl-2/Bax ratio, reducing the expressions of P53, Bax and Cleaved-caspase-3. Interestingly, QSKL also regulated the phosphorylated expressions of PI3K and Akt without significantly affecting PTEN. Taken together, the protective and anti-apoptotic effects of QSKL could be mediated partly through modulating the PI3K/Akt-P53 apoptotic pathway.
Germination Biology of Two Invasive Physalis Species and Implications for Their Management in Arid and Semi-arid Regions
Authors: Ozaslan Cumali , Farooq Shahid , Onen Huseyin , Ozcan Selcuk , Bukun Bekir , Gunal Hikmet
Published: November 2017

Two Solanaceae invasive plant species (Physalis angulata L. and P. philadelphica Lam. var. immaculata Waterfall) infest several arable crops and natural habitats in Southeastern Anatolia region, Turkey. However, almost no information is available regarding germination biology of both species. We performed several experiments to infer the effects of environmental factors on seed germination and seedling emergence of different populations of both species collected from various locations with different elevations and habitat characteristics. Seed dormancy level of all populations was decreased with increasing age of the seeds. Seed dormancy of freshly harvested and aged seeds of all populations was effectively released by running tap water. Germination was slightly affected by photoperiods, which suggests that seeds are slightly photoblastic. All seeds germinated under wide range of temperature (15–40 °C), pH (4–10), osmotic potential (0 to −1.2 MPa) and salinity (0–400 mM sodium chloride) levels. The germination ability of both plant species under wide range of environmental conditions suggests further invasion potential towards non-infested areas in the country. Increasing seed burial depth significantly reduced the seedling emergence, and seeds buried below 4 cm of soil surface were unable to emerge. In arable lands, soil inversion to maximum depth of emergence (i.e., 6 cm) followed by conservational tillage could be utilized as a viable management option.
Induction of antimicrobial peptides secretion by IL-1β enhances human amniotic membrane for regenerative medicine
Authors: Tehrani Fatemeh A. , Modaresifar Khashayar , Azizian Sara , Niknejad Hassan
Published: November 2017

Due to antibacterial characteristic, amnion has been frequently used in different clinical situations. Developing an in vitro method to augment endogenous antibacterial ingredient of amniotic epithelial and mesenchymal stem cells is desirable for a higher efficacy of this promising biomaterial. In this study, epithelial or mesenchymal side dependent effect of amniotic membrane (AM) on antibacterial activity against some laboratory and clinical isolated strains was investigated by modified disk diffusion method and colony count assay. The effect of exposure to IL-1β in production and release of antibacterial ingredients was investigated by ELISA assay. The results showed that there is no significant difference between epithelial and mesenchymal sides of amnion in inhibition of bacterial growth. Although the results of disk diffusion showed that the AM inhibitory effect depends on bacterial genus and strain, colony count assay showed that the extract of AM inhibits all investigated bacterial strains. The exposure of AM to IL-1β leads to a higher level of antibacterial peptides secretion including elafin, HBD-2, HBD-3 and cathelicidic LL-37. Based on these results, amniotic cells possess antibacterial activity which can be augmented by inflammatory signal inducers; a process which make amnion and its epithelial and mesenchymal stem cells more suitable for tissue engineering and regenerative medicine.