bluuebunny/crossref_metadata_2025 huggingface dataset:
Isogeometric based framework for aeroelastic wind turbine blade analysis
Authors: Ferede Etana , Abdalla Mostafa M. , van Bussel Gerard J. W.
Published: June 2016

A framework based on isogeometric analysis is presented for parametrizing a wind turbine rotor blade and evaluating its response. The framework consists of a multi‐fidelity approach for wind turbine rotor analysis. The aeroelastic loads are determined using a low‐fidelity model. The model is based on isogeometric approach to model both the structural and aerodynamic properties. The structural deformations are solved using an isogeometric formulation of geometrically exact 3D beam theory. The aerodynamic loads are calculated using a standard Blade Element Momentum(BEM) theory. Moreover, the aerodynamic loads calculated using BEM theory are modified to account for the change in the blade shape due to blade deformation. The aeroelastic loads are applied in finite element solver Nastran, and both the stress response and buckling response are extracted. Furthermore, the capabilities of Nastran are extended such that design dependent loads can be applied, resulting in correct aeroelastic sensitivities of Nastran responses, making this framework suitable for optimization. The framework is verified against results from the commercial codes FAST and GH Bladed, using the NREL 61.5m rotor blade as a baseline for comparison, showing good agreement. Copyright © 2016 John Wiley & Sons, Ltd.
Global stability of a class of futile cycles
Authors: Rao Shodhan
Published: June 2016

In this paper, we prove the global asymptotic stability of a class of mass action futile cycle networks which includes a model of processive multisite phosphorylation networks. The proof consists of two parts. In the first part, we prove that there is a unique equilibrium in every positive compatibility class. In the second part, we make use of a piecewise linear in rates Lyapunov function in order to prove the global asymptotic stability of the unique equilibrium corresponding to a given initial concentration vector. The main novelty of the paper is the use of a simple algebraic approach based on the intermediate value property of continuous functions in order to prove the uniqueness of equilibrium in every positive compatibility class.
A flow-to-equity approach to coordinate supply chain network planning and financial planning with annual cash outflows to an institutional investor
Authors: Steinrücke Martin , Albrecht Wolfgang
Published: June 2016

A common side effect of cross-linked global economies is that well-positioned middle class companies are acquired by institutional investors, which formulate unreasonable return expectations in many cases. As a consequence, the resulting payouts are often not in line with business operations so that even world market leaders get into trouble or close down. In this context, we consider the case of a sanitary company, which had to manage the described situation after a business takeover. In order to coordinate the annual cash outflows to the investor with intra-organizational supply chain planning and financial planning, we propose a mixed-integer non-linear programming model that is based on the flow-to-equity discounted cash flow method. The objective is to maximize the present value of equity while determining annual cash outflows to the institutional investor during his engagement. As the decisions of the investor during his engagement influence possible operations of the company after his engagement, the residual value of equity (that influences the selling price) is taken into account. The modeling is based on cash flow series, which result from supply chain operations and restructuring on the one hand, and from financial transactions on the other. Financing is characterized by interest rates depending on the time period the credit starts, the credit period, the debt limit of the company and the current total debt. As the latter is a result of the optimization, non-linearity arises. Nevertheless, both the expected demand scenario and further randomly generated demand scenarios of the sanitary company could be solved to the optimum with the commercial optimization package GAMS 23.8/SCIP 2.1.1 within acceptable computation times, if capacity profiles are assigned to the locations to depict feasible and/or preferred capacity developments.
RETRACTED: p53 Loses grip on PIK3CA expression leading to enhanced cell survival during platinum resistance
Authors: Thakur Bhushan , Ray Pritha
Published: June 2016

Tumour suppressor p53, a master transcriptional regulator determines cell fate through preferential activation/repression of a myriad of genes during stress. Till date, activation and preferential binding of p53 on different promoters was reported to be influenced by the nature, strength and duration of stress which mediates its post translational modifications. Cisplatin, a widely used cytotoxic drug represses PIK3CA promoter activity and attenuates PI3K/AKT cell survival pathway through p53 activation in sensitive cells. However, very little is understood about the overall mechanism of p53‐PIK3CA interaction and influence of p53 on the transcriptional status of PIK3CA during cisplatin resistance. Here we showed that cisplatin could dynamically alter p53 occupancy between the p53 binding sequences present in PIK3CA promoter in ovarian and breast cancer cells. This altered occupancy is dictated by higher acetylation and hyper‐phosphorylation at serine 15, serine 20 and serine 46 residues. Interestingly, cisplatin resistant cells when challenged with cisplatin demonstrated abolished PIK3CA promoter attenuation, low level of p53 binding, and loss of p53 serine 46 phosphorylation. A phosphorylation deficient S46A mutant failed to repress PIK3CA in p53 deficient cells. Elevated expression of Bcl2, P27 and cFLIP indicated a pro‐survival state in these resistant cells. Non‐invasive real time imaging using two different luciferase reporters showed that cisplatin could simultaneously induce PIK3CA attenuation and p53 activation with growth regression in sensitive tumours but not in the resistant tumours where only low level of p53 activation and sustained growth was observed. This is the first report on phosphorylation of p53 serine 46 as a modulator of p53‐PIK3CA promoter interaction which influences altered binding of p53 at different consensus sequences in the same promoter in response to chemotherapeutic stress. Absence of such modulation in resistant cellular milieu influences cellular homoeostasis in platinum‐resistant cells probably due to altered post translational modification of p53.
On the trajectory of leading-edge vortices under the influence of Coriolis acceleration
Authors: Limacher Eric , Morton Chris , Wood David
Published: June 2016

Leading-edge vortices (LEVs) can form and remain attached to a rotating wing indefinitely, but the mechanisms of stable attachment are not well understood. Taking for granted that such stable structures do form, a practical question arises: what is the trajectory of the LEV core? Noting that span-wise flow exists within the LEV core, it is apparent that a mean streamline aligned with the axis of the stable LEV must exist. The present work uses the Navier–Stokes equations along such a steady, axial streamline in order to consider the accelerations that act in the streamline-normal direction to affect its local curvature. With some simplifying assumptions, a coupled system of ordinary differential equations is derived that describes the trajectory of an axial streamline through the vortex core. The model is compared to previous work, and is found to predict the trajectory of the LEV core well at span-wise locations inboard of the midspan. This result suggests that Coriolis acceleration is responsible for limiting the span-wise extent of a stable LEV by tilting it into the wake within several chord lengths from the centre of rotation. The downwash due to the tip vortex also appears to play a role, as the only significant differences between model-predicted LEV trajectories and previous results are in the plate-normal direction.
FRAGMENTS OF FREGE’SGRUNDGESETZEAND GÖDEL’S CONSTRUCTIBLE UNIVERSE
Authors: WALSH SEAN
Published: June 2016

Frege’sGrundgesetzewas one of the 19th century forerunners to contemporary set theory which was plagued by the Russell paradox. In recent years, it has been shown that subsystems of theGrundgesetzeformed by restricting the comprehension schema are consistent. One aim of this paper is to ascertain how much set theory can be developed within these consistent fragments of theGrundgesetze, and our main theorem (Theorem 2.9) shows that there is a model of a fragment of theGrundgesetzewhich defines a model of all the axioms of Zermelo–Fraenkel set theory with the exception of the power set axiom. The proof of this result appeals to Gödel’s constructible universe of sets and to Kripke and Platek’s idea of the projectum, as well as to a weak version of uniformization (which does not involve knowledge of Jensen’s fine structure theory). The axioms of theGrundgesetzeare examples ofabstraction principles, and the other primary aim of this paper is to articulate a sufficient condition for the consistency of abstraction principles with limited amounts of comprehension (Theorem 3.5). As an application, we resolve an analogue of the joint consistency problem in the predicative setting.
A RAMSEY THEOREM ON SEMIGROUPS AND A GENERAL VAN DER CORPUT LEMMA
Authors: TSERUNYAN ANUSH
Published: June 2016

A major theme in arithmetic combinatorics is proving multiple recurrence results on semigroups (such as Szemerédi’s theorem) and this can often be done using methods of ergodic Ramsey theory. What usually lies at the heart of such proofs is that, for actions of semigroups, a certain kind of one recurrence (mixing along a filter) amplifies itself to multiple recurrence. This amplification is proved using a so-called van der Corput difference lemma for a suitable filter on the semigroup. Particular instances of this lemma (for concrete filters) have been proven before (by Furstenberg, Bergelson–McCutcheon, and others), with a somewhat different proof in each case. We define a notion of differentiation for subsets of semigroups and isolate the class of filters that respect this notion. The filters in this class (call them ∂-filters) include all those for which the van der Corput lemma was known, and our main result is a van der Corput lemma for ∂-filters, which thus generalizes all its previous instances. This is done via proving a Ramsey theorem for graphs on the semigroup with edges between the semigroup elements labeled by their ratios.
INDEFINITENESS IN SEMI-INTUITIONISTIC SET THEORIES: ON A CONJECTURE OF FEFERMAN
Authors: RATHJEN MICHAEL
Published: June 2016

The paper proves a conjecture of Solomon Feferman concerning the indefiniteness of the continuum hypothesis relative to a semi-intuitionistic set theory.
QUANTUM LOGIC ASSOCIATED TO FINITE DIMENSIONAL INTERVALS OF MODULAR ORTHOLATTICES
Authors: GIUNTINI R. , FREYTES H. , SERGIOLI G.
Published: June 2016

In this work we study an abstract formulation of a problem posed by J.M. Dunn, T.J. Hagge et al. about the inclusion of varieties generated by the modular ortholattice of subspaces of ℂn. We shall prove that, this abstract formulation is equivalent to the direct irreducibility for atomic complete modular ortholattices.
Validation of annulus formation and growth estimation of South Atlantic swordfish
Authors: Garcia Alexandra , Tserpes George , Santos Miguel Neves
Published: June 2016

Swordfish (Xiphias gladius) is heavily exploited in the Atlantic Ocean by several European fleets and age and growth studies are essential for the accomplishment of the stock assessments carried out by ICCAT. The present study aims to validate the periodicity of growth increments on swordfish fin spines and provide first estimates of the growth parameters of South Atlantic swordfish. A total of 502 (231 males and 271 females) spine samples were collected from swordfish specimens onboard commercial longline vessels, from 2006 to 2009. Estimated ages ranged between 0 and 12 years, with age groups 3 and 4 dominating the samples. Marginal increment analysis suggested that growth bands were deposited annually in mid-spring. Fitted standard von Bertalanffy growth parameters (sexes combined) were L∞ = 317.133, k = 0.085 and t0 = −2.488. Minor, but insignificant, growth differences were observed between sexes.
The Attalid victory at Magnesia on a lost plaque from Pergamon
Authors: Taylor Michael J.
Published: June 2016

This article explores the battle scene on a small bronze plaque recovered during the 19th-century excavation of Pergamon, initially published in 1913 and subsequently lost. It argues that the most likely identification of the scene is the Battle of Magnesia, fought in 190 BC. The scene features Attalid cavalry riding to the rescue of distressed Roman legionaries, both fighting in opposition to Antiochus the Great's heavy phalanx and Gallic cavalry. The heroics of the Attalid cavalry are central to the scene, and likely reflect a courtly narrative that gave Eumenes II and his small contingent outsized credit for the joint victory.
New inscriptions from the Choria Considiana: Çalçak Roman necropolis
Authors: Güney Hale
Published: June 2016

This paper presents the initial results of an epigraphic survey of a Roman imperial estate, carried out in 2014 in northern Choria Considiana, today encompassing the area of Mihalıççık in Eskişehir, located between the Sakarya (Sangarios) river to the north and the Porsuk (Tembris) river to the south. The paper focuses on ten funerary inscriptions found in situ in the Çalçak Roman necropolis, 4km distant from Dinek village in Mihalıççık. All these inscriptions, found on the northern edge of the Choria Considiana, contain information relating to the social and economic status of the inhabitants of the estate, and also offer evidence about stone quarries and stonemasonry in the region. The paper begins with a presentation of the historical geography of the region, and then evaluates the new inscriptions against the existing evidence about the Choria Considiana with reference to the social and economic infrastructure of the area; important questions about the social, economic and cultural life of the region are posed. The article concludes with a catalogue of the inscriptions.
Pagan angels in Roman Asia Minor: revisiting the epigraphic evidence
Authors: Horsley G.H.R. , Luxford Jean M.
Published: June 2016

Franz Cumont's influential article on pagan angels in Revue de l’histoire des religions, published just over a century ago in 1915, remains the point de départ for work on that subject. The present essay offers a brief evaluation of some of its features, and then concentrates on Greek epigraphic evidence from Asia Minor in the Roman imperial period. Most of these texts were not published when Cumont wrote, or else he treated them briefly since his focus lay largely on ancient philosophical discussions about angeloi by both insiders and outsiders to the Christian movement; and geographically he ranged more widely than we have chosen to do. The main aim of the present essay, however, is to test the widely-accepted hypothesis of A.R.R. Sheppard (1980/1981) that Jewish influence on pagan notions of angeloi is visible in these inscriptions even though that influence was applied by non-Jews in a confused manner.
A late antique ceramic workshop complex: evidence for workshop organisation at Sagalassos (southwest Turkey)
Authors: Murphy Elizabeth A. , Poblome Jeroen
Published: June 2016

Sites of ceramic production have been discovered throughout the area that was once the Roman Empire; as a result, it is becoming increasingly clear that this industry was, in the Roman and late antique worlds, organised in numerous ways. In consideration of the organisational diversity in ceramic production attested during the period, this article presents some of the findings from the excavations of a late antique complex of ceramic workshops at the site of Sagalassos in order to consider archaeological evidence in terms of, not only the organisation of the manufacturing process, but also structures of workshop decision-making. Several lines of archaeological evidence are outlined, and argue for a model of independent work units integrated into a larger organisational structure of decision-making, and possibly even ownership, across the complex. In addition, the motivation to invest in a multi-workshop complex during the late antique period at Sagalassos is contextualised within the wider history of local and regional economic development.
Perpetual decline or persistent dominance? Uncovering Anglo-America’s true structural power in global finance
Authors: Fichtner Jan
Published: June 2016

The prediction of America’s decline is a regularly recurring phenomenon; this also pertains to the pivotal field of global finance. This article argues that, first we have to consider the United States together with the other Anglophone countries. The English-speaking countries and territories – Anglo-America – have deep common political and socioeconomic roots, of which the unique global Five Eyes intelligence cooperation is merely one manifestation. In finance, New York and London (NY-LON) constitute the decision-making core of this transnational formation. Second, to analyse the highly complex phenomenon of structural power in the globalised international political economy we have to dig deeper to uncover truly meaningful data. Thus, this article evaluates data for nine central segments of global finance from around the year 2000 to 2014. Contrary to the assertions of many declinists, these data show that Anglo-America’s dominant structural power has been persistent during this period. Moreover, four novel visualisations show that the US-UK axis is the fulcrum of the international financial system. However, contemporary global finance is characterised by a high degree of latent fragility; significant imbalances, inequalities and contradictions persist and are even likely to grow, potentially undermining the legitimacy and the stability of the whole system.
Exploring Past Ontologies: Bodies, Jugs and Figurines from the Phoenician-Punic Western Mediterranean
Authors: López-Bertran Mireia
Published: June 2016

This paper focuses on ideas of body construction in the Phoenician-Punic western Mediterranean. I concentrate on the study of ‘bottle-shaped’ terracottas and examine their connections with anthropomorphized and zoomorphic jugs and the bottle-shaped idol, a symbol engraved on the stelae of tophets. Exploring the Phoenician-Punic isomorphism between jugs, figurines and bodies introduces us to the study of the creation of a specific body world in terms of fluids: a world in which bodies were perceived as containers of liquids. I argue that this way of defining bodies is materialized in the figurines in two ways: first, via the transformation of the body into a bottle-shaped form, and second, via the emphasis on representing mouths, noses, breasts or genitalia, all parts of the body through which fluids circulate. I also examine the social and ritual contexts of the figurines and discuss issues of personhood and relational identities.
The use of psychiatric services by young adults who came to Sweden as teenage refugees: a national cohort study
Authors: Manhica H. , Almquist Y. , Rostila M. , Hjern A.
Published: June 2016

Aims.

To investigate the patterns of use of different forms of psychiatric care in refugees who settled in Sweden as teenagers.

Method.

Cox proportional hazards models were used to estimate the use of different forms of psychiatric care from 2009 to 2012 in a population of 35 457 refugees, aged from 20 to 36, who had settled in Sweden as teenagers between 1989 and 2004. These findings were compared with 1.26 million peers from the same birth cohorts in the general Swedish population.

Results.

Unaccompanied and accompanied refugees were more likely to experience compulsory admission to a psychiatric hospital compared with the native Swedish population, with hazard ratios (HRs) of 2.76 (1.86–4.10) and 1.89 (1.53–2.34), respectively, as well as psychiatric inpatient care, with HRs of 1.62 (1.34–1.94) and 1.37 (1.25–1.50). Outpatient care visits by the young refugees were similar to the native Swedish population. The longer the refugees had residency in Sweden, the more they used outpatient psychiatric care. Refugees born in the Horn of Africa and Iran were most likely to undergo compulsory admission, with HRs of 3.98 (2.12–7.46) and 3.07 (1.52–6.19), respectively. They were also the groups who were most likely to receive inpatient care, with HRs of 1.55 (1.17–2.06) and 1.84 (1.37–2.47), respectively. Our results also indicated that the use of psychiatric care services increased with the level of education in the refugee population, while the opposite was true for the native Swedish population. In fact, the risks of compulsory admissions were particularly higher among refugees who had received a secondary education, compared with native Swedish residents, with HRs of 4.72 (3.06–7.29) for unaccompanied refugees and 2.04 (1.51–2.73) for accompanied refugees.

Conclusions.

Young refugees received more psychiatric inpatient care than the native Swedish population, with the highest rates seen in refugees who were not accompanied by their parents. The discrepancy between the use of inpatient and outpatient care by young refugees suggests that there are barriers to outpatient care, but we did note that living in Sweden longer increased the use of outpatient services. Further research is needed to clarify the role that education levels among Sweden's refugee populations have on their mental health and health-seeking behaviour.
The Water World of the Orang Suku Laut in Southeast Asia
Authors: Chou Cynthia
Published: June 2016

This article explores how the Orang Suku Laut, an indigenous Malay roving fishing community, perceives the water world in Southeast Asia. Their rites of childbirth, naming and the enculturation of their young present invaluable ethnographic data that challenge us to develop new ways to conceptualise ‘water spaces’ as well as to widen our academic inquiry into the less understood ways of spatial imaginings.
Eyjafjallajökull Gave Lava and Ice Researchers an Eyeful
Authors: Deatrick Elizabeth
Published: June 2016

New insights from the 2010 eruption may help volcanologists determine how glaciers shaped ancient lava flows.
Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer
Authors: Chiorean E Gabriela , Von Hoff Daniel D , Tabernero Josep , El-Maraghi Robert , Ma Wen Wee , Reni Michele , Harris Marion , Whorf Robert , Liu Helen , Li Jack Shiansong , Manax Victoria , Romano Alfredo , Lu Brian , Goldstein David
Published: June 2016

Background:

This exploratory analysis evaluated second-line (2L) therapy for metastatic pancreatic cancer in a large phase 3 trial (MPACT).

Methods:

Patients who received first-line (1L) nab-paclitaxel+gemcitabine (nab-P+Gem) or Gem were assessed for survival based on 2L treatment received. Multivariate analyses tested influence of treatment effect and prognostic factors on survival.

Results:

The majority of 2L treatments (267 out of 347, 77%) contained a fluoropyrimidine (5-fluorouracil or capecitabine). Median total survival (1L randomisation to death) for patients who received 2L treatment after 1L nab-P+Gem vs Gem alone was 12.8 vs 9.9 months (P=0.015). Median total survival for patients with a fluoropyrimidine-containing 2L therapy after nab-P+Gem vs Gem was 13.5 vs 9.5 months (P=0.012). Median 2L survival (duration from start of 2L therapy to death) was 5.3 vs 4.5 months for nab-P+Gem vs Gem, respectively (P=0.886). Factors significantly associated with longer post-1L survival by multivariate analyses included 1L nab-P+Gem, receiving 2L treatment, longer 1L progression-free survival, and Karnofsky performance status⩾70 and neutrophil-to-lymphocyte ratio⩽5 at the end of 1L treatment.

Conclusions:

These findings support the use of 2L therapy for patients with metastatic pancreatic cancer. Fluoropyrimidine-containing treatment after 1L nab-P+Gem is an active regimen with significant clinical effect.
Droplet barcoding for massively parallel single-molecule deep sequencing
Authors: Lan Freeman , Haliburton John R. , Yuan Aaron , Abate Adam R.
Published: June 2016

The ability to accurately sequence long DNA molecules is important across biology, but existing sequencers are limited in read length and accuracy. Here, we demonstrate a method to leverage short-read sequencing to obtain long and accurate reads. Using droplet microfluidics, we isolate, amplify, fragment and barcode single DNA molecules in aqueous picolitre droplets, allowing the full-length molecules to be sequenced with multi-fold coverage using short-read sequencing. We show that this approach can provide accurate sequences of up to 10 kb, allowing us to identify rare mutations below the detection limit of conventional sequencing and directly link them into haplotypes. This barcoding methodology can be a powerful tool in sequencing heterogeneous populations such as viruses.
Surface engineering of hierarchical platinum-cobalt nanowires for efficient electrocatalysis
Authors: Bu Lingzheng , Guo Shaojun , Zhang Xu , Shen Xuan , Su Dong , Lu Gang , Zhu Xing , Yao Jianlin , Guo Jun , Huang Xiaoqing
Published: June 2016

Despite intense research in past decades, the lack of high-performance catalysts for fuel cell reactions remains a challenge in realizing fuel cell technologies for transportation applications. Here we report a facile strategy for synthesizing hierarchical platinum-cobalt nanowires with high-index, platinum-rich facets and ordered intermetallic structure. These structural features enable unprecedented performance for the oxygen reduction and alcohol oxidation reactions. The specific/mass activities of the platinum-cobalt nanowires for oxygen reduction reaction are 39.6/33.7 times higher than commercial Pt/C catalyst, respectively. Density functional theory simulations reveal that the active threefold hollow sites on the platinum-rich high-index facets provide an additional factor in enhancing oxygen reduction reaction activities. The nanowires are stable in the electrochemical conditions and also thermally stable. This work may represent a key step towards scalable production of high-performance platinum-based nanowires for applications in catalysis and energy conversion.
Finite particle size drives defect-mediated domain structures in strongly confined colloidal liquid crystals
Authors: Gârlea Ioana C. , Mulder Pieter , Alvarado José , Dammone Oliver , Aarts Dirk G. A. L. , Lettinga M. Pavlik , Koenderink Gijsje H. , Mulder Bela M.
Published: June 2016

When liquid crystals are confined to finite volumes, the competition between the surface anchoring imposed by the boundaries and the intrinsic orientational symmetry-breaking of these materials gives rise to a host of intriguing phenomena involving topological defect structures. For synthetic molecular mesogens, like the ones used in liquid-crystal displays, these defect structures are independent of the size of the molecules and well described by continuum theories. In contrast, colloidal systems such as carbon nanotubes and biopolymers have micron-sized lengths, so continuum descriptions are expected to break down under strong confinement conditions. Here, we show, by a combination of computer simulations and experiments with virus particles in tailor-made disk- and annulus-shaped microchambers, that strong confinement of colloidal liquid crystals leads to novel defect-stabilized symmetrical domain structures. These finite-size effects point to a potential for designing optically active microstructures, exploiting the as yet unexplored regime of highly confined liquid crystals.
Th17/Treg Imbalance Induced by Dietary Salt Variation Indicates Inflammation of Target Organs in Humans
Authors: Luo Tao , Ji Wen-jie , Yuan Fei , Guo Zhao-zeng , Li Yun-xiao , Dong Yan , Ma Yong-qiang , Zhou Xin , Li Yu-ming
Published: June 2016

The functions of T helper 17 (Th17) and regulatory T (Treg) cells are tightly orchestrated through independent differentiation pathways that are involved in the secretion of pro- and anti-inflammatory cytokines induced by high-salt dietary. However, the role of imbalanced Th17/Treg ratio implicated in inflammation and target organ damage remains elusive. Here, by flow cytometry analysis, we demonstrated that switching to a high-salt diet resulted in decreased Th17 cells and reciprocally increased Treg cells, leading to a decreased Th17/Treg ratio. Meanwhile, Th17-related pathway was down-regulated after one day of high salt loading, with the increase in high salt loading as shown by microarray and RT-PCR. Subsequently, blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) observed hypoxia in the renal medulla (increased R2* signal) during high-salt loading, which was regressed to its baseline level in a step-down fashion during low-salt feeding. The flow-mediated vasodilatation (FMD) of the branchial artery was significantly higher on the first day of high salt loading. Collectively, these observations indicate that a short-term increase in dietary salt intake could induce reciprocal switches in Th17/Treg ratio and related cytokines, which might be the underlying cellular mechanism of high-salt dietary induced end organ inflammation and potential atherosclerotic risk.
Propylene/propane permeation properties of ethyl cellulose (EC) mixed matrix membranes fabricated by incorporation of nanoporous graphene nanosheets
Authors: Yuan Bingbing , Sun Haixiang , Wang Tao , Xu Yanyan , Li Peng , Kong Ying , Niu Q. Jason
Published: June 2016

Nanopore containing graphene nanosheets were synthesized by graphene oxide and a reducing agent using a facile hydrothermal treatment in sodium hydroxide media. The as-prepared nanoporous graphene was incorporated into ethyl cellulose (EC) to prepare the mixed matrix membranes (MMMs) for C3H6/C3H8 separation. Transmission electron microscopy (TEM) photograph and X-ray photoelectron spectroscopy (XPS) analysis of nanoporous graphene nanosheets indicated that the structure of nano-pore was irregular and the oxygen-containing groups in the surface were limited. More importantly, the as-prepared MMMs presented better separation performance than that of pristine EC membrane due to simultaneous enhancement of C3H6 permeability and ideal selectivity. The ideal selectivity of the MMMs with 1.125 wt‰ nanoporous graphene content for C3H6/C3H8 increased from 3.45 to 10.42 and the permeability of C3H6 increased from 57.9 Barrer to 89.95 Barrer as compared with the pristine membrane. The presumed facilitated mechanism was that the high specific surface area of nanoporous graphene in polymer matrix increased the length of the tortuous pathway formed by nanopores for the gas diffusion as compared with the pristine graphene nanosheets, and generated a rigidified interface between the EC chains and fillers, thus enhanced the diffusivity selectivity. Therefore, it is expected that nanoporous graphene would be effective material for the C3H6/C3H8 separation.
Enlarged colitogenic T cell population paradoxically supports colitis prevention through the B-lymphocyte-dependent peripheral generation of CD4+Foxp3+ Treg cells
Authors: do Canto Fábio Barrozo , Campos Sylvia Maria Nicolau , Granato Alessandra , da Silva Rafael F. , de Paiva Luciana Souza , Nóbrega Alberto , Bellio Maria , Fucs Rita
Published: June 2016

Intestinal inflammation can be induced by the reconstitution of T/B cell-deficient mice with low numbers of CD4+ T lymphocytes depleted of CD25+Foxp3+ regulatory T cells (Treg). Using RAG-knockout mice as recipients of either splenocytes exclusively depleted of CD25+ cells or FACS-purified CD4+CD25−Foxp3− T cells, we found that the augmentation of potentially colitogenic naïve T cell numbers in the inoculum was unexpectedly beneficial for the suppression of colon disease and maintenance of immune homeostasis. Protection against T cell-mediated colitis correlated with a significant increment in the frequency of peripherally-induced CD4+CD25+Foxp3+ T (pTreg) cells, especially in the mesenteric lymph nodes, an effect that required the presence of B cells and CD4+CD25−Foxp3+ cells in physiological proportions. Our findings support a model whereby the interplay between B lymphocytes and a diversified naïve T cell repertoire is critical for the generation of CD4+CD25+Foxp3+ pTreg cells and colitis suppression.
Expression and purification of the modification-dependent restriction enzyme BisI and its homologous enzymes
Authors: Xu Shuang-yong , Klein Pernelle , Degtyarev Sergey Kh. , Roberts Richard J.
Published: June 2016

The methylation-dependent restriction endonuclease (REase) BisI (Gm5C ↓ NGC) is found in Bacillus subtilis T30. We expressed and purified the BisI endonuclease and 34 BisI homologs identified in bacterial genomes. 23 of these BisI homologs are active based on digestion of m5C-modified substrates. Two major specificities were found among these BisI family enzymes: Group I enzymes cut GCNGC containing two to four m5C in the two strands, or hemi-methylated sites containing two m5C in one strand; Group II enzymes only cut GCNGC sites containing three to four m5C, while one enzyme requires all four cytosines to be modified for cleavage. Another homolog, Esp638I cleaves GCS ↓ SGC (relaxed specificity RCN ↓ NGY, containing at least four m5C). Two BisI homologs show degenerate specificity cleaving unmodified DNA. Many homologs are small proteins ranging from 150 to 190 amino acid (aa) residues, but some homologs associated with mobile genetic elements are larger and contain an extra C-terminal domain. More than 156 BisI homologs are found in >60 bacterial genera, indicating that these enzymes are widespread in bacteria. They may play an important biological function in restricting pre-modified phage DNA.
Tsunami-generated magnetic fields may constrain focal mechanisms of earthquakes
Authors: Kawashima Issei , Toh Hiroaki
Published: June 2016

A geomagnetic observatory named SFEMS is being operated on the deep seafloor in the northwest Pacific since August, 2001. SFEMS is capable of measuring both scalar and vector geomagnetic fields as well as the seafloor instrument’s precise attitudes, which makes it a powerful tool in detecting the so-called oceanic dynamo effect. It was found that SFEMS captured clear magnetic signals generated by the giant tsunamis of the 2011 Tohoku Earthquake even for an epicentral distance of larger than 1500 km. Here we report estimates of the focal mechanism of a closer tsunamigenic earthquake in January, 2007 on the seaward slope of the Kuril Trench using tsunami-generated variations in the observed downward magnetic component. Three-dimensional solutions of the tsunami-generated magnetic components were calculated by a new numerical code based on non-uniform thin-sheet approximation and particle motions of seawater using the linear Boussinesq approximation. As a result, a southeast dipping fault alone reproduced the dispersive nature of the downward magnetic component, while any northwest dipping faults could not. This implies that the tsunami-generated electromagnetic fields are useful for determination of focal mechanisms of tsunamigenic earthquakes, since fault dips are one of the most difficult source parameters to estimate even in modern seismology.
Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels
Authors: Liu Dong-Dong , Lu Jun-Mei , Zhao Qian-Ru , Hu Changlong , Mei Yan-Ai
Published: June 2016

Growth differentiation factor-15 (GDF-15) has been implicated in ischemic brain injury and synapse development, but its involvement in modulating neuronal excitability and synaptic transmission remain poorly understood. In this study, we investigated the effects of GDF-15 on non-evoked miniature excitatory post-synaptic currents (mEPSCs) and neurotransmitter release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with GDF-15 for 60 min significantly increased the frequency of mEPSCs without effect on their amplitude. GDF-15 also significantly elevated presynaptic glutamate release, as shown by HPLC. These effects were blocked by dual TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII) antagonists, but not by a TβRI antagonist alone. Meanwhile, GDF-15 enhanced pERK level and inhibition of MAPK/ERK activity attenuated the GDF-15-induced increases in mEPSC and glutamate release. Blocking T-type calcium channels reduced the GDF-15 induced up-regulation of synaptic transmission. Membrane-protein extraction and use of an intracellular protein-transport inhibitor showed that GDF-15 promoted CaV3.1 and CaV3.3 α-subunit expression by trafficking to the membrane. These results confirm previous findings in cerebellar granule neurons, in which GDF-15 induces its neurobiological effects via TβRII and activation of the ERK pathway, providing novel insights into the mechanism of GDF-15 function in cortical neurons.
The dynamics of the HIV epidemic among men who have sex with men (MSM) from 2005 to 2012 in Shenzhen, China
Authors: Zhao Jin , Chen Lin , Chaillon Antoine , Zheng Chenli , Cai Wende , Yang Zhengrong , Li Guilian , Gan Yongxia , Wang Xiaohui , Hu Yihong , Zhong Ping , Zhang Chiyu , Smith Davey M.
Published: June 2016

HIV-1 epidemics among MSM are a major public health concern in China, especially in large cities. This study sought to better understand the dynamics of HIV molecular epidemiology among MSM in Shenzhen, a rapidly developing city with over 13.8 million people. HIV-1 pol sequences were obtained from 996 (53.5%) of 1862 HIV-infected MSM and 403(9.0%) of 4498 heterosexuals and injection drug users in Shenzhen, China from 2005-2012. Eight HIV-1 subtypes and some inter-subtype recombinants were identified among sampled MSM with CRF07_BC (39.1%) and CRF01_AE (35.1%) being the most predominant. From 2006 to 2012, the prevalence of CRF07_BC and CRF55_01B rapidly increased, while the prevalence of subtypes B and CRF01_AE gradually decreased. The genetic distances within CRF07_BC and CRF55_01B groups were significantly lower than within CRF01_AE and B groups. The vast majority (90.3%) of HIV-1 infected MSM in Shenzhen were migrants who came from 31 of the 34 provinces of China and these migrants had significantly different HIV-1 subtype distributions from the local MSM. This study highlighted the importance of CRF07_BC and migrants in the changing HIV epidemic among MSM in China and provides a molecular epidemiology framework for understanding how HIV-1 epidemics can change in large cities with diverse risk groups.
Urinary albumin-to-creatinine ratio is associated with endothelial dysfunction in HIV-infected patients receiving antiretroviral therapy
Authors: Pirro Matteo , Mannarino Massimo R. , Francisci Daniela , Schiaroli Elisabetta , Bianconi Vanessa , Bagaglia Francesco , Sahebkar Amirhossein , Mannarino Elmo , Baldelli Franco
Published: June 2016

Endothelial dysfunction, a marker of cardiovascular (CV) risk, is common in human immunodeficiency virus (HIV)-infected patients. Microalbuminuria is frequent in HIV-infected patients and is a predictor of renal impairment and CV risk. We investigated the association between microalbuminuria and endothelial dysfunction among HIV-infected patients receiving highly-active antiretroviral therapy (HAART). Endothelial function, measured by brachial artery flow-mediated dilatation (bFMD) and urine albumin-to-creatinine ratio (UACR), were measured in 170 HAART-treated HIV-infected adults. The relationship between UACR and bFMD was evaluated. The prevalence of increased UACR, defined by two cut-off levels (20 mg/g and 30 mg/g), was 29% and 17%. UACR was significantly higher while bFMD was lower among patients with metabolic syndrome (MS). UACR was associated with bFMD (r = −0.31; p < 0.001). This association was stronger in MS-patients (r = −0.44; p = 0.003). UACR above 20 mg/g was associated with an increased risk (OR 2.37, 95% CI 1.15–4.89, p = 0.020) of severely impaired bFMD (bFMD ≤ 2.1%). Patients with MS and increased UACR had the lowest bFMD compared with those with none or one of the two conditions. Microalbuminuria and endothelial dysfunction are positively associated in HIV-infected patients regardless of known confounders. The coexistence of microalbuminuria and MS amplifies their deleterious influence on endothelial function.
Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies
Authors: Tiwari Amit , Bahr Angela , Bähr Luzy , Fleischhauer Johannes , Zinkernagel Martin S. , Winkler Niklas , Barthelmes Daniel , Berger Lieselotte , Gerth-Kahlert Christina , Neidhardt John , Berger Wolfgang
Published: June 2016

Inherited monogenic diseases of the retina and vitreous affect approximately 1 in 2000 individuals. They are characterized by tremendous genetic heterogeneity and clinical variability involving mutations in approximately 250 genes and more than 20 different clinical phenotypes. Clinical manifestations of retinal dystrophies (RDs) range from mild retinal dysfunctions to severe congenital forms of blindness. A detailed clinical diagnosis and the identification of causative mutations are crucial for genetic counseling of affected patients and their families, for understanding genotype-phenotype correlations and developing therapeutic approaches. Using whole exome sequencing (WES) we have established a reliable and efficient high-throughput analysis pipeline to identify disease-causing mutations. Our data indicate that this approach enables us to genetically diagnose approximately 64% of the patients (n = 58) with variant(s) in known disease-associated genes. We report 20 novel and 26 recurrent variants in genes associated with RDs. We also identified a novel phenotype for mutations in C2orf71 and provide functional evidence for exon skipping due to a splice-site variant identified in FLVCR1. In conclusion, WES can rapidly identify variants in various families affected with different forms of RDs. Our study also expands the clinical and allelic spectrum of genes associated with RDs in the Swiss population.
Molecular characterization of woodchuck IFI16 and AIM2 and their expression in woodchucks infected with woodchuck hepatitis virus (WHV)
Authors: Yan Qi , Li Mengmeng , Liu Qin , Li Fanghui , Zhu Bin , Wang Junzhong , Lu Yinping , Liu Jia , Wu Jun , Zheng Xin , Lu Mengji , Wang Baoju , Yang Dongliang
Published: June 2016

IFI16 and AIM2 are important DNA sensors in antiviral immunity. To characterize these two molecules in a woodchuck model, which is widely used to study hepatitis B virus (HBV) infection, we cloned and analyzed the complete coding sequences (CDSs) of woodchuck IFI16 and AIM2 and found that AIM2 was highly conserved in mammals, whereas the degree of sequence identity between woodchuck IFI16 and its mammalian orthologues was low. IFI16 and IFN-β were upregulated following VACV ds 70 mer transfection, while AIM2 and IL-1β were upregulated following poly (dA:dT) transfection, both in vitro and in vivo; IFI16-targeted siRNA decreased the transcription of IFI16 and IFN-β stimulated by VACV ds 70 mer and AIM2 siRNA interference downregulated AIM2 and IL-1β transcripts stimulated by poly (dA:dT), in vitro, suggesting that woodchuck IFI16 and AIM2 may play pivotal roles in the DNA-mediated induction of IFN-β and IL-1β, respectively. IFI16 and AIM2 transcripts were upregulated in the liver and spleen following acute WHV infection, while IFI16 was downregulated in the liver following chronic infection, implying that IFI16 and AIM2 may be involved in WHV infection. These data provide the basis for the study of IFI16- and AIM2-mediated innate immunity using the woodchuck model.
Projected asymmetric response of Adélie penguins to Antarctic climate change
Authors: Cimino Megan A. , Lynch Heather J. , Saba Vincent S. , Oliver Matthew J.
Published: June 2016

The contribution of climate change to shifts in a species’ geographic distribution is a critical and often unresolved ecological question. Climate change in Antarctica is asymmetric, with cooling in parts of the continent and warming along the West Antarctic Peninsula (WAP). The Adélie penguin (Pygoscelis adeliae) is a circumpolar meso-predator exposed to the full range of Antarctic climate and is undergoing dramatic population shifts coincident with climate change. We used true presence-absence data on Adélie penguin breeding colonies to estimate past and future changes in habitat suitability during the chick-rearing period based on historic satellite observations and future climate model projections. During the contemporary period, declining Adélie penguin populations experienced more years with warm sea surface temperature compared to populations that are increasing. Based on this relationship, we project that one-third of current Adélie penguin colonies, representing ~20% of their current population, may be in decline by 2060. However, climate model projections suggest refugia may exist in continental Antarctica beyond 2099, buffering species-wide declines. Climate change impacts on penguins in the Antarctic will likely be highly site specific based on regional climate trends, and a southward contraction in the range of Adélie penguins is likely over the next century.
Evolutionary inactivation of a sialidase in group B Streptococcus
Authors: Yamaguchi Masaya , Hirose Yujiro , Nakata Masanobu , Uchiyama Satoshi , Yamaguchi Yuka , Goto Kana , Sumitomo Tomoko , Lewis Amanda L. , Kawabata Shigetada , Nizet Victor
Published: June 2016

Group B Streptococcus (GBS) is a leading cause of bacterial sepsis and meningitis in newborns. GBS possesses a protein with homology to the pneumococcal virulence factor, NanA, which has neuraminidase (sialidase) activity and promotes blood-brain barrier penetration. However, phylogenetic sequence and enzymatic analyses indicate the GBS NanA ortholog has lost sialidase function – and for this distinction we designate the gene and encoded protein nonA/NonA. Here we analyze NonA function in GBS pathogenesis, and through heterologous expression of active pneumococcal NanA in GBS, potential costs of maintaining sialidase function. GBS wild-type and ΔnonA strains lack sialidase activity, but forced expression of pneumococcal NanA in GBS induced degradation of the terminal sialic acid on its exopolysaccharide capsule. Deletion of nonA did not change GBS-whole blood survival or brain microvascular cell invasion. However, forced expression of pneumococcal NanA in GBS removed terminal sialic acid residues from the bacterial capsule, restricting bacterial proliferation in human blood and in vivo upon mouse infection. GBS expressing pneumococcal NanA had increased invasion of human brain microvascular endothelial cells. Thus, we hypothesize that nonA lost enzyme activity allowing the preservation of an effective survival factor, the sialylated exopolysaccharide capsule.