bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Prediction Models for Colorectal Cancer Patients After Curative Resection
Authors: Miyoshi Norikatsu , Ohue Masayuki , Noura Shingo , Yasui Masayoshi , Sugimura Keijiro , Tomokuni Akira , Akita Hirofumi , Kobayashi Shogo , Takahashi Hidenori , Omori Takeshi , Fujiwara Yoshiyuki , Yano Masahiko
Published: November 2016

To develop a prediction tool for recurrence and survival in colorectal cancer (CRC) patients following surgically curative resections. We developed a reliable prediction model for CRC patients after surgically curative resections. Using clinicopathologic factors, novel prediction models were constructed with the area under the curve (AUC) of 0.841 and 0.876 for DFS and CSS, respectively. Between January 2004 and December 2007, 376 CRC patients were investigated at the Osaka Medical Center for Cancer and Cardiovascular Diseases. Patients with at least 1 of the following criteria were excluded: preoperative treatment, synchronous distant metastasis, noncurative resection, and incomplete follow-up after operation. All patients were retrospectively analyzed. A Cox proportional hazards model was used to develop a prediction model for disease-free survival (DFS) and cancer-specific survival (CSS). In univariate and multivariate analyses of clinicopathologic factors, the following factors had significant correlation with DFS and CSS: tumor location, preoperative serum carcinoembryonic antigen (CEA), pathologically defined tumor invasion, and lymph node metastasis. Using these variables, novel prediction models were constructed by the logistic regression model with AUC of 0.840 and 0.876 for DFS and CSS, respectively. The prediction models were validated by external datasets in an independent patient group. This study showed novel and reliable personalized prognostic models, integrating not only TNM factors but also tumor location and preoperative serum CEA to predict patient prognosis. These individualized prediction models could help clinicians in the treatment of postoperative CRC patients.
Visibility deterioration and hygroscopic growth of biomass burning aerosols over a tropical coastal city: a case study over Singapore's airport
Authors: Lee Shao‐Yi , Gan Christopher , Chew Boon Ning
Published: November 2016

Biomass burning in the Maritime Continent frequently results in region‐wide haze pollution, causing concerns for aviation and maritime navigation. Indonesian peat smoke is high in sulfates and water soluble organic carbon, and we show that in Singapore, particle hygroscopic growth results in a strongly non‐linear relationship between visibility and aerosol concentration under humid conditions. Thus, even for a tropical coastal city, the consideration of ambient relative humidity is desirable when forecasting for visibility deterioration caused by haze aerosols.
Identifying the Active Sites on N‐doped Graphene toward Oxygen Evolution Reaction
Authors: Kong Xiangkai , Liu Qiangchun , Chen Debao , Chen Guilin
Published: November 2016

Identifying and generating more active sites with high activity on N‐doped graphene for oxygen evolution reaction (OER) are challenging in the renewable energy conversion and storage technologies. However, the local electronic/chemical environment on graphene surface is significantly influenced and can be controlled by doping with foreign atoms, which will contribute to its improved catalytic performance. Henceforth, different N‐doping formats, diverse N distributions and concentrations, as well as the edge effect are investigated on the basis of density functional theory, to discover the ideal N‐doping condition for high OER behavior. By analyzing the free‐energy‐change diagrams, adsorbed interactions of reactant intermediates, electrostatic potential surfaces, and other obtained data, it is suggested that graphitic N with low doping concentration and N atoms distributed near edge sites is the ideal candidate for high OER activity, which is efficient as a carbon‐based electrocatalyst for water splitting and metal–air batteries applications.
Assessing variation across 8 established East Asian loci for type 2 diabetes mellitus in American Indians: Suggestive evidence for new sex‐specific diabetes signals in GLIS3 and ZFAND3
Authors: Muller Yunhua L. , Piaggi Paolo , Chen Peng , Wiessner Gregory , Okani Chidinma , Kobes Sayuko , Knowler William C. , Bogardus Clifton , Hanson Robert L. , Baier Leslie J.
Published: November 2016

Background

Eight new loci for type 2 diabetes mellitus (T2DM) were identified in an East Asian genome‐wide association study meta‐analysis. We assess tag SNPs across these loci for associations with T2DM in American Indians.

Methods

A total of 435 SNPs that tag (R2 ≥ .85) common variation across the 8 loci were analyzed for association with T2DM (n = 7710), early onset T2DM (n = 1060), body mass index (n = 6839), insulin sensitivity (n = 555), and insulin secretion (n = 298).

Results

Tag SNPs within FITM2‐R3HDML‐HNF4A, GLIS3, KCNK16, and ZFAND3 associated with T2DM after accounting for locus‐wide multiple testing. The T2DM association in FITM2‐R3HDML‐HNF4A (rs3212183; P = .0002; OR = 1.19 [1.09‐1.30]) was independent from the East Asian lead SNP (rs6017317), which did not associate with T2DM in American Indians. The top signals in GLIS3 (rs7875253; P = .0004; OR = 1.23 [1.10‐1.38]) and KCNK16 (rs1544050; P = .002; OR = 1.16 [1.06‐1.27]) were attenuated after adjustment for the East Asian lead SNPs (rs7041847 in GLIS3; rs1535500 in KCNK16), both of which also associated with T2DM in American Indians (P = .02; OR = 1.11 [1.01‐1.21]; P = .007; OR = 1.19 [1.05‐1.36] respectively). The top SNP in ZFAND3 (rs9470794; P = .002; OR = 1.43 [1.14‐1.80]) was the identical East Asian lead SNP. Additional SNPs in GLIS3 (rs180867004) and ZFAND3 (rs4714120 and rs9470701) had significant genotype × sex interactions (P ≤ .008). The GLIS3 SNP (rs180867004) associated with T2DM only in men (P = .00006, OR = 1.94 [1.40‐2.68]). The ZFAND3 SNPs (rs4714120 and rs9470701) associated with T2DM only in women (P = .0002, OR = 1.35 [1.16‐1.59]; P = .0003, OR = 1.37 [1.16‐1.63] respectively).

Conclusions

Replication of lead T2DM SNPs in GLIS3, KCNK16, and ZFAND3 was observed in American Indians. Sex‐specific T2DM signals in GLIS3 and ZFAND3, which are distinct from the East Asian GWAS signals, were also identified.
Evaluation of the LacZ reporter assay in cryopreserved primary hepatocytes for In vitro genotoxicity testing
Authors: Luijten Mirjam , Zwart Edwin P. , Dollé Martijn E.T. , de Pooter Maaike , Cox Julie A. , White Paul A. , van Benthem Jan
Published: November 2016

Assessment of genotoxic potential is an important step in the safety evaluation of chemical substances. Under most regulatory jurisdictions, the first tier of testing comprises a standard battery of in vitro genotoxicity tests in bacterial and mammalian cells. However, the mammalian cell tests commonly used exhibit a relatively high rate of misleading positive results, which may lead to unnecessary in vivo testing. We previously established a proof‐of‐concept for the LacZ reporter assay in proliferating primary hepatocytes as a promising alternative genotoxicity test. Here, cryopreserved instead of freshly isolated hepatocytes were used and the assay was evaluated in more detail. We examined the effect of cryopreservation on phenotype and metabolic capacity of the LacZ hepatocytes, and assessed the predictive performance of the assay by testing a set of substances comprising true positive, true negative, and misleading positive substances. Additionally, a historical negative control database was created and the type of mutations induced was analyzed for two of the substances tested. Our findings indicate that proliferating cryopreserved primary hepatocytes derived from LacZ plasmid mice retain their hepatocyte‐specific characteristics and metabolic competence. Furthermore, we demonstrate that both gene mutations and genome rearrangements due to large deletions can be detected with the LacZ reporter assay. The assay seems to have a lower rate of misleading positive test results compared to the assays currently used. Together, our findings strongly support the use of the LacZ reporter assay in cryopreserved primary hepatocytes as follow‐up to the standard in vitro test battery for genotoxicity testing. Environ. Mol. Mutagen. 57:643–655, 2016. © 2016 Wiley Periodicals, Inc.
The quest for best suited references for configuration interaction singles calculations of core excited states
Authors: Ehlert Christopher , Klamroth Tillmann
Published: November 2016

Near edge X‐ray absorption fine structure (NEXAFS) simulations based on the conventional configuration interaction singles (CIS) lead to excitation energies, which are systematically blue shifted. Using a (restricted) open shell core hole reference instead of the Hartree Fock (HF) ground state orbitals improves (Decleva et al., Chem. Phys., 1992, 168, 51) excitation energies and the shape of the spectra significantly. In this work, we systematically vary the underlying SCF approaches, that is, based on HF or density functional theory, to identify best suited reference orbitals using a series of small test molecules. We compare the energies of the K edges and NEXAFS spectra to experimental data. The main improvement compared to conventional CIS, that is, using HF ground state orbitals, is due to the electrostatic influence of the core hole. Different SCF approaches, density functionals, or the use of fractional occupations lead only to comparably small changes. Furthermore, to account for bigger systems, we adapt the core‐valence separation for our approach. We demonstrate that the good quality of the spectrum is not influenced by this approximation when used together with the non‐separated ground state wave function. Simultaneously, the computational demands are reduced remarkably. © 2016 Wiley Periodicals, Inc.
Noninvasive hepatic fibrosis staging using mr elastography: The usefulness of the bayesian prediction method
Authors: Ichikawa Shintaro , Motosugi Utaroh , Enomoto Nobuyuki , Matsuda Masanori , Onishi Hiroshi
Published: November 2016

Purpose

To evaluate the usefulness of the Bayesian method for hepatic fibrosis staging with magnetic resonance elastography (MRE).

Materials and Methods

The sample of this retrospective study comprised patients with chronic liver disease (n = 309), in whom histopathological fibrosis staging and MRE using either a 1.5T (n = 214) or a 3T magnetic resonance imaging (MRI) system (n = 95) had been performed. The optimal cutoff stiffness value was determined and used to calculate the discrimination ability of fibrosis staging by the cutoff method. The Bayesian method calculated post‐MRE probability of each fibrosis stage, yielding MRE‐based fibrosis staging without a cutoff value as well as the confidence of staging. We compared the discrimination ability in all patients and in a subgroup of patients with high (≥90%) posterior probability.

Results

The discrimination ability for hepatic fibrosis staging was comparable between the Bayesian method and the cutoff method in all patients because the accuracy of staging with the Bayesian method and the cutoff method in all patients was not different (P = 1.0000). However, in patients with high posterior probability by the Bayesian method, the accuracy of staging with the Bayesian method was significantly improved compared with that of the cutoff method in all patients; for discriminating stage ≥F2 from F0–F1 (98.9% vs. 94.8%, P = 0.0069); for ≥F3 (99.6% vs. 92.6%, P < 0.0001); and for F4 (100% vs. 94.2%, P = 0.0002).

Conclusion

The Bayesian method has a highly accurate discrimination ability for noninvasive hepatic fibrosis staging using MRE, if the posterior probability is high.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. MAGN. RESON. IMAGING 2017;46:375–382
Uniform attractors for a nonautonomous extensible plate equation with a strong damping
Authors: Feng Baowei , Yang Xin‐Guang , Qin Yuming
Published: November 2016

In this paper, we study the long‐time dynamics of solutions to a nonlinear nonautonomous extensible plate equation with a strong damping. Under some suitable assumptions on the initial data, the nonlinear term and external force, we establish the existence of global solutions that generate a family of processes for the problem and obtain uniform attractors corresponding to strong and weak symbol spaces in a bounded domain
. Copyright © 2016 John Wiley & Sons, Ltd.
Measuring the ICD‐11 adjustment disorder concept: Validity and sensitivity to change of the Adjustment Disorder – New Module questionnaire in a clinical intervention study
Authors: Bachem Rahel , Perkonigg Axel , Stein Dan J. , Maercker Andreas
Published: November 2016

Adjustment disorder (AjD) is a frequent but under‐researched diagnosis due in part to a lack of specific symptom criteria and adequate tools of measurement. The ICD‐11 for the first time proposes a positive symptom catalogue to define AjD. This study presents a validation of the Adjustment Disorder – New Module (ADNM), the first symptom severity measure for AjD according to the ICD‐11 concept. Validity and sensitivity to change were investigated in a sample of 190 individuals with a DSM‐IV diagnosis of AjD. The ADNM scales demonstrated convergent and discriminant validity for anxiety symptoms (Hamilton Anxiety Scale; psychic anxiety r = 0.18–0.31), functional impairment (Sheehan Disability Scale; r = 0.18–0.47), and depression (Montgomery–Asberg Depression Scale; r = 0.13–0.30). At baseline 78% of the individuals with a DSM‐IV diagnosis of AjD were also classified so by the ADNM. Repeated‐measures ANOVA indicated significant ADNM‐symptom decrease during treatment, replicating the patterns of the Hamilton Anxiety Scale, Sheehan Disability Scale, and Clinical Global Impression Scale. This article presents the first use of the ADNM as a measure for ICD‐11 AjD in a randomized‐controlled intervention study of AjD. It provides support for the construct validity and sensitivity to symptom change of this scale during pharmacological treatment.
Semi‐decentralized nonlinear cooperative control strategies for a network of heterogeneous autonomous underwater vehicles
Authors: Enayat Maria , Khorasani Khashayar
Published: November 2016

In this paper, we develop nonlinear distributed or semi‐decentralized cooperative control schemes for a team of heterogeneous autonomous underwater vehicles (AUVs). The objective is to have the network of AUVs follow a desired trajectory, while the agents maintain a desired formation when there is a virtual leader whose position information is only available and known to a very small subset of the agents. The virtual leader does not receive any feedback and information from the other agents and the agents only communicate with their nearest neighboring agents. It is assumed that the model parameters associated with each vehicle/agent is different, although the order of the agents is the same. The developed and proposed nonlinear distributed cooperative control schemes are based on the dynamic surface control methodology for a network of heterogeneous autonomous vehicles with uncertainties. The development and investigation of the dynamic surface control methodology for a team of cooperative heterogenous multi‐agent nonlinear systems is accomplished for the first time in the literature. Simulation results corresponding to a team of six AUVs are provided to demonstrate and illustrate the advantages and superiority of our proposed cooperative control strategies as compared to the methods that are available in the literature. Copyright © 2016 John Wiley & Sons, Ltd.
Privacy‐preserving outsourced gene data search in encryption domain
Authors: Fengxiao Huang , Zhangjie Fu , Xingming Sun , Ching‐Nung Yang
Published: November 2016

Human genome project is a grand scale scientific work, which aims at measuring three billion base pairs in human chromosomes (haploid). It brings a great challenging task to store and utilize these gene sequences (GS) securely and effectively. With the development of the cloud computing, the storage of gene information can be out of consideration. However, their secure utilization still puzzles data owners and data users. One popular way is to encrypt these GS and construct searchable indexes for secure retrieval. In this paper, we first define and solve the problem of privacy‐preserving outsourced gene data search in encryption domain. We transfer GS into numerical vectors by reasonable mapping for ease of similarity calculation. We employ secure KNN algorithm to encrypt the query, index, and gene data and compute relevance scores securely. We test our scheme through a real‐world dataset: plant GS from National Center of Biotechnology Information. Extensive experiments are conducted to demonstrate the efficiency of the proposed scheme. Copyright © 2016 John Wiley & Sons, Ltd.
The Economic Significance of the Film Business: An Empirical Analysis of the Italian Market
Authors: Teti Emanuele , Dell'Acqua Alberto , Etro Leonardo
Published: November 2016

Most studies indicate Hollywood's economic and financial leadership in the movie markets from the 1910s onward. There is a shortfall in the literature concerning the analysis of the efficacy of other minor film industries. This article examines the Italian film industry in the 1990s and beginning of the twenty‐first century. The research suggests that the Italian film industry is very risky and unpredictable, but while the extreme uncertainty surrounding the business is offset by the considerable economic success that Hollywood movies achieve at the box office, as indicated by previous literature contributions, a different business scenario emerges in Italy. The value of this article is first represented by the data used—provided by the Osservatorio of Cinecittà—which is unique and has not been published before. © 2016 Wiley Periodicals, Inc.
Actuality Entailments: When the Modality is in the Presupposition
Authors: Mari Alda
Published: November 2016

In natural language, modals are not implicative. However, when the modality is combined with the perfective, it shows an implicative (or factive) behavior. This phenomenon is called ‘actuality entailment’. We show that actuality entailments arise with goal-oriented modality only and endorse Belnap’s view of that goal-oriented modals use historical accessibility with a fixed past and an open future. This modal-theoretic assumption allows us to spell out the precise modal-temporal configuration in which the actuality entailment arises and our predictions are borne out by the data, cross-linguistically. We also show that, when any assumption about the identity of worlds at branching point is leveled - which appears to be the case with generic deontic and opportunity modals, the actuality entailments disappear. We also predict that the entailment disappears with prospectivity. Finally, we argue that modal sentences giving rise to actuality entailments are informative, insofar as the contribution of the modality survives as a presupposition that the modal base is non-homogeneous.
Context Update for Lambdas and Vectors
Authors: Muskens Reinhard , Sadrzadeh Mehrnoosh
Published: November 2016

Vector models of language are based on the contextual aspects of words and how they co-occur in text. Truth conditional models focus on the logical aspects of language, the denotations of phrases, and their compositional properties. In the latter approach the denotation of a sentence determines its truth conditions and can be taken to be a truth value, a set of possible worlds, a context change potential, or similar. In this short paper, we develop a vector semantics for language based on the simply typed lambda calculus. Our semantics uses techniques familiar from the truth conditional tradition and is based on a form of dynamic interpretation inspired by Heim’s context updates.
A Compositional Semantics for ‘If Then’ Conditionals
Authors: Vidal Mathieu
Published: November 2016

This paper presents the first compositional semantics for if then conditionals. The semantics of each element are first examined separately. The meaning of if is modeled according to a possible worlds semantics. The particle then is analyzed as an anaphoric word that places its focused element inside the context settled by a previous element. Their meanings are subsequently combined in order to provide a formal semantics of if A then C conditionals, which differs from the simple if A, C form. This semantics has the particularity of validating contraposition for the first type but invalidating it for the second type. Finally, a detailed examination of the sentences presented in the literature opposing this schema of reasoning shows that these counterexamples do not generally concern if then conditionals but, rather, even if conditionals and that contraposition is therefore a valid means of reasoning with regard to if then conditionals in natural language, as this system predicts.
On Classical Nonassociative Lambek Calculus
Authors: Buszkowski Wojciech
Published: November 2016

CNL, intoduced by de Groote and Lamarche [11], is a conservative extension of Nonassociative Lambek Calculus (NL) by a De Morgan negation $$^{\sim }$$

∼

, satisfying $$A^{\sim }/B\Leftrightarrow A\backslash B^{\sim }$$

A
∼

/
B
⇔
A
\

B
∼

. [11] provides a fine theory of proof nets for CNL and shows cut elimination and polynomial decidability. Here the purely proof-theoretic approach of [11] is enriched with algebras and phase spaces for CNL. We prove that CNL is a strongly conservative extension of NL, CNL has the strong finite model property, the grammars based on CNL (also with assumptions) generate the context-free languages, and the finitary consequence relation for CNL is decidable in polynomial time.
Proof Assistants for Natural Language Semantics
Authors: Chatzikyriakidis Stergios , Luo Zhaohui
Published: November 2016

In this paper we discuss the use of interactive theorem provers (also called proof assistants) in the study of natural language semantics. It is shown that these provide useful platforms for NL semantics and reasoning on the one hand, and allow experiments to be performed on various frameworks and new theories, on the other. In particular, we show how to use Coq, a prominent type theory based proof assistant, to encode type theoretical semantics of various NL phenomena. In this respect, we can encode the NL semantics based on type theory for quantifiers, adjectives, common nouns, and tense, among others, and it is shown that Coq is a powerful engine for checking the formal validity of these accounts as well as a powerful reasoner about the implemented semantics. We further show some toy semantic grammars for formal semantic systems, like the Montagovian Generative Lexicon, Type Theory with Records and neo-Davidsonian semantics. It is also explained that experiments on new theories can be done as well, testing their validity and usefulness. Our aim is to show the importance of using proof assistants as useful tools in natural language reasoning and verification and argue for their wider application in the field.
Compositional Event Semantics in Pregroup Grammars
Authors: Gaudreault Gabriel
Published: November 2016

A derivational approach to event semantics using pregroup grammars as syntactic framework is defined. This system relies on three crucial components: the explicit introduction of event variables which are linked to the basic types of a lexical item’s grammatical type; the unification of event variables following a concatenation of two expressions and the associated type contraction; and the correspondence between pregroup orderings and the change of the available event variables associated to a lexical item, which the meaning predicates take scope over.
Soft 3D-Printed Phantom of the Human Kidney with Collecting System
Authors: Adams Fabian , Qiu Tian , Mark Andrew , Fritz Benjamin , Kramer Lena , Schlager Daniel , Wetterauer Ulrich , Miernik Arkadiusz , Fischer Peer
Published: November 2016

Organ models are used for planning and simulation of operations, developing new surgical instruments, and training purposes. There is a substantial demand for in vitro organ phantoms, especially in urological surgery. Animal models and existing simulator systems poorly mimic the detailed morphology and the physical properties of human organs. In this paper, we report a novel fabrication process to make a human kidney phantom with realistic anatomical structures and physical properties. The detailed anatomical structure was directly acquired from high resolution CT data sets of human cadaveric kidneys. The soft phantoms were constructed using a novel technique that combines 3D wax printing and polymer molding. Anatomical details and material properties of the phantoms were validated in detail by CT scan, ultrasound, and endoscopy. CT reconstruction, ultrasound examination, and endoscopy showed that the designed phantom mimics a real kidney’s detailed anatomy and correctly corresponds to the targeted human cadaver’s upper urinary tract. Soft materials with a tensile modulus of 0.8–1.5 MPa as well as biocompatible hydrogels were used to mimic human kidney tissues. We developed a method of constructing 3D organ models from medical imaging data using a 3D wax printing and molding process. This method is cost-effective means for obtaining a reproducible and robust model suitable for surgical simulation and training purposes.
Regulatory T‐cells promote hepatitis B virus infection and hepatocellular carcinoma progression
Authors: Li Wei , Han Jun , Wu Hong
Published: November 2016

Regulatory T‐cells (Tregs), known for their immune suppressive function, have been reported in higher numbers, with activated phenotypes and greater potency, in hepatitis B virus (HBV)‐related liver diseases than in normal conditions. The numbers, phenotypes, and function of intrahepatic and/or tumor‐infiltrating Tregs in HBV‐related liver diseases also differ from those of Tregs in the peripheral blood. By inhibiting the function of effector T‐cells (Teffs), Tregs play a substantial role in the formation and maintenance of the liver's suppressive microenvironment, which might account for the progression of HBV‐related hepatitis and hepatocellular carcinoma (HCC). In acute hepatitis B virus infection, Tregs can safeguard the liver from damage at the cost of prolonged antiviral processes, which results in chronic HBV infection in the liver. Furthermore, Tregs play a role in the development of cirrhosis, the transformation of cirrhosis to HCC, and the progression and metastasis of HCC. Higher levels of Tregs in the peripheral blood and/or tumor sites signify a poorer prognosis in HBV‐related liver conditions, and observational data from mouse models and human patients support the theory that depleting Tregs may be therapeutic in HBV‐related liver diseases by inducing antiviral and antitumor immunity.
Evaluation Set Size and Purchase: Evidence from a Product Search Engine☆
Authors: Choudhary Vidyanand , Currim Imran , Dewan Sanjeev , Jeliazkov Ivan , Mintz Ofer , Turner John
Published: November 2016

The last decade has seen a dramatic increase in the popularity of product search engines, yet the analysis of consumer behavior at such sites remains a challenging research problem despite its timeliness and importance. In this article, we develop and estimate a copula model of evaluation set size and purchase behavior employing data from 3,182 hotel searches by customers at a large travel search engine. The model allows us to jointly study purchase behavior, evaluation sets, and their antecedents. Our results reveal that evaluation set size and purchase are negatively correlated and that factors typically presumed to be associated with purchase—i.e., when users sort search results by price or quality, request many rooms, disclose that there are many guests in their party, or arrive from other search engines and/or partner sites—actually relate to larger evaluation sets but lower purchase probability. In contrast, when users filter the search results, we observe smaller evaluation sets and higher purchase probability. The theoretical background and practical implications of our findings suggest that efforts to increase purchases need not necessarily be predicated on cultivating larger evaluation sets.
The complexity of millennial-scale variability in southwestern Europe during MIS 11
Authors: Oliveira Dulce , Desprat Stephanie , Rodrigues Teresa , Naughton Filipa , Hodell David , Trigo Ricardo , Rufino Marta , Lopes Cristina , Abrantes Fatima , Goni Maria Fernanda Sánchez
Published: November 2016

Climatic variability of Marine Isotope Stage (MIS) 11 is examined using a new high-resolution direct land—sea comparison from the SW Iberian margin Site U1385. This study, based on pollen and biomarker analyses, documents regional vegetation, terrestrial climate and sea surface temperature (SST) variability. Suborbital climate variability is revealed by a series of forest decline events suggesting repeated cooling and drying episodes in SW Iberia throughout MIS 11. Only the most severe events on land are coeval with SST decreases, under larger ice volume conditions. Our study shows that the diverse expression (magnitude, character and duration) of the millennial-scale cooling events in SW Europe relies on atmospheric and oceanic processes whose predominant role likely depends on baseline climate states. Repeated atmospheric shifts recalling the positive North Atlantic Oscillation mode, inducing dryness in SW Iberia without systematical SST changes, would prevail during low ice volume conditions. In contrast, disruption of the Atlantic meridional overturning circulation (AMOC), related to iceberg discharges, colder SST and increased hydrological regime, would be responsible for the coldest and driest episodes of prolonged duration in SW Europe.
Laminarisation of flow at low Reynolds number due to streamwise body force
Authors: He S. , He K. , Seddighi M.
Published: November 2016

It is well established that when a turbulent flow is subjected to a non-uniform body force, the turbulence may be significantly suppressed in comparison with that of the flow of the same flow rate and hence the flow is said to be laminarised. This is the situation in buoyancy-aided mixed convection when severe heat transfer deterioration may occur. Here we report results of direct numerical simulations of flow with a linear or a step-change profile of body force. In contrast to the conventional view, we show that applying a body force to a turbulent flow while keeping the pressure force unchanged causes little changes to the key characteristics of the turbulence. In particular, the mixing characteristics of the turbulence represented by the turbulent viscosity remain largely unaffected. The so-called flow laminarisation due to a body force is in effect a reduction in the apparent Reynolds number of the flow, based on an apparent friction velocity associated with only the pressure force of the flow (i.e. excluding the contribution of the body force). The new understanding allows the level of the flow ‘laminarisation’ and when the full laminarisation occurs to be readily predicted. In terms of the near-wall turbulence structure, the numbers of ejections and sweeps are little influenced by the imposition of the body force, whereas the strength of each event may be enhanced if the coverage of the body force extends significantly away from the wall. The streamwise turbulent stress is usually increased in accordance with the observation of more and stronger elongated streaks, but the wall-normal and the circumferential turbulent stresses are largely unchanged.
On the generation of large-scale eddy-driven patterns: the average eddy model
Authors: Radko Timour
Published: November 2016

A theoretical model is developed which illustrates the dynamics of the spontaneous generation of large-scale structures in baroclinically unstable eddying flows. Techniques of asymptotic multiscale analysis are used to identify instabilities resulting from the positive feedback of the background eddies on large-scale perturbations. The novelty of the proposed approach lies in the choice of a dynamically consistent time-dependent background eddy field, which is taken from simulations of baroclinic instability in the Phillips two-layer system. The resulting solutions differ considerably from those of traditional multiscale models, in which the background eddy field is represented by steady analytical patterns. The present formulation makes it possible to (i) test the multiscale theory against the corresponding numerical simulations, (ii) unambiguously interpret the key physical processes at play and (iii) rationalize the emergence of large-scale patterns for certain background parameters. While the proposed approach to multiscale modelling is illustrated on a particular example of the Phillips baroclinic instability model, it is our belief that the presented technique is readily adaptable to a wide range of applications.
Lift force on spherical nanoparticles in shear flows of rarefied binary gas mixtures
Authors: Luo Shuang , Wang Jun , Xia Guodong , Li Zhigang
Published: November 2016

In this work, we study the lift force on spherical nanoparticles suspended in a shear flow of rarefied binary gas mixtures. Analytical formulae are developed using the gas kinetic theory by considering non-rigid-body intermolecular interactions between the particle and gas molecules. It has been shown that the lift force formulae can be reduced to those in pure gases. It is also found that the direction of the lift force on nanoparticles in binary gas mixtures can be changed by varying the temperature, gas–particle interaction and/or gas concentrations.
Flow and Heat Transfer of Gold-Blood Nanofluid in a Porous Channel with Moving/Stationary Walls
Authors: Srinivas S. , Vijayalakshmi A. , Subramanyam Reddy A.
Published: November 2016

The present study investigates the flow and heat transfer characteristics of blood carrying gold nanoparticles in a porous channel with moving/stationary walls in the presence of thermal radiation. Blood is considered as Newtonian fluid which is the base fluid and gold (Au) as nanoparticles. The governing equations are transformed into system of ordinary differential equations by using similarity transformations. The analytical solutions are obtained for the flow variables by employing homotopy analysis method (HAM). The analytical solutions are compared with the numerical solutions which are obtained by shooting technique along with Runge-Kutta scheme. It was noticed that there is a good agreement between analytical and numerical results. The influence of various parameters on velocity, temperature and heat transfer rate of gold-blood nanofluid has been discussed in detail. The temperature of the nanofluid increases with increasing the nanoparticle volume fraction. The heat transfer rate at the top wall increases with increasing nanoparticle volume fraction while it decreases for a given increase in radiation parameter.
Nonlinear Rupture of Thin Micropolar Liquid Film Under a Magnetic Field
Authors: Cheng P.-J. , Chen C.-K. , Wang Y.-C. , Lin M.-C. , Yang C.-K.
Published: November 2016

This paper investigates the rupture problem of a thin micropolar liquid film under a magnetic field on a horizontal plate, using long-wave perturbation to resolve nonlinear evolution equations with a free film interface. The governing equation is resolved using a finite difference method as part of an initial value problem for spatial periodic boundary conditions. The effect of a micropolar liquid under a magnetic field on the nonlinear rupture mechanism is studied in terms of the micropolar parameter, R, the Hartmann constant, m and the initial disturbance amplitude, H0. Modeling results indicate that the R, m and H0 parameters strongly affect the film flow. Enhancing the micropolar and magnetic effects is found to delay the rupture time. In addition, the results show that the film rupture time increases as the values of initial disturbance magnitude decrease. The micropolar and magnetic parameters indeed play a significant role in the film flow on a horizontal plate. Moreover, the optimum conditions can be found to alter stability of the film flow by controlling the applied magnetic field.
Good practice guide to setting inputs for operational risk models
Authors: Kelliher P. O. J. , Acharyya M. , Couper A. , Grant K. , Maguire E. , Nicholas P. , Smerald C. , Stevenson D. , Thirlwell J. , Cantle N.
Published: November 2016

This paper seeks to establish good practice in setting inputs for operational risk models for banks, insurers and other financial service firms. It reviews Basel, Solvency II and other regulatory requirements as well as publicly available literature on operational risk modelling. It recommends a combination of historic loss data and scenario analysis for modelling of individual risks, setting out issues with these data, and outlining good practice for loss data collection and scenario analysis. It recommends the use of expert judgement for setting correlations, and addresses information requirements for risk mitigation allowances and capital allocation, before briefly covering Bayesian network methods for modelling operational risks.
Gulf Stream Destabilization Point Is on the Move
Authors: Stanley Sarah
Published: November 2016

Westward migration of the wavelike Gulf Stream pattern could have big effects on ocean mixing and heat transport off the U.S. East Coast.
Increasing the density of passive photonic-integrated circuits via nanophotonic cloaking
Authors: Shen Bing , Polson Randy , Menon Rajesh
Published: November 2016

Photonic-integrated devices need to be adequately spaced apart to prevent signal cross-talk. This fundamentally limits their packing density. Here we report the use of nanophotonic cloaking to render neighbouring devices invisible to one another, which allows them to be placed closer together than is otherwise feasible. Specifically, we experimentally demonstrated waveguides that are spaced by a distance of ∼λ0/2 and designed waveguides with centre-to-centre spacing as small as 600 nm (<λ0/2.5). Our experiments show a transmission efficiency >−2 dB and an extinction ratio >15 dB over a bandwidth larger than 60 nm. This performance can be improved with better design algorithms and industry-standard lithography. The nanophotonic cloak relies on multiple guided-mode resonances, which render such devices very robust to fabrication errors. Our devices are broadly complimentary-metal-oxide-semiconductor compatible, have a minimum pitch of 200 nm and can be fabricated with a single lithography step. The nanophotonic cloaks can be generally applied to all passive integrated photonics.
Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase
Authors: Cinesi Cinzia , Aeschbach Lorène , Yang Bin , Dion Vincent
Published: November 2016

CAG/CTG repeat expansions cause over 13 neurological diseases that remain without a cure. Because longer tracts cause more severe phenotypes, contracting them may provide a therapeutic avenue. No currently known agent can specifically generate contractions. Using a GFP-based chromosomal reporter that monitors expansions and contractions in the same cell population, here we find that inducing double-strand breaks within the repeat tract causes instability in both directions. In contrast, the CRISPR-Cas9 D10A nickase induces mainly contractions independently of single-strand break repair. Nickase-induced contractions depend on the DNA damage response kinase ATM, whereas ATR inhibition increases both expansions and contractions in a MSH2- and XPA-dependent manner. We propose that DNA gaps lead to contractions and that the type of DNA damage present within the repeat tract dictates the levels and the direction of CAG repeat instability. Our study paves the way towards deliberate induction of CAG/CTG repeat contractions in vivo.
Chaperone addiction of toxin–antitoxin systems
Authors: Bordes Patricia , Sala Ambre Julie , Ayala Sara , Texier Pauline , Slama Nawel , Cirinesi Anne-Marie , Guillet Valérie , Mourey Lionel , Genevaux Pierre
Published: November 2016

Bacterial toxin–antitoxin (TA) systems, in which a labile antitoxin binds and inhibits the toxin, can promote adaptation and persistence by modulating bacterial growth in response to stress. Some atypical TA systems, known as tripartite toxin–antitoxin–chaperone (TAC) modules, include a molecular chaperone that facilitates folding and protects the antitoxin from degradation. Here we use a TAC module from Mycobacterium tuberculosis as a model to investigate the molecular mechanisms by which classical TAs can become ‘chaperone-addicted’. The chaperone specifically binds the antitoxin at a short carboxy-terminal sequence (chaperone addiction sequence, ChAD) that is not present in chaperone-independent antitoxins. In the absence of chaperone, the ChAD sequence destabilizes the antitoxin, thus preventing toxin inhibition. Chaperone–ChAD pairs can be transferred to classical TA systems or to unrelated proteins and render them chaperone-dependent. This mechanism might be used to optimize the expression and folding of heterologous proteins in bacterial hosts for biotechnological or medical purposes.
BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization
Authors: Gray Felicia , Cho Hyo Je , Shukla Shirish , He Shihan , Harris Ashley , Boytsov Bohdan , Jaremko Łukasz , Jaremko Mariusz , Demeler Borries , Lawlor Elizabeth R. , Grembecka Jolanta , Cierpicki Tomasz
Published: November 2016

BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and emerging data support a role of BMI1 in cancer. The central domain of BMI1 is involved in protein–protein interactions and is essential for its oncogenic activity. Here, we present the structure of BMI1 bound to the polyhomeotic protein PHC2 illustrating that the central domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a β-hairpin conformation. Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1. We demonstrate that both the interaction of BMI1 with polyhomeotic proteins and homo-oligomerization via UBL domain are necessary for H2A ubiquitination activity of PRC1 and for clonogenic potential of U2OS cells. Here, we also emphasize need for joint application of NMR spectroscopy and X-ray crystallography to determine the overall structure of the BMI1–PHC2 complex.
Recurrence Rates and Risk Factors for Primary Giant Cell Tumors around the Knee: A Multicentre Retrospective Study in China
Authors: Hu Pan , Zhao Liming , Zhang Huilin , Yu Xiuchun , Wang Zhen , Ye Zhaoming , Wu Sujia , Guo Shibing , Zhang Guochuan , Wang Jinghua , Ning Xianjia , Hu Yongcheng , Zhang Yingze
Published: November 2016

Giant cell tumors of the bone (GCTBs) are commonly diagnosed in Asian populations, usually around the knee. Herein, we aimed to determine the clinical characteristics, local recurrence rates, and relevant risk factors of primary GCTB around the knee. Univariate and multivariate survival analyses were used to identify the risk factors for local recurrence. Four hundred ten patients with primary GCTB around the knee, treated between March 2000 and June 2014, were recruited from 7 institutions in China. The overall local recurrence rate was 23.4%, but was higher in patients aged 20–39 years (28.5%; P = 0.039). The local recurrence rate was the highest in patients treated with intralesional curettage (53.4%), and the lowest in those treated with resection (4.9%). We found a higher risk of tumor recurrence in the proximal fibula compared to the distal femur (hazard ratio: 28.52, 95% confidence interval: 5.88–138.39; P < 0.0001), and in patients treated with curettage compared to those treated with resection (hazard ratio: 12.07, 95% confidence interval: 4.99–29.18; P < 0.0001). Thus, the tumor location must be considered when selecting the optimal surgical treatment approach to reduce the risk of local recurrence and preserve joint function, especially in young patients.
Heterogeneity of executive functions among comorbid neurodevelopmental disorders
Authors: Dajani Dina R. , Llabre Maria M. , Nebel Mary Beth , Mostofsky Stewart H. , Uddin Lucina Q.
Published: November 2016

Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) — prevalent and often highly comorbid neurodevelopmental disorders — others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and children with ASD and ADHD. We employed a latent profile analysis using indicators of EF (e.g., working memory, inhibition, and flexibility) in a mixed group of 8–13 year-olds including TD children (n = 128), children with ASD without ADHD (n = 30), children with ADHD (n = 93), and children with comorbid ASD and ADHD (n = 66). Three EF classes emerged: “above average,” “average,” and “impaired.” EF classes did not reproduce diagnostic categories, suggesting that differences in EF abilities are present within the ASD and ADHD groups. Further, greater EF dysfunction predicted more severe socioemotional problems, such as anxiety/depression. These results highlight the heterogeneity of current diagnostic groups and identify an “impaired” EF group, consisting of children with both ASD and ADHD, which could specifically be targeted for EF intervention.
Micrometre-scale deformation observations reveal fundamental controls on geological rifting
Authors: Thun Johannes , Lokmer Ivan , Bean Christopher J. , Eibl Eva P. S. , Bergsson Bergur H. , Braiden Aoife
Published: November 2016

Many of the world’s largest volcanic eruptions are associated with geological rifting where major fractures open at the Earth’s surface, yet fundamental controls on the near-surface response to the rifting process are lacking. New high resolution observations gleaned from seismometer data during the 2014 Bárðarbunga basaltic dyke intrusion in Iceland allow us unprecedented access to the associated graben formation process on both sub-second and micrometre scales. We find that what appears as quasi steady-state near-surface rifting on lower resolution GPS observation comprises discrete staccato-like deformation steps as the upper crust unzips through repetitive low magnitude (MW < 0) failures on fracture patches estimated between 300 m2and 1200 m2in size. Stress drops for these events are one to two orders of magnitude smaller than expected for tectonic earthquakes, demonstrating that the uppermost crust in the rift zone is exceptionally weak.
TM1-IR680 peptide for assessment of surgical margin and lymph node metastasis in murine orthotopic model of oral cancer
Authors: Suganya S. Annie A. , Kochurani K. J. , Nair Madhumathy G. , Louis Jiss Maria , Sankaran Santhosh , Rajagopal R. , Kumar K. Santhosh , Abraham Parvin , P. G. Balagopal , Sebastian Paul , Somananthan Thara , Maliekal Tessy Thomas
Published: November 2016

Treatment outcome after surgical removal in oral carcinoma is poor due to inadequate methodologies available for marking surgical margins. Even though some methodologies for intraoperative margin assessment are under clinical and preclinical trials for other solid tumours, a promising modality for oral cancer surgery is not developed. Fluorescent-based optical imaging using Near Infrared (NIR) dyes tagged to tumour specific target will be an optimal tool for this purpose. One such target, Gastrin Releasing Peptide Receptor (GRPR) was selected for the study, and its binding peptide, TM1-IR680, was tested for its efficacy for surgical margin prediction in murine orthotopic model of oral cancer, derived from primary samples. Here, for the first time in a preclinical analysis, we show that the size and margin of oral cancer can be predicted, as revealed by 3D-imaging. Interestingly, the peptide was sensitive enough to detect lymph nodes that harboured dispersed tumour cells before colonization, which was impossible to identify by conventional histopathology. We recommend the use of TM1-NIR dyes alone or in combination with other technologies to improve the clinical outcome of oral cancer surgery.