bluuebunny/crossref_metadata_2025 huggingface dataset:
Erste zielgerichtete Therapie bei Ovarialkarzinom für BRCA1/2-Mutationsträgerinnen zugelassen
Authors: Schmutzler Rita Katharina , Meindl Alfons
Published: July 2015

Olaparib (Lynparza™) ist ein Poly-(ADP-ribose)-polymerase (PARP)-Inhibitor, der zur Behandlung von soliden Tumoren oral eingenommen wird. Die primäre Indikation, für die Olaparib durch die EMA im Dezember 2014 zugelassen wurde, ist das platin-sensitive, seröse Ovarialkarzinomrezidiv, G3 mit einer Keimbahn- oder somatischen Mutation in den Genen BRCA1 oder BRCA2. Um beide Arten der Mutation zu identifizieren, wird deshalb eine initiale Untersuchung der Tumor-DNA, die aus Paraffingewebe isoliert werden muss, diskutiert. Diese in der Indikationsstellung zur Therapie begründete Verlagerung des Nachweises von Mutationen aus Blut-DNA in Tumor-DNA bringt sowohl technische wie auch gesundheitsökonomische und -rechtliche Herausforderungen mit sich: Die Sensitivität des Mutationsnachweises ist in der Tumor-DNA (derzeit noch?) geringer. Der Anteil somatischer Varianten mit unklarer Bedeutung (variant of unknown significance, VUS) ist vermutlich hoch und die meisten der im Tumormaterial nachweisbaren Mutationen stellen Keimbahnmutationen dar. Aus Letzterem ergibt sich ferner die Frage, wie der Schutz vor Benachteiligung und die Sicherstellung des informationellen Selbstbestimmungsrechts der Patientinnen angesichts der unklaren bzw. fehlenden Abbildung dieses Sachverhaltes im Gendiagnostikgesetz gewährleistet werden kann.

Aus unserer Sicht lassen sich die vielfältigen und dringlichen Fragestellungen, einhergehend mit einer Lynparza-Indikationsstellung, nur durch eine qualitätskontrollierte sektorenübergreifende Zusammenarbeit im Rahmen einer begleitenden systematischen Verlaufsstudie zur Erfassung der genetischen, histopathologischen und klinischen Verlaufsdaten beantworten.
Beyond work-hour restrictions: a qualitative study of residents’ subjective workload
Authors: Nishigori Hiroshi , Deshpande Gautam A. , Obara Haruo , Takahashi Osamu , Busari Jamiu , Dornan Tim
Published: July 2015

Introduction Following the introduction of work-hour restrictions, residents’ workload has become an important theme in postgraduate training. The efficacy of restrictions on workload, however, remains controversial, as most research has only examined objective workload. The purpose of this study was to explore the less clearly understood component of subjective workload and, in particular, the factors that influenced residents’ subjective workload.

Method This study was conducted in Japan at three community teaching hospitals. We recruited a convenience sample of 31 junior residents in seven focus groups at the three sites. Audio-recorded and transcribed data were read iteratively and analyzed thematically, identifying, analyzing and reporting themes within the data and developing an interpretive synthesis of the topic.

Results Seven factors influenced residents’ subjective workload: (1) interaction within the professional community, (2) feedback from patients, (3) being in control, (4) professional development, (5) private life, (6) interest and (7) protected free time.

Discussion and conclusion Our findings indicate that residents who have good interaction with colleagues and patients, are competent enough to control their work, experience personal development through working, have greater interest in their work, and have fulfilling private lives will have the least subjective workload.
Late Glacial to Holocene relative sea-level change in Assynt, northwest Scotland, UK
Authors: Hamilton Christine A. , Lloyd Jeremy M. , Barlow Natasha L.M. , Innes James B. , Flecker Rachel , Thomas Caleb P.
Published: July 2015

Relative sea-level change (RSL), from the Late Glacial through to the late Holocene, is reconstructed for the Assynt region, northwest Scotland, based on bio- and lithostratigraphical analysis. Four new radiocarbon-dated sea-level index points help constrain RSL change for the Late Glacial to the late Holocene. These new data, in addition to published material, capture the RSL fall during the Late Glacial and the rise and fall associated with the mid-Holocene highstand. Two of these index points constrain the Late Glacial RSL history in Assynt for the first time, reconstructing RSL falling from 2.47 ± 0.59 m OD to 0.15 ± 0.59 m OD at c. 14,000–15,000 cal yr BP. These new data test model predictions of glacial isostatic adjustment (GIA), particularly during the early deglacial period which is currently poorly constrained throughout the British Isles. Whilst the empirical data from the mid- to late-Holocene to present matches quite well with the recent GIA model output, there is a relatively poor fit between the timing of the Late Glacial RSL fall and early Holocene RSL rise. This mismatch, also evident elsewhere in northwest Scotland, may result from uncertainties associated with both the global and local ice components of GIA models.
Effects of inertia and viscoelasticity on sedimenting anisotropic particles
Authors: Dabade Vivekanand , Marath Navaneeth K. , Subramanian Ganesh
Published: July 2015

An axisymmetric particle sedimenting in an otherwise quiescent Newtonian fluid, in the Stokes regime, retains its initial orientation. For the special case of a spheroidal geometry, we examine analytically the effects of weak inertia and viscoelasticity in driving the particle towards an eventual steady orientation independent of initial conditions. The generalized reciprocal theorem, together with a novel vector spheroidal harmonics formalism, is used to find closed-form analytical expressions for the$O(\mathit{Re})$inertial torque and the$O(\mathit{De})$viscoelastic torque acting on a sedimenting spheroid of an arbitrary aspect ratio. Here,$\mathit{Re}=UL/{\it\nu}$is the Reynolds number, with$U$being the sedimentation velocity,$L$the semi-major axis and${\it\nu}$the fluid kinematic viscosity, and is a measure of the inertial forces acting at the particle scale. The Deborah number,$\mathit{De}=({\it\lambda}U)/L$, is a dimensionless measure of the fluid viscoelasticity, with${\it\lambda}$being the intrinsic relaxation time of the underlying microstructure. The analysis is valid in the limit$\mathit{Re},\mathit{De}\ll 1$, and the effects of viscoelasticity are therefore modelled using the constitutive equation of a second-order fluid. The inertial torque always acts to turn the spheroid broadside-on, while the final orientation due to the viscoelastic torque depends on the ratio of the magnitude of the first ($N_{1}$) to the second normal stress difference ($N_{2}$), and the sign (tensile or compressive) of$N_{1}$. For the usual case of near-equilibrium complex fluids – a positive and dominant$N_{1}$($N_{1}>0$,$N_{2}<0$and$|N_{1}/N_{2}|>1$) – both prolate and oblate spheroids adopt a longside-on orientation. The viscoelastic torque is found to be remarkably sensitive to variations in${\it\kappa}$in the slender-fibre limit (${\it\kappa}\gg 1$), where${\it\kappa}=L/b$is the aspect ratio,$b$being the radius of the spheroid (semi-minor axis). The angular dependence of the inertial and viscoelastic torques turn out to be identical, and one may then characterize the long-time orientation of the sedimenting spheroid based solely on a critical value ($\mathit{El}_{c}$) of the elasticity number,$\mathit{El}=\mathit{De}/\mathit{Re}$. For$\mathit{El}<\mathit{El}_{c}~({>}\mathit{El}_{c})$, inertia (viscoelasticity) prevails with the spheroid settling broadside-on (longside-on). The analysis shows that$\mathit{El}_{c}\sim O[(1/\text{ln}\,{\it\kappa})]$for${\it\kappa}\gg 1$, and the viscoelastic torque thus dominates for a slender rigid fibre. For a slender fibre alone, we also briefly analyse the effects of elasticity on fibre orientation outside the second-order fluid regime.
Cracks in bursting soap films
Authors: Bico J.
Published: July 2015

The rupture of soap films is traditionally described by a law accounting for a balance between momentum and surface tension forces, derived independently by Taylor and Culick in the 1960s. This law is highly relevant to the dynamics of thin liquid films of jets when viscous effects are negligible. However, the minute amounts of surfactant molecules present in soap films play a major role in interfacial rheology, and may result in complex behaviour. Petit et al. (J. Fluid Mech., vol. 774, 2015, R3) challenge standard thin film dynamics via intriguing experiments conducted with highly elastic surfactants. Unexpected structures reminiscent of faults are observed.
FRACTAL BASES FOR BANACH SPACES OF SMOOTH FUNCTIONS
Authors: NAVASCUÉS M. A. , VISWANATHAN P. , CHAND A. K. B. , SEBASTIÁN M. V. , KATIYAR S. K.
Published: July 2015

This article explores the properties of fractal interpolation functions with variable scaling parameters, in the context of smooth fractal functions. The first part extends the Barnsley–Harrington theorem for differentiability of fractal functions and the fractal analogue of Hermite interpolation to the present setting. The general result is applied on a special class of iterated function systems in order to develop differentiability of the so-called$\boldsymbol{{\it\alpha}}$-fractal functions. This leads to a bounded linear map on the space${\mathcal{C}}^{k}(I)$which is exploited to prove the existence of a Schauder basis for${\mathcal{C}}^{k}(I)$consisting of smooth fractal functions.
Levels of Toxocara infections in dogs and cats from urban Vietnam together with associated risk factors for transmission
Authors: Anh N. Thi Lan , Thuy D. Thi Thu , Hoan D. Huu , Hop N. Thi , Dung D. Trung
Published: July 2015

The aims of the present study were to assess the prevalence of Toxocara infection in household cats and dogs, together with the presence of anti-Toxocara IgG antibodies in humans and the level of egg contamination in soil and vegetable samples from the local environment. Prevalence values of 47.8% of 253 cats and 37.7% of 284 dogs were recorded, together with 35.8% of eggs in soil samples, 25.0% in garden vegetables and in 56.3% of 16 dog-hair samples. The risk of the infection was higher for dogs and cats in households with egg-contaminated soil compared to those without evidence of soil contamination. The high prevalence of dog and cat Toxocara infection and their indiscriminate defecation behaviour contribute to a significant risk of transmission to humans as 58.7% of human blood samples were seropositive for Toxocara. Anthelmintic treatment of dogs and cats, plus educating household members, must be emphasized in any prevention programme in Vietnam.
Conflict Transformation through Prior Consultation? Lessons from Peru
Authors: SCHILLING-VACAFLOR ALMUT , FLEMMER RICCARDA
Published: July 2015

This article analyses the background to and the content of the Peruvian prior consultation law – the only one enacted in Latin America to date – and its regulating decree. In contrast to the widespread conception that prior consultation is a means for preventing and resolving conflict, it argues that this new legislation will not help to transform conflicts as long as the normative framework itself is contested and the preconditions for participatory governance are not in place. Establishing these preconditions would result in state institutions capable of justly balancing the diverse interests at stake; measures that reduce power asymmetries within consultations; and joint decision-making processes with binding agreements.
The Shifting Origins of International Law
Authors: DE LA RASILLA DEL MORAL IGNACIO
Published: July 2015

Both state-centrism and Eurocentrism are under challenge in international law today. This article argues that this double challenge is mirrored back into the study of the history of international law. It examines the effects of the rise of positivism as a method of norm-identification and the role of methodological nationalism upon the study of the history of international law in the modern foundational period of international law. It extends this by examining how this bequeathed a double exclusionary bias regarding time and space to the study of the history of international law as well as a reiterative focus on a series of canonical events and authors to the exclusion of others such as those related to the Islamic history of international law. It then analyses why this state of historiographical affairs is changing, highlighting intra-disciplinary developments within the field of the history of international law and the effects that the ‘international turn in the writing of history’ is having on the writing of a new history of international law for a global age. It concludes with a reflection on some of the tasks ahead, providing a series of historiographical signposts for the history of international law as a field of new research.
Was There Something Missing in the Decolonization Process in Africa?: The Territorial Dimension
Authors: HÉBIÉ MAMADOU
Published: July 2015

Five decades after the wave of independence of the 1960s, have all African territories been decolonized in accordance with international law? On the basis of the General Assembly and state practice, this study argues that only the continuing possession of African territories by colonial powers is contrary to the obligation to decolonize under international law. Thus, colonialism is still persisting in Africa with regard to the Glorious Islands, Mayotte, the Chagos, Ceuta and Melilla, the islands Alhucemas, Chafarinas, Leïla, and Peñon de Vélez de la Gomera. These territories belong respectively to Madagascar, the Comoros Islands, Mauritius, and Morocco. However, the obligation to decolonize under international law, which is premised on the existence of a colonial possession, does not provide any legal basis to claims directed against independent African states. Besides, the maintenance of boundaries existing upon the achievement of African countries to independence is not a case of enduring colonialism.
Expropriation in Transition: Evolving Chinese Investment Treaty Practices in Local and Global Contexts
Authors: WEI SHEN
Published: July 2015

The doctrine and case law on expropriation in international investment law is an unsettled area due to a variety of factors such as the diversity of interests between capital importing and exporting states, the divergence in legal, economic, and cultural concepts of property rights, and, more importantly, the regulatory role of the state in cross-border investment activities. Although China has been an active ‘treaty-maker’ in the universe of international investment arbitration, evidenced by its nearly 130 bilateral investment treaties (BITs), the notion of expropriation in these BITs is in a state of flux. This article scrutinizes the expropriation clauses in China's BITs, in particular, the Peru–China BIT and the Peru–China free trade agreement, by reference to the final award ofTza Yap Shumv.The Republic of Peru, the first Chinese BIT arbitration case. This article attempts, in a comparative context, to understand the underlying rationale for China's evolving stance on expropriation.
Duress: From Nuremberg to the International Criminal Court, Finding the Balance Between Justification and Excuse
Authors: JOYCE MARCUS
Published: July 2015

Article 31(1)(d)1of the Rome Statute of the International Criminal Court (ICC Statute) presents an important opportunity to reconsider the defence of duress in cases of unlawful killing. While the case ofErdemovićhas done much to substantiate the existence of the defence of duress at international law it appears to have curtailed the doctrine by interpreting it with reference to a strict form of proportionality characteristic of duress as justification. On the other hand, duress as excuse requires some measure of proportionality. This article will contend that the hybrid approach of Nuremberg Military Tribunals (NMTs), defined duress and the moral choice test primarily by reference toculpa in causa, not resorting to duress, and a ‘softer’ proportionality and in doing so, provided a more flexible and workable model for duress. Article 31(1)(d) of the ICC Statute, although an interesting attempt to find the balance between duress as excuse and justification, is a missed opportunity to redefine the defence in international criminal law. An alternative test for duress, with reference to the principles that emerged from the jurisprudence of the NMTs, is required in order to find the correct balance between duress as excuse and justification.
Appraisal-Based and Flexible Approaches to External Precedent in International Criminal Law
Authors: ZAMMIT BORDA ALDO
Published: July 2015

This article focuses on the approaches of international criminal judges to using external precedent, distinguishing between the appraisal-based and flexible approaches. On the one hand, the appraisal-based approach refers to uses of external judicial decisions which are preceded by an express legal appraisal. On the other hand, the flexible approach denotes a less stringent use of such decisions. It finds that, in a number of cases, international criminal judges have adopted a flexible approach to decisions and have assimilated them within the legal framework of the referring court or tribunal without the necessary adjustment. This may have important implications for the principle of legality and the fairness of the proceedings. The paper indicates that the adoption of either the appraisal-based or flexible approaches to external judicial decisions is not necessarily linked to the specific legal backgrounds of the judges involved, and different judges hailing from varying legal backgrounds have shifted between these approaches in different cases. This suggests that there is need for greater rigour in the judicial methodology for using external judicial decisions and, in particular, the importance of the appraisal-based approach to using such decisions, to ensure their the congruence with the legal framework of the referring court or tribunal.
Inverse obstacle backscattering problems with phaseless data
Authors: SHIN JAEMIN
Published: July 2015

In this article, we provide a numerical algorithm to reconstruct a convex sound-soft scatterer from phaseless backscattering data, assuming sufficiently high frequency. Certain uniqueness and existence results for the case of circular scatterers are given as well, based on the asymptotic expansion for the normal derivative of the total field.
Homework Adherence and Cognitive Behaviour Treatment Outcome for Children and Adolescents with Anxiety Disorders
Authors: Arendt Kristian , Thastum Mikael , Hougaard Esben
Published: July 2015

Background: Homework assignments are considered an essential component for a successful outcome of cognitive behavioural therapy for youths with anxiety disorders. However, only two studies have examined the association between homework adherence and outcome of cognitive behavioural therapy for youths with anxiety disorders. Aims: The study examined the association between homework adherence and treatment outcome following a generic group cognitive behaviour treatment program (Cool Kids) for anxiety disordered youths and their parents. Method: The treatment program was completed by 98 children and adolescents (ages 7–16). Homework adherence was measured as time spent doing homework assignments between each session, reported by youths as well as parents. Outcome criteria consisted of youth-reported anxiety symptoms and clinician rated severity of primary anxiety diagnosis at posttreatment and 3-month follow-up. Results: Results did not support an association between homework adherence and treatment outcome when controlling for pretreatment severity. Conclusions: The study found no convincing evidence that homework adherence predicted outcome of cognitive behavioural therapy for youths with anxiety disorders. Reasons for divergent findings on homework adherence in cognitive behavioural therapy for youths compared to adults are discussed.
Treating Sleep Problems in Patients with Schizophrenia
Authors: Waite Felicity , Myers Elissa , Harvey Allison G. , Espie Colin A. , Startup Helen , Sheaves Bryony , Freeman Daniel
Published: July 2015

Background: Sleep disturbance is increasingly recognized as a major problem for patients with schizophrenia but it is rarely the direct focus of treatment. The main recommended treatment for insomnia is cognitive behavioural therapy, which we have been evaluating for patients with current delusions and hallucinations in the context of non-affective psychosis. Aims: In this article we describe the lessons we have learned about clinical presentations of sleep problems in schizophrenia and the adaptations to intervention that we recommend for patients with current delusions and hallucinations. Method: Twelve factors that may particularly contribute to sleep problems in schizophrenia are identified. These include delusions and hallucinations interfering with sleep, attempts to use sleep as an escape from voices, circadian rhythm disruption, insufficient daytime activity, and fear of the bed, based upon past adverse experiences. Specific adaptations for psychological treatment related to each factor are described. Conclusions: Our experience is that patients want help to improve their sleep; sleep problems in schizophrenia should be treated with evidence-based interventions, and that the interventions may have the added benefit of lessening the psychotic experiences. A treatment technique hierarchy is proposed for ease of translation to clinical practice.
Health advisor facilitated mouth care regime for patients with head and neck cancers undergoing intensity-modulated radiotherapy
Authors: Stringer J. , Knowles R. , Finchett C. , Mackereth P. , Mannan J. , Slevin N.
Published: July 2015

Aim

To develop a regime of care for patients with head and neck cancers undergoing intensity-modulated radiotherapy (IMRT), with the support of a health advisor (HA) and temporary access to the mouth care product Caphosol™.

Materials and methods

A HA was temporarily employed to assess, monitor and refer patients as appropriate and ensure patients received and utilised supplies of Caphosol™. A retrospective audit was undertaken to provide a gap analysis of current service. The data were used to develop a pro forma for documenting assessments and monitoring lifestyle factors for IMRT patients. Assessments referrals and compliance, plus hospital admissions owing to treatment-related issues, were documented during the baseline audit and the temporary HA service and provision of Caphosol™.

Results

The presence of a HA facilitated 100% compliance with appropriate assessments, referrals and adherence to treatment. The data suggests that the additional provision of Caphosol™ may have reduced levels of mucositis and associated pain.

Conclusion

It is recommended that a HA role be established within radiotherapy departments to facilitate lifestyle assessments, referrals and compliance with positive behaviour changes (e.g., stopping smoking). The use of Caphosol™ as a routine part of mouth care regime for IMRT patients also warrants further investigation.
Dieback of cocoa (Theobroma cacao L.) plant tissues caused by the brown cocoa mirid Sahlbergella singularis Haglund (Hemiptera: Miridae) and associated pathogenic fungi
Authors: Anikwe Joseph Chuks , Otuonye Henry Azuka
Published: July 2015

The brown cocoa mirid,Sahlbergella singularisis the most important insect pest of cocoa for field damage has been classified into three categories that include blast, stagheadedness and mirid pocket. The mirid attack predisposes the cocoa plant to secondary infection by opportunistic pathogenic fungi. This study evaluated the dieback conditions associated with mirid damage due to associated fungi from lesions on pods, twigs and pin punctures. The relationship betweenPhytophthorablack pod infection and mirid infestation in the field was also established. The results indicated that dieback progression from the mirid lesions (8.5 mm) was significantly different (P< 0.05) from that of pin punctures (7.8 mm).Lasiodiplodia theobromaehad the highest proportion of isolates from pods (33%), twigs (47%), and pin punctures (38%).Fusarium decemcellulare(Albonectria rigidiuscula) accounted for 27.8% and 31.6% from pods and twigs; however, it was not recovered from pin punctures. Other isolated pathogens wereAspergillusspecies andRhizoctoniaspecies. There was a significantly strong positive correlation coefficient of 0.74 between the mirid population and the black pod disease infection in the field. The major fruit-bearing season of cocoa witnessed an increase in mirid infestation and blackpod infection. The effect of mirid–pathogenic fungi-associated damage could be ameliorated through effective crop husbandry practices to ensure that cocoa plant tissues are not unduly exposed to biological and mechanical injuries.
Transnational Environmental Law and Grass-Root Initiatives: The Case of the Latin American Water Tribunal
Authors: Olmos Giupponi Belén
Published: July 2015

This article analyzes the role played by the Latin American Water Tribunal (Tribunal Latinoamericano del Agua – TRAGUA) (LAWT) in the resolution of environmental disputes over water resources. Since its inception in 1998, the LAWT has emerged as a non-governmental body with a multidisciplinary composition and a mandate based on both formal and informal sources of law, which holds public hearings in order to address water-related complaints. This article explores whether (and the ways in which) the LAWT is contributing to the resolution of environmental disputes concerning water resources. The main underlying thesis is that, whereas the traditional model for interstate dispute settlement offers only limited possibilities of redress to non-state actors (mainly individuals and groups), the LAWT provides them with the opportunity to present their demands before an environmental justice forum.
The geometric phase controls ultracold chemistry
Authors: Kendrick B. K. , Hazra Jisha , Balakrishnan N.
Published: July 2015

The geometric phase is shown to control the outcome of an ultracold chemical reaction. The control is a direct consequence of the sign change on the interference term between two scattering pathways (direct and looping), which contribute to the reactive collision process in the presence of a conical intersection (point of degeneracy between two Born–Oppenheimer electronic potential energy surfaces). The unique properties of the ultracold energy regime lead to an effective quantization of the scattering phase shift enabling maximum constructive or destructive interference between the two pathways. By taking the O+OH→H+O2 reaction as an illustrative example, it is shown that inclusion of the geometric phase modifies ultracold reaction rates by nearly two orders of magnitude. Interesting experimental control possibilities include the application of external electric and magnetic fields that might be used to exploit the geometric phase effect reported here and experimentally switch on or off the reactivity.
The GINA asthma strategy report: what’s new for primary care?
Authors: Reddel Helen K , Levy Mark L ,   on behalf of the Global Initiative for Asthma Scientific Committee and Dissemination and Implementation Committee
Published: July 2015

The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and National Heart Lung and Blood Institute to develop a global strategy for managing and preventing asthma. GINA reports, now funded independently through the sale of GINA products, have provided the foundation for many national guidelines. They are prepared by international experts from primary, secondary and tertiary care, and are annually updated following a review of evidence. In 2014, a major revision of the GINA report was published, that took into account advances in evidence not only about asthma and its treatment, but also about how to improve implementation of evidence-based recommendations in clinical practice. This paper summarises key changes relevant to primary care in the new GINA report. A noticeable difference is the report’s radically different approach, now clinically-focussed, with multiple practical tools and flow charts to improve its utility for busy frontline clinicians. Key changes in recommendations include a new, diagnosis-centred definition of asthma; more detail about how to assess current symptom control and future risk; a comprehensive approach to tailoring treatment for individual patients; expanded indications for commencing inhaled corticosteroids; new recommendations for written asthma action plans; a new chapter on diagnosis and initial treatment of patients with asthma–COPD overlap syndrome; and a revised approach to diagnosing asthma in preschool children. The 2014 GINA report (further updated in 2015) moved away from a ‘textbook’ approach to provide clinicians with up-to-date evidence about strategies to control symptoms and minimise asthma risk, in a practical, practice-centred format.
Mixed Linear Model Approaches of Association Mapping for Complex Traits Based on Omics Variants
Authors: Zhang Fu-Tao , Zhu Zhi-Hong , Tong Xiao-Ran , Zhu Zhi-Xiang , Qi Ting , Zhu Jun
Published: July 2015

Precise prediction for genetic architecture of complex traits is impeded by the limited understanding on genetic effects of complex traits, especially on gene-by-gene (GxG) and gene-by-environment (GxE) interaction. In the past decades, an explosion of high throughput technologies enables omics studies at multiple levels (such as genomics, transcriptomics, proteomics and metabolomics). The analyses of large omics data, especially two-loci interaction analysis, are very time intensive. Integrating the diverse omics data and environmental effects in the analyses also remain challenges. We proposed mixed linear model approaches using GPU (Graphic Processing Unit) computation to simultaneously dissect various genetic effects. Analyses can be performed for estimating genetic main effects, GxG epistasis effects and GxE environment interaction effects on large-scale omics data for complex traits and for estimating heritability of specific genetic effects. Both mouse data analyses and Monte Carlo simulations demonstrated that genetic effects and environment interaction effects could be unbiasedly estimated with high statistical power by using the proposed approaches.
Teleportation of a Toffoli gate among distant solid-state qubits with quantum dots embedded in optical microcavities
Authors: Hu Shi , Cui Wen-Xue , Wang Dong-Yang , Bai Cheng-Hua , Guo Qi , Wang Hong-Fu , Zhu Ai-Dong , Zhang Shou
Published: July 2015

Teleportation of unitary operations can be viewed as a quantum remote control. The remote realization of robust multiqubit logic gates among distant long-lived qubit registers is a key challenge for quantum computation and quantum information processing. Here we propose a simple and deterministic scheme for teleportation of a Toffoli gate among three spatially separated electron spin qubits in optical microcavities by using local linear optical operations, an auxiliary electron spin, two circularly-polarized entangled photon pairs, photon measurements and classical communication. We assess the feasibility of the scheme and show that the scheme can be achieved with high average fidelity under the current technology. The scheme opens promising perspectives for constructing long-distance quantum communication and quantum computation networks with solid-state qubits.
Green tea extract decreases starch digestion and absorption from a test meal in humans: a randomized, placebo-controlled crossover study
Authors: Lochocka Klaudia , Bajerska Joanna , Glapa Aleksandra , Fidler-Witon Ewa , Nowak Jan K. , Szczapa Tomasz , Grebowiec Philip , Lisowska Aleksandra , Walkowiak Jaroslaw
Published: July 2015

Green tea is known worldwide for its beneficial effects on human health. However, objective data evaluating this influence in humans is scarce. The aim of the study was to assess the impact of green tea extract (GTE) on starch digestion and absorption. The study comprised of 28 healthy volunteers, aged 19 to 28 years. In all subjects, a starch 13C breath test was performed twice. Subjects randomly ingested naturally 13C-abundant cornflakes during the GTE test (GTE 4 g) or placebo test. The cumulative percentage dose recovery (CPDR) was significantly lower for the GTE test than for the placebo test (median [interquartile range]: 11.4% [5.5–15.5] vs. 16.1% [12.7–19.5]; p = 0.003). Likewise, CPDR expressed per hour was considerably lower in each point of the measurement. In conclusion, a single dose of green tea extract taken with a test meal decreases starch digestion and absorption.
Meshing complex macro-scale objects into self-assembling bricks
Authors: Hacohen Adar , Hanniel Iddo , Nikulshin Yasha , Wolfus Shuki , Abu-Horowitz Almogit , Bachelet Ido
Published: July 2015

Self-assembly provides an information-economical route to the fabrication of objects at virtually all scales. However, there is no known algorithm to program self-assembly in macro-scale, solid, complex 3D objects. Here such an algorithm is described, which is inspired by the molecular assembly of DNA and based on bricks designed by tetrahedral meshing of arbitrary objects. Assembly rules are encoded by topographic cues imprinted on brick faces while attraction between bricks is provided by embedded magnets. The bricks can then be mixed in a container and agitated, leading to properly assembled objects at high yields and zero errors. The system and its assembly dynamics were characterized by video and audio analysis, enabling the precise time- and space-resolved characterization of its performance and accuracy. Improved designs inspired by our system could lead to successful implementation of self-assembly at the macro-scale, allowing rapid, on-demand fabrication of objects without the need for assembly lines.
Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology
Authors: Pérez Cecilia V. , Gómez Leticia G. , Gualdoni Gisela S. , Lustig Livia , Rabinovich Gabriel A. , Guazzone Vanesa A.
Published: July 2015

Galectin-1 (Gal-1), a proto-type member of galectin family, is highly expressed in immune privileged sites, including the testis. However, in spite of considerable progress the relevance of endogenous and exogenous Gal-1 in testis pathophysiology have not yet been explored. Here we evaluated the in vivo roles of Gal-1 in experimental autoimmune orchitis (EAO), a well-established model of autoimmune testicular inflammation associated with subfertility and infertility. A significant reduction in the incidence and severity of EAO was observed in mice genetically deficient in Gal-1 (Lgals1−/−) versus wild-type (WT) mice. Testicular histopathology revealed the presence of multifocal testicular damage in WT mice characterized by an interstitial mononuclear cell infiltrate and different degrees of germ cell sloughing of seminiferous tubules. TUNEL assay and assessment of active caspase-3 expression, revealed the prevalence of apoptotic spermatocytes mainly localized in the adluminal compartment of seminiferous tubules in EAO mice. A significant increased number of TUNEL-positive germ cells was detected in EAO testis from WT compared with Lgals1−/− mice. In contrast, exogenous administration of recombinant Gal-1 to WT mice undergoing EAO attenuated the severity of the disease. Our results unveil a dual role of endogenous versus exogenous Gal-1 in the control of autoimmune testis inflammation.
Ant trophallactic networks: simultaneous measurement of interaction patterns and food dissemination
Authors: Greenwald Efrat , Segre Enrico , Feinerman Ofer
Published: July 2015

Eusocial societies and ants, in particular, maintain tight nutritional regulation at both individual and collective levels. The mechanisms that underlie this control are far from trivial since, in these distributed systems, information about the global supply and demand is not available to any single individual. Here we present a novel technique for non-intervening frequent measurement of the food load of all individuals in an ant colony, including during trophallactic events in which food is transferred by mouth-to-mouth feeding. Ants are imaged using a dual camera setup that produces both barcode-based identification and fluorescence measurement of labeled food. This system provides detailed measurements that enable one to quantitatively study the adaptive food distribution network. To demonstrate the capabilities of our method, we present sample observations that were unattainable using previous techniques and could provide insight into the mechanisms underlying food exchange.
Evidence for Coexistence of Bulk Superconductivity and Itinerant Antiferromagnetism in the Heavy Fermion System CeCo(In1−xCdx)5
Authors: Howald Ludovic , Stilp Evelyn , de Réotier Pierre Dalmas , Yaouanc Alain , Raymond Stéphane , Piamonteze Cinthia , Lapertot Gérard , Baines Christopher , Keller Hugo
Published: July 2015

In the generic phase diagram of heavy fermion systems, tuning an external parameter such as hydrostatic or chemical pressure modifies the superconducting transition temperature. The superconducting phase forms a dome in the temperature—tuning parameter phase diagram, which is associated with a maximum of the superconducting pairing interaction. Proximity to antiferromagnetism suggests a relation between the disappearance of antiferromagnetic order and superconductivity. We combine muon spin rotation, neutron scattering and x-ray absorption spectroscopy techniques to gain access to the magnetic and electronic structure of CeCo(In1−xCdx)5 at different time scales. Different magnetic structures are obtained that indicate a magnetic order of itinerant character, coexisting with bulk superconductivity. The suppression of the antiferromagnetic order appears to be driven by a modification of the bandwidth/carrier concentration, implying that the electronic structure and consequently the interplay of superconductivity and magnetism is strongly affected by hydrostatic and chemical pressure.
Comparative analysis of essential genes in prokaryotic genomic islands
Authors: Zhang Xi , Peng Chong , Zhang Ge , Gao Feng
Published: July 2015

Essential genes are thought to encode proteins that carry out the basic functions to sustain a cellular life and genomic islands (GIs) usually contain clusters of horizontally transferred genes. It has been assumed that essential genes are not likely to be located in GIs, but systematical analysis of essential genes in GIs has not been explored before. Here, we have analyzed the essential genes in 28 prokaryotes by statistical method and reached a conclusion that essential genes in GIs are significantly fewer than those outside GIs. The function of 362 essential genes found in GIs has been explored further by BLAST against the Virulence Factor Database (VFDB) and the phage/prophage sequence database of PHAge Search Tool (PHAST). Consequently, 64 and 60 eligible essential genes are found to share the sequence similarity with the virulence factors and phage/prophages-related genes, respectively. Meanwhile, we find several toxin-related proteins and repressors encoded by these essential genes in GIs. The comparative analysis of essential genes in genomic islands will not only shed new light on the development of the prediction algorithm of essential genes, but also give a clue to detect the functionality of essential genes in genomic islands.
miRNA-133 augments coelomocyte phagocytosis in bacteria-challenged Apostichopus japonicus via targeting the TLR component of IRAK-1 in vitro and in vivo
Authors: Lu Meng , Zhang Peng-Juan , Li Cheng-Hua , Lv Zhi-Meng , Zhang Wei-Wei , Jin Chun-Hua
Published: July 2015

In this study, we explored the potential roles of miRNA-133 in regulating TLR pathways in the sea cucumber Apostichopus japonicus. Target screening of RNA-Seq data successfully identified interleukin-1 receptor-associated kinase (AjIRAK−1) as a putative target of miR-133. This result was further validated by negative expression profiles in Vibrio splendidus-challenged coelomocytes and lipopolysaccharide (LPS)-exposed cell cultures. HEK-293T cells transfected with a dual-luciferase reporter fused to the 3′UTR of wild-type or mutant AjIRAK-1 exhibited a 52.9% reduction in luciferase activity (p < 0.01) compared to controls. Co-infection with a miR-133 mimics or a specific siRNA targeting AjIRAK-1 significantly repressed the mRNA and protein expression levels of AjIRAK-1 and its downstream molecules, such as AjTRAF6 and Ajp105, in primary coelomocytes. In contrast, a miR-133 inhibitor significantly increased the expression of these TLR pathway members. The injection of miR-133 agomir or AjIRAK-1 siRNA into sea cucumbers not only decreased the expression of AjIRAK-1 and its downstream molecules but also significantly increased V. splendidus coelomocyte phagocytosis. All of the present data provide direct evidence that miR-133 is involved in TLR cascade modulation through AjIRAK-1 targeting to promote V. splendidus coelomocyte phagocytosis in these non-model invertebrates.
Decrease of mRNA Editing after Spinal Cord Injury is Caused by Down-regulation of ADAR2 that is Triggered by Inflammatory Response
Authors: Narzo Antonio Fabio Di , Kozlenkov Alexey , Ge Yongchao , Zhang Bin , Sanelli Leo , May Zacnicte , Li Yanqing , Fouad Karim , Cardozo Christopher , Koonin Eugene V , Bennett David J , Dracheva Stella
Published: July 2015

We recently showed that spinal cord injury (SCI) leads to a decrease in mRNA editing of serotonin receptor 2C (5-HT2CR) contributing to post-SCI spasticity. Here we study post-SCI mRNA editing and global gene expression using massively parallel sequencing. Evidence is presented that the decrease in 5-HT2CR editing is caused by down-regulation of adenosine deaminase ADAR2 and that editing of at least one other ADAR2 target, potassium channel Kv1.1, is decreased after SCI. Bayesian network analysis of genome-wide transcriptome data indicates that down-regulation of ADAR2 (1) is triggered by persistent inflammatory response to SCI that is associated with activation of microglia and (2) results in changes in neuronal gene expression that are likely to contribute both to post-SCI restoration of neuronal excitability and muscle spasms. These findings have broad implications for other diseases of the Central Nervous System and could open new avenues for developing efficacious antispastic treatments.
Volatile organic compounds in truffle (Tuber magnatum Pico): comparison of samples from different regions of Italy and from different seasons
Authors: Vita Federico , Taiti Cosimo , Pompeiano Antonio , Bazihizina Nadia , Lucarotti Valentina , Mancuso Stefano , Alpi Amedeo
Published: July 2015

In this paper volatile organic compounds (VOCs) fromTuber magnatumfruiting bodies were analyzed using a PTR-TOF-MS instrument. The aim was to characterize the VOC's profile of the fruiting bodies and identify if any VOCs were specific to a season and geographical areas. Multiple factorial analysis (MFA) was carried out on the signals obtained by MS. Experiments using ITS region sequencing proved that theT. magnatumlife cycle includes the formation of fruiting bodies at two different times of the year. The VOCs profiles diverge when different seasonal and geographical productions are considered. Using PTR-TOF-MS, compounds present at levels as low pptv were detected. This made it possible to determine both the origin of fruiting bodies (Alba and San Miniato) and the two biological phases of fruiting bodies formation in San Miniato truffles.
Functional diversity and properties of multiple xylanases from Penicillium oxalicum GZ-2
Authors: Liao Hanpeng , Zheng Haiping , Li Shuixian , Wei Zhong , Mei Xinlan , Ma Hongyu , Shen Qirong , Xu Yangchun
Published: July 2015

A multiple xylanase system with high levels of xylanase activity produced from Penicillium oxalicum GZ-2 using agricultural waste as a substrate has been previously reported. However, the eco-physiological properties and origin of the multiplicity of xylanases remain unclear. In the present study, eight active bands were detected using zymography and all bands were identified as putative xylanases using MALDI-TOF-MS/MS. These putative xylanases are encoded by six different xylanase genes. To evaluate the functions and eco-physiological properties of xylanase genes, xyn10A, xyn11A, xyn10B and xyn11B were expressed in Pichia pastoris. The recombinant enzymes xyn10A and xyn10B belong to the glycoside hydrolase (GH) family 10 xylanases, while xyn11A and xyn11B belong to GH11 xylanases. Biochemical analysis of the recombinant proteins revealed that all enzymes exhibited xylanase activity against xylans but with different substrate specificities, properties and kinetic parameters. These results demonstrated that the production of multiple xylanases in P. oxalicum GZ-2 was attributed to the genetic redundancy of xylanases and the post-translational modifications, providing insight into a more diverse xylanase system for the efficient degradation of complex hemicelluloses.
Enhanced cuticular penetration as the mechanism for synergy of insecticidal constituents of rosemary essential oil in Trichoplusia ni
Authors: Tak Jun-Hyung , Isman Murray B.
Published: July 2015

Synergistic interactions between constituents of essential oils have been reported for several areas of research. In the present study, mechanisms that could explain the synergistic action of the two major insecticidal constituents of rosemary oil, 1,8-cineole and camphor against the cabbage looper, Trichoplusia ni were investigated. 1,8-Cineole was more toxic than camphor when applied topically to larvae and when coadministered in their ratio naturally occurring in rosemary oil, the binary mixture was synergistic. However, when injected directly into larvae, camphor was more toxic than 1,8-cineole. GC-MS analyses showed that penetration of topically-applied camphor was significantly enhanced when it was mixed with 1,8-cineole in the natural ratio. A bioassay combining injection and topical application methods confirmed the increased penetration of both compounds when mixed, showing the same bioactivity as seen for higher amounts applied individually. Lowered surface tension as well as increased solubility of camphor by 1,8-cineole, along with the interaction between 1,8-cineole and the lipid layer of the insect’s cuticle may explain the enhanced penetration of camphor. Because of the similarities in biological function of animal and microbial membranes, our finding has potential for application in other fields of study.
Identification and characterization of a novel ISG15-ubiquitin mixed chain and its role in regulating protein homeostasis
Authors: Fan Jun-Bao , Arimoto Kei-lchiro , Motamedchaboki Khatereh , Yan Ming , Wolf Dieter A. , Zhang Dong-Er
Published: July 2015

As a ubiquitin-like modifier, ISG15 is conjugated to many cellular proteins in a process termed protein ISGylation. However, the crosstalk between protein ISGylation and the ubiquitin proteasome system is not fully understood. Here, we report that cellular ubiquitin is a substrate of ISG15 and Lys 29 on ubiquitin is the major ISG15 acceptor site. Using a model substrate, we demonstrate that ISG15 can modify ubiquitin, which is immobilized on its substrate, to form ISG15-ubiquitin mixed chains. Furthermore, our results indicate that ISG15-ubiquitin mixed chains do not serve as degradation signals for a ubiquitin fusion degradation substrate. Accordingly, an ISG15-ubiquitin fusion protein, which mimics an ISG15-ubiquitin mixed chain, negatively regulates cellular turnover of ubiquitylated proteins. In addition, ISG15-ubiquitin mixed chains, which are detectable on endogenously ubiquitylated proteins, dampen cellular turnover of these proteins. Thus, our studies unveil an unanticipated interplay between two protein modification systems and highlight its role in coordinating protein homeostasis.