bluuebunny/crossref_metadata_2025 huggingface dataset:
Common and unique associations of adolescents' affective and cognitive empathy development with conflict behavior towards parents
Authors: Van Lissa Caspar J. , Hawk Skyler T. , Branje Susan , Koot Hans M. , Meeus Wim H.J.
Published: January 2016

Adolescents' development of two empathy dimensions, affective empathic concern and cognitive perspective taking, may be associated with shifts towards more constructive behaviors in conflict with parents. This six‐year longitudinal study (ages 13–18) used multivariate latent growth curve modeling to investigate correlations between the developmental trajectories of adolescents' (N = 497) empathic dispositions and trajectories of their conflict behaviors towards both parents. There were some similarities between the associations of both empathy dimensions with conflict behaviors. Both empathy dimensions were associated with reduced conflict escalation with mothers, and increased problem solving with both parents. However, these associations were consistently stronger for perspective taking than for empathic concern. Furthermore, higher levels of compliance with mothers in early adolescence were uniquely associated with over‐time increasing empathic concern. Perspective taking was uniquely associated with decreased withdrawal from conflicts. Perspective taking thus appears to be more strongly associated with a pattern of constructive conflict behaviors.
Measuring the Impact of Positive and Negative Word of Mouth: A Reappraisal
Authors: East Robert , Uncles Mark D. , Romaniuk Jenni , Lomax Wendy
Published: January 2016

Negative information normally has more impact on attitude and cognition than positive information, but there is evidence that positive word of mouth (PWOM) usually has more effect on purchase intention than negative word of mouth (NWOM). We explain how this apparent inconsistency may come about when measures of attitude and intention are used as indicators of behavior. We argue that on/off behaviors, such as purchase, should be predicted better by a measure of intention, rather than attitude, and that consideration should be given to a measure of intention that is proportional to the maximum change that could occur as this reflects the movement toward or away from purchase. A large database is analyzed to show the differences between proportional and absolute measures. In addition, we examine the proportions of respondents reaching certainty (i.e. 0% or 100% probability of purchase) after NWOM and PWOM. Findings from these new analyses show that PWOM has more impact than NWOM on purchase intention (both proportional and absolute), but a higher proportion of respondents reach certainty after NWOM.
Genome Editing and Its Applications in Model Organisms
Authors: Ma Dongyuan , Liu Feng
Published: January 2016

Technological advances are important for innovative biological research. Development of molecular tools for DNA manipulation, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly-interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas), has revolutionized genome editing. These approaches can be used to develop potential therapeutic strategies to effectively treat heritable diseases. In the last few years, substantial progress has been made in CRISPR/Cas technology, including technical improvements and wide application in many model systems. This review describes recent advancements in genome editing with a particular focus on CRISPR/Cas, covering the underlying principles, technological optimization, and its application in zebrafish and other model organisms, disease modeling, and gene therapy used for personalized medicine.
Use of onabotulinum toxin A in patients with idiopathic overactive bladder and a lack of efficacy, intolerance or contraindication with anticholinergics
Authors: Ospina-Galeano Irma , Medina-Polo José , Rosa-Kerhmann Susana , Villacampa-Aubá Felipe , Guerrero-Ramos Felix , Passas-Martínez Juan
Published: January 2016

Objective To assess the efficacy and safety of onabotulinum toxin A in patients with idiopathic overactive bladder inadequately managed with anticholinergics.

Materials and Methods A prospective, open-label, single centre, and interventional study was conducted, from 2008 to 2013, on consecutive patients with idiophatic overactive bladder that showed lack of efficacy or intolerance to anticholinergic agents.

Results The study included 73 female patients aged 58.9 ± 12.9 years. A dose of 100 and 200 units of toxin were administered in 89 and 5 cases, respectively. Nineteen patients received a second injection, 8 patients received 3, and one patient was treated 4 times. Clinically, it was observed that 98% patients had urge urinary incontinence at baseline, as compared with 42% under treatment. Similar results were obtained regarding the number of pads used per day, from 2.8 at baseline to 0.5 after treatment as regards the urodynamic parameters, the first desire to void volume improved from 97 ± 63 mL to 139 ± 81 mL. Similar results were obtained as regards cystometric capacity and the volume of the first involuntary detrusor contraction. One patient had a positive urine culture resolved using a conventional oral antibiotic regimen. Intermittent catheterisation was required in 5 patients during the first week.

Conclusions Onabotulinum toxin A injections significantly improved, not only the clinical symptoms, but also the urodynamic parameters in patients with idiopathic overactive bladder inadequately managed with anticholinergic drugs. This is a simple technique with minimal adverse effects and generally well tolerated.
Environmental history recorded in aeolian deposits under stone pavements, Mojave Desert, USA
Authors: Dietze Michael , Dietze Elisabeth , Lomax Johanna , Fuchs Markus , Kleber Arno , Wells Stephen G.
Published: January 2016

Reconstructing the evolution of arid landscapes is challenged by limited availability of appropriate environmental archives. A widespread surface feature — stone pavement — traps aeolian fines and forms a special accretionary archive. Seven stone pavement-covered sections on basalt flows in the eastern Mojave Desert are condensed into a composite section, comprising five sedimentological units supported by an OSL-based chronology. Three of the units are of accretionary nature and each is covered by a stone pavement. They were deposited > 50.9–36.6 ka, < 36.6–14.2 ka and < 14.2 ka, and they are intimately coupled with the history of nearby Lake Mojave, which advances the current understanding of regional aeolian activity. End-member modeling analysis of grain-size distributions yielded seven sediment transport regimes. The accretionary system operates in two modes: A) episodic formation of a stone pavement by lateral processes once a vesicular horizon has formed on a barren surface; and B) accretion of dust and eventual burial of the clast layer. These findings improve current concepts about stone pavement evolution and their environmental proxy function in arid landscapes. Stone pavement-covered accretionary deposits are a new key archive that allows quantifying the relative importance of dust accretion, slope processes, soil formation and vegetation cover.
The centrifugal instability of the boundary-layer flow over a slender rotating cone in an enforced axial free stream
Authors: Hussain Z. , Garrett S. J. , Stephen S. O. , Griffiths P. T.
Published: January 2016

In this study, a new centrifugal instability mode, which dominates within the boundary-layer flow over a slender rotating cone in still fluid, is used for the first time to model the problem within an enforced oncoming axial flow. The resulting problem necessitates an updated similarity solution to represent the basic flow more accurately than previous studies in the literature. The new mean flow field is subsequently perturbed, leading to disturbance equations that are solved via numerical and short-wavelength asymptotic approaches, yielding favourable comparisons with existing experiments. Essentially, the boundary-layer flow undergoes competition between the streamwise flow component, due to the oncoming flow, and the rotational flow component, due to effect of the spinning cone surface, which can be described mathematically in terms of a control parameter, namely the ratio of streamwise to axial flow. For a slender cone rotating in a sufficiently strong axial flow, the instability mode breaks down into Görtler-type counter-rotating spiral vortices, governed by an underlying centrifugal mechanism, which is consistent with experimental and theoretical studies for a slender rotating cone in otherwise still fluid.
Landscape history of the Oer-IJ tidal system, Noord-Holland (the Netherlands)
Authors: Vos P. , de Koning J. , van Eerden R.
Published: January 2016

The prehistoric Oer-IJ tidal system in the coastal area of Noord-Holland, between Castricum, Uitgeest, Velsen and Amsterdam, was the successor of the Haarlem tidal system when this was silted up around 3000 BC and large peat bogs formed in the Zaanstreek and Haarlemmermeer areas. Since then the Oer-IJ has been the natural outlet to the sea, draining the peat hinterlands. About 800 BC the Oer-IJ system was connected to the fluvial system of the Utrechtse Vecht and became the northern branch of the river Rhine. During the Late Iron Age, when the Flevo lakes in the IJsselmeer region and the Utrechtse Vecht were connected with the Wadden Sea, the Oer-IJ lost its discharge function. The tidal area silted up and was closed between 200 and 100 BC by a barrier ridge. The settlement history of the Oer-IJ system and the archaeological heritage in the subsurface is closely related to the geological and hydrological development throughout the ages. The shape and location of the continuously migrating outlet determined the opportunities for human settlements and activities. The best locations were beach ridges, higher, silted-up salt marshes and marginal zones of the peatland. In the Late Iron Age the sand flats also became habitable since tidal activity had stopped. In the Early Roman period there was no direct connection from the harbour of Castellum Flevum at Velsen to the North Sea, but ships could navigate from the Oer-IJ channel between Velsen and Amsterdam, through the Flevo lakes and the Utrechtse Vecht to the Wadden Sea, and to the Roman border (Limes) along the Oude Rijn. Here the data used for the palaeogeographic landscape reconstruction of the Oer-IJ are presented and explained, and the most important landscape-forming processes, which led to the emergence and closure of the Oer-IJ, are described. The landscape reconstructions give a new perspective on the migration of the main tidal channel and the formation of the tidal-inlet system near Castricum, which was the result of the progradation of the beach ridges south and north of the Castricummerpolder (Binnendelta according to De Roo, 1953). The geological and archaeological observations in the Binnendelta prove that the Oer-IJ was closed from the open sea in the early Late Iron Age.
Fluvial history of the Vecht-Amstel area in the Holocene: Interdisciplinary collaborations, controversies and progress
Authors: Kluiving Sjoerd J. , Borger Guus J.
Published: January 2016

The history of the Amstel and Vecht rivers in the central part of the Netherlands during the Holocene has been debated for a considerable time (Bos et al., 2009; De Bont, 1994, 2000, 2008; De Bont & Kleij, 2012; De Gans, 2011; De Gans & Bunnik, 2011, 2012). Many publications in different disciplines have made their contribution to solve issues such as initiation and cessation of river flow, different and opposing river flow directions, and different chronologies.
FOOD SECURITY AND THE RIGHT TO FOOD: FINDING BALANCE IN THE 2012 FOOD ASSISTANCE CONVENTION
Authors: La Chimia Annamaria
Published: January 2016

On 25 April 2012, after years of negotiations delayed by halts and setbacks, the Food Assistance Convention was adopted—the latest in a series of agreements that since 1967 have regulated the international provision of food aid. Great expectations have been placed on the adoption of the Convention. In particular it was hoped that the Convention would answer the call for a new system of food aid governance, introduce more effective mechanisms to address world's food insecurity and, ultimately, improve and modernize the rules applicable to food aid. This article provides the first critical commentary of the Convention's text, assesses the strengths and weaknesses of its provisions and considers whether and how the Convention has modified the architecture of international food aid regulation. The article also indicates where amendments to the rules might be needed to make the international regulation of food aid more effective. The article concludes that the Convention is, on balance, a positive instrument that could improve governance and adequacy of food assistance. The Convention is also important for the international human rights discourse on how States can fulfil their obligation to assist countries in need in that it offers guidance on how to meet such obligation in the specific context of the right to food. States should therefore be urged to sign and ratify it.
EUROPEAN UNION DATA PROTECTION LAW AND MEDIA EXPRESSION: FUNDAMENTALLY OFF BALANCE
Authors: Erdos David
Published: January 2016

The European Data Protection Directive 95/46/EC requires all European Economic Area (EEA) jurisdictions to provide an equivalent regime protecting the privacy and other fundamental rights and freedoms of natural persons in relation to personal data processing, whilst also shielding media expression from the default substantive requirements as necessary to ensure a balance between fundamental rights. Through a comprehensive coding of the derogations set out in each jurisdiction's data protection laws, this article provides the first systematic analysis of whether this has in fact been achieved. It is demonstrated that there is a total lack of even minimal harmonization in this area, with many laws providing for patently unbalanced results especially as regards the publication of sensitive information, which includes criminal convictions and political opinion, and the collection of information without notice direct from the data subject. This reality radically undermines European data protection's twin purposes of ensuring the free flow of personal data and protecting fundamental rights, an outcome which remains largely unaddressed by the proposed new Data Protection Regulation. Practical suggestions are put forward to ameliorate these troubling inconsistencies within the current process of reform.
STATE IMMUNITY AND THE RIGHT OF ACCESS TO A COURT UNDER THE EU CHARTER OF FUNDAMENTAL RIGHTS
Authors: Sanger Andrew
Published: January 2016

This article examines the application of the right of access to a court as guaranteed by Article 47 of the EU Charter of Fundamental Rights in cases involving State immunity. First, it considers the scope of the right of access to a court under the Charter, including its relationship with Article 6(1) of the European Convention on Human Rights, and the ways in which the Charter is given effect within UK law. Second, the article critically examines the Court of Appeal’s application of both Article 6(1) ECHR and Article 47 of the EU Charter in Benkharbouche v Sudan, a case brought by domestic service staff of foreign embassies based in London against Sudan and Libya respectively. It argues that the Court’s statement that the right of access to a court is not engaged in immunity cases because the court has no jurisdiction to exercise – an analysis which relies on Lord Millett’s reasoning in Holland v Lampen-Wolfe and the dicta of Lords Bingham and Hoffmann in Jones v Saudi Arabia – is erroneousness: the right of access to a court is always engaged in immunity cases because immunity does not deprive the courts of jurisdiction ab initio. The article also argues that contrary to the Court’s reasoning on Article 47 of the EU Charter, the right of access to a court does not need to have horizontal effect in a private between private parties: the right is always enforced against the forum State; it has indirect, not horizontal, effect.
THE ADMISSIBILITY CRITERION UNDER ARTICLE 35(3)(b) ECHR: A ‘SIGNIFICANT DISADVANTAGE’ TO HUMAN RIGHTS PROTECTION?
Authors: Vogiatzis Nikos
Published: January 2016

The purpose of this contribution is to provide a critical overview of issues of principle related to the ‘significant disadvantage’ admissibility criterion under 35(3)(b) ECHR, in light of the ongoing debate on the Court's reform. It argues that the admissibility criterion: undermines direct access to justice at the international level; affects the right of individual petition to the Strasbourg Court; constitutes a misunderstanding of the subsidiarity principle within the Convention machinery; urges the Court to consider the merits during the admissibility stage in a sensitive area of adjudication such as human rights; and entails the risk of an indirect classification of rights on the basis of the financial damage suffered by the applicant. The article links these points with the discussion on the Court's reform and considers alternative proposals to reduce its workload. It concludes by underlining that the ‘significant disadvantage’ criterion could be a suitable opportunity to address questions related to the Court's legitimacy, including the ECtHR's precise role and function within the Convention.
XIX.—On the Reciprocation of Certain Matrices
Authors: Collar A. R.
Published: January 2016

In a recent paper (Frazer, Jones, and Skan, 1937) some methods are discussed for the approximate representation of functions by means of polynomials. The coefficients in the polynomials are determined by the equation

where c is the column of coefficients, h is a column of known constants, and M is a matrix which depends on the method of representation adopted. The present paper shows how the reciprocal matrix M-1 can be computed rapidly and simply in the two cases where M is a moment matrix or an alternant matrix.
Counting Connected Hypergraphs via the Probabilistic Method
Authors: BOLLOBÁS BÉLA , RIORDAN OLIVER
Published: January 2016

In 1990 Bender, Canfield and McKay gave an asymptotic formula for the number of connected graphs on [n] = {1,2,. . .,n} withmedges, whenevernand the nullitym−n+1 tend to infinity. LetCr(n,t) be the number of connectedr-uniform hypergraphs on [n] with nullityt= (r−1)m−n+1, wheremis the number of edges. Forr≥ 3, asymptotic formulae forCr(n,t) are known only for partial ranges of the parameters: in 1997 Karoński and Łuczak gave one fort=o(logn/log logn), and recently Behrisch, Coja-Oghlan and Kang gave one fort=Θ(n). Here we prove such a formula for any fixedr≥ 3 and anyt=t(n) satisfyingt=o(n) andt→∞ asn→∞, complementing the last result. This leaves open only the caset/n→∞, which we expect to be much simpler, and will consider in future work. The proof is based on probabilistic methods, and in particular on a bivariate local limit theorem for the number of vertices and edges in the largest component of a certain random hypergraph. We deduce this from the corresponding central limit theorem by smoothing techniques.
A National Framework for Disaster Health Education in Australia
Authors: FitzGerald Gerard J. , Aitken Peter , Arbon Paul , Archer Frank , Cooper David , Leggat Peter , Myers Colin , Robertson Andrew , Tarrant Michael , Davis Elinor R.
Published: January 2016

Introduction:

Recent events have heightened awareness of disaster health issues and the need to prepare the health workforce to plan for and respond to major incidents. This has been reinforced at an international level by the World Association for Disaster and Emergency Medicine, which has proposed an international educational framework.

Objective:

The aim of this paper is to outline the development of a national educational framework for disaster health in Australia.

Methods:

The framework was developed on the basis of the literature and the previous experience of members of a National Collaborative for Disaster Health Education and Research. The Collaborative was brought together in a series of workshops and teleconferences, utilizing a modified Delphi technique to finalize the content at each level of the framework and to assign a value to the inclusion of that content at the various levels.

Framework:

The framework identifies seven educational levels along with educational outcomes for each level. The framework also identifies the recommended contents at each level and assigns a rating of depth for each component. The framework is not intended as a detailed curriculum, but rather as a guide for educationalists to develop specific programs at each level.

Conclusions:

This educational framework will provide an infrastructure around which future educational programs in Disaster Health in Australia may be designed and delivered. It will permit improved articulation for students between the various levels and greater consistency between programs so that operational responders may have a consistent language and operational approach to the management of major events.
Psychotropic prescribing in seriously violent men with schizophrenia or personality disorder in a UK high security hospital
Authors: Stone-Brown Keir , Naji Mahmood , Francioni Alex , Myers Kyle , Samarendra Harsh , Mushtaq-Chaudhry Haseeb , Heslop Stephen , Sengupta Samrat , Ross Callum C. , Larkin Fintan , Das Mrigendra
Published: January 2016

Objectives

To analyze antipsychotic prescribing patterns in a UK high security hospital (HSH) that treats seriously violent men with either schizophrenia or personality disorder and examine how different groups consented to treatment and prescribing for metabolic conditions. We hypothesized that there would be high prevalence of antipsychotic polypharmacy, and high-dose antipsychotic and clozapine prescribing.

Background

HSHs treat seriously violent, mentally disordered offenders, and the extant literature on prescribing patterns in forensic settings is sparse.

Methods

Prescribing and clinical data on all 189 patients in a UK HSH were collected from the hospital’s databases. Data were analyzed using SPSS.

Results

The population was split into the following groups: schizophrenia spectrum disorder (SSD-only), personality disorder (PD-only), and comorbid schizophrenia spectrum disorder and PD. The majority (93.7%) of all patients were prescribed at least one antipsychotic, and (27.5%) were on clozapine. Polypharmacy was prevalent in 22.2% and high-dose antipsychotic in 27.5%. Patients on clozapine were more likely to be prescribed antidiabetic, statins, or antihypertensive medication. Patients in the PD-only group were more likely to be deemed to have the capacity to consent to treatment and be prescribed clozapine in contrast to the SSD-only group.

Conclusions

Rates of clozapine and high-dose antipsychotic prescribing were higher than in other psychiatric settings, while polypharmacy prescribing rates were lower. Higher clozapine prescribing rates may be a function of a treatment-resistant and aggressive population. A higher proportion of PD-only patients consented to treatment and received clozapine compared with in-house SSD-only as well as other psychiatric settings. Implications of the findings are discussed.
One FIB Does It All: From Massive Ablation to Nanometer Precision
Authors: Kübler C. , Fladischer K. , Schultheiß K. , Hill R.
Published: January 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1
Authors: Yamaguchi Tomoya , Lu Can , Ida Lisa , Yanagisawa Kiyoshi , Usukura Jiro , Cheng Jinglei , Hotta Naoe , Shimada Yukako , Isomura Hisanori , Suzuki Motoshi , Fujimoto Toyoshi , Takahashi Takashi
Published: January 2016

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signalling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. Here we report an unanticipated function of this receptor tyrosine kinase (RTK) as a scaffold of cavin-1 and caveolin-1 (CAV1), two essential structural components of caveolae. This kinase-independent function of ROR1 facilitates the interactions of cavin-1 and CAV1 at the plasma membrane, thereby preventing the lysosomal degradation of CAV1. Caveolae structures and prosurvival signalling towards AKT through multiple RTKs are consequently sustained. These findings provide mechanistic insight into how ROR1 inhibition can overcome EGFR–tyrosine kinase inhibitor (TKI) resistance due to bypass signalling via diverse RTKs such as MET and IGF-IR, which is currently a major clinical obstacle. Considering its onco-embryonic expression, inhibition of the scaffold function of ROR1 in patients with lung adenocarcinoma is an attractive approach for improved treatment of this devastating cancer.
Unlocking new contrast in a scanning helium microscope
Authors: Barr M. , Fahy A. , Martens J. , Jardine A. P. , Ward D. J. , Ellis J. , Allison W. , Dastoor P. C.
Published: January 2016

Delicate structures (such as biological samples, organic films for polymer electronics and adsorbate layers) suffer degradation under the energetic probes of traditional microscopies. Furthermore, the charged nature of these probes presents difficulties when imaging with electric or magnetic fields, or for insulating materials where the addition of a conductive coating is not desirable. Scanning helium microscopy is able to image such structures completely non-destructively by taking advantage of a neutral helium beam as a chemically, electrically and magnetically inert probe of the sample surface. Here we present scanning helium micrographs demonstrating image contrast arising from a range of mechanisms including, for the first time, chemical contrast observed from a series of metal–semiconductor interfaces. The ability of scanning helium microscopy to distinguish between materials without the risk of damage makes it ideal for investigating a wide range of systems.
Multistep assembly of DNA condensation clusters by SMC
Authors: Kim HyeongJun , Loparo Joseph J.
Published: January 2016

SMC (structural maintenance of chromosomes) family members play essential roles in chromosome condensation, sister chromatid cohesion and DNA repair. It remains unclear how SMCs structure chromosomes and how their mechanochemical cycle regulates their interactions with DNA. Here we used single-molecule fluorescence microscopy to visualize how Bacillus subtilis SMC (BsSMC) interacts with flow-stretched DNAs. We report that BsSMC can slide on DNA, switching between static binding and diffusion. At higher concentrations, BsSMCs form clusters that condense DNA in a weakly ATP-dependent manner. ATP increases the apparent cooperativity of DNA condensation, demonstrating that BsSMC can interact cooperatively through their ATPase head domains. Consistent with these results, ATPase mutants compact DNA more slowly than wild-type BsSMC in the presence of ATP. Our results suggest that transiently static BsSMC molecules can nucleate the formation of clusters that act to locally condense the chromosome while forming long-range DNA bridges.
PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)
Authors: Liu Minetta C , Pitcher Brandelyn N , Mardis Elaine R , Davies Sherri R , Friedman Paula N , Snider Jacqueline E , Vickery Tammi L , Reed Jerry P , DeSchryver Katherine , Singh Baljit , Gradishar William J , Perez Edith A , Martino Silvana , Citron Marc L , Norton Larry , Winer Eric P , Hudis Clifford A , Carey Lisa A , Bernard Philip S , Nielsen Torsten O , Perou Charles M , Ellis Matthew J , Barry William T
Published: January 2016

PAM50 intrinsic breast cancer subtypes are prognostic independent of standard clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS) and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy. A significant interaction between intrinsic subtypes and DD-therapy benefit was hypothesized. Suitable tumor samples were available from 1,471 (73%) of 2,005 subjects. Multiplexed gene-expression profiling generated the PAM50 subtype call, proliferation score, and risk of recurrence score (ROR-PT) for the evaluable subset of 1,311 treated patients. The interaction between DD-therapy benefit and intrinsic subtype was tested in a Cox proportional hazards model using two-sided alpha=0.05. Additional multivariable Cox models evaluated the proliferation and ROR-PT scores as continuous measures with selected clinical covariates. Improved outcomes for DD therapy in the evaluable subset mirrored results from the complete data set (RFS; hazard ratio=1.20; 95% confidence interval=0.99–1.44) with 12.3-year median follow-up. Intrinsic subtypes were prognostic of RFS (P<0.0001) irrespective of treatment assignment. No subtype-specific treatment effect on RFS was identified (interaction P=0.44). Proliferation and ROR-PT scores were prognostic for RFS (both P<0.0001), but no association with treatment benefit was seen (P=0.14 and 0.59, respectively). Results were similar for OS. The prognostic value of PAM50 intrinsic subtype was greater than estrogen receptor/HER2 immunohistochemistry classification. PAM50 gene signatures were highly prognostic but did not predict for improved outcomes with DD anthracycline- and taxane-based therapy. Clinical validation studies will assess the ability of PAM50 and other gene signatures to stratify patients and individualize treatment based on expected risks of distant recurrence.
Effects of Testosterone Administration on Strategic Gambling in Poker Play
Authors: van Honk Jack , Will Geert-Jan , Terburg David , Raub Werner , Eisenegger Christoph , Buskens Vincent
Published: January 2016

Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone’s primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players’ bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one’s reputation by revealing deceptive intent and secondly, not calling the other players’ bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous.
Disorder-assisted quantum transport in suboptimal decoherence regimes
Authors: Novo Leonardo , Mohseni Masoud , Omar Yasser
Published: January 2016

We investigate quantum transport in binary tree structures and in hypercubes for the disordered Frenkel-exciton Hamiltonian under pure dephasing noise. We compute the energy transport efficiency as a function of disorder and dephasing rates. We demonstrate that dephasing improves transport efficiency not only in the disordered case, but also in the ordered one. The maximal transport efficiency is obtained when the dephasing timescale matches the hopping timescale, which represent new examples of the Goldilocks principle at the quantum scale. Remarkably, we find that in weak dephasing regimes, away from optimal levels of environmental fluctuations, the average effect of increasing disorder is to improve the transport efficiency until an optimal value for disorder is reached. Our results suggest that rational design of the site energies statistical distributions could lead to better performances in transport systems at nanoscale when their natural environments are far from the optimal dephasing regime.
Single-photon-multi-layer-interference lithography for high-aspect-ratio and three-dimensional SU-8 micro-/nanostructures
Authors: Ghosh Siddharth , Ananthasuresh G. K.
Published: January 2016

We report microstructures of SU-8 photo-sensitive polymer with high-aspect-ratio, which is defined as the ratio of height to in-plane feature size. The highest aspect ratio achieved in this work exceeds 250. A multi-layer and single-photon lithography approach is used in this work to expose SU-8 photoresist of thickness up to 100 μm. Here, multi-layer and time-lapsed writing is the key concept that enables nanometer localised controlled photo-induced polymerisation. We use a converging monochromatic laser beam of 405 nm wavelength with a controllable aperture. The reflection of the converging optics from the silicon substrate underneath is responsible for a trapezoidal edge profile of SU-8 microstructure. The reflection induced interfered point-spread-function and multi-layer-single-photon exposure helps to achieve sub-wavelength feature sizes. We obtained a 75 nm tip diameter on a pyramid shaped microstructure. The converging beam profile determines the number of multiple optical focal planes along the depth of field. These focal planes are scanned and exposed non-concurrently with varying energy dosage. It is notable that an un-automated height axis control is sufficient for this method. All of these contribute to realising super-high-aspect-ratio and 3D micro-/nanostructures using SU-8. Finally, we also address the critical problems of photoresist-based micro-/nanofabrication and their solutions.
A general way for quantitative magnetic measurement by transmitted electrons
Authors: Song Dongsheng , Li Gen , Cai Jianwang , Zhu Jing
Published: January 2016

EMCD (electron magnetic circular dichroism) technique opens a new door to explore magnetic properties by transmitted electrons. The recently developed site-specific EMCD technique makes it possible to obtain rich magnetic information from the Fe atoms sited at nonequivalent crystallographic planes in NiFe2O4, however it is based on a critical demand for the crystallographic structure of the testing sample. Here, we have further improved and tested the method for quantitative site-specific magnetic measurement applicable for more complex crystallographic structure by using the effective dynamical diffraction effects (general routine for selecting proper diffraction conditions, making use of the asymmetry of dynamical diffraction for design of experimental geometry and quantitative measurement, etc) and taken yttrium iron garnet (Y3Fe5O12, YIG) with more complex crystallographic structure as an example to demonstrate its applicability. As a result, the intrinsic magnetic circular dichroism signals, spin and orbital magnetic moment of iron with site-specific are quantitatively determined. The method will further promote the development of quantitative magnetic measurement with high spatial resolution by transmitted electrons.
Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
Authors: Jenum Synne , Dhanasekaran S. , Lodha Rakesh , Mukherjee Aparna , Kumar Saini Deepak , Singh Sarman , Singh Varinder , Medigeshi Guruprasad , Haks Marielle C. , Ottenhoff Tom H. M. , Doherty Timothy Mark , Kabra Sushil K. , Ritz Christian , Grewal Harleen M. S.
Published: January 2016

The World Health Organization (WHO) calls for an accurate, rapid and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1 and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).
Overexpression of HER-2 in MDA-MB-435/LCC6 Tumours is Associated with Higher Metabolic Activity and Lower Energy Stress
Authors: Dragowska Wieslawa H. , Ginj Mihaela , Kozlowski Piotr , Yung Andrew , Ruth Thomas J. , Adam Michael J. , Sossi Vesna , Bally Marcel B. , Yapp Donald T. T.
Published: January 2016

Overexpresssion of HER-2 in the MDA-MB-435/LCC6 (LCC6HER-2) tumour model is associated with significantly increased hypoxia and reduced necrosis compared to isogenic control tumours (LCC6Vector); this difference was not related to tumour size or changes in vascular architecture. To further evaluate factors responsible for HER-2-associated changes in the tumour microenvironment, small animal magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure tumour tissue perfusion and metabolism, respectively. The imaging data was further corroborated by analysis of molecular markers pertaining to energy homeostasis and measurements of hypoxia and glucose consumption. The results showed a strong trend towards higher perfusion rates (~58% greater, p = 0.14) and significantly higher glucose uptake in LCC6HER-2 (~2-fold greater; p = 0.025), relative to control tumours. The expression of proteins related to energy stress (P-AMPK, P-ACC) and glucose transporters (GLUT1) were lower in LCC6HER-2 tumours (~2- and ~4-fold, respectively). The in vitro analysis showed that LCC6HER-2 cells become more hypoxic in 1% oxygen and utilise significantly more glucose in normoxia compared to LCC6Vectorcells (p < 0.005). Amalgamation of all the data points suggests a novel metabolic adaptation driven by HER-2 overexpression where higher oxygen and glucose metabolic rates produce rich energy supply but also a more hypoxic tumour mass.
An Intriguing Correlation Based on the Superimposition of Residue Pairs with Inhibitors that Target Protein-Protein Interfaces
Authors: Nakadai Masakazu , Tomida Shuta , Sekimizu Kazuhisa
Published: January 2016

Druggable sites on protein-protein interfaces are difficult to predict. To survey inhibitor-binding sites onto which residues are superimposed at protein-protein interfaces, we analyzed publicly available information for 39 inhibitors that target the protein-protein interfaces of 8 drug targets. By focusing on the differences between residues that were superimposed with inhibitors and non-superimposed residues, we observed clear differences in the distances and changes in the solvent-accessible surface areas (∆SASA). Based on the observation that two or more residues were superimposed onto inhibitors in 37 (95%) of 39 protein-inhibitor complexes, we focused on the two-residue relationships. Application of a cross-validation procedure confirmed a linear negative correlation between the absolute value of the dihedral angle and the sum of the ∆SASAs of the residues. Finally, we applied the regression equation of this correlation to four inhibitors that bind to new sites not bound by the 39 inhibitors as well as additional inhibitors of different targets. Our results shed light on the two-residue correlation between the absolute value of the dihedral angle and the sum of the ∆SASA, which may be a useful relationship for identifying the key two-residues as potential targets of protein-protein interfaces.
Efficient Solar Energy Conversion Using CaCu3Ti4O12 Photoanode for Photocatalysis and Photoelectrocatalysis
Authors: Kushwaha H. S. , Madhar Niyaz A , Ilahi B. , Thomas P. , Halder Aditi , Vaish Rahul
Published: January 2016

A highly efficient third generation catalyst, CaCu3Ti4O12 (CCTO) shows excellent photoelectrochemical (PEC) and photocatalytic ability. As only 4% part of the solar spectrum covers UV light, thus it is highly desirable to develop visible light active photocatalyst materials like CCTO for effective solar energy conversion. A direct band transition with a narrow band gap (1.5 eV) was observed. Under light irradiation, high photocurrent density was found to be 0.96 mA/cm2, indicating the visible light induced photocatalytic ability of CCTO. Visible light mediated photocatalytic and photoelectrocatalytic degradation efficiency of CaCu3Ti4O12 pellets (CCTO) was investigated for three classes of pharmaceutical waste: erythrosin (dye), ciprofloxacin (antibiotic) and estriol (steroid). It is found that the degradation process follows first order kinetic reaction in electrocatalysis, photocatalysis and photoelectrocatalysis and high kinetic rate constant was observed in photoelectrocatalysis. This was quite high in comparison to previously reported methods.
The basal function of teleost prolactin as a key regulator on ion uptake identified with zebrafish knockout models
Authors: Shu Yuqin , Lou Qiyong , Dai Ziru , Dai Xiangyan , He Jiangyan , Hu Wei , Yin Zhan
Published: January 2016

Prolactin (PRL) is an anterior pituitary hormone with a broad range of functions. Its ability to stimulate lactogenesis, maternal behavior, growth and development, osmoregulation and epithelial ion transport has been reported in many vertebrates. In our present study, we have targeted the zebrafish prl locus via transcription activator-like effector nucleases (TALENs). Two independent targeted mutant lines with premature termination of the putative sequence of PRL peptides were generated. All prl-deficient zebrafish progeny died at 6–16 days post-fertilization stage (dpf) in egg water. However, the prl-deficient larvae thrived and survived through adulthood in brackish water (5175 mg/L ocean salts), without obvious defects in somatic growth or reproduction. When raised in egg water, the expression levels of certain key Na+/Cl− cotransporters in the gills and Na+/K+-ATPase subunits, Na+/H+ exchangers and Na+/Cl− transporters in the pronephros of prl-deficient larvae were down-regulated at 5 dpf, which caused Na+/K+/Cl− uptake defects in the mutant fish at 6 dpf. Our present results demonstrate that the primary function of zebrafish prl is osmoregulation via governing the uptake and homeostasis of Na+, K+ and Cl−. Our study provides valuable evidence to understand the mechanisms of PRL function better through both phylogenetic and physiological perspectives.
Snord116 is critical in the regulation of food intake and body weight
Authors: Qi Yue , Purtell Louise , Fu Melissa , Lee Nicola J. , Aepler Julia , Zhang Lei , Loh Kim , Enriquez Ronaldo F. , Baldock Paul A. , Zolotukhin Sergei , Campbell Lesley V. , Herzog Herbert
Published: January 2016

Prader-Willi syndrome (PWS) is the predominant genetic cause of obesity in humans. Recent clinical reports have suggested that micro-deletion of the Snord116 gene cluster can lead to PWS, however, the extent of the contributions of the encoded snoRNAs is unknown. Here we show that mice lacking Snord116 globally have low birth weight, increased body weight gain, energy expenditure and hyperphagia. Consistent with this, microarray analysis of hypothalamic gene expression revealed a significant alteration in feeding related pathways that was also confirmed by in situ hybridisation. Importantly, selective deletion of Snord116 only from NPY expressing neurons mimics almost exactly the global deletion phenotype including the persistent low birth weight, increased body weight gain in early adulthood, increased energy expenditure and hyperphagia. Mechanistically, the lack of Snord116 in NPY neurons leads to the upregulation of NPY mRNA consistent with the hyperphagic phenotype and suggests a critical role of Snord116 in the control of NPY neuronal functions that might be dysregulated in PWS.
Interspecific hybridization, polyploidization and backcross of Brassica oleracea var. alboglabra with B. rapa var. purpurea morphologically recapitulate the evolution of Brassica vegetables
Authors: Zhang Xiaohui , Liu Tongjin , Li Xixiang , Duan Mengmeng , Wang Jinglei , Qiu Yang , Wang Haiping , Song Jiangping , Shen Di
Published: January 2016

Brassica oleracea and B. rapa are two important vegetable crops. Both are composed of dozens of subspecies encompassing hundreds of varieties and cultivars. Synthetic B. napus with these two plants has been used extensively as a research model for the investigation of allopolyploid evolution. However, the mechanism underlying the explosive evolution of hundreds of varieties of B. oleracea and B. rapa within a short period is poorly understood. In the present study, interspecific hybridization between B. oleracea var. alboglabra and B. rapa var. purpurea was performed. The backcross progeny displayed extensive morphological variation, including some individuals that phenocopied subspecies other than their progenitors. Numerous interesting novel phenotypes and mutants were identified among the backcross progeny. The chromosomal recombination between the A and C genomes and the chromosomal asymmetric segregation were revealed using Simple Sequence Repeats (SSR) markers. These findings provide direct evidence in support of the hypothesis that interspecific hybridization and backcrossing have played roles in the evolution of the vast variety of vegetables among these species and suggest that combination of interspecific hybridization and backcrossing may facilitate the development of new mutants and novel phenotypes for both basic research and the breeding of new vegetable crops.
Physical activity and genetic predisposition to obesity in a multiethnic longitudinal study
Authors: Reddon Hudson , Gerstein Hertzel C. , Engert James C. , Mohan Viswanathan , Bosch Jackie , Desai Dipika , Bailey Swneke D. , Diaz Rafael , Yusuf Salim , Anand Sonia S. , Meyre David
Published: January 2016

Physical activity (PA) has been shown to reduce the impact of FTO variation and obesity genetic risk scores (GRS) on BMI. We examined this interaction using a quantitative measure of PA and two adiposity indexes in a longitudinal multi-ethnic study. We analyzed the impact of PA on the association between 14 obesity predisposing variants (analyzed independently and as a GRS) and baseline/follow-up obesity measures in the multi-ethnic prospective cohort EpiDREAM (17423 participants from six ethnic groups). PA was analyzed using basic (low-moderate-high) and quantitative measures (metabolic equivalents (METS)), while BMI and the body adiposity index (BAI) were used to measure obesity. Increased PA was associated with decreased BMI/BAI at baseline/follow-up. FTO rs1421085, CDKAL1 rs2206734, TNNl3K rs1514176, GIPR rs11671664 and the GRS were associated with obesity measures at baseline and/or follow-up. Risk alleles of three SNPs displayed nominal associations with increased (NTRK2 rs1211166, BDNF rs1401635) or decreased (NPC1 rs1805081) basic PA score independently of BMI/BAI. Both basic and quantitative PA measures attenuated the association between FTO rs1421085 risk allele and BMI/BAI at baseline and follow-up. Our results show that physical activity can blunt the genetic effect of FTO rs1421085 on adiposity by 36–75% in a longitudinal multi-ethnic cohort.