bluuebunny/crossref_metadata_2025 huggingface dataset:
p62 Binding to Protein Kinase C ζ Regulates Tumor Necrosis Factor α–Induced Apoptotic Pathway in Endothelial Cells
Authors: Kim Geun-Young , Nigro Patrizia , Fujiwara Keigi , Abe Jun-ichi , Berk Bradford C.
Published: September 2012

Objective—

Protein kinase C (PKC) ζ is a key pathological mediator of endothelial cell apoptosis. p62 is a scaffold protein that regulates several cell signaling pathways by binding to target proteins. Because PKCζ and p62 contain Phox/Bem1p (PB1) modules that mediate protein–protein interactions, we hypothesized that an interaction between p62 and PKCζ is required for tumor necrosis factor α–induced PKCζ signaling in endothelial cells.

Methods and Results—

In human umbilical vein endothelial cell, tumor necrosis factor α (10 ng/mL) enhanced the interaction between p62 and PKCζ. Transfection with p62 small interfering RNA reduced the activation of both PKCζ and its downstream targets JNK and caspase 3, suggesting that p62 is necessary for PKCζ signaling. Overexpression of only the PB1 domain of p62 inhibited p62–PKCζ interaction, showing that binding of these 2 proteins is mediated by their PB1 domains. Furthermore, overexpression of the p62 PB1 domain suppressed tumor necrosis factor α–induced PKCζ activation and subsequent activation of JNK and caspase 3. Finally, transfection of either p62 small interfering RNA or the PB1 domain of p62 inhibited human umbilical vein endothelial cell apoptosis.

Conclusion—

Our results suggest a novel function of p62 that regulates the activity of PKCζ by binding to PKCζ, thereby activating the PKCζ-JNK-caspase 3 apoptotic pathway in endothelial cells.
Multimarker Risk Assessment Including Osteoprotegerin and CXCL16 in Acute Coronary Syndromes
Authors: Jansson Anna M. , Hartford Marianne , Omland Torbjørn , Karlsson Thomas , Lindmarker Per , Herlitz Johan , Ueland Thor , Aukrust Pål , Caidahl Kenneth
Published: September 2012

Objective—

CXCL16 and osteoprotegerin (OPG) both predict mortality in acute coronary syndromes. We hypothesized that a combination of CXCL16 and OPG concentrations would add prognostic information to the Global Registry of Acute Coronary Events (GRACE) score in patients hospitalized for acute coronary syndromes.

Methods and Results—

We assessed the associations between circulating OPG and soluble CXCL16 levels, obtained within 24 hours of admission (day 1) and after 3 months, and mortality, heart failure and reinfarction in 1322 patients admitted with acute coronary syndromes. After adjustment for the GRACE score, medication, diabetes mellitus and sex, the combination of high values (fourth quartile) for OPG and CXCL16 at baseline was associated with increased short-term (3 months) cardiovascular mortality (hazard ratio, 3.28; 95% CI, 1.84–5.82;
P
<0.0001). The combined high values were also significantly associated with the long-term (median 91 months) prognosis after adjustment, with hazard ratios 2.18 for cardiovascular mortality (95% CI, 1.62–2.92;
P
<0.0001), and 2.22 for heart failure (95% CI, 1.67–2.96;
P
<0.0001). These long-term associations remained significant after further adjustment for left ventricular ejection fraction, C-reactive protein, and pro B-type natriuretic peptide. For 635 patients with blood samples within 24 hours and at 3 months, the combination of high CXCL16 and OPG values (fourth quartile) in the early or stable phase was of a similar order associated with mortality and morbidity beyond 3 months.

Conclusion—

Circulating CXCL16 and OPG are independent predictors of long-term mortality and heart failure development in acute coronary syndromes patients, even after extensive adjustments. Their combination gives more information than either marker alone.
Myeloid Deletion of Nuclear Factor Erythroid 2−Related Factor 2 Increases Atherosclerosis and Liver Injury
Authors: Collins Alan R. , Gupte Anisha A. , Ji Ruirui , Ramirez Maricela R. , Minze Laurie J. , Liu Joey Z. , Arredondo Magda , Ren Yuelan , Deng Tuo , Wang Jun , Lyon Christopher J. , Hsueh Willa A.
Published: September 2012

Objective—

To determine the impact of hematopoietic deletion of nuclear factor− (erythroid-derived 2) like 2 factor (Nrf2) on the development of atherosclerosis and liver injury in an obese, hypercholesterolemic mouse model.

Methods and Results—

Two-month-old male low-density lipoprotein receptor–deficient mice were lethally irradiated and transplanted with either wild type or Nrf2-deficient (Nrf2
−/−
) bone marrow cells. At 3 months of age, mice were placed on an obesogenic high-fat diet (HFD), high-cholesterol diet for 7 months. Despite no differences in body weight, body fat percentage, liver fat, plasma glucose, lipids, or insulin, the HFD-fed Nrf2
−/−
bone marrow recipients had increased proinflammatory vascular gene expression, a significant increase in atherosclerosis area (18% versus 28%;
P
=0.018) and lesion complexity, and a marked increase in liver fibrosis. The acceleration of vascular and liver injury may arise from enhanced macrophage migration, inflammation, and oxidative stress resulting from myeloid Nrf2 deficiency.

Conclusion—

Myeloid-derived Nrf2 activity attenuates atherosclerosis development and liver inflammation and fibrosis associated with obesity. Prevention of oxidative stress in macrophage and other myeloid lineage cells may be an important therapeutic target to reduce inflammation-driven complications of obesity.
Opposing Actions of Heat Shock Protein 90 and 70 Regulate Nicotinamide Adenine Dinucleotide Phosphate Oxidase Stability and Reactive Oxygen Species Production
Authors: Chen Feng , Yu Yanfang , Qian Jin , Wang Yusi , Cheng Bo , Dimitropoulou Christiana , Patel Vijay , Chadli Ahmed , Rudic R. Dan , Stepp David W. , Catravas John D. , Fulton David J.R.
Published: September 2012

Objective—

Excessive reactive oxygen species contribute to vascular dysfunction. We have previously shown that heat shock protein (Hsp90) inhibitors potently suppress Nox 1 to 3 and 5, and the goals of this study were to identify how molecular chaperones regulate Nox function.

Methods and Results—

In vitro, protein expression of Nox 1 to 2, 5 was decreased by Hsp90 inhibitors in multiple cell types (human pulmonary artery endothelial cells, neutrophils, macrophages, and human saphenous vein). In mice treated with Hsp90 inhibitors, Nox1 expression was reduced in lung along with reduced reactive oxygen species from leukocytes. Elevated reactive oxygen species production in obese (db/db) aorta was suppressed by Hsp90 inhibition. Hsp90 inhibitors did not alter Nox5 micro RNA levels, and proteasome inhibition prevented Nox2 and 5 protein degradation and increased ubiquitin incorporation. Inhibition of Hsp90 upregulated the expression of Hsp70 and Hsp70-bound Nox2, 5 and promoted degradation. Silencing Hsp70 prevented Hsp90 inhibitor–mediated degradation of Nox5. The Hsp70-regulated ubiquitin ligase, carboxyl terminus of Hsp70-interacting protein (CHIP), also bound Nox5 and promoted increased Nox5 ubiquitination and degradation. The chaperone binding and ubiquitination domains of CHIP were required, and the silencing of CHIP blunted Hsp90 inhibitor–mediated degradation of Nox2 and 5.

Conclusion—

We conclude that Hsp90 binds to and regulates Nox protein stability. These actions are opposed by Hsp70 and CHIP, which promote the ubiquitination and degradation of Nox proteins and reduce reactive oxygen species production.
Redox Signaling in Cardiac Physiology and Pathology
Authors: Burgoyne Joseph R. , Mongue-Din Héloïse , Eaton Philip , Shah Ajay M.
Published: September 2012

Redox signaling refers to the specific and usually reversible oxidation/reduction modification of molecules involved in cellular signaling pathways. In the heart, redox signaling regulates several physiological processes (eg, excitation-contraction coupling) and is involved in a wide variety of pathophysiological and homoeostatic or stress response pathways. Reactive oxygen species involved in cardiac redox signaling may derive from many sources, but NADPH oxidases, as dedicated sources of signaling reactive oxygen species, seem to be especially important. An increasing number of specific posttranslational oxidative modifications involved in cardiac redox signaling are being defined, along with the reactive oxygen species sources that are involved. Here, we review current knowledge on the molecular targets of signaling reactive oxygen species in cardiac cells and their involvement in cardiac physiopathology. Advances in this field may allow the development of targeted therapeutic strategies for conditions such as heart failure as opposed to the general antioxidant approaches that have failed to date.
The Great Divide: Campaign Media in the American Mind
Authors: Mutz Diana C.
Published: October 2012

There is a huge difference between public perceptions of the power of media in elections and academic evidence of its influence. This gap stems from the fact that the public uses different forms of evidence than academics use to infer media power. This essay outlines the reasons for this great divide, then highlights the seriousness of its consequences for the allocation of political resources. Public beliefs in omnipotent media contribute to wasted time and money; ultimately, they undermine the legitimacy of election outcomes.
Long-term Memories Bias Sensitivity and Target Selection in Complex Scenes
Authors: Patai Eva Zita , Doallo Sonia , Nobre Anna Christina
Published: September 2012

In everyday situations, we often rely on our memories to find what we are looking for in our cluttered environment. Recently, we developed a new experimental paradigm to investigate how long-term memory (LTM) can guide attention and showed how the pre-exposure to a complex scene in which a target location had been learned facilitated the detection of the transient appearance of the target at the remembered location [Summerfield, J. J., Rao, A., Garside, N., & Nobre, A. C. Biasing perception by spatial long-term memory. The Journal of Neuroscience, 31, 14952–14960, 2011; Summerfield, J. J., Lepsien, J., Gitelman, D. R., Mesulam, M. M., & Nobre, A. C. Orienting attention based on long-term memory experience. Neuron, 49, 905–916, 2006]. This study extends these findings by investigating whether and how LTM can enhance perceptual sensitivity to identify targets occurring within their complex scene context. Behavioral measures showed superior perceptual sensitivity (d′) for targets located in remembered spatial contexts. We used the N2pc ERP to test whether LTM modulated the process of selecting the target from its scene context. Surprisingly, in contrast to effects of visual spatial cues or implicit contextual cueing, LTM for target locations significantly attenuated the N2pc potential. We propose that the mechanism by which these explicitly available LTMs facilitate perceptual identification of targets may differ from mechanisms triggered by other types of top–down sources of information.
Disentangling Spatial Perception and Spatial Memory in the Hippocampus: A Univariate and Multivariate Pattern Analysis fMRI Study
Authors: Lee Andy C. H. , Brodersen Kay H. , Rudebeck Sarah R.
Published: September 2012

Although the role of the hippocampus in spatial cognition is well accepted, it is unclear whether its involvement is restricted to the mnemonic domain or also extends to perception. We used fMRI to scan neurologically healthy participants during a scene oddity judgment task that placed no explicit demand on long-term memory. Crucially, a surprise recognition test was administered after scanning so that each trial could be categorized not only according to oddity accuracy but also according to subsequent memory. Univariate analyses showed significant hippocampal activity in association with correct oddity judgment, whereas greater parahippocampal place area (PPA) activity was observed during incorrect oddity trials, both irrespective of subsequent recognition performance. Consistent with this, multivariate pattern analyses revealed that a linear support vector machine was able to distinguish correct from incorrect oddity trials on the basis of activity in voxels within the hippocampus or PPA. Although no significant regions of activity were identified by univariate analyses in association with memory performance, a classifier was able to predict subsequent memory using voxels in either the hippocampus or PPA. Our findings are consistent with the idea that the hippocampus is important for processes beyond long-term declarative memory and that this structure may also play a role in complex spatial perception.
Less Is Not More: Neural Responses to Missing and Superfluous Accents in Context
Authors: Dimitrova Diana V. , Stowe Laurie A. , Redeker Gisela , Hoeks John C. J.
Published: September 2012

Prosody, particularly accent, aids comprehension by drawing attention to important elements such as the information that answers a question. A study using ERP registration investigated how the brain deals with the interpretation of prosodic prominence. Sentences were embedded in short dialogues and contained accented elements that were congruous or incongruous with respect to a preceding question. In contrast to previous studies, no explicit prosodic judgment task was added. Robust effects of accentuation were evident in the form of an “accent positivity” (200–500 msec) for accented elements irrespective of their congruity. Our results show that incongruously accented elements, that is, superfluous accents, activate a specific set of neural systems that is inactive in case of incongruously unaccented elements, that is, missing accents. Superfluous accents triggered an early positivity around 100 msec poststimulus, followed by a right-lateralized negative effect (N400). This response suggests that redundant information is identified immediately and leads to the activation of a neural system that is associated with semantic processing (N400). No such effects were found when contextually expected accents were missing. In a later time window, both missing and superfluous accents triggered a late positivity on midline electrodes, presumably related to making sense of both kinds of mismatching stimuli. These results challenge previous findings of greater processing for missing accents and suggest that the natural processing of prosody involves a set of distinct, temporally organized neural systems.
Ten Trenches: A Science-Art Collaboration
Authors: Cohen T.J. , Cohen M.A. , Kermode S.J.K , Leggett Mike
Published: September 2012

Collaborative and cross-disciplinary research by a group of artists and scientists in an Australian rural setting generates data and ideas that form the basis of a wider understanding of the ramifications of global warming and cooling within the local, regional and national community. The work is viewed as an initial educational platform that will allow the public to see and understand the complexities of climate-based research.
Collaboration and Coordination in the Creation of New Music
Authors: Hooper Michael
Published: September 2012

Christopher Redgate is developing a new oboe for the 21st century and is working with composers to develop new music for the instrument. This article addresses the early stages of his collaboration with Sam Hayden. It demonstrates some of the coordination problems at the inception of a project that includes an instrument with a long history. The article sets out some of the ongoing concerns in documenting this work, arguing that the oboe itself is one of the principle forces shaping a collaboration that is future-focused.
Readymade and Assemblage in Database Art
Authors: Hsu Wun-Ting , Lai Wen-Shu
Published: September 2012

This paper aims to elucidate the concept of data as readymade and to discuss how data collection and viewer intervention constitute assemblage in database art. After a brief overview of the concepts, insights are provided into how they may be rendered in database art and what meaningful implications such process might yield.
Cloud Chamber: A Performance with Real Time Two-Way Interaction between Subatomic Particles and Violinist
Authors: Kirke Alexis , Miranda Eduardo , Chiaramonte Antonino , Troisi Anna R. , Matthias John , Fry Nicholas , McCabe Catherine , Radtke Jeff , Bull Martyn
Published: September 2012

‘Cloud Chamber’ - a composition by Alexis Kirke, Antonino Chiaramonte, and Anna Troisi - is a live performance in which the invisible quantum world becomes visible as a violinist and subatomic particle tracks interact together. An electronic instrument was developed which can be “played” live by radioactive atomic particles. Electronic circuitry was developed enabling a violin to create a physical force field that directly affects the ions generated by cosmic radiation particles. This enabled the violinist and the ions to influence each other musically in real time. A glass cloud chamber was used onstage to make radioactivity visible in bright white tracks moving within, with the tracks projected onto a large screen.
The Medium-Sensitive Experience and the Paradigmatic Experience of the Grotesque, “Unnatural” or “Monstrous”
Authors: van den Oever A.M.A.
Published: September 2012

To create the conceptual space to analyze the evident and structural similarities between the art experience, the (new) media experience, and the media art experience, the author approaches the “medium” as “techniques” which “make [the seen] strange.” A disruption of the perceptual process, a destabilization of the cognitive routines, a sudden sensitivity to the medium and an instant emotional response are at the heart of these (art) experiences. The author argues that the (well-studied) experience of the grotesque provides a model for the analysis of these (understudied) medium-sensitive experiences of the “strange” or “unnatural,” for which the grotesque experience is emblematic.
Point-Process Principal Components Analysis via Geometric Optimization
Authors: Solo Victor , Pasha Syed Ahmed
Published: September 2012

There has been a fast-growing demand for analysis tools for multivariate point-process data driven by work in neural coding and, more recently, high-frequency finance. Here we develop a true or exact (as opposed to one based on time binning) principal components analysis for preliminary processing of multivariate point processes. We provide a maximum likelihood estimator, an algorithm for maximization involving steepest ascent on two Stiefel manifolds, and novel constrained asymptotic analysis. The method is illustrated with a simulation and compared with a binning approach.
Computing Sparse Representations of Multidimensional Signals Using Kronecker Bases
Authors: Caiafa Cesar F. , Cichocki Andrzej
Published: September 2012

Recently there has been great interest in sparse representations of signals under the assumption that signals (data sets) can be well approximated by a linear combination of few elements of a known basis (dictionary). Many algorithms have been developed to find such representations for one-dimensional signals (vectors), which requires finding the sparsest solution of an underdetermined linear system of algebraic equations. In this letter, we generalize the theory of sparse representations of vectors to multiway arrays (tensors)—signals with a multidimensional structure—by using the Tucker model. Thus, the problem is reduced to solving a large-scale underdetermined linear system of equations possessing a Kronecker structure, for which we have developed a greedy algorithm, Kronecker-OMP, as a generalization of the classical orthogonal matching pursuit (OMP) algorithm for vectors. We also introduce the concept of multiway block-sparse representation of N-way arrays and develop a new greedy algorithm that exploits not only the Kronecker structure but also block sparsity. This allows us to derive a very fast and memory-efficient algorithm called N-BOMP (N-way block OMP). We theoretically demonstrate that under the block-sparsity assumption, our N-BOMP algorithm not only has a considerably lower complexity but is also more precise than the classic OMP algorithm. Moreover, our algorithms can be used for very large-scale problems, which are intractable using standard approaches. We provide several simulations illustrating our results and comparing our algorithms to classical algorithms such as OMP and BP (basis pursuit) algorithms. We also apply the N-BOMP algorithm as a fast solution for the compressed sensing (CS) problem with large-scale data sets, in particular, for 2D compressive imaging (CI) and 3D hyperspectral CI, and we show examples with real-world multidimensional signals.
A Model of the Differential Representation of Signal Novelty in the Local Field Potentials and Spiking Activity of the Ventrolateral Prefrontal Cortex
Authors: Lee Jung Hoon , Tsunada Joji , Cohen Yale E.
Published: September 2012

Local field potentials (LFPs) and spiking activity reflect different types of information procssing. For example, neurophysiological studies indicate that signal novelty in the ventrolateral prefrontal cortex is differentially represented by LFPs and spiking activity: LFPs habituate to repeated stimulus presentations, whereas spiking activity does not. The neural mechanisms that allow for this differential representation between LFPs and spiking activity are not clear. Here, we model and simulate LFPs and spiking activity of neurons in the ventrolateral prefrontal cortex in order to elucidate potential mechanisms underlying this differential representation. We demonstrate that dynamic negative-feedback loops cause LFPs to habituate in response to repeated presentations of the same stimulus while spiking activity is maintained. This disassociation between LFPs and spiking activity may be a mechanism by which LFPs code stimulus novelty, whereas spiking activity carries abstract information, such as category membership and decision-related activity.
The Importance of Accurately Measuring the Range Correlation for Range-Oversampling Processing
Authors: Torres Sebastián M. , Curtis Christopher D.
Published: September 2012

A fundamental assumption for the application of range-oversampling techniques is that the correlation of oversampled signals in range is accurately known. In this paper, a theoretical framework is derived to quantify the effects of inaccurate range correlation measurements on the performance of such techniques, which include digital matched filtering and those based on decorrelation (whitening) transformations. It is demonstrated that significant reflectivity biases and increased variance of estimates can occur if the range correlation is not accurately measured. Simulations and real data are used to validate the theoretical results and to illustrate the detrimental effects of mismeasurements. Results from this work underline the need for reliable calibration in the context of range-oversampling processing, and they can be used to establish appropriate accuracy requirements for the measurement of the range correlation on modern weather radars.
School Leaders’ Perceptions About Incompetent Teachers
Authors: Range Bret G. , Duncan Heather E. , Scherz Susan Day , Haines Courtney A.
Published: September 2012

This study explored Wyoming school leaders’ perceptions about the traits of incompetent teachers, strategies used to work with incompetent teachers, and the barriers to their dismissal. Most importantly, this study differentiated how principals and superintendents viewed incompetency issues. Some major findings include school leaders’ beliefs that classroom management problems were an indicator of incompetence, counseling to leave the profession was a strategy used with incompetent teachers, and teacher unions were a barrier to their dismissal.
Legal status and positive practice in Community Order enforcement
Authors: Cairns Ralph
Published: September 2012

The status of enforcement procedures may appear at first glance to be an academic debate with little application to probation practice. Yet the answer to this singular question determines how probation trusts should respond to a variety of court based challenges, which if mishandled has the potential to open the door to litigation against individual trusts. A breach of a community order is not a criminal offence, nor do enforcement proceedings form part of the criminal law. Regulatory statutes such as the Criminal Procedures and Investigations Act therefore do not apply. However, English case law has determined that a criminal standard of proof applies to enforcement cases and therefore some elements of the Criminal Procedure Rules do have resonance. Yet there is no right of appeal against a finding of breach and avenues of redress for both offender and the prosecution are limited to general provisions enshrined in English Law. Uncertainty surrounds the admissibility of other evidential areas. The robustness of evidence presented to the court can be improved by relatively modest amendments to practice and forestall possible 'reasonable excuse' defences. However other initiatives derived from general legal practice, are fraught with potential dangers when applied to Community Order enforcement.
Working with South Asian male perpetrators of intimate partner violence in British Columbia, Canada
Authors: Thandi Gurjit
Published: September 2012

This article outlines effective intervention strategies for probation officers working with South Asian men in British Columbia, Canada, who have assaulted their partners. It is part of a larger qualitative research study aimed at determining effective intervention strategies for frontline personnel that work with South Asian men, as well as determining effective prevention strategies aimed at policy makers and members of South Asian communities. Seventeen in-depth interviews were conducted with South Asian frontline workers that included police officers, probation officers, counsellors, child protection workers and victim service workers. The audio-taped data was transcribed and analysed by identification of themes and subthemes. Probation officers need to respect their clients’ cultural values while still holding these men accountable for their behaviour. Interventions that address patriarchal attitudes, the stressors arising out of immigration/acculturation, influence of extended family, and substance abuse were identified as being key factors in changing behaviour.
Counterfeit DVD street sellers
Authors: McDermott Shelly-Ann
Published: September 2012

Capturing ‘serious career criminals’ is pivotal within intellectual property crime enforcement (SOCA, 2010a: 1; SOCA, 2010b). There is also acknowledgement that organized criminals often trap undocumented migrants ‘into a cycle of exploitation’ to perform street level offences (SOCA, 2010c: 1; Chin, 2000). Fifteen magistrates’ court pre-sentence reports were analysed in order to identify whether these classifications adequately describe counterfeit DVD street sellers. The key findings suggest that a humanistic perspective is needed to highlight that street sellers encounter poor material circumstances (Grover, 2005).
Vision narratives, hope and transitions in the Antipodes
Authors: Opie Anne
Published: September 2012

The transition from prison is a crucial phase in the complex and lengthy desistance process but there is little New Zealand-based research on prisoners’ experiences of transitions. This article reports on one aspect of a qualitative study on transitions by focusing on two prisoners’ ‘vision narratives’ about hopeful accounts of becoming people who can make a positive contribution in the future. The article argues that working with those still in prison to develop vision narratives could be a valuable, initial means of enabling them to begin the journey towards desistance. This approach, however, would require a substantial modification of public and criminal justice discourses and correctional policies and practices.
‘Asset: An assessment tool that safeguards or stigmatizes young offenders?’
Authors: Shepherd Becky
Published: September 2012

This article is a response to Tracy Almond’s article ‘Asset: an assessment tool that safeguards or stigmatizes young offenders?’ Almond takes the position that Asset, the Youth Justice Board assessment tool, is poorly designed, labels young people unhelpfully, and that the criminal justice system (CJS)’s approach to dealing with young people is increasingly out of step with the social care approach. She explores developments in alternative approaches to working with young people which would be more ethical, and concludes that Asset is structurally inadequate and morally unsound.
Fractional order controller design for desired response
Authors: Boudjehem Badreddine , Boudjehem Djalil
Published: October 2012

This article presents a design method for a fractional order controller based on using fractional order systems with time delay as the desired transfer function response. The method is applied to various typical stable processes. Obtained fractional controllers may be considered as a special case of fractional proportional–integral–derivatives. Analytical expressions are derived to determine the fractional controller parameters. Diffusive representation is used to achieve the fractional systems by a rational transfer function. Illustrative examples are considered to show the effectiveness of the proposed method. The desired specifications are fulfilled with a good accuracy using fractional controllers, in comparison with the conventional controllers.
Framing the consumer
Authors: Edwards Lee , Klein Bethany , Lee David , Moss Giles , Philip Fiona
Published: September 2012

With illegal downloading at the centre of debates about the creative economy, various policy initiatives and regulatory attempts have tried (and largely failed) to control, persuade and punish users into adhering to copyright law. Rights holders, policymakers, intermediaries and users each circulate and maintain particular attitudes about appropriate uses of digital media. This article maps the failure of regulation to control user behaviour, considers various policy and academic research approaches to understanding users, and introduces an analytical framework that re-evaluates user resistance as expressions of legitimate justifications. A democratic copyright policymaking process must accommodate the modes of justification offered by users to allow copyright law to reconnect with the public interest goals at its foundation.
Digital technologies and musical participation for people with intellectual disabilities
Authors: Adkins Barbara , Summerville Jennifer , Knox Marie , Brown Andrew R. , Dillon Steven
Published: October 2012

Research on the aspirations of people with intellectual disabilities documents the importance of alternative zones of inclusion where they can assert their own definitions of ability and normality. This stands in contrast to assumptions concerning technology and disability that position technology as ‘normalizing’ the disabled body. This paper reports on the role of a digital music jamming tool in providing access to creative practice by people with intellectual disabilities. The tool contributed to the development of a spatio-temporal zone to enable aesthetic agency within and beyond the contexts of deinstitutionalized care. The research identifies the interactions between tools, individuals and groups that facilitated participants’ agency in shaping the form of musical practice. Furthermore, we document the properties of emergent interaction − supported by a tool oriented to enabling music improvisation − as potentially resisting assumptions regarding normalization.
Nocturnal gastro-oesophageal reflux, asthma and symptoms of OSA: a longitudinal, general population study
Authors: Emilsson Össur I. , Bengtsson Anna , Franklin Karl A. , Torén Kjell , Benediktsdóttir Bryndís , Farkhooy Amir , Weyler Joost , Dom Sandra , De Backer Wilfried , Gislason Thorarinn , Janson Christer
Published: September 2012

Nocturnal gastro-oesophageal reflux (nGOR) is associated with asthma and obstructive sleep apnoea (OSA). Our aim was to investigate whether nGOR is a risk factor for onset of asthma and onset of respiratory and OSA symptoms in a prospective population-based study.

We invited 2640 subjects from Iceland, Sweden and Belgium for two evaluations over a 9-year interval. They participated in structured interviews, answered questionnaires, and underwent spirometries and methacholine challenge testing. nGOR was defined by reported symptoms.

Subjects with persistent nGOR (n=123) had an independent increased risk of new asthma at follow-up (OR 2.3, 95% CI 1.1–4.9). Persistent nGOR was independently related to onset of respiratory symptoms (OR 3.0, 95% CI 1.6–5.6). The risk of developing symptoms of OSA was increased in subjects with new and persistent nGOR (OR 2.2, 95% CI 1.3–1.6, and OR 2.0, 95% CI 1.0–3.7, respectively). No significant association was found between nGOR and lung function or bronchial responsiveness.

Persistent symptoms of nGOR contribute to the development of asthma and respiratory symptoms. New onset of OSA symptoms is higher among subjects with symptoms of nGOR. These findings provide evidence that nGOR may play a role in the genesis of respiratory symptoms and diseases.
Echocardiographic abnormalities in patients with COPD at their first hospital admission
Authors: Freixa Xavier , Portillo Karina , Paré Carles , Garcia-Aymerich Judith , Gomez Federico P. , Benet Marta , Roca Josep , Farrero Eva , Ferrer Jaume , Fernandez-Palomeque Carlos , Antó Josep M. , Barberà Joan Albert
Published: September 2012

Cardiovascular disease accounts for significant morbidity and mortality in chronic obstructive pulmonary disease (COPD). Its prevalence and mechanisms of association have not been elucidated. The study aimed to assess the prevalence of echocardiographic abnormalities and potential risk factors in patients with COPD at their first exacerbation requiring hospital admission.

Transthoracic echocardiography was prospectively performed in 342 patients (forced expiratory volume in 1 s 52±16% predicted) 3 months after discharge.

Significant cardiac alterations were present in 64% of patients; 27% left- and 48% right-heart disorders. The most common were right ventricle enlargement (30%) and pulmonary hypertension (19%). Left ventricle enlargement was present in 6%, left ventricle systolic dysfunction in 13%, left ventricle diastolic impairment in 12% and left atrial dilatation in 29%. Echocardiographic abnormalities were unrelated to COPD severity and were more frequent in patients with self-reported cardiac disease. They were also observed in 63% of patients with no known cardiac disease or cardiovascular risk factors other than smoking.

We conclude that cardiac abnormalities are highly prevalent in COPD patients at the time of their first severe exacerbation, even in the absence of established cardiac disease or cardiovascular risk factors. Considering the prognostic and therapeutic implications of cardiac comorbidity, echocardiography should be considered in the assessment of patients with clinically significant COPD.
Aquaporin 3 (AQP3) participates in the cytotoxic response to nucleoside-derived drugs
Authors: Trigueros-Motos Laia , Pérez-Torras Sandra , Casado F Javier , Molina-Arcas Míriam , Pastor-Anglada Marçal
Published: September 2012

Background

Nucleoside analogs used in the chemotherapy of solid tumors, such as the capecitabine catabolite 5′-deoxy-5-fluorouridine (5′-DFUR) trigger a transcriptomic response that involves the aquaglyceroporin aquaporin 3 along with other p53-dependent genes. Here, we examined whether up-regulation of aquaporin 3 (AQP3) mRNA in cancer cells treated with 5′-DFUR represents a collateral transcriptomic effect of the drug, or conversely, AQP3 participates in the activity of genotoxic agents.

Methods

The role of AQP3 in cell volume increase, cytotoxicity and cell cycle arrest was analyzed using loss-of-function approaches.

Results

5′-DFUR and gemcitabine, but not cisplatin, stimulated AQP3 expression and cell volume, which was partially and significantly blocked by knockdown of AQP3. Moreover, AQP3 siRNA significantly blocked other effects of nucleoside analogs, including G1/S cell cycle arrest, p21 and FAS up-regulation, and cell growth inhibition. Short incubations with 5-fluorouracil (5-FU) also induced AQP3 expression and increased cell volume, and the inhibition of AQP3 expression significantly blocked growth inhibition triggered by this drug. To further establish whether AQP3 induction is related to cell cycle arrest and apoptosis, cells were exposed to long incubations with escalating doses of 5-FU. AQP3 was highly up-regulated at doses associated with cell cycle arrest, whereas at doses promoting apoptosis induction of AQP3 mRNA expression was reduced.

Conclusions

Based on the results, we propose that the aquaglyceroporin AQP3 is required for cytotoxic activity of 5’-DFUR and gemcitabine in the breast cancer cell line MCF7 and the colon adenocarcinoma cell line HT29, and is implicated in cell volume increase and cell cycle arrest.
Effect of surface ligands on the optical properties of aqueous soluble CdTe quantum dots
Authors: Silva Fernanda O , Carvalho Melissa S , Mendonça Renato , Macedo Waldemar AA , Balzuweit Karla , Reiss Peter , Schiavon Marco A
Published: September 2012

We investigate systematically the influence of the nature of thiol-type capping ligands on the optical and structural properties of highly luminescent CdTe quantum dots synthesized in aqueous media, comparing mercaptopropionic acid (MPA), thioglycolic acid (TGA), 1-thioglycerol (TGH), and glutathione (GSH). The growth rate, size distribution, and quantum yield strongly depend on the type of surface ligand used. While TGH binds too strongly to the nanocrystal surface inhibiting growth, the use of GSH results in the fastest growth kinetics. TGA and MPA show intermediate growth kinetics, but MPA yields a much lower initial size distribution than TGA. The obtained fluorescence quantum yields range from 38% to 73%. XPS studies unambiguously put into evidence the formation of a CdS shell on the CdTe core due to the thermal decomposition of the capping ligands. This shell is thicker when GSH is used as ligand, as compared with TGA ligands.
Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma
Authors: Saelen Marie Grøn , Ree Anne Hansen , Kristian Alexandr , Fleten Karianne Giller , Furre Torbjørn , Hektoen Helga Helseth , Flatmark Kjersti
Published: September 2012

Background

The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials.

Methods

Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models.

Results

Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth.

Conclusions

Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.
Impaired self-other differentiation in frontotemporal dementia due to the C9ORF72 expansion
Authors: Downey Laura E , Mahoney Colin J , Rossor Martin N , Crutch Sebastian J , Warren Jason D
Published: September 2012

Introduction

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as an important cause of frontotemporal dementia and motor neuron disease; however, the phenotypic spectrum of this entity and its pathophysiologic basis have yet to be fully defined. Psychiatric features may be early and prominent, although a putative cortico-thalamo-cerebellar network has been implicated in the pathogenesis of the clinical phenotype. Differentiation of self from others is a core cognitive operation that could potentially link network disintegration with neuropsychiatric symptoms in C9ORF72-associated frontotemporal dementia.

Methods

We undertook a detailed behavioral analysis of self-other attribution in a 67-year-old male patient with behavioral variant frontotemporal dementia (bvFTD) due to the C9ORF72 expansion by using a novel paradigm requiring differentiation of the effects of self- and non-self-generated actions. The patient's performance was assessed in relation to two older male patients with bvFTD not attributable to the C9ORF72 expansion and four healthy older male subjects.

Results

Compared with the healthy control group, the patient with the C9OFR72 mutation showed a deficit of self-other differentiation that was disproportionate to his otherwise relatively indolent clinical phenotype. The performance of the other patients with bvFTD was similar to that of healthy subjects.

Conclusion

We propose that impaired self-other differentiation is a candidate mechanism for neuropsychiatric decline in association with the C9ORF72 expansion. We offer this preliminary observation as a stimulus to further work.
Numerical simulation of radiation, reflection, and reception of elastic waves from a borehole dipole source
Authors: Wei Zhou-Tuo , Tang Xiao-Ming
Published: September 2012

A recent advance in single-well reflection imaging is the use of a dipole acoustic system in a borehole to radiate and receive elastic waves to and from a remote geologic reflector in formation. This dipole-acoustic imaging technology is evaluated by numerically simulating the radiation and reflection of the wavefield generated by the borehole dipole source and analyzing the receiving sensitivity of the dipole system to the incoming reflected waves. The analyses show that a borehole dipole source can radiate a compressional wave (P-wave) and two types of shear waves (i.e., SV- and SH-waves) into the formation. The SH-wave has wide radiation coverage and the best receiving sensitivity, and is most suitable for dipole-shear imaging. In an acoustically slow formation, the dipole-generated P-wave has strong receiving sensitivity and can also be used for reflection imaging. An important feature of dipole imaging is its sensitivity to reflector azimuth, which results from the directivity of the dipole source. By using a 4C data acquisition method to record the dipole-generated reflected signal, the reflector azimuth can be determined. The numerical simulation and theoretical analysis results are in good agreement, providing a solid foundation for the dipole acoustic imaging technology.
A cracked porous medium elastic wave theory and its application to interpreting acoustic data from tight formations
Authors: Tang Xiao-Ming , Chen Xue-lian , Xu Xiao-kai
Published: September 2012

Rocks in the earth’s crust usually contain pores and cracks. Typical examples include tight sandstone and shale rocks that have low porosity but contain abundant microcracks. By extending the classic Biot’s poroelastic wave theory to include the effects of cracks, we obtain an elastic wave theory for porous rocks containing cracks, adding crack density and aspect ratio as two important parameters to the original theory. Because the flat- or narrow-shaped cracks can easily deform under acoustic wave excitation, the acoustic property of a cracked porous rock is quite different for different saturation conditions. The predicted fluid sensitivity is used to interpret acoustic velocity log data from tight sand and shale gas formations. In both scenarios, the new theory correctly predicts the trend of velocity variation with gas saturation. The results confirm that the presence of cracks in tight rocks can give rise to significant hydrocarbon signature in the acoustic measurement data, allowing for identifying hydrocarbons from the data.
Standard metabolic rate is associated with gestation duration, but not clutch size, in speckled cockroachesNauphoeta cinerea
Authors: Schimpf Natalie G. , Matthews Philip G. D. , White Craig R.
Published: September 2012

Metabolic rate varies significantly between individuals, and these differences persist even when the wide range of biotic and abiotic factors that influence metabolism are accounted for. It is important to understand the life history implications of variation in metabolic rate, but they remain poorly characterised despite a growing body of work examining relationships between metabolism and a range of traits. In the present study we used laboratory-bred families (one sire to three dams) of Nauphoeta cinerea (Olivier) (speckled cockroaches) to examine the relationship between standard metabolic rate (SMR) and reproductive performance (number of offspring and gestation duration). We show that SMR is negatively associated with female gestation duration. Age at mating is negatively associated with gestation duration for females, and mass is negatively associated with the average gestation duration of the females a male was mated with. In addition to the results in the current literature, the results from the present study suggest that the association between metabolism and life history is more complex than simple relationships between metabolism and various fitness traits. Future work should consider longitudinal, ontogenetic as well as selective and quantitative genetic breeding approaches to fully examine the associations between metabolism and fitness.
Longer-Term Impacts of Mentoring, Educational Services, and Learning Incentives: Evidence from a Randomized Trial in the United States
Authors: Rodríguez-Planas Núria
Published: September 2012

This paper reports on a randomized evaluation of a program designed to improve high school graduation and postsecondary education enrollment among low-performing high school students. Treated youths were offered mentoring, educational services, and financial rewards. The program was evaluated when the youths were 19, 21, and 24 years old. Treated youths obtained their high school diplomas earlier and were more likely than controls to attend postsecondary education. Five years after the end of the program, we find no significant overall effects of this intervention on employment outcomes. The program improved outcomes to a greater extent for the female enrollees than the male ones. (JEL D83, I21, I28, J13)
Deregulation, Consolidation, and Efficiency: Evidence from US Nuclear Power
Authors: Davis Lucas W , Wolfram Catherine
Published: September 2012

Beginning in the late 1990s, electricity markets in many US states were deregulated, and almost half of the nation's 103 nuclear power reactors were sold to independent power producers. Deregulation has been accompanied by substantial market consolidation, and today the three largest companies control one-third of US nuclear capacity. We find that deregulation and consolidation are associated with a 10 percent increase in operating performance, achieved primarily by reducing the duration of reactor outages. At average wholesale prices, this increased operating performance is worth $2.5 billion annually and implies an annual decrease of 35 million tons of carbon dioxide emissions. (JEL L11, L51, L94, L98, Q42, Q48)