bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances of Cobalt(II/III) Redox Couples for Dye‐Sensitized Solar Cell Applications
Authors: Giribabu Lingamallu , Bolligarla Ramababu , Panigrahi Mallika
Published: June 2015

In recent years dye‐sensitized solar cells (DSSCs) have emerged as one of the alternatives for the global energy crisis. DSSCs have achieved a certified efficiency of >11% by using the I−/I3− redox couple. In order to commercialize the technology almost all components of the device have to be improved. Among the various components of DSSCs, the redox couple that regenerates the oxidized sensitizer plays a crucial role in achieving high efficiency and durability of the cell. However, the I−/I3− redox couple has certain limitations such as the absorption of triiodide up to 430 nm and the volatile nature of iodine, which also corrodes the silver‐based current collectors. These limitations are obstructing the commercialization of this technology. For this reason, one has to identify alternative redox couples. In this regard, the Co(II/III) redox couple is found to be the best alternative to the existing I−/I3− redox couple. Recently, DSSC test cell efficiency has risen up to 13% by using the cobalt redox couple. This review emphasizes the recent development of Co(II/III) redox couples for DSSC applications.
Sensitivity, Causality, and Statistical Evidence in Courts of Law
Authors: Blome-Tillmann Michael ,   Philosophy Documentation Center
Published: June 2015

Recent attempts to resolve the Paradox of the Gatecrasher rest on a now familiar distinction between individual and bare statistical evidence. This paper investigates two such approaches, the causal approach to individual evidence and a recently influential (and award-winning) modal account that explicates individual evidence in terms of Nozick’s notion of sensitivity. This paper offers counterexamples to both approaches, explicates a problem concerning necessary truths for the sensitivity account, and argues that either view is implausibly committed to the impossibility of no-fault wrongful convictions. The paper finally concludes that the distinction between individual and bare statistical evidence cannot be maintained in terms of causation or sensitivity. We have to look elsewhere for a solution of the Paradox of the Gatecrasher.
Here to Stay: Anti-establishment Parties in Europe
Authors: Hartleb Florian
Published: June 2015

Public attention has been drawn to the recent successes of the far right. This article claims that a new wave of anti-establishment parties has shaken European politics. A diverse array of outsiders from the left, right and no fixed ideological abode are attacking the mainstream centre–left and centre–right. Their anti-elitist approaches to politics have strategy, topics and style in common. Examples such as Syriza (The Coalition of the Radical Left), Podemos (We can!) and the Five Star Movement (MoVimento Cinque Stelle) show that this provocative new spectre of the twenty-first century is not just right wing.
Induction of Antioxidant and Heat Shock Protein Responses During Torpor in the Gray Mouse Lemur, Microcebus Murinus
Authors: Wu Cheng-Wei , Biggar Kyle K. , Zhang Jing , Tessier Shannon N. , Pifferi Fabien , Perret Martine , Storey Kenneth B.
Published: June 2015

A natural tolerance of various environmental stresses is typically supported by various cytoprotective mechanisms that protect macromolecules and promote extended viability. Among these are antioxidant defenses that help to limit damage from reactive oxygen species and chaperones that help to minimize protein misfolding or unfolding under stress conditions. To understand the molecular mechanisms that act to protect cells during primate torpor, the present study characterizes antioxidant and heat shock protein (HSP) responses in various organs of control (aroused) and torpid gray mouse lemurs, Microcebus murinus. Protein expression of HSP70 and HSP90α was elevated to 1.26 and 1.49 fold, respectively, in brown adipose tissue during torpor as compared with control animals, whereas HSP60 in liver of torpid animals was 1.15 fold of that in control (P  < 0.05). Among antioxidant enzymes, protein levels of thioredoxin 1 were elevated to 2.19 fold in white adipose tissue during torpor, whereas Cu–Zn superoxide dismutase 1 levels rose to 1.1 fold in skeletal muscle (P  < 0.05). Additionally, total antioxidant capacity was increased to 1.6 fold in liver during torpor (P  < 0.05), while remaining unchanged in the five other tissues. Overall, our data suggest that antioxidant and HSP responses are modified in a tissue-specific manner during daily torpor in gray mouse lemurs. Furthermore, our data also show that cytoprotective strategies employed during primate torpor are distinct from the strategies in rodent hibernation as reported in previous studies.
Cytokine and Antioxidant Regulation in the Intestine of the Gray Mouse Lemur (Microcebus Murinus) During Torpor
Authors: Tessier Shannon N. , Katzenback Barbara A. , Pifferi Fabien , Perret Martine , Storey Kenneth B.
Published: June 2015

During food shortages, the gray mouse lemur (Microcebus murinus) of Madagascar experiences daily torpor thereby reducing energy expenditures. The present study aimed to understand the impacts of torpor on the immune system and antioxidant response in the gut of these animals. This interaction may be of critical importance given the trade-off between the energetically costly immune response and the need to defend against pathogen entry during hypometabolism. The protein levels of cytokines and antioxidants were measured in the small intestine (duodenum, jejunum, and ileum) and large intestine of aroused and torpid lemurs. While there was a significant decrease of some pro-inflammatory cytokines (IL-6 and TNF-α) in the duodenum and jejunum during torpor as compared to aroused animals, there was no change in anti-inflammatory cytokines. We observed decreased levels of cytokines (IL-12p70 and M-CSF), and several chemokines (MCP-1 and MIP-2) but an increase in MIP-1α in the jejunum of the torpid animals. In addition, we evaluated antioxidant response by examining the protein levels of antioxidant enzymes and total antioxidant capacity provided by metabolites such as glutathione (and others). Our results indicated that levels of antioxidant enzymes did not change between torpor and aroused states, although antioxidant capacity was significantly higher in the ileum during torpor. These data suggest a suppression of the immune response, likely as an energy conservation measure, and a limited role of antioxidant defenses in supporting torpor in lemur intestine.
Using baseline cognitive severity for enriching Alzheimer's disease clinical trials: How does Mini‐Mental State Examination predict rate of change?
Authors: Kennedy Richard E. , Cutter Gary R. , Wang Guoqiao , Schneider Lon S.
Published: June 2015

Background

Post hoc analyses from clinical trials in Alzheimer's disease (AD) suggest that more cognitively impaired participants respond differently from less impaired on cognitive outcomes. We examined pooled clinical trials data to assess the utility of enriching trials using baseline cognition.

Methods

We included 2882 participants with mild to moderate AD in seven studies from a meta‐database. We used mixed effects models to estimate the rate of decline in Alzheimer's disease Assessment Scale‐cognitive (ADAS‐Cog) scores among Mini‐Mental State Examination (MMSE) groups.

Findings

Baseline MMSE category was associated with baseline scores and rate of decline on the ADAS‐Cog, adjusting for age and education (both P < .001). Greater baseline cognitive impairment was associated with more rapid progression.

Interpretations

Although we found significant differences in rate of decline, most differences between individuals were from baseline ADAS‐Cog values. Since enrichment based on MMSE would reduce the recruitment pool while adding only slightly to detecting differences in rate of progression, it is not advised.
Body brain life: A randomized controlled trial of an online dementia risk reduction intervention in middle‐aged adults at risk of Alzheimer's disease
Authors: Anstey Kaarin J. , Bahar‐Fuchs Alex , Herath Pushpani , Kim Sarang , Burns Richard , Rebok George W. , Cherbuin Nicolas
Published: June 2015

Objective

To examine the efficacy of body brain life (BBL), a 12‐week online dementia risk reduction intervention.

Methods

BBL was evaluated in a randomized controlled trial in 176 middle‐aged adults with >2 risk factors and <2 protective factors for Alzheimer's disease (AD) assessed on a brief screening instrument. Participants were randomized to BBL, BBL plus face‐to‐face group sessions (BBL + FF) or active control (control). Score on the Australian National University‐Alzheimer's disease risk index (ANU‐ADRI), a validated index of AD risk, was the primary outcome measure assessed at baseline, 12, and 26 weeks.

Results

A group by time interaction at 26 weeks showed a significant reduction in ANU‐ADRI score for BBL compared with control. Planned contrasts showed the BBL and BBL + FF groups had improvement in ANU‐ADRI scores at 12 weeks (BBL + FF: z = −0.25; P = .021; BBL: z = −0.25; P = .008) and 26 weeks (BBL + FF: z = −0.48; P < .001; BBL: z = −0.28; P = .004) due to increase in protective factors.

Conclusions

This short intervention resulted in dementia risk reduction. Online dementia risk reduction interventions show promise for reducing the overall dementia risk in middle‐aged adults with multiple risk factors.

Clinical Trial Registration: The study is registered under Trial Registration: Reg. # ACTRN12612000147886.
AEOLIC AND ITALIAN AT HORACE, ODES 3.30.13–14
Authors: Kovacs David
Published: June 2015

dicar, qua uiolens obstrepit Aufiduset qua pauper aquae Daunus agrestiumregnauit populorum ex humili potensprinceps Aeolium carmen ad Italos 13deduxisse modos.
Surely there is something puzzling about 13–14? What Horace was the first to do was to write Latin poetry using the metrical schemes of the Greek lyricists, principally Alcaeus and Sappho, who wrote in the Aeolic dialect of Lesbos. There can be no reasonable doubt that Aeolium carmen refers in the first instance to Horace's adoption of Aeolic metre. For deduxisse there are two possibilities, and conceivably Horace meant both to operate. The first involves motion, bringing something or someone home or into port (for example, captives in triumph to Rome or a colonizing expedition to its destination in a foreign land). So Horace took Greek metres and moved them in one way or another to Italy. Secondarily deducere might mean ‘to produce (by spinning)’, a usage found at Sat. 2.1.2-4 similisque meorum mille die uersus deduci posse.
Changes in cocaine consumption are associated with fluctuations in self-reported impulsivity and gambling decision-making
Authors: Hulka L. M. , Vonmoos M. , Preller K. H. , Baumgartner M. R. , Seifritz E. , Gamma A. , Quednow B. B.
Published: June 2015

Background.

In cross-sectional studies, cocaine users generally display elevated levels of self-reported and cognitive impulsivity. To what extent these impairments are stablev.variable markers of cocaine use disorder, and, thus, are pre-existing or drug-induced, has not yet been systematically investigated.

Method.

We conducted a longitudinal study with cocaine users who changed or maintained their consumption intensity, measuring self-reported impulsivity with the Barratt Impulsiveness Scale (BIS-11), and cognitive impulsivity with the Rapid Visual Processing task (RVP), Iowa Gambling task (IGT), and Delay Discounting task (DD) at baseline and at 1-year follow-up. We assessed 48 psychostimulant-naive controls and 19 cocaine users with decreased, 19 users with increased, and 19 users with unchanged cocaine intake after 1 year as confirmed by hair analysis.

Results.

Results of linear multilevel modelling showed significant group × time interactions for the BIS-11 total score and the IGT total card ratio.Increasersshowed a trend for elevated scores, whereasdecreasersexhibited reduced self-reported impulsivity scores within 1 year. Surprisingly,increasers’ IGT performance was improved after 1 year, whereasdecreasers’ performance deteriorated. By contrast, neither RVP response bias B″ nor DD total score showed substantial group × time interactions. Importantly, BIS-11 and DD revealed strong test–retest reliabilities.

Conclusion.

Self-reported impulsivity (BIS-11) and decision-making impulsivity (IGT) covary with changing cocaine use, whereas response bias and delay discounting remain largely unaffected. Thus, self-reported impulsivity and gambling decision-making were strongly state-dependent in a stimulant-using population and may be suitable to monitor treatment success, whereas delay of gratification was confirmed as a potential endophenotype of stimulant addiction.
Task-space dynamics and motion/force control of fixed-base manipulators under reaction null-space-based redundancy resolution
Authors: Nenchev Dragomir , Okawa Ryohei , Sone Hiroki
Published: June 2015

This paper introduces a task-space dynamics formulation for fixed-base serial-link kinematically redundant manipulators and a motion/force controller based on it. The aim is to alleviate joint-space instability problems that have been observed with other motion/force controllers. The dynamics are represented in floating-base coordinates, wherein the end effector is regarded as the floating base. This representation gives rise to a momentum-conserving redundancy resolution scheme based on the reaction null-space (RNS) method used in past studies on free-floating and flexible-base space robots. A generalized inverse is obtained that is shown to satisfy the conditions for dynamic consistency in the sense of the operational space (OS) formulation, but may lead to the joint-space instabilities observed earlier. The proposed controller is based on the pseudoinverse of the coupling inertia matrix and ensures reactionless link motion that does not disturb the force balance at the end effector. The performance of the RNS motion/force controller is examined by comparison to that with an OS motion/force controller. It is shown that while the performance in task-space of both controllers is satisfactory, the joint-space performance of the proposed controller is superior.
Antioxidant-related gene polymorphisms associated with the cardio-ankle vascular index in young Russians
Authors: Sorokin Alexander V. , Kotani Kazuhiko , Bushueva Olga Y. , Polonikov Alexey V.
Published: June 2015

The cardio-ankle vascular index is a measure of arterial stiffness, whereas oxidative stress underlies arterial pathology. This study aimed to investigate the association between the cardio-ankle vascular index and antioxidant-related gene polymorphisms in young Russians. A total of 89 patients (mean age, 21.6 years) were examined by the cardio-ankle vascular index and for 15 gene polymorphisms related to antioxidant enzymes including FMO3 (flavin-containing monooxygenase 3), GPX1 (glutathione peroxidase 1), and GPX4 (glutathione peroxidase 4). A higher cardio-ankle vascular index level was detected in carriers with the KK-genotype of FMO3 polymorphism rs2266782 than in those without (mean levels: 6.2 versus 5.6, respectively, p<0.05). Similarly, a higher cardio-ankle vascular index level was seen in carriers with the CC-genotype of GPX4 polymorphism rs713041 than in those without (6.0 versus 5.5, respectively, p<0.05). We did not observe significant associations between the cardio-ankle vascular index levels and the other gene polymorphisms. Although carriers with the LL-genotype of GPX1 polymorphism rs1050450 showed a higher diastolic blood pressure level than those without, the polymorphism did not affect the cardio-ankle vascular index level. This study showed a significant association between rs2266782 and rs713041 polymorphisms and arterial stiffness, as measured by the cardio-ankle vascular index, in young Russians. The pathways utilised by antioxidant enzymes may be responsible for early arterial stiffening in the Russian population.
Executive function deficits in congenital heart disease: why is intervention important?
Authors: Calderon Johanna , Bellinger David C.
Published: June 2015

It is widely recognised that children with congenital heart disease (CHD) are at high risk for neurodevelopmental impairments including attention deficit hyperactivity disorder and autism spectrum disorder symptoms. Executive function impairments are one of the most prominent neurodevelopmental features associated with CHD. These deficits can have widespread debilitating repercussions in children’s neurocognitive, behavioural, and psycho-social development. There is a crucial gap in research regarding the efficacy of preventive or treatment strategies for these important cognitive morbidities. Executive functions are complex neurocognitive skills highly amenable to improvement. Evidence-based interventions have shown promising results in other paediatric populations, strongly suggesting that they might also benefit the growing population of children with CHD. In this review, we summarise the available data on executive function impairments in children and adolescents with CHD. We underline the important co-morbidity of executive dysfunction with other cognitive and psychiatric issues in CHD, which raises awareness of the crucial need to prevent or at least mitigate these deficits. Finally, we summarise future avenues for research in terms of interventions that may help reduce executive function impairments in youth with CHD.
Food and beverage cues in children’s television programmes: the influence of programme genre
Authors: Scully Paul , Reid Orlaith , Macken Alan , Healy Mark , Saunders Jean , Leddin Des , Cullen Walter , Dunne Colum , O’Gorman Clodagh S
Published: June 2015

Objective

The link between childhood obesity and both television viewing and television advertising have previously been examined. We sought to investigate the frequency and type of food and beverage placements in children-specific television broadcasts and, in particular, differences between programme genres.

Method

Content of five weekdays of children-specific television broadcasting on both UK (BBC) and Irish (RTE) television channels was summarized. Food and beverage placements were coded based on type of product, product placement, product use and characters involved. A comparison was made between different programme genres: animated, cartoon, child-specific, film, quiz, tween and young persons’ programming.

Results

A total of 1155 (BBC=450; RTE=705) cues were recorded giving a cue every 4·2 min, an average of 12·3 s/cue. The genre with most cues recorded was cartoon programming (30·8 %). For the majority of genres, cues related to sweet snacks (range 1·8–23·3 %) and sweets/candy (range 3·6–25·8 %) featured highly. Fast-food (18·0 %) and sugar-sweetened beverage (42·3 %) cues were observed in a high proportion of tween programming. Celebratory/social motivation factors (range 10–40 %) were most common across all genres while there were low proportions of cues based on reward, punishment or health-related motivating factors.

Conclusions

The study provides evidence for the prominence of energy-dense/nutrient-poor foods and beverages in children’s programming. Of particular interest is the high prevalence of fast-food and sugar-sweetened beverage cues associated with tween programming. These results further emphasize the need for programme makers to provide a healthier image of foods and beverages in children’s television.
The Maturation of The Secular Organ Recital In America's Gilded Age
Authors: Owen Barbara
Published: June 2015

While organs had been built in the United States since the eighteenth century, until the middle of the nineteenth century what passed as an ‘organ concert’ consisted of a mélange of transcriptions from choral music and simple improvisations, interspersed with choral music and vocal solos. As larger organs began to appear by the middle of the nineteenth century, solo organ recitals by players such as George W. Morgan were occasionally performed. In the 1850s Americans such as Dudley Buck and John K. Paine travelled to Germany to study organ performance and composition, and others followed. The opening of a large organ in Boston's Music Hall in 1863 and the building of large churches in the post-war period gave impetus to public organ recitals, which along with compositions by Bach, Mendelssohn, Rinck and Batiste etc. usually included transcriptions from operas and orchestral works, and compositions by the performers. At first, the emphasis was on Germanic music, but as the second half of the century progressed and more organists were studying abroad, works by British and French composers began to appear. By the end of the century the emphasis had become strongly French, particularly after the concert tours of Parisian virtuoso Alexandre Guilmant, and America's first true concert organist, Clarence Eddy, began making tours to European countries. By this time many large organs had been built for concert halls, cathedrals, colleges, and urban churches, providing excellent venues for solo organ recitals as the twentieth century opened.
Comparison of the estimated prevalence of mood and/or anxiety disorders in Canada between self-report and administrative data
Authors: O'Donnell S. , Vanderloo S. , McRae L. , Onysko J. , Patten S. B. , Pelletier L.
Published: June 2015

Background.

To compare trends in the estimated prevalence of mood and/or anxiety disorders identified from two data sources (self-report and administrative). Reviewing, synthesising and interpreting data from these two sources will help identify potential factors that underlie the observed estimates and inform public health action.

Method.

We used self-reported, diagnosed mood and/or anxiety disorder cases from the Canadian Community Health Survey (CCHS) across a 5-year span (from 2003 to 2009) to estimate the prevalence among the Canadian population aged ≥15 years. We also estimated the prevalence of mood and/or anxiety disorders using the Canadian Chronic Disease Surveillance System (CCDSS), which identified cases using ICD-9/-10-CA codes from physician billing claims and hospital discharge records during the same time period. The prevalence rates for mood and/or anxiety disorders were compared across the CCHS and CCDSS by age and sex for all available years of data from 2003 to 2009. Summary rates were age-standardised to the Canadian population as of 1 October 1991.

Results.

In 2009, the prevalence of mood and/or anxiety disorders was 9.4% using self-reported datav.11.3% using administrative data. Prevalence rates obtained from administrative data were consistently higher than those from self-report for both men and women. However, due to an increase in the prevalence of self-reported cases, these differences decreased over time (rate ratios for both sexes: 1.6–1.2). Prevalence estimates were consistently higher among females compared with males irrespective of data source. While differences in the prevalence estimates between the two data sources were evident across all age groups, the reduction of these differences was greater among adolescent, young and middle-aged adults compared with those 70 years and older.

Conclusions.

The overall narrowing of differences over time reflects a convergence of information regarding the prevalence of mood and/or anxiety disorders trends between self-report and administrative data sources. While the administrative data-based prevalences remained relatively stable, the self-reported prevalences increased over time. These observations may reflect positive societal changes in the perceptions of mental health (declining stigma) and/or increasing mental health literacy. Additional research using non-ecological data is required to further our understanding of the observed findings and trends, including a data linkage exercise permitting a comparison of prevalence estimates and population characteristics from these two data sources both separately and merged.
Aktuelle Behandlung der stabilen Angina pectoris
Authors: Toggweiler Stefan , Jamshidi Peiman , Cuculi Florim
Published: June 2015

Zur zeitgemässen Therapie der Angina pectoris gehört primär die chirurgische oder perkutane Revaskularisation, die sich im Verlauf der letzten Jahrzehnte stark weiterentwickelt hat. Zur Prävention von Ereignissen sind Nikotinkarenz und regelmässige körperliche Betätigung wichtig. Die medikamentöse Therapie umfasst zum einen die Therapie von kardiovaskulären Risikofaktoren, aber auch die antiagreggatorische Therapie, die in gewissen Situationen eine Herausforderung sein kann. Wegen der Verfügbarkeit der perkutanen Revaskularisation hat die Bedeutung der medikamentösen antianginösen Therapie während der letzten Jahre abgenommen. Dieser Artikel liefert einen aktuellen Überblick über das Management von Patienten mit stabiler Angina pectoris im Jahr 2015.
Vulväres Brennen: Stellenwert der Chirurgie bei entzündlichen und präkanzerösen Vulvapathologien
Authors: Ghisu Gian-Piero , Fink Daniel
Published: June 2015

Mit Brennen und Berührungsschmerz als Leitsymptom einhergehende Vulvaerkrankungen können auf Infektionen, entzündliche Dermatosen oder andere Ursachen zurückgeführt werden. In der Gruppe der entzündlichen Dermatosen finden sich Krankheitsbilder, die einer chirurgischen Intervention bedürfen können. Die Vulvodynie kann ebenfalls vulväres Brennen verursachen. In dieser Mini-Review wird der chirurgische Aspekt der Behandlung der entzündlichen Erkrankungen und Präkanzerosen der Vulva beleuchtet.
The Impact of Learning Demands, Work-Related Resources, and Job Stressors on Creative Performance and Health
Authors: Glaser Jürgen , Seubert Christian , Hornung Severin , Herbig Britta
Published: June 2015

We propose an integrated model of learning demands, work-related resources, and job stressors that incorporates core assumptions of work design in predicting processes of learning and performance as well as health impairment. The model was tested in a heterogeneous sample of 830 employees using structural equation modeling. Empirical results largely support theoretical assumptions. Learning demands and work-related resources were positively related to intrinsic motivation and creative performance. Job stressors and low work-related resources were predictive for health impairment. The suggested tripartite taxonomy reconciles inconsistent research findings on the impact of work characteristics. The model provides practical guidance for work analysis and design by clarifying relationships between established work characteristics, job performance, and worker health.
Tandem C–H oxidation/cyclization/rearrangement and its application to asymmetric syntheses of (−)-brussonol and (−)-przewalskine E
Authors: Jiao Zhi-Wei , Tu Yong-Qiang , Zhang Qing , Liu Wen-Xing , Zhang Shu-Yu , Wang Shao-Hua , Zhang Fu-Min , Jiang Sen
Published: June 2015

Natural products are a vital source of lead compounds in drug discovery. Development of efficient tandem reactions to build useful compounds and apply them to the synthesis of natural products is not only a significant challenge but also an important goal for chemists. Here we describe a tandem C–H oxidation/cyclization/rearrangement of isochroman-derived allylic silylethers, promoted by DDQ and InCl3. This method allows the efficient construction of tricyclic benzoxa[3.2.1]octanes with a wide substrate scope. We employ this tandem reaction to achieve the asymmetric total syntheses of (−)-brussonol and (−)-przewalskine E.
Surface determination through atomically resolved secondary-electron imaging
Authors: Ciston J. , Brown H. G. , D’Alfonso A. J. , Koirala P. , Ophus C. , Lin Y. , Suzuki Y. , Inada H. , Zhu Y. , Allen L. J. , Marks L. D.
Published: June 2015

Unique determination of the atomic structure of technologically relevant surfaces is often limited by both a need for homogeneous crystals and ambiguity of registration between the surface and bulk. Atomically resolved secondary-electron imaging is extremely sensitive to this registration and is compatible with faceted nanomaterials, but has not been previously utilized for surface structure determination. Here we report a detailed experimental atomic-resolution secondary-electron microscopy analysis of the c(6 × 2) reconstruction on strontium titanate (001) coupled with careful simulation of secondary-electron images, density functional theory calculations and surface monolayer-sensitive aberration-corrected plan-view high-resolution transmission electron microscopy. Our work reveals several unexpected findings, including an amended registry of the surface on the bulk and strontium atoms with unusual seven-fold coordination within a typically high surface coverage of square pyramidal TiO5 units. Dielectric screening is found to play a critical role in attenuating secondary-electron generation processes from valence orbitals.
NELL-1 in the treatment of osteoporotic bone loss
Authors: James Aaron W. , Shen Jia , Zhang Xinli , Asatrian Greg , Goyal Raghav , Kwak Jin H. , Jiang Lin , Bengs Benjamin , Culiat Cymbeline T. , Turner A. Simon , Seim III Howard B. , Wu Benjamin M. , Lyons Karen , Adams John S. , Ting Kang , Soo Chia
Published: June 2015

NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack ofNell-1expression is associated with skeletal undermineralization. Here we show thatNell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss.
Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours
Authors: Ince Tan A. , Sousa Aurea D. , Jones Michelle A. , Harrell J. Chuck , Agoston Elin S. , Krohn Marit , Selfors Laura M. , Liu Wenbin , Chen Ken , Yong Mao , Buchwald Peter , Wang Bin , Hale Katherine S. , Cohick Evan , Sergent Petra , Witt Abigail , Kozhekbaeva Zhanna , Gao Sizhen , Agoston Agoston T. , Merritt Melissa A. , Foster Rosemary , Rueda Bo R. , Crum Christopher P. , Brugge Joan S. , Mills Gordon B.
Published: June 2015

Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy.
Dynamical properties induced by state-dependent delays in photonic systems
Authors: Martínez-Llinàs Jade , Porte Xavier , Soriano Miguel C. , Colet Pere , Fischer Ingo
Published: June 2015

In many dynamical systems and complex networks time delays appear naturally in feedback loops or coupling connections of individual elements. Moreover, in a whole class of systems, these delay times can depend on the state of the system. Nevertheless, so far the understanding of the impact of such state-dependent delays remains poor with a particular lack of systematic experimental studies. Here we fill this gap by introducing a conceptually simple photonic system that exhibits dynamics of self-organised switching between two loops with two different delay times, depending on the state of the system. On the basis of experiments and modelling on semiconductor lasers with frequency-selective feedback mirrors, we characterize the switching between the states defined by the individual delays. Our approach opens new perspectives for the study of this class of dynamical systems and enables applications in which the self-organized switching can be exploited.
Exponential self-replication enabled through a fibre elongation/breakage mechanism
Authors: Colomb-Delsuc Mathieu , Mattia Elio , Sadownik Jan W. , Otto Sijbren
Published: June 2015

Self-replicating molecules are likely to have played a central role in the origin of life. Most scenarios of Darwinian evolution at the molecular level require self-replicators capable of exponential growth, yet only very few exponential replicators have been reported to date and general design criteria for exponential replication are lacking. Here we show that a peptide-functionalized macrocyclic self-replicator exhibits exponential growth when subjected to mild agitation. The replicator self-assembles into elongated fibres of which the ends promote replication and fibre growth. Agitation results in breakage of the growing fibres, generating more fibre ends. Our data suggest a mechanism in which mechanical energy promotes the liberation of the replicator from the inactive self-assembled state, thereby overcoming self-inhibition that prevents the majority of self-replicating molecules developed to date from attaining exponential growth.
KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
Authors: Kamimura Daisuke , Katsunuma Kokichi , Arima Yasunobu , Atsumi Toru , Jiang Jing-jing , Bando Hidenori , Meng Jie , Sabharwal Lavannya , Stofkova Andrea , Nishikawa Naoki , Suzuki Hironao , Ogura Hideki , Ueda Naoko , Tsuruoka Mineko , Harada Masaya , Kobayashi Junya , Hasegawa Takanori , Yoshida Hisahiro , Koseki Haruhiko , Miura Ikuo , Wakana Shigeharu , Nishida Keigo , Kitamura Hidemitsu , Fukada Toshiyuki , Hirano Toshio , Murakami Masaaki
Published: June 2015

KDEL receptors are responsible for retrotransporting endoplasmic reticulum (ER) chaperones from the Golgi complex to the ER. Here we describe a role for KDEL receptor 1 (KDELR1) that involves the regulation of integrated stress responses (ISR) in T cells. Designing and using an N-ethyl-N-nitrosourea (ENU)-mutant mouse line, T-Red (naïve T-cell reduced), we show that a point mutation in KDELR1 is responsible for the reduction in the number of naïve T cells in this model owing to an increase in ISR. Mechanistic analysis shows that KDELR1 directly regulates protein phosphatase 1 (PP1), a key phosphatase for ISR in naïve T cells. T-Red KDELR1 does not associate with PP1, resulting in reduced phosphatase activity against eIF2α and subsequent expression of stress responsive genes including the proapoptotic factor Bim. These results demonstrate that KDELR1 regulates naïve T-cell homeostasis by controlling ISR.
Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus
Authors: Taft Andrew S. , Ozawa Makoto , Fitch Adam , Depasse Jay V. , Halfmann Peter J. , Hill-Batorski Lindsay , Hatta Masato , Friedrich Thomas C. , Lopes Tiago J. S. , Maher Eileen A. , Ghedin Elodie , Macken Catherine A. , Neumann Gabriele , Kawaoka Yoshihiro
Published: June 2015

Avian influenza viruses of the H5N1 subtype pose a serious global health threat due to the high mortality (>60%) associated with the disease caused by these viruses and the lack of protective antibodies to these viruses in the general population. The factors that enable avian H5N1 influenza viruses to replicate in humans are not completely understood. Here we use a high-throughput screening approach to identify novel mutations in the polymerase genes of an avian H5N1 virus that confer efficient polymerase activity in mammalian cells. Several of the identified mutations (which have previously been found in natural isolates) increase viral replication in mammalian cells and virulence in infected mice compared with the wild-type virus. The identification of amino-acid mutations in avian H5N1 influenza virus polymerase complexes that confer increased replication and virulence in mammals is important for the identification of circulating H5N1 viruses with an increased potential to infect humans.
White Light Emission from Vegetable Extracts
Authors: Singh Vikram , Mishra Ashok K.
Published: June 2015

A mixture of extracts from two common vegetables, red pomegranate and turmeric, when photoexcited at 380 nm, produced almost pure white light emission (WLE) with Commission Internationale d’Eclairage (CIE) chromaticity index (0.35, 0.33) in acidic ethanol. It was also possible to obtain WLE in polyvinyl alcohol film (0.32, 0.25) and in gelatin gel (0.26, 0.33) using the same extract mixture. The colour temperature of the WLE was conveniently tunable by simply adjusting the concentrations of the component emitters. The primary emitting pigments responsible for contributing to WLE were polyphenols and anthocyanins from pomegranate and curcumin from turmeric. It was observed that a cascade of Forster resonance energy transfer involving polyphenolics, curcumin and anthocyanins played a crucial role in obtaining a CIE index close to pure white light. The optimized methods of extraction of the two primary emitting pigments from their corresponding plant sources are simple, cheap and fairly green.
Nicotine absorption from electronic cigarette use: comparison between experienced consumers (vapers) and naïve users (smokers)
Authors: Farsalinos Konstantinos E. , Spyrou Alketa , Stefopoulos Christos , Tsimopoulou Kalliroi , Kourkoveli Panagiota , Tsiapras Dimitris , Kyrzopoulos Stamatis , Poulas Konstantinos , Voudris Vassilis
Published: June 2015

Electronic cigarettes (ECs) are nicotine delivery devices that are proposed as tobacco harm reduction products to smokers. Nicotine delivery from ECs is potentially important in their efficacy as smoking substitutes. Herein, nicotine delivery from using a new-generation EC device (variable-wattage, set at 9 W) was evaluated, comparing experienced (vapers) with naïve users (smokers). Twenty-four vapers and 23 smokers participated to the study. They were asked to obtain 10 puffs in 5 minutes and then use the EC ad lib for 60 more minutes (total duration of use: 65 minutes). An 18 mg/mL nicotine-containing liquid was used. Blood samples were obtained at baseline, 5-minutes and every 15 minutes thereafter, while number of puffs and average puff duration were recorded. Although at baseline both groups had similar plasma nicotine levels, smokers consistently exhibited lower levels at all time-periods; at 5-minutes the levels were lower by 46%, while during the subsequent period they were lower by 43% (at 65-minutes) to 54% (at 20-minutes). Both groups took similar number of puffs, but smokers had average puff duration of 2.3 s compared to 3.5 s in vapers. Even in vapers, plasma nicotine levels at 5 minutes were lower than those observed after smoking 1 tobacco cigarette.
Increased cerebrospinal fluid fibrinogen in major depressive disorder
Authors: Hattori Kotaro , Ota Miho , Sasayama Daimei , Yoshida Sumiko , Matsumura Ryo , Miyakawa Tomoko , Yokota Yuuki , Yamaguchi Shinobu , Noda Takamasa , Teraishi Toshiya , Hori Hiroaki , Higuchi Teruhiko , Kohsaka Shinichi , Goto Yu-ichi , Kunugi Hiroshi
Published: June 2015

Major depressive disorder (MDD) presumably includes heterogeneous subgroups with differing pathologies. To obtain a marker reflecting such a subgroup, we analyzed the cerebrospinal fluid (CSF) levels of fibrinogen, which has been reported to be elevated in the plasma of patients with MDD. Three fibrinogen-related proteins were measured using aptamer-based analyses and CSF samples of 30 patients with MDD and 30 controls. The numbers of patients with an excessively high level (>99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson’s r = 0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9–39.1, p = 0.0011). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities.
Momentum Distribution of Near-Zero-Energy Photoelectrons in the Strong-Field Tunneling Ionization in the Long Wavelength Limit
Authors: Xia Q. Z. , Ye D. F. , Fu L. B. , Han X. Y. , Liu J.
Published: June 2015

We investigate the ionization dynamics of Argon atoms irradiated by an ultrashort intense laser of a wavelength up to 3100 nm, addressing the momentum distribution of the photoelectrons with near-zero-energy. We find a surprising accumulation in the momentum distribution corresponding to meV energy and a “V”-like structure at the slightly larger transverse momenta. Semiclassical simulations indicate the crucial role of the Coulomb attraction between the escaping electron and the remaining ion at an extremely large distance. Tracing back classical trajectories, we find the tunneling electrons born in a certain window of the field phase and transverse velocity are responsible for the striking accumulation. Our theoretical results are consistent with recent meV-resolved high-precision measurements.
Different Flavours of Fragments
Authors: Abell Chris , Dagostin Claudio
Published: June 2015

Fragment has been in the pharma vocabulary for around 20 years. To most medicinal chemists the word means fragment-based drug discovery (FBDD), but from an academic perspective it can be much broader and it can range from trying to identify substrates for orphan proteins to understanding binding interactions involved in riboswitch regulation. Even within drug discovery the approach to FBDD can vary significantly in terms of library size, and screening techniques. The roles for fragments are also expanding. They have now been used in assessing druggability, identifying hotspots on protein surfaces, finding allosteric pockets etc. In this chapter we will briefly give a perspective on these different flavours of fragments, starting with the most well understood in FBDD.
Getting the Most Value from Your Screens: Advances in Hardware, Software, and Methodologies to Enhance Surface Plasmon Resonance Based Fragment Screening and Hit-to-Lead Support
Authors: Giannetti Anthony M. , Gilbert Houston N. , Huddler Donald P. , Reiter Mac , Strande Chris , Pitts Keith E. , Bravo Brandon J.
Published: June 2015

The development and adoption of fragment-based lead discovery is partly driven by the deployment and refinement of the technologies that enable this drug-discovery approach. Advances in the capabilities of the core discovery functions have historically impacted various elements of the discovery process. For example, early fragment screens produced more structure information earlier in a screening cascade through use of high-resolution protein-detected NMR or crystallography based screening approaches. These screens were rich in information but slow, expensive, and limited to small libraries. The wider spread adoption of ligand-detected NMR and surface plasmon resonance (SPR) binding assays, with their higher throughput and lower sample consumption, allowed fragment screening cascades to be reformulated to more closely resemble HTS. The lower cost, high-throughput, lower information single-dose experiments are performed early, followed by more information-rich, but slower and more costly structural experiments on the reduced set of characterized binders. Refinements and innovations in hardware, software, and practical methodologies have continued to advance the ease and scope of the implementation of SPR-based biosensors. In this chapter we describe a number of these recent advances that streamline the workflow and can give screening groups more options and flexibility to bring higher information content data to teams earlier. With these tools in hand, third-generation screening cascades can be proposed that can give fragment discovery efforts more traction and momentum in the early lead-discovery setting.
Fragment Screening of G Protein-Coupled Receptors
Authors: Congreve Miles , Cooke Robert
Published: June 2015

Fragment screening and fragment-based drug discovery (FBDD) are still in their infancy for membrane-associated protein targets such as G protein-coupled receptors (GPCRs). However, with the advent of a new era of structural insight from X-ray crystal structures of multiple GPCRs and advances in the purification and isolation of these sensitive proteins, rapid progress is being made in the establishment, validation and practice of FBDD for this important class of drug targets. In this chapter the recent literature is reviewed, outlining key developments in the structural biology, biophysics and fragment-based screening of GPCRs. A case study of FBDD with the β1 adrenergic receptor is described in some depth. Finally, a perspective on likely future developments is given.
A detailed study of kinking in indium-catalyzed silicon nanowires
Authors: He Zhanbing , Nguyen Hung Tran , Duc Toan Le , Pribat Didier
Published: June 2015

The turning angles of kinked Si nanowires are governed by the different combinations of three types of {111} twins, where TBs are normal to (Twin I), inclined to (Twin II) or parallel to (Twin III) the axes of Si nanowires.
Theoretical study of the dark photochemistry of 1,3-butadiene via the chemiexcitation of Dewar dioxetane
Authors: Farahani Pooria , Lundberg Marcus , Lindh Roland , Roca-Sanjuán Daniel
Published: June 2015

We report on the molecular basis of excited-state chemical processes that are induced by intramolecular chemiexcitation rather than by irradiation.
The HAlF4 superacid fragmentation induced by an excess electron attachment
Authors: Czapla Marcin , Skurski Piotr
Published: June 2015

The HAlF4 superacid binds an excess electron and undergoes a spontaneous fragmentation that leads to a H atom and an AlF4− superhalogen anion.
Simultaneous investigation of the structure and surface of a Co/alumina catalyst during Fischer–Tropsch synthesis: discrimination of various phenomena with beneficial or disadvantageous impact on activity
Authors: Scalbert Julien , Clémençon Isabelle , Lecour Philippe , Braconnier Laure , Diehl Fabrice , Legens Christèle
Published: June 2015

Simultaneous investigation of structure and surface of a Co/Al2O3 catalyst during Fischer–Tropsch synthesis: identification of beneficial and disadvantageous phenomena.
Redox properties and catalytic performance of ceria–zirconia nanorods
Authors: Chen Aling , Zhou Yan , Ta Na , Li Yong , Shen Wenjie
Published: June 2015

The shape effect of Ce1−xZrxO2 nanomaterials is associated with the amount of zirconia that is incorporated into the ceria lattice.
Polarization effects in lattice–STED microscopy
Authors: Yang B. , Fang C.-Y. , Chang H.-C. , Treussart F. , Trebbia J.-B. , Lounis B.
Published: June 2015

Massive parallelization of STED-like nanoscopies is now achievable using well-designed optical lattices for state depletion. Yet, only the lattice intensity distribution was considered for the description of the super-resolved point spread function. This holds for fast-rotating fluorescent emitters. Here, we study the effects of electric field topography in lattice–STED microscopy. The dependence of the super-resolved point spread function on the number of dipoles and their orientation is investigated. Single fluorescent nano-diamonds are imaged using different optical lattice configurations and the measured resolutions are compared to theoretical simulations.