bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term mortality of hospitalized pneumonia in the EPIC-Norfolk cohort
Authors: MYINT P. K. , HAWKINS K. R. , CLARK A. B. , LUBEN R. N. , WAREHAM N. J. , KHAW K.-T. , WILSON A. M.
Published: August 2015

Little is known about cause-specific long-term mortality beyond 30 days in pneumonia. We aimed to compare the mortality of patients with hospitalized pneumonia compared to age- and sex-matched controls beyond 30 days. Participants were drawn from the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study. Hospitalized pneumonia cases were identified from record linkage (ICD-10: J12-J18). For this study we excluded people with hospitalized pneumonia who died within 30 days. Each case identified was matched to four controls and followed up until the end June 2012 (total 15 074 person-years, mean 6·1 years, range 0·08–15·2 years). Cox regression models were constructed to examine the all-cause, respiratory and cardiovascular mortality using date of pneumonia onset as baseline with binary pneumonia status as exposure. A total of 2465 men and women (503 cases, 1962 controls) [mean age (s.d.) 64·5 (8·3) years] were included in the study. Between a 30-day to 1-year period, hazard ratios (HRs) of all-cause and cardiovascular mortality were 7·3 [95% confidence interval (CI) 5·4–9·9] and 5·9 (95% CI 3·5–9·7), respectively (with very few respiratory deaths within the same period) in cases compared to controls after adjusting for age, sex, asthma, smoking status, pack years, systolic and diastolic blood pressure, diabetes, physical activity, waist-to-hip ratio, prevalent cardiovascular and respiratory diseases. All outcomes assessed also showed increased risk of death in cases compared to controls after 1 year; respiratory cause of death being the most significant during that period (HR 16·4, 95% CI 8·9–30·1). Hospitalized pneumonia was associated with increased all-cause and specific-cause mortality beyond 30 days.
Cancer in the older person
Authors: Kelly Emma , Stephens Peter
Published: August 2015

The challenges of treating malignant disease in the elderly population have gained greater prominence over the last 5–10 years. Developed nations all have ageing populations, and cancer in older people is an increasing physical and financial burden on both healthcare systems and populations.

When assessing oncology patients, oncologists have traditionally used the Eastern Cooperative Oncology Group or Karnofsky performance status. However, it has been shown that sometimes this does not detect potential problems in older patients, and that a comprehensive geriatric assessment may be a better tool. However good surgeons and oncologists are at adapting their services for older patients, there is little value if they are inappropriately referred or filtered out by either primary or secondary care.

Surgery forms the basis of most curative treatment options. The elderly have more peri-operative risk factors including multiple co-morbidities, poly-pharmacy, malnutrition, frailty, cognitive dysfunction and an increased anaesthetic risk, which can create obstacles.

Treating older patients with systemic cytotoxic therapy often relies on extrapolating evidence from younger patients. In previous decades, the majority of trials had upper age limits of 65 or 70 years. More recent trials normally include patients of all ages, and entry is based on performance status. Radiotherapy may be chosen as a potentially curative option in patients with an operable tumour, who are unfit. However, oncologists should not underestimate the burden that multiple frequent visits to hospital for treatment may have on an elderly patient population.

This article looks at the assessment of elderly oncology patients, referral patterns, surgery, systemic therapies, radiotherapy, supportive therapies and long-term side-effects from treatment.
Fast, clean and green: Cold War ideologies and urban reforms in Buenos Aires, 1976–1983
Authors: HOYT JENNIFER T.
Published: August 2015

The last military dictatorship to come to power in Argentina is most well known for its atrocious human rights violations. However, this campaign of terror represents just one act carried out in the regime's efforts to counter leftist activities. The military sought to provide responsive administration as a means to pacify the nation. In the national capital, Buenos Aires, the military pursued a comprehensive set of urban reforms meant to streamline and control the metropolis. Cold War ideologies deeply penetrated the every-day and profoundly changed how citizens lived in Buenos Aires.
A method based on rules and machine learning for logic form identification in Spanish
Authors: MARTÍNEZ-SANTIAGO F. , DÍAZ-GALIANO M. C. , GARCÍA-CUMBRERAS M. Á. , MONTEJO-RÁEZ A.
Published: August 2015

Logic Forms (LF) are simple, first-order logic knowledge representations of natural language sentences. Each noun, verb, adjective, adverb, pronoun, preposition and conjunction generates a predicate. LF systems usually identify the syntactic function by means of syntactic rules but this approach is difficult to apply to languages with a high syntax flexibility and ambiguity, for example, Spanish. In this study, we present a mixed method for the derivation of the LF of sentences in Spanish that allows the combination of hard-coded rules and a classifier inspired on semantic role labeling. Thus, the main novelty of our proposal is the way the classifier is applied to generate the predicates of the verbs, while rules are used to translate the rest of the predicates, which are more straightforward and unambiguous than the verbal ones. The proposed mixed system uses a supervised classifier to integrate syntactic and semantic information in order to help overcome the inherent ambiguity of Spanish syntax. This task is accomplished in a similar way to the semantic role labeling task. We use properties extracted from the AnCora-ES corpus in order to train a classifier. A rule-based system is used in order to obtain the LF from the rest of the phrase. The rules are obtained by exploring the syntactic tree of the phrase and encoding the syntactic production rules. The LF algorithm has been evaluated by using shallow parsing with some straightforward Spanish phrases. The verb argument labeling task achieves 84% precision and the proposed mixed LFi method surpasses 11% a system based only on rules.
A Preliminary Investigation into Worry about Mental Health: Development of the Mental Health Anxiety Inventory
Authors: Commons Della , Greenwood Kenneth Mark , Anderson Rebecca A.
Published: August 2015

Background: Worry about physical health is broadly referred to as health anxiety and can range from mild concern to severe or persistent anxiety such as that found in DSM-IV hypochondriasis. While much is known about anxiety regarding physical health, little is known about anxiety regarding mental health. However, recent conceptualizations of health anxiety propose that individuals can experience severe and problematic worry about mental health in similar ways to how people experience extreme worry about physical health. Aims: Given the paucity of research in this area, the aim of the current study was to explore anxiety regarding mental health through validation of the Mental Health Anxiety Inventory (MHAI), a modified version of the Short Health Anxiety Inventory. Method: The MHAI, and measures of state anxiety (Depression, Anxiety and Stress Scales-21), trait worry (Penn State Worry Questionnaire), and health anxiety (Short Health Anxiety Inventory) were administered to 104 adult volunteers from the general community. Results: The MHAI demonstrated high internal consistency, acceptable test-retest reliability, and good construct validity when correlated with other measures of anxiety. Results also indicated that participants worried about their mental health and physical health equally, and that almost 9% of participants reported levels of mental health anxiety that were potentially problematic. Conclusion: Preliminary results suggest that a small proportion of adults in the community may experience high levels of mental health anxiety requiring treatment, and that the MHAI, if validated further, could be a useful tool for assessing this form of anxiety.
The Perseverative Thinking Questionnaire in Patients with Persecutory Delusions
Authors: Černis Emma , Dunn Graham , Startup Helen , Kingdon David , Wingham Gail , Evans Nicole , Lister Rachel , Pugh Katherine , Cordwell Jacinta , Mander Helen , Freeman Daniel
Published: August 2015

Background: Ruminative negative thinking has typically been considered as a factor maintaining common emotional disorders and has recently been shown to maintain persecutory delusions in psychosis. The Perseverative Thinking Questionnaire (PTQ) (Ehring et al., 2011) is a transdiagnostic measure of ruminative negative thinking that shows promise as a “content-free” measure of ruminative negative thinking. Aims: The PTQ has not previously been studied in a psychosis patient group. In this study we report for the first time on the psychometric properties of Ehring et al.'s PTQ in such a group. Method: The PTQ was completed by 142 patients with current persecutory delusions and 273 non-clinical participants. Participants also completed measures of worry and paranoia. A confirmatory factor analysis was performed on the clinical group's PTQ responses to assess the factor structure of the measure. Differences between groups were used to assess criterion reliability. Results: A three lower-order factor structure of the PTQ (core characteristics of ruminative negative thinking, perceived unproductiveness, and capturing mental capacity) was replicated in the clinical sample. Patients with persecutory delusions were shown to experience significantly higher levels of ruminative negative thinking on the PTQ than the general population sample. The PTQ demonstrated high internal reliability. Conclusions: This study did not include test-retest data, and did not compare the PTQ against a measure of depressive rumination but, nevertheless, lends support for the validity of the PTQ as a measure of negative ruminative thinking in patients with psychosis.
Context is Everything: An Investigation of Responsibility Beliefs and Interpretations and the Relationship with Obsessive-Compulsive Symptomatology across the Perinatal Period
Authors: Barrett Roxanne , Wroe Abigail L. , Challacombe Fiona L.
Published: August 2015

Background: The cognitive-behavioural model of perinatal OCD suggests the role of increased sense of responsibility during the perinatal period in the development and maintenance of obsessive-compulsive symptoms. However, the idiosyncratic nature of responsibility attitudes and interpretations of intrusions is not fully understood. Aims: To investigate how responsibility interpretations regarding intrusions vary across the perinatal period and how this relates to obsessive-compulsive symptomatology. Method: 94 women (26 antenatal, 35 postpartum and 33 non-childbearing controls) completed measures of responsibility attitudes and interpretations regarding specific intrusions (either general or baby-related), as well as obsessive-compulsive symptomatology, anxiety and depression. Results: Postpartum ratings of responsibility interpretations regarding baby-related intrusions were significantly higher than: i) postpartum ratings of responsibility interpretations regarding non-baby intrusions; and ii) control group responsibility interpretations. The groups were not significantly different regarding general responsibility ratings. Ratings of baby-related responsibility interpretations predicted variance in obsessive-compulsive symptomatology. Conclusion: The postpartum group showed significant differences in responsibility interpretations regarding baby-related intrusions. These responsibility interpretations were shown to predict obsessive-compulsive symptomatology.
A study of enhanced dynamic wedge dosimetry using a 2D ion chamber array detector
Authors: Syam Kumar S. A. , Aparna P. , Anjana P. T. , Aswathi C. P. , Sitha G. P.
Published: August 2015

The purpose of this work was to study the dosimetric properties of the enhanced dynamic wedge using a Seven29 ion chamber array. The PTW Seven29 ion chamber array and solid water phantoms were used for the study. Primarily, the solid water phantoms with the two-dimensional (2D) array were scanned using a computed tomography scanner at different depths. Using these scanned images, planning was performed for different wedge angles at 6 and 15 MV. A dose of 100 CGy was delivered in each case. For each delivery, the required monitoring units (MUs) were calculated. Using the same setup with a Varian Clinac iX, the calculated MU was delivered for different wedge angles. Subsequently, the different wedged dose distributions that had been obtained were analysed using Verisoft software. A shoulder-like region was observed in the profile; this region reduced as depth increased. The percentage deviation between the planned and measured doses at the shoulder region fell within the range of 0·9–4·3%. The standard deviation between planned and measured doses at shoulder region in the profile fell within 0·08±0·02 at different depths. The standard deviations between planned and measured wedge factors for different depths (2·5, 5, 10 and 15 cm) were 0·0021, 0·0007, 0·0050 and 0·0001 for 6 MV and 0·0024, 0·0191, 0·0013 and 0·0005 for 15 MV, respectively. On the basis of the studies that we performed, it can be concluded that the 2D ion chamber array is a good tool for enhanced dynamic wedge dosimetry.
An Assessment of macro-scalein situRaman and ultraviolet-induced fluorescence spectroscopy for rapid characterization of frozen peat and ground ice
Authors: Laing Janelle R. , Robichaud Hailey C. , Cloutis Edward A.
Published: August 2015

The search for life on other planets is an active area of research. Many of the likeliest planetary bodies, such as Europa, Enceladus, and Mars are characterized by cold surface environments and ice-rich terrains. Both Raman and ultraviolet-induced fluorescence (UIF) spectroscopies have been proposed as promising tools for the detection of various kinds of bioindicators in these environments. We examined whether macro-scale Raman and UIF spectroscopy could be applied to the analysis of unprocessed terrestrial frozen peat and clear ground ice samples for detection of bioindicators. It was found that this approach did not provide unambiguous detection of bioindicators, likely for a number of reasons, particularly due to strong broadband induced fluorescence. Other contributing factors may include degradation of organic matter in frozen peat to the point that compound-specific emitted fluorescence or Raman peaks were not resolvable. Our study does not downgrade the utility of either UIF or Raman spectroscopy for astrobiological investigations (which has been demonstrated in previous studies), but does suggest that the choice of instrumentation, operational conditions and sample preparation are important factors in ensuring the success of these techniques.
INTERNATIONAL MOZART CONFERENCE STIFTUNG MOZARTEUM SALZBURG, 2–5 OCTOBER 2014
Authors: MIKUSI BALÁZS
Published: August 2015

Conferences organized by the Stiftung Mozarteum Salzburg inevitably serve as a kind of touchstone: one tends to view the programme as a representative muster of international Mozart scholarship. Since on this occasion the organizers explicitly devoted part of the event to analysis (broadly understood as ‘scholarly work interpretation’), the October 2014 snapshot proved especially rich in insights, suggesting that the tools recently developed for the analysis of ‘galant style’ have much to offer for Mozart scholars, while ‘old-school’ source research still bears its fruits as well.
GLUCK AND THE MAP OF EIGHTEENTH-CENTURY MUSIC WESTERN ILLINOIS UNIVERSITY, 17–19 OCTOBER 2014
Authors: SMITH ANNALISE
Published: August 2015

The year 2014 marked the tercentenary of the birth of Christoph Gluck, an anniversary shared with his fellow operatic reformer Niccolò Jommelli and the most famous Bach son, Carl Philipp Emanuel. For most people, the mention of Gluck brings to mind his involvement in the reform of eighteenth-century opera and seminal works such as Orfeo ed Euridice, associations that have had the effect of minimizing Gluck's other accomplishments, including the majority of his dramatic oeuvre. The conference and festival Gluck and the Map of Eighteenth-Century Music, organized by Brian Locke and Anita Hardeman at Western Illinois University, focused less on Gluck's involvement in operatic reform than on the many ways in which he engaged with operatic and balletic traditions. Encompassing studies of genre, performance and reception history, the papers portrayed Gluck as a composer enmeshed in the musical culture of his time, whose works still leave much to be discovered by both scholars and performers.
C. P. E. BACH TERCENTENARY CONFERENCE: C. P. E. BACH AND EIGHTEENTH-CENTURY KEYBOARD CULTURE UNIVERSITY OF OXFORD, 29–30 NOVEMBER 2014
Authors: IRVINE THOMAS
Published: August 2015

There was a time when C. P. E. Bach's music was mostly interesting as a connection between periods of music history. Indeed, perhaps no composer was done a greater injustice by such un-useful terms as ‘pre-classical’, meant to place Bach in various grand narratives and often forcing him into the role of bearing the spirit of his father to the Viennese classics. Such fussy periodizations of eighteenth-century music history are now mostly passé. So it was a pleasure to attend this conference, held at the Faculty of Music of Oxford University, at which speakers explored the varied terrain of Bach's place in eighteenth-century keyboard culture without for the most part framing their arguments in terms of influence and legacy. They examined this most fascinating (and in some ways enigmatic) of composers on his own merits.
TWENTY-NINTH ANNUAL CONFERENCE ON MUSIC IN EIGHTEENTH-CENTURY BRITAIN THE FOUNDLING MUSEUM, LONDON, 28 NOVEMBER 2014
Authors: BABINGTON AMANDA
Published: August 2015

This conference, now in its thirtieth year, and run very capably by Katherine Hogg and Colin Colman (both Gerald Coke Handel Collection, The Foundling Museum), together with Claire Sharpe (Royal Academy of Music), is a personal favourite of mine. The variety of papers always means that one is drawn into at least one subject about which one knows almost nothing, but which invariably informs or enriches one's own area of expertise.
MUSICAL IMPROVISATION IN THE AGE OF BEETHOVEN AND ‘OPEN’ FORMS FONDAZIONE GIORGIO CINI, ISOLA DI SAN GIORGIO MAGGIORE, VENICE, 28–29 NOVEMBER 2014
Authors: STEWART-MACDONALD ROHAN H.
Published: August 2015

The multi-dimensional topic of improvisation in the eighteenth and nineteenth centuries has been explored in various recent publications and international conferences. For example, the proceedings of the conference L’improvvisazione nella musica occidentale del Settecento all’Ottocento, held at La Spezia in 2010, were published as Beyond Notes: Improvisation in Western Music of the Eighteenth and Nineteenth Centuries (Turnhout: Brepols, 2011), edited by Rudolf Rasch. Rasch (Universiteit Utrecht) was one of several participants at La Spezia who reappeared in Venice for the third in a series of conferences on improvisation, organized like the previous two by the Fondazione Giorgio Cini. The first two (November 2012, 2013) dealt with different eras. ‘Musical Improvisation in the Age of Beethoven’, held over two days, brought together scholars of varying provenance, from Belgium, Canada, Germany, Holland, Italy, Switzerland, the United Kingdom and the United States of America. The first day of papers was followed by an evening recital from Mozart scholar and fortepianist John Irving (Trinity Laban Conservatoire of Music and Dance) and violinist Davide Amodio. Scott Burnham (Princeton University), scheduled to speak on the second day, was absent, but a ‘draft outline’ of his paper was read by William Caplin (McGill University) and distributed as a handout. In the face of an unreliable broadband connection, Elaine Sisman (Columbia University) read her paper over Skype and participated frequently in the other sessions.
SOLOMON, SUSANNA AND MOSES: LOCATING HANDEL’S LOST LIBRETTIST
Authors: PINK ANDREW
Published: August 2015

A mystery surrounds the identity of Handel's librettist for the 1749 Covent Garden oratorios Solomon (hwv67) and Susanna (hwv66). There are no known contemporary references to the texts’ authorship, whether in wordbooks (published by Tonson and Draper), the composer's autograph, printed scores (published by Walsh), press reports, financial records, correspondence or diaries. Indeed, there is very little contemporary comment of any sort relating to these two works, although we do know that they were profitable in so far as Handel had banked £300 after the first performance of Solomon and some £577 after performances of Susanna.
EDITORIAL
Authors: BURGESS GEOFFREY
Published: August 2015

The passing of pioneering figures – musicians Christopher Hogwood, Frans Brüggen, Gustav Leonhardt and Bruce Haynes, as well as harpsichord builder Martin Skowroneck and flute maker and recording engineer Andreas Glatt – all in the short space of the past couple of years might suggest that early music has reached its end, or at least entered a new phase. As we look back over the past forty-five years since the term ‘early music’ was trademarked in England by Early Music Shop founder Richard Wood, we may well ask if the movement's function and goals remain the same. Early music, which initially rode on the tailcoats of counterculture and actively disparaged the mainstream, has reached a high level of professionalism, and more than anything has become institutionalized. It now forms part of music training in conservatories around the world, as early-instrument orchestras proliferate and opera companies are increasingly turning to pre-romantic opera. For some, the professionalization of early music is an indication of its far-reaching impact, but to others the price paid is only too evident.
Diversity and genetic structure of cassava landraces and their wild relatives (Manihotspp.) in Colombia revealed by simple sequence repeats
Authors: Tovar E. , Bocanegra J. L. , Villafañe C. , Fory L. , Velásquez A. , Gallego G. , Moreno R.
Published: August 2015

Understanding the genetic composition and population structure of plant species at a molecular level is essential for the development of adequate strategies aimed at enhancing the conservation and use of their genetic resources. In addition, such knowledge can help to plan ahead for a scenario under which wild and cultivated species come into contact with their genetically modified (GM) counterpart(s). Using ten simple sequence repeat markers, we genotyped 409 samples pertaining to the species in theManihotgenus known to occur in Colombia, i.e. cassava (Manihot esculenta)and its wild relativesManihot brachyloba,Manihot carthaginensisandManihot tristis. High genetic variation was observed in all the species (HE= 0.212–0.603), with cassava showing highest diversity. Most of the genetic variation was found within species populations. Our results suggest that outcrossing events among populations occur much more frequently inM. tristisandM. esculenta, and particularly so in the latter, where the exchange of varieties among local farmers plays a key role in maintaining and introducing new genetic diversity. The occurrence of gene flow within and among populations ofManihotspecies in Colombia becomes relevant in a biosafety context, where gene flow from GM cassava, if introduced to the country, might have detrimental effects on the structure and dynamics of populations of wild species. The baseline information on the genetic diversity and structure of the four Colombian species that we have presented here provides a first and indispensable step towards the development of targeted interventions necessary to preserve their genetic resources.
REFLEXIVE-INSENSITIVE MODAL LOGICS
Authors: GILBERT DAVID R. , VENTURI GIORGIO
Published: August 2015

We analyze a class of modal logics rendered insensitive to reflexivity by way of a modification to the semantic definition of the modal operator. We explore the extent to which these logics can be characterized, and prove a general completeness theorem on the basis of a translation between normal modal logics and their reflexive-insensitive counterparts. Lastly, we provide a sufficient semantic condition describing when a similarly general soundness result is also available.
Rap1-mediated nuclear factor-kappaB (NF-κB) activity regulates the paracrine capacity of mesenchymal stem cells in heart repair following infarction
Authors: Zhang Y , Chiu S , Liang X , Gao F , Zhang Z , Liao S , Liang Y , Chai Y-H , Low D J H , Tse H-F , Tergaonkar V , Lian Q
Published: August 2015

Paracrine effect is the major mechanism that underlies mesenchymal stem cells (MSC)-based therapy. This study aimed to examine how Rap1, telomeric repeat-binding factor 2-interacting protein 1 (Terf2IP), which is a novel modulator involved in the nuclear factor-kappaB (NF-κB) pathway, regulates the paracrine effects of MSC-mediated heart repair following infarction. NF-κB activity of stromal cells was increased by Rap1 as measured by pNF-κB-luciferase reporter activity, and this was abolished by IkB-dominant-negative protein. Knockdown of Rap1 with shRap1 resulted in diminished translocation of p65-NF-κB from the cytoplasm to nuclei in response to tumor necrosis factor-α (TNF-α) stimulation. Compared with BM-MSCs, Rap1−/−-BM-MSCs displayed a significantly reduced ratio of phosphorylated NF-κB to NF-κB-p65 and of Bax to Bcl-2, and increased resistance to hypoxia-induced apoptosis by the terminal deoxynucleotidal transferase-mediated dUTP nick end labeling (TUNEL) assay. In contrast, re-expression of Rap1 in Rap1−/−-BM-MSCs resulted in loss of resistance to apoptosis in the presence of hypoxia. Moreover, absence of Rap1 in BM-MSCs led to downregulation of NF-κB activity accompanied by reduced pro-inflammatory paracrine cytokines TNF-α, IL (interleukin)-6 and monocyte chemotactic protein-1 in Rap1−/−-BM-MSCs compared with BM-MSCs. The apoptosis of neonatal cardiomyocytes (NCMCs) induced by hypoxia was significantly reduced when cocultured with Rap1−/−-BM-MSC hypoxic-conditioned medium (CdM). The increased cardioprotective effects of Rap1−/−-BM-MSCs were reduced when Rap1−/−-BM-MSCs were reconstituted with Rap1 re-expression. Furthermore, in vivo study showed that transplantation of Rap1−/−-BM-MSCs significantly improved heart function, decreased infarct size, prevented cardiomyocyte apoptosis and inhibited inflammation compared with controls and BM-MSCs (P<0.01). This study reveals that Rap1 has a critical role in the regulation of MSC paracrine actions. Compared with BM-MSCs, Rap1−/−-BM-MSCs decreased NF-κB sensitivity to stress-induced pro-inflammatory cytokine production and reduced apoptosis. Selective inhibition of Rap1 in BM-MSCs may be a novel strategy to enhance MSC-based therapeutic efficacy in myocardial infarction.
Accommodating lithium into 3D current collectors with a submicron skeleton towards long-life lithium metal anodes
Authors: Yang Chun-Peng , Yin Ya-Xia , Zhang Shuai-Feng , Li Nian-Wu , Guo Yu-Guo
Published: August 2015

Lithium metal is one of the most attractive anode materials for electrochemical energy storage. However, the growth of Li dendrites during electrochemical deposition, which leads to a low Coulombic efficiency and safety concerns, has long hindered the application of rechargeable Li-metal batteries. Here we show that a 3D current collector with a submicron skeleton and high electroactive surface area can significantly improve the electrochemical deposition behaviour of Li. Li anode is accommodated in the 3D structure without uncontrollable Li dendrites. With the growth of Li dendrites being effectively suppressed, the Li anode in the 3D current collector can run for 600 h without short circuit and exhibits low voltage hysteresis. The exceptional electrochemical performance of the Li-metal anode in the 3D current collector highlights the importance of rational design of current collectors and reveals a new avenue for developing Li anodes with a long lifespan.
Diacylglycerol kinase-ζ regulates mTORC1 and lipogenic metabolism in cancer cells through SREBP-1
Authors: Torres-Ayuso P , Tello-Lafoz M , Mérida I , Ávila-Flores A
Published: August 2015

Diacylglycerol kinases (DGKs) transform diacylglycerol (DAG) into phosphatidic acid (PA), balancing the levels of these key metabolic and signaling lipids. We previously showed that PA derived from the DGKζ isoform promotes mammalian target of rapamycin complex 1 (mTORC1) activation. This function might be crucial for the growth and survival of cancer cells, especially for those resistant to the allosteric mTOR inhibitor rapamycin. How this positive function of DGKζ coordinates with DAG metabolism and signaling is unknown. In this study, we used a rapamycin-resistant colon cancer cell line as a model to address the role of DGKζ in tumor cells. We found that DGKζ predominated over other PA sources such as DGKα or phospholipase D to activate mTORC1, and that its activity was a component of the rapamycin-induced feedback loops. We show that the DGKζ DAG-consuming function is central to cell homeostasis, as DAG negatively regulates levels of the lipogenic transcription factor SREBP-1. Our findings suggest a model in which simultaneous regulation of DAG and PA levels by DGKζ is integrated with mTOR function to maintain tumor cell homeostasis; we provide new evidence of the crosstalk between mTOR and lipid metabolism that will be advantageous in the design of drug therapies.
Systemic Administration of siRNA via cRGD-containing Peptide
Authors: Huang Yuanyu , Wang Xiaoxia , Huang Weiyan , Cheng Qiang , Zheng Shuquan , Guo Shutao , Cao Huiqing , Liang Xing-Jie , Du Quan , Liang Zicai
Published: August 2015

Although small interfering RNAs (siRNAs) have been demonstrated to specifically silence their target genes in disease models and clinical trials, in vivo siRNA delivery is still the technical bottleneck that limits their use in therapeutic applications. In this study, a bifunctional peptide named RGD10-10R was designed and tested for its ability to deliver siRNA in vitro and in vivo. Because of their electrostatic interactions with polyarginine (10R), negatively charged siRNAs were readily complexed with RGD10-10R peptides, forming spherical RGD10-10R/siRNA nanoparticles. In addition to enhancing their serum stability by preventing RNase from attacking siRNA through steric hindrance, peptide binding facilitated siRNA transfection into MDA-MB-231 cells, as demonstrated by FACS and confocal microscopy assays and by the repressed expression of target genes. When RGD10 peptide, a receptor competitor of RGD10-10R, was added to the transfection system, the cellular internalization of RGD10-10R/siRNA was significantly compromised, suggesting a mechanism of ligand/receptor interaction. Tissue distribution assays indicated that the peptide/siRNA complex preferentially accumulated in the liver and in several exocrine/endocrine glands. Furthermore, tumor-targeted delivery of siRNA was also demonstrated by in vivo imaging and cryosection assays. In summary, RGD10-10R might constitute a novel siRNA delivery tool that could potentially be applied in tumor treatment.
A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos
Authors: Bliman David , Nilsson Jesper R. , Kettunen Petronella , Andréasson Joakim , Grøtli Morten
Published: August 2015

Proto-oncogene tyrosine-protein kinase receptor RET is implicated in the development and maintenance of neurons of the central and peripheral nervous systems. Attaching activity-compromising photocleavable groups (caging) to inhibitors could allow for external spatiotemporally controlled inhibition using light, potentially providing novel information on how these kinase receptors are involved in cellular processes. Here, caged RET inhibitors were obtained from 3-substituted pyrazolopyrimidine-based compounds by attaching photolabile groups to the exocyclic amino function. The most promising compound displayed excellent inhibitory effect in cell-free, as well as live-cell assays upon decaging. Furthermore, inhibition could be efficiently activated with light in vivo in zebrafish embryos and was shown to effect motoneuron development.
Use of double-stranded DNA mini-circles to characterize the covalent topoisomerase-DNA complex
Authors: Millet Armêl , Strauss François , Delagoutte Emmanuelle
Published: August 2015

The enzymatic DNA relaxation requires the DNA to be transiently nicked and rejoined, the covalent topoisomerase-DNA complex being a key intermediate of the nicking-joining reaction. Practically, this reaction is most often characterized by oligonucleotides. However, the incision-religation of an oligonucleotide does not fully recapitulate the incision-religation occuring during relaxation and the preferred substrate for such reaction characterization is supercoiled DNA. We therefore developed a method that used radiolabeled supercoiled DNA mini-circles to characterize the covalent enzyme-DNA complex formed during a relaxation reaction. Resolution of the relaxation products under different conditions permitted to quantify the proportion of covalent complex formed during the relaxation catalyzed by two topoisomerase models, the Escherichia coli topoisomerase I and the calf thymus topoisomerase I. As expected, the covalent complex formed with the calf thymus topoisomerase I was significantly enriched by camptothecin, a widely-used inhibitor of this topoisomerase and a salt jump permitted the multiple topoisomerases trapped per mini-circle to complete the reaction cycle. The identified positions of the camptothecin-induced incision sites were shown to be independent of the linking number and the substrate circular nature Overall, our results demonstrate that supercoiled mini-circles constitute a powerful and polyvalent substrate to characterize the mechanism of action of novel topoisomerases and inhibitors, including the incision-religation reaction.
Highlighting Indication of extracorporeal membrane oxygenation in endocrine emergencies
Authors: Chao Anne , Wang Chih-Hsien , You Hao-Chun , Chou Nai-Kwoun , Yu Hsi-Yu , Chi Nai-Hsin , Huang Shu-Chien , Wu I-Hui , Tseng Li-Jung , Lin Ming-Hsien , Chen Yih-Sharng
Published: August 2015

Extracorporeal membrane oxygenation (ECMO) has been repeatedly used to rescue patients with cardiopulmonary arrest. However, its clinical utility in endocrine emergencies remains unclear. Herein, we describe a case series of 12 patients presenting with refractory shock secondary to endocrine emergencies who were rescued by ECMO support. Patients were identified between 2005 and 2012 from our ECMO registry. The diagnostic distribution was as follows: pheochromocytoma crisis (n = 4), thyroid storm (n = 5) and diabetic ketoacidosis (n = 3). The initial presentation of pheochromocytoma crisis was indistinguishable from acute myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension and limb ischemia. Thyroid storm was characterized by hyperbilirubinemia and severe gastrointestinal bleeding, whereas neurological symptoms were common in diabetic ketoacidosis. The clinical outcomes of patients with endocrine emergencies were compared with those of 80 cases with AMI who received ECMO because of cardiogenic shock. The cardiac function and the general conditions showed a significantly faster recovery in patients with endocrine emergencies than in those with AMI. We conclude that ECMO support can be clinically useful in endocrine emergencies. The screening of endocrine diseases should be considered during the resuscitation of patients with refractory circulatory shock.
Study of spin-ordering and spin-reorientation transitions in hexagonal manganites through Raman spectroscopy
Authors: Chen Xiang-Bai , Hien Nguyen Thi Minh , Han Kiok , Nam Ji-Yeon , Huyen Nguyen Thi , Shin Seong-Il , Wang Xueyun , Cheong S. W. , Lee D. , Noh T. W. , Sung N. H. , Cho B. K. , Yang In-Sang
Published: August 2015

Spin-wave (magnon) scattering, when clearly observed by Raman spectroscopy, can be simple and powerful for studying magnetic phase transitions. In this paper, we present how to observe magnon scattering clearly by Raman spectroscopy, then apply the Raman method to study spin-ordering and spin-reorientation transitions of hexagonal manganite single crystal and thin films and compare directly with the results of magnetization measurements. Our results show that by choosing strong resonance condition and appropriate polarization configuration, magnon scattering can be clearly observed and the temperature dependence of magnon scattering can be simple and powerful quantity for investigating spin-ordering as well as spin-reorientation transitions. Especially, the Raman method would be very helpful for investigating the weak spin-reorientation transitions by selectively probing the magnons in the Mn3+ sublattices, while leaving out the strong effects of paramagnetic moments of the rare earth ions.
Smoking Gun or Circumstantial Evidence? Comparison of Statistical Learning Methods using Functional Annotations for Prioritizing Risk Variants
Authors: Gagliano Sarah A. , Ravji Reena , Barnes Michael R. , Weale Michael E. , Knight Jo
Published: August 2015

Although technology has triumphed in facilitating routine genome sequencing, new challenges have been created for the data-analyst. Genome-scale surveys of human variation generate volumes of data that far exceed capabilities for laboratory characterization. By incorporating functional annotations as predictors, statistical learning has been widely investigated for prioritizing genetic variants likely to be associated with complex disease. We compared three published prioritization procedures, which use different statistical learning algorithms and different predictors with regard to the quantity, type and coding. We also explored different combinations of algorithm and annotation set. As an application, we tested which methodology performed best for prioritizing variants using data from a large schizophrenia meta-analysis by the Psychiatric Genomics Consortium. Results suggest that all methods have considerable (and similar) predictive accuracies (AUCs 0.64–0.71) in test set data, but there is more variability in the application to the schizophrenia GWAS. In conclusion, a variety of algorithms and annotations seem to have a similar potential to effectively enrich true risk variants in genome-scale datasets, however none offer more than incremental improvement in prediction. We discuss how methods might be evolved for risk variant prediction to address the impending bottleneck of the new generation of genome re-sequencing studies.
CAMKII-conditional deletion of histone deacetylase 2 potentiates acute methamphetamine-induced expression of immediate early genes in the mouse nucleus accumbens
Authors: Torres Oscar V. , McCoy Michael T. , Ladenheim Bruce , Jayanthi Subramaniam , Brannock Christie , Tulloch Ingrid , Krasnova Irina N. , Cadet Jean Lud
Published: August 2015

Methamphetamine (METH) produces increases in the expression of immediate early genes (IEGs) and of histone deacetylase 2 (HDAC2) in the rat nucleus accumbens (NAc). Here, we tested whether HDAC2 deletion influenced the effects of METH on IEG expression in the NAc. Microarray analyses showed no baseline differences in IEG expression between wild-type (WT) and HDAC2 knockout (KO) mice. Quantitative-PCR analysis shows that an acute METH injection produced time-dependent increases in mRNA levels of several IEGs in both genotypes. Interestingly, HDAC2KO mice displayed greater METH-induced increases in Egr1 and Egr2 mRNA levels measured at one hour post-injection. The levels of Fosb, Fra2, Egr1 and Egr3 mRNAs stayed elevated in the HDAC2KO mice 2 hours after the METH injection whereas these mRNAs had normalized in the WT mice. In WT mice, METH caused increased HDAC2 recruitment to the promoters some IEGs at 2 hours post injection. METH-induced prolonged increases in Fosb, Fra2, Egr1 and Egr3 mRNA levels in HDAC2KO mice were associated with increased enrichment of phosphorylated CREB (pCREB) on the promoters of these genes. Based on our observations, we hypothesize that HDAC2 may regulate the expression of these genes, in part, by prolonging the actions of pCREB in the mouse NAc.
Efficient nitrogen incorporation in ZnO nanowires
Authors: Stehr Jan E. , Chen Weimin M. , Reddy Nandanapalli Koteeswara , Tu Charles W. , Buyanova Irina A.
Published: August 2015

One-dimensional ZnO nanowires (NWs) are a promising materials system for a variety of applications. Utilization of ZnO, however, requires a good understanding and control of material properties that are largely affected by intrinsic defects and contaminants. In this work we provide experimental evidence for unintentional incorporation of nitrogen in ZnO NWs grown by rapid thermal chemical vapor deposition, from electron paramagnetic resonance spectroscopy. The incorporated nitrogen atoms are concluded to mainly reside at oxygen sites (NO). The NO centers are suggested to be located in proximity to the NW surface, based on their reduced optical ionization energy as compared with that in bulk. This implies a lower defect formation energy at the NW surface as compared with its bulk value, consistent with theoretical predictions. The revealed facilitated incorporation of nitrogen in ZnO nanostructures may be advantageous for realizing p-type conducting ZnO via N doping. The awareness of this process can also help to prevent such unintentional doping in structures with desired n-type conductivity.
STAT1 deficiency redirects IFN signalling toward suppression of TLR response through a feedback activation of STAT3
Authors: Kim Hun Sik , Kim Dong Chan , Kim Hong-Mi , Kwon Hyung-Joon , Kwon Soon Jae , Kang Suk-Jo , Kim Sun Chang , Choi Go-Eun
Published: August 2015

Interferons (IFNs) potentiate macrophage activation typically via a STAT1-dependent pathway. Recent studies suggest a functioning of STAT1-independent pathway in the regulation of gene expression by IFN-γ, thus pointing to the diversity in cellular responses to IFNs. Many functions of IFNs rely on cross-regulation of the responses to exogenous inflammatory mediators such as TLR ligands. Here we investigated the contribution of STAT1-independent pathway to macrophage activation and its underlying mechanism in the context of combined stimulation of IFN and TLR. We found that TLR-induced production of inflammatory cytokines (TNF-α, IL-12) was not simply nullified but was significantly suppressed by signaling common to IFN-γ and IFN-β in STAT1-null macrophages. Such a shift in the suppression of TLR response correlated with a sustained STAT3 activation and attenuation of NF-κB signaling. Using a JAK2/STAT3 pathway inhibitor or STAT3-specific siRNA, blocking STAT3 in that context restored TNF-α production and NF-κB signaling, thus indicating a functional cross-regulation among STAT1, STAT3 and NF-κB. Our results suggest that STAT1 deficiency reprograms IFN signaling from priming toward suppression of TLR response via feedback regulation of STAT3, which may provide a new insight into the host defense response against microbial pathogens in a situation of STAT1 deficiency.
Metallic Sn spheres and SnO2@C core-shells by anaerobic and aerobic catalytic ethanol and CO oxidation reactions over SnO2 nanoparticles
Authors: Kim Won Joo , Lee Sung Woo , Sohn Youngku
Published: August 2015

SnO2 has been studied intensely for applications to sensors, Li-ion batteries and solar cells. Despite this, comparatively little attention has been paid to the changes in morphology and crystal phase that occur on the metal oxide surface during chemical reactions. This paper reports anaerobic and aerobic ethanol and CO oxidation reactions over SnO2 nanoparticles (NPs), as well as the subsequent changes in the nature of the NPs. Uniform SnO2@C core-shells (10 nm) were formed by an aerobic ethanol oxidation reaction over SnO2 NPs. On the other hand, metallic Sn spheres were produced by an anaerobic ethanol oxidation reaction at 450 °C, which is significantly lower than that (1200 °C) used in industrial Sn production. Anaerobic and aerobic CO oxidation reactions were also examined. The novelty of the methods for the production of metallic Sn and SnO2@C core-shells including other anaerobic and aerobic reactions will contribute significantly to Sn and SnO2-based applications.
An immunoprecipitation assay in the multicommutated flow analysis format
Authors: Strzelak Kamil , Koncki Robert
Published: August 2015

In this contribution, a multicommutated flow analysis (MCFA) system for immunoprecipitation assays is presented.
A new label-free and turn-on fluorescence probe for hydrogen peroxide and glucose detection based on DNA–silver nanoclusters
Authors: Han Hui-Xia , Tian Xue , Kong Xiang-Juan , Yu Ru-Qin , Chu Xia
Published: August 2015

A label-free and turn-on strategy for H2O2 and glucose detection based on the cleavage of ssDNA by ˙OH and the fluorescence enhancement effect when guanine-rich (G-rich) DNA sequences are in proximity to DNA–silver nanoclusters (DNA–Ag NCs).
Electronic promoter or reacting species? The role of LiNH2 on Ru in catalyzing NH3 decomposition
Authors: Guo Jianping , Chen Zheng , Wu Anan , Chang Fei , Wang Peikun , Hu Daqiang , Wu Guotao , Xiong Zhitao , Yu Pei , Chen Ping
Published: August 2015

Li creates a NHx-rich environment and Ru mediates the electron transfer facilitating NHx coupling.
Boiling water synthesis of ultrastable thiolated silver nanoclusters with aggregation-induced emission
Authors: Zheng Kaiyuan , Yuan Xun , Kuah Kavan , Luo Zhentao , Yao Qiaofeng , Zhang Qingbo , Xie Jianping
Published: August 2015

Boiling water synthesis of core–shell Ag(0)@Ag(i)–thiolate structured Ag NCs with a strong red luminescence via aggregation-induced-emission (AIE).
Graphene laminated gold bipyramids as sensitive detection platforms for antibiotic molecules
Authors: Lee Seunghyun , Kumar Prashant , Hu Yaowu , Cheng Gary J. , Irudayaraj Joseph
Published: August 2015

Graphene is integrated into gold bipyramids by optomechanical wrapping with atomic scale integration. This structure is used as an SERS platform for the sensitive detection of antibiotic tetracycline molecules.
Simple addition of silica to an alkane solution of a Wilkinson WMe6 or Schrock W alkylidyne complex gives an active complex for saturated and unsaturated hydrocarbon metathesis
Authors: Callens Emmanuel , Riache Nassima , Talbi Karima , Basset Jean-Marie
Published: August 2015

Hydrocarbon metathesis by simple impregnation of Schrock W-alkylidyne on silica.
A two-photon activatable amino acid linker for the induction of fluorescence
Authors: Friedrich Felix , Klehs Kathrin , Fichte Manuela A. H. , Junek Stephan , Heilemann Mike , Heckel Alexander
Published: August 2015

The first photolabile quencher for ATTO565 is presented and the application of the new construct in super-resolution microscopy is demonstrated.
Site-selective multi-porphyrin attachment enables the formation of a next-generation antibody-based photodynamic therapeutic
Authors: Maruani Antoine , Savoie Huguette , Bryden Francesca , Caddick Stephen , Boyle Ross , Chudasama Vijay
Published: August 2015

A next-generation antibody-based photodynamic therapeutic is assembled and shown to be potent and selectivein vitro.
Black strontium titanate nanocrystals of enhanced solar absorption for photocatalysis
Authors: Zhao Wenli , Zhao Wei , Zhu Guilian , Lin Tianquan , Xu Fangfang , Huang Fuqiang
Published: August 2015

Black SrTiO3 nanocrystals with enhanced visible-light and even IR absorption have been successfully synthesized by aluminum reduction.
Amylin–Aβ oligomers at atomic resolution using molecular dynamics simulations: a link between Type 2 diabetes and Alzheimer's disease
Authors: Baram Michal , Atsmon-Raz Yoav , Ma Buyong , Nussinov Ruth , Miller Yifat
Published: August 2015

Aβ1–42 oligomers prefer to interact with Amylin1–37 oligomers to form single layer conformations.