bluuebunny/crossref_metadata_2025 huggingface dataset:
Futility and the Care of Surgical Patients: Ethical Dilemmas
Authors: Grant Scott B. , Modi Parth K. , Singer Eric A.
Published: May 2014

Futility has been a contentious topic in medicine for several decades. Surgery in critical or end‐of‐life situations often raises difficult questions about futility. In this article, we discuss the definition of futility, methods for resolving futility disputes, and some ways to reframe the futility debate to a more fruitful discussion about the goals of care, better communication between surgeon and patient/surrogate, and palliative surgical care. Many definitions of futile therapy have been discussed. The most controversial of these is “qualitative futility” which describes a situation in which the treatment provided is likely to result in an unacceptable quality of life. This is an area of continued controversy because it has been impossible to identify universally held beliefs about acceptable quality of life. Many authors have described methods for resolving futility disputes, including community standards and legalistic multi‐step due process protocols. Others, however, have abandoned the concept of futility altogether as an unhelpful term. Reframing the issue of futility as one of inadequate physician–patient communication, these authors have advocated for methods of improving communication and strengthening the patient–physician relationship. Finally, we discuss the utilization of consultants who may be of use in resolving futility disputes: ethics committees, palliative care specialists, pastoral care teams, and dedicated patient advocates. Involving these specialists in a futility conflict can help improve communication and provide invaluable assistance in arriving at the appropriate treatment decision.
Effective clearance of GL‐3 in a human iPSC‐derived cardiomyocyte model of Fabry disease
Authors: Itier Jean‐Michel , Ret Gwénaëlle , Viale Sandra , Sweet Lindsay , Bangari Dinesh , Caron Anne , Le‐Gall Françoise , Bénichou Bernard , Leonard John , Deleuze Jean‐François , Orsini Cécile
Published: May 2014

Fabry disease, a rare X‐linked α‐galactosidase A deficiency, causes progressive lysosomal accumulation of globotriaosylceramide (GL‐3) in a variety of cell types. As the disease progresses, renal failure, left ventricular hypertrophy, and strokes may occur. Enzyme replacement therapy (ERT), with recombinant α‐galactosidase A, is currently available for use to reduce GL‐3 deposits. However, although it improves cardiac function and decreases left ventricular mass, GL‐3 clearance upon ERT has been demonstrated in cardiac capillary endothelium but not in cardiomyocytes of patients. Relevant models are needed to understand the pathogenesis of cardiac disease and explore new therapeutic approaches. We generated induced pluripotent stem cells (iPSC) from Fabry patients and differentiated them into cardiomyocytes. In these cells, GL‐3 accumulates in the lysosomes over time, resulting in phenotypic changes similar to those found in cardiac tissue from Fabry patients. Using this human in vitro model, we demonstrated that substrate reduction therapy via glucosylceramide synthase inhibition was able to prevent accumulation and to clear lysosomal GL‐3 in cardiomyocytes. This new in vitro model recapitulates essential features of cardiomyocytes from patients with Fabry disease and therefore provides a useful and relevant tool for further investigations of new therapy.
Crystal structure of an efficacious gonococcal adherence inhibitor: An enolase from Lactobacillus gasseri
Authors: Raghunathan Kannan , Harris Paul T. , Spurbeck Rachel R. , Arvidson Cindy G. , Arvidson Dennis N.
Published: May 2014

Enolases are highly conserved metalloenzymes ubiquitous to cellular metabolism. While these enzymes share a large degree of sequence and structural similarity, they have been shown to possess a wide range of moonlighting functions. Recent studies showed that an enolase from Lactobacillus gasseri impedes the ability of Neisseria gonorrhoeae to adhere to epithelial cells. We present the crystal structure of this enolase, the first from Lactobacillus, with one of its Mg2+ cofactors. Determined using molecular replacement to 2.08 Å, the structure has a flexible and surface exposed catalytic loop containing lysines, and may play a role in the inhibitory function.
Parenting From the Outside-In: A Paradigm Shift in Parent Training?
Authors: Mazzucchelli Trevor G. , Sanders Matthew R.
Published: May 2014

It has recently been asserted that a paradigm shift is emerging in the delivery of parenting programs. Specifically, it has been suggested that interventions from the field of interpersonal neurobiology represent sophisticated alternatives to positive parenting interventions based on social learning models and behavioural principles, and better reflect how contemporary practitioners consider parenting. We examine this assertion, dispel a number of myths, and conclude that characterisations of positive parenting programs are frequently misleading and do not adequately reflect contemporary models of practice. There is little justification to support the claim that the field should abandon this ‘paradigm’. Indeed, there has been a considerable expansion in the evidence base supporting positive parenting programs and the emergence of a public health framework that blends universal and indicated interventions that can greatly increase the reach and lower the costs of delivering parenting interventions.
Family Inclusive Child Protection Practice: The History of the Family Inclusion Network and Beyond
Authors: Ainsworth Frank , Berger John
Published: May 2014

This article records briefly the history of the Family Inclusion Network as an organisation that promotes family inclusive child protection practice. Since its inception in Queensland in 2006, Family Inclusion Network organisations have been formed elsewhere and now exist in Western Australia, South Australia, Victoria, Tasmania, Australian Capital Territory and New South Wales. In 2010, developments at a national level saw the formation of the Family Inclusion Network Australia. Most organisations are incorporated and some have achieved charitable status. Each organisation endorses a common set of aims and objectives. There are, however, differences in terms of whether state or territory organisations accept government funding or not, are staffed by professionals or rely entirely on volunteer personnel, and have a capacity or otherwise to provide direct casework services to parents. Some state organisations focus on information and advice services, and legislative and policy reform efforts. All have telephone advice lines and a webpage presence. This article also focuses on a code of ethics for child protection practice and on the contribution parents can make to child protection services, and their rights to do so.
Family Inclusive Child Protection Practice: The Need for Rigorous Evaluation
Authors: Hawkins Russell M.F.
Published: May 2014

Historical and current child protection practice in Australia has been subject to severe criticism, yet in spite of a persuasive case for an alternative family inclusive form of child protection practice – something that offers the potential for improved client outcomes and improved worker job satisfaction – the model is not yet in widespread use. An international review of promising innovations in child protection, including examples of programmes from Australia, resulted in a list of eight identified trends. Common to all of these trends was evidence that good-quality evaluation had contributed to their recognition. If family inclusive practice is to gain greater acceptance, especially by bureaucrats, policy makers and holders of the purse strings, sophisticated forms of programme evaluation will be required. Such evaluations might emphasise practice-based research where researchers and frontline practitioners work together on all aspects of evaluation, including the initial design stage. While gold-standard randomised controlled trials may be included, methodological pluralism should allow inclusion of alternative approaches, such as realist evaluation and the involvement of practice research networks. The use of external evaluators might be usefully replaced with greater reliance on evaluation partnerships between evaluation experts (researchers) and frontline agency staff. Follow-up systematic reviews and meta-analyses might then allow the development of evidence-based arguments for change. Some Australian programmes have shown how rigorous evaluation practices have underpinned success and this evaluation focus could be emulated.
Families Can Do Coping: Parenting Skills in the Early Years
Authors: Frydenberg Erica , Deans Jan , Liang Rachel
Published: May 2014

Parenting programmes are very much a part of the international landscape in Western communities. Coping skills provide a useful resource for parents and children in managing their everyday lives, both together and individually. Following a 5-year research programme with parents and children in an early years setting, Families Can Do Coping was developed as a comprehensive parenting skills programme that incorporates parents’ understanding of their own coping and that of their children. The programme was delivered with the twin aims of teaching communication and coping skills to parents. In 2012, five 2-hour sessions were delivered to 19 parents in an Early Learning Centre at the University of Melbourne. The five-session programme focused on providing parents with information regarding coping skills and the use of visual tools to assist parents to engage with their children in conversations about coping. Additionally, parents completed a pencil-and-paper coping skills evaluation for their child. The programme outcomes included perceptions of parents’ enhancement of their wellbeing, and development of proactive and productive coping skills in both parents and children. After a 3-month period three parents provided feedback on their progress and use of the new tools and strategies for maintaining helpful parenting.
Blurred Lines? Responding to ‘Sexting’ and Gender-based Violence among Young People
Authors: Powell Anastasia , Henry Nicola
Published: May 2014

The emerging phenomenon of youth ‘sexting’ presents a range of unique legal, policy and educative challenges. In this article we consider four key issues in recent responses to youth sexting behaviours: (1) the definitional dilemmas surrounding the term ‘sexting’; (2) the inadequacy of existing legislative frameworks for responding to these behaviours; (3) the problematic messages conveyed in anti-sexting campaigns; and (4) the relative silence around gender-based violence in non-consensual and abusive encounters. We argue that the non-consensual creation and distribution of sexual images has largely been framed in public debates as a problem of youth naiveté, with the effect of censuring young women's ‘risky’ sexual behaviour, and leaving unproblematised gender-based violence. We suggest that more nuanced understandings of sexting that distinguishes between the consensual and non-consensual creation and distribution of sexual images must inform legal, policy and education-based prevention responses to the misuse of new technologies.
The incremental and cumulative effects of dynamic capability building on service innovation in collaborative service organizations
Authors: Agarwal Renu , Selen Willem
Published: May 2014

Increasingly, innovation in services is brought to market by a network of firms, or alliance networks, asset orchestration, knowledge sharing capabilities, resources and competencies, and operated in a coordinated manner. Recent literature has recognized the evolutionary nature of dynamic capabilities in that managers may adapt their alliance networks dynamically to sustain competitive advantage, as well as identified a continuing gap in the lack of empirical studies on feedbacks between network environments, dynamic capabilities, and innovation performance. In addition, other literature calls for more quantitative research on examining dynamic capabilities in a network environment to provide a better understanding of how firms should direct their resources and capabilities to successfully respond to competition. This study contributes towards closing both gaps by empirically examining thecumulative and incrementaleffects of fostering and deploying different dynamic capabilities on services innovation, and by quantifying their impact, thus providing managers with a better account of how services innovation comes about in a service value network. It does so using empirical data from 449 respondents from a telecommunications service provider in Australia and its partnering organizations, using structural equation modelling.
Inward−outward guanxi contagion and employees’ responses to managerial guanxi practices
Authors: Jiang Han , Cannella Albert , Gao Lifang , Jiao Jie
Published: May 2014

Our study develops a new conceptual framework in which guanxi practices (managerial use of interpersonal ties to benefit their organizations) are analyzed by their focus (resources flowing inward or resources flowing outward) and their base (familiar – based on friendship ties; or family – based on kinship ties). Using this framework, we highlight the linkage between costs and benefits from using guanxi in Chinese business organizations, and show how the linkage depends on the guanxi base. Finally, we show how guanxi focus and guanxi base importantly affect employee responses to the use of guanxi practices in their organizations.
Special Issue Dedicated to ICFP 2012: Editorial
Authors: SINGH SATNAM , FINDLER ROBERT BRUCE
Published: May 2014

The 17th ACM SIGPLAN International Conference on Functional Programming (ICFP) took place on September 10–12, 2012 in Copenhagen, Denmark. After the conference, the programme committee selected several outstanding papers and invited their authors to submit to this special issue of Journal of Functional Programming. Robby Findler and Satnam Singh acted as editors for these submissions. This issue includes the accepted papers, each of which provides substantial new material beyond the original conference version.
Hair Calcium Concentration is Associated with Calcium Intake and Bone Mineral Density
Authors: Park Soo-Jung , Lee Sang-Hoon , Cho Doo-Yeoun , Kim Kwang-Min , Lee Duk-Joo , Kim Bom-Taeck
Published: May 2014

Calcium concentration in hair, representing intracellular calcium levels, is associated with systemic diseases such as coronary artery disease. To date, there are no previous studies which investigate the regulation of hair calcium levels. The aim of the study is to investigate whether hair calcium concentration is related to calcium intake and calcium content in bone - bone mineral density (BMD). An observational research study was conducted with 55 women over the age of 20 who visited a university hospital in Suwon, Korea. The average age of the women was 51.45. Depending on the concentration of hair calcium, participants were divided into quartiles to compare calcium intake and BMD. There was no difference in demographic, anthropometric, and biochemical characteristics between the highest quartile of hair calcium concentration and the rest of the quartiles. However, the highest quartile ingested significantly less calcium compared to the rest of the quartiles (p < 0.05). The highest quartile of hair calcium concentration also showed significantly lower BMD and T-score in the L1 - 4 vertebrae compared to the rest of the quartiles (p < 0.05). These results show that high hair calcium concentration was associated with low calcium intake and low BMD.
Qualität unfreiwilliger Klinikeinweisungen in der Schweiz
Authors: Jäger Matthias , Ospelt Isabelle , Kawohl Wolfram , Theodoridou Anastasia , Rössler Wulf , Hoff Paul
Published: May 2014

Fragestellung: Diese Studie hat zum Ziel, die vor Einführung des neuen Kindes- und Erwachsenenschutzrechts per Januar 2013 bestehende Praxis der Fürsorgerischen Freiheitsentziehung (FFE) anhand formaler und inhaltlicher Kriterien der Zuweisungsschreiben zu untersuchen. Hinweise auf Unterschiede zwischen Zuweisern mit verschiedenen professionellen Hintergründen sollen überprüft und die eingewiesenen Personen charakterisiert werden. Methode: Retrospektive Auswertung der Zuweisungsformulare und der Krankenakten sämtlicher per FFE in die Psychiatrische Universitätsklinik Zürich eingetretenen Patienten in einem Zeitraum von sechs Monaten (n=489). Resultate: Es bestehen erhebliche Mängel bezüglich formaler und insbesondere inhaltlicher Qualitätskriterien. Psychiatrische Fachärzte erstellen die Zeugnisse mit der höchsten Qualität, gefolgt von Notärzten sowie Spitälern und Hausärzten. Die Patienten dieser Zuweisergruppen unterscheiden sich bezüglich soziodemographischer und klinischer Variablen. Schlussfolgerungen: Die formale und insbesondere inhaltliche Qualität der Zwangseinweisungen ist angesichts der schwerwiegenden ethischen und juristischen Konsequenzen für die betroffene Person verbesserungsbedürftig. Die Auswirkungen der neuen Gesetzgebung auf die Qualität der Zuweisungen sollten überprüft werden, sodass etwaige Defizite in der Anwendung freiheitsbeschränkender Massnahmen in der Aus- und Weiterbildungspraxis adressiert werden können.
The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB
Authors: Wagner Amy K , Scanion Joelle M , Becker Carl R , Ritter Anne C , Niyonkuru Christian , Dixon Clifton E , Conley Yvette P , Price Julie C
Published: May 2014

Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [11C]βCFT and [11C]raclopride. We examined subjects with moderate/severe TBI ( N = 12) ~1 year post injury and similarly matched healthy controls ( N = 13). The variable number of tandem repeat polymorphism within the DAT gene and the Taql restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.
Neuroprotection after Traumatic Brain Injury in Heat-Acclimated Mice Involves Induced Neurogenesis and Activation of Angiotensin Receptor Type 2 Signaling
Authors: Umschweif Gali , Shabashov Dalia , Alexandrovich Alexander G , Trembovler Victoria , Horowitz Michal , Shohami Esther
Published: May 2014

Long-term exposure of mice to mild heat (34°C ± 1°C) confers neuroprotection against traumatic brain injury (TBI); however, the underling mechanisms are not fully understood. Heat acclimation (HA) increases hypothalamic angiotensin II receptor type 2 (AT2) expression and hypothalamic neurogenesis. Accumulating data suggest that activation of the brain AT2 receptor confers protection against several types of brain pathologies, including ischemia, a hallmark of the secondary injury occurring following TBI. As AT2 activates the same pro-survival pathways involved in HA-mediated neuroprotection (e.g., Akt phosphorylation, hypoxia-inducible factor 1α (HIF-1α), and brain-derived neurotrophic factor (BDNF)), we examined the role of AT2 in HA-mediated neuroprotection after TBI. Using an AT2-specific antagonist PD123319, we found that the improvements in motor and cognitive recovery as well as reduced lesion volume and neurogenesis seen in HA mice were all diminished by AT2 inhibition, whereas no significant alternations were observed in control mice. We also found that nerve growth factor/tropomyosin-related kinase receptor A (TrkA), BDNF/TrkB, and HIF-1α pathways are upregulated by HA and inhibited on PD123319 administration, suggesting that these pathways play a role in AT2 signaling in HA mice. In conclusion, AT2 is involved in HA-mediated neuroprotection, and AT2 activation may be protective and should be considered a novel drug target in the treatment of TBI patients.
Mesenchymal Stromal Cells in Stroke: Improvement of Motor Recovery or Functional Compensation?
Authors: Boltze Johannes , Lukomska Barbara , Jolkkonen Jukka , consortium MEMS-IRBI
Published: May 2014

Experimental stroke treatment by mesenchymal stem cell (MSC) populations is an attractive paradigm in stroke research. There are many studies describing improved functional outcomes after MSC delivery in stroke, but the mechanisms through which the transferred cells exert these effects are less well understood. Moreover, commonly applied functional tests may not be suitable for discriminating real functional recovery from compensation, which is a frequently encountered phenomenon in rodents. This commentary highlights some of the potential risks for the translational process associated with these tests and proposes some alternative test arrays which may achieve more specific functional phenotyping.
Postglacial Fringing-Reef to Barrier-Reef conversion on Tahiti links Darwin's reef types
Authors: Blanchon Paul , Granados-Corea Marian , Abbey Elizabeth , Braga Juan C. , Braithwaite Colin , Kennedy David M. , Spencer Tom , Webster Jody M. , Woodroffe Colin D.
Published: May 2014

In 1842 Charles Darwin claimed that vertical growth on a subsiding foundation caused fringing reefs to transform into barrier reefs then atolls. Yet historically no transition between reef types has been discovered and they are widely considered to develop independently from antecedent foundations during glacio-eustatic sea-level rise. Here we reconstruct reef development from cores recovered by IODP Expedition 310 to Tahiti and show that a fringing reef retreated upslope during postglacial sea-level rise and transformed into a barrier reef when it encountered a Pleistocene reef-flat platform. The reef became stranded on the platform edge, creating a lagoon that isolated it from coastal sediment and facilitated a switch to a faster-growing coral assemblage dominated by acroporids. The switch increased the reef's accretion rate, allowing it to keep pace with rising sea level and transform into a barrier reef. This retreat mechanism not only links Darwin's reef types, but explains the re-occupation of reefs during Pleistocene glacio-eustacy.
Titanium dioxide supported on MWCNTs as an eco-friendly catalyst in the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones accelerated under microwave irradiation
Authors: Safari Javad , Gandomi-Ravandi Soheila
Published: May 2014

Some transition metal oxides supported on MWCNTs were prepared as novel heterogeneous catalysts using the facile processes. These catalysts were used for the synthesis of Biginelli compounds under microwave irradiation.
Rhodium-catalyzed intramolecular annulation via C–H activation leading to fused tricyclic indole scaffolds
Authors: Tao Pengyu , Jia Yanxing
Published: May 2014

A new method for the synthesis of fused tricyclic indoles via a rhodium catalyzed intramolecular C–H activation reaction is described.
Thermodynamic limits of extractable energy by pressure retarded osmosis
Authors: Lin Shihong , Straub Anthony P. , Elimelech Menachem
Published: May 2014

The maximum specific energy obtainable in pressure retarded osmosis and the corresponding optimal operating conditions are analytically determined for three different operation modes: an ideal reversible process, and constant-pressure systems with either co-current flow or counter-current flow in a membrane module.
Highly active hydrogen evolution catalysis from metallic WS2 nanosheets
Authors: Lukowski Mark A. , Daniel Andrew S. , English Caroline R. , Meng Fei , Forticaux Audrey , Hamers Robert J. , Jin Song
Published: May 2014

Metallic WS2 nanosheets chemically exfoliated from chemical vapour deposited WS2 nanostructures display excellent catalytic activity for the hydrogen evolution reaction.
Inkjet printing of graphene
Authors: Arapov Kirill , Abbel Robert , de With Gijsbertus , Friedrich Heiner
Published: May 2014

The inkjet printing of graphene is a cost-effective, and versatile deposition technique for both transparent and non-transparent conductive films. Printing graphene on paper is aimed at low-end, high-volume applications,i.e., in electromagnetic shielding, photovoltaics or,e.g., as a replacement for the metal in antennas of radio-frequency identification devices, thereby improving their recyclability and biocompatibility. Here, we present a comparison of two graphene inks, one prepared by the solubilization of expanded graphite in the presence of a surface active polymer, and the other by covalent graphene functionalization followed by redispersion in a solvent but without a surfactant. The non-oxidative functionalization of graphite in the form of a donor-type graphite intercalation compound was carried out by a Birch-type alkylation, where graphene can be viewed as a macrocarbanion. To increase the amount of functionalization we employed a graphite precursor with a high edge to bulk carbon ratio, thus, allowing us to achieve up to six weight percent of functional groups. The functionalized graphene can be readily dispersed at concentrations of up to 3 mg ml−1in non-toxic organic solvents, and is colloidally stable for more than 2 months. The two inks are readily inkjet printable with good to satisfactory spreading. Analysis of the sheet resistance of the deposited films demonstrated that the inks based on expanded graphite outperform the functionalized graphene inks, possibly due to the significantly larger graphene sheet size in the former, which minimizes the number of sheet-to-sheet contacts along the conductive path. We found that the sheet resistance of printed large-area films decreased with an increase of the number of printed layers. Conductivity levels reached approximately 1–2 kΩ □−1for 15 printing passes, which roughly equals a film thickness of 800 nm for expanded graphite based inks, and 2 MΩ □−1for 15 printing passes of functionalized graphene, having a film thickness of 900 nm. Our results show that ink preparation and inkjet printing of graphene-based inks is simple and efficient, and therefore has a high potential to compete with other conductive ink formulations for large-area printing of conductive films.
Highly efficient single-cell analysis of microbial cells by time-resolved inductively coupled plasma mass spectrometry
Authors: Miyashita Shin-ichi , Groombridge Alexander S. , Fujii Shin-ichiro , Minoda Ayumi , Takatsu Akiko , Hioki Akiharu , Chiba Koichi , Inagaki Kazumi
Published: May 2014

Highly efficient single-cell elemental analysis of microbial cells was achieved using a developed ICP-MS system with approximately 100% cell introduction efficiency and high time resolution.
Hepatic metabolic response to restricted copper intake in a Niemann–Pick C murine model
Authors: Argüello Graciela , Martinez Pablo , Peña Juan , Chen Oscar , Platt Frances , Zanlungo Silvana , González Mauricio
Published: May 2014

Niemann–Pick C disease (NPC) is a vesicular trafficking disorder primarily caused by mutations in theNpc1gene and characterized by liver dysfunction and neuropathology.
Transformed yeast (Schizosaccharomyces pombe) overexpressing rice Tau class glutathione S-transferase (OsGSTU30 and OsGSTU41) shows enhanced resistance to hexavalent chromium
Authors: Tripathi Ankita , Indoliya Yuvraj , Tiwari Madhu , Tiwari Poonam , Srivastava Dipali , kumar Verma Pankaj , Verma Shikha , Gautam Neelam , Chakrabarty Debasis
Published: May 2014

Two Tau class GSTs that are up-regulated in rice roots upon exposure to Cr(vi), showed resistance when expressed in yeast.
Tandem ATRP/Diels–Alder synthesis of polyHEMA-based hydrogels
Authors: Galbis E. , de Paz M. V. , McGuinness K. L. , Angulo M. , Valencia C. , Galbis J. A.
Published: May 2014

An efficient controlled process for the preparation of HEMA-based hydrogels by means of the Diels–Alder reaction.
From cage-jump motion to macroscopic diffusion in supercooled liquids
Authors: Pastore Raffaele , Coniglio Antonio , Pica Ciamarra Massimo
Published: May 2014

Investigating the single-particle motion of structural glasses, we show that the diffusivity can be predicted well before the diffusive regime.
Semiconducting:insulating polymer blends for optoelectronic applications—a review of recent advances
Authors: Scaccabarozzi A. D. , Stingelin N.
Published: May 2014

The working principle of semiconductor:insulator blends are discussed, examining the different approaches that have recently been reported in literature.
Targeted delivery of a SNARE protease to sensory neurons using a single chain antibody (scFv) against the extracellular domain of P2X3 inhibits the release of a pain mediator
Authors: Ma Hui , Meng Jianghui , Wang Jiafu , Hearty Stephen , Dolly J. Oliver , O’Kennedy Richard
Published: May 2014

P2X3 (P2X purinoceptor 3) is predominantly expressed on nociceptive sensory neurons and plays a crucial role in signalling leading to chronic inflammatory pain and some features of neuropathic pain. Thus it represents a potential target for pain therapeutics. BoNT/A (botulinum neurooxin type A) effectively relieves certain types of pain through inhibiting the neuronal release of pain peptides. A recombinant single-chain variable fragment (scFv) antibody designated MH7C was generated against the extracellular domain of P2X3 using phage display. The genes encoding the scFv and activated di-chain form of BoNT/A without the C-terminal-binding subdomain (LC–HN–HCN/A) were ligated and expressed in Escherichia coli cells as a composite fusion protein. The purified protein bound and entered P2X3-containing sensory neurons, cleaved synaptosomal-associated protein of 25 kDa and inhibited the release of a pain peptide. This novel fusion protein designated ‘LC–HN–HCN/A–MH7C’ has potential clinical applications in the treatment of chronic inflammatory and sympathetically maintained neuropathic pain.
HEXIM1 plays a critical role in the inhibition of the androgen receptor by anti-androgens
Authors: Yeh I-Ju , Song Kyung , Wittmann Bryan M. , Bai Xiaodong , Danielpour David , Montano Monica M.
Published: May 2014

We show that HEXIM1 (hexamethylene bis-acetamide inducible 1) functions as an AR (androgen receptor) co-repressor as it physically interacts with the AR and is required for the ability of anti-androgens to inhibit androgen-induced target gene expression and cell proliferation. Oncomine™ database and IHC (immunohistochemistry) analyses of human prostate tissues revealed that expression of HEXIM1 mRNA and protein are down-regulated during the development and progression of prostate cancer. Enforced down-regulation of HEXIM1 in parental hormone-dependent LNCaP cells results in resistance to the inhibitory action of anti-androgens. Conversely, ectopic expression of HEXIM1 in the CRPC (castration-resistant prostate cancer) cell line, C4-2, enhances their sensitivity to the repressive effects of the anti-androgen bicalutamide. Novel insight into the mechanistic basis for HEXIM1 inhibition of AR activity is provided by the present studies showing that HEXIM1 induces expression of the histone demethylase KDM5B (lysine-specific demethylase 5B) and inhibits histone methylation, resulting in the inhibition of FOXA1 (forkhead box A1) licensing activity. This is a new mechanism of action attributed to HEXIM1, and distinct from what has been reported so far to be involved in HEXIM1 regulation of other nuclear hormone receptors, including the oestrogen receptor.
Fibrin binds to collagen and provides a bridge for αVβ3 integrin-dependent contraction of collagen gels
Authors: Reyhani Vahid , Seddigh Pegah , Guss Bengt , Gustafsson Renata , Rask Lars , Rubin Kristofer
Published: May 2014

The functional significance of fibrin deposits typically seen in inflammatory lesions, carcinomas and in healing wounds is not fully understood. In the present study, we demonstrate that fibrinogen/fibrin specifically bound to native Col I (collagen type I) and used the Col I fibre network as a base to provide a functional interface matrix that connects cells to the Col I fibres through αVβ3 integrins. This allowed murine myoblast C2C12 cells to contract the collagenous composite gel via αVβ3 integrin. We show that fibrinogen specifically bound to immobilized native Col I at the site known to bind matrix metalloproteinase-1, discoidin domain receptor-2 and fibronectin, and that binding had no effect on Col I fibrillation. A specific competitive inhibitor blocking the Col-I-binding site for fibrinogen abolished the organization of fibrin into discernable fibrils, as well as the C2C12-mediated contraction of Col I gels. Our data show that fibrin can function as a linkage protein between Col I fibres and cells, and suggest that fibrin at inflammatory sites indirectly connects αVβ3 integrins to Col I fibres and thereby promotes cell-mediated contraction of collagenous tissue structures.
Impaired selenoprotein expression in brain triggers striatal neuronal loss leading to co-ordination defects in mice
Authors: Seeher Sandra , Carlson Bradley A. , Miniard Angela C. , Wirth Eva K. , Mahdi Yassin , Hatfield Dolph L. , Driscoll Donna M. , Schweizer Ulrich
Published: May 2014

Secisbp2 [SECIS (selenocysteine insertion sequence)-binding protein 2] binds to SECIS elements located in the 3′-UTR region of eukaryotic selenoprotein mRNAs. It facilitates the incorporation of the rare amino acid selenocysteine in response to UGA codons. Inactivation of Secisbp2 in hepatocytes greatly reduced selenoprotein levels. Neuron-specific inactivation of Secisbp2 (CamK-Cre; Secisbp2fl/fl) reduced cerebral expression of selenoproteins to a lesser extent than inactivation of tRNA[Ser]Sec. This allowed us to study the development of cortical PV (parvalbumin)+ interneurons, which are completely lost in tRNA[Ser]Sec mutants. PV+ interneuron density was reduced in the somatosensory cortex, hippocampus and striatum. In situ hybridization for Gad67 (glutamic acid decarboxylase 67) confirmed the reduction of GABAergic (where GABA is γ-aminobutyric acid) interneurons. Because of the obvious movement phenotype involving a broad dystonic gait, we suspected basal ganglia dysfunction. Tyrosine hydroxylase expression was normal in substantia nigra neurons and their striatal terminals. However the densities of striatal PV+ and Gad67+ neurons were decreased by 65% and 49% respectively. Likewise, the density of striatal cholinergic neurons was reduced by 68%. Our observations demonstrate that several classes of striatal interneurons depend on selenoprotein expression. These findings may offer an explanation for the movement phenotype of selenoprotein P-deficient mice and the movement disorder and mental retardation described in a patient carrying SECISBP2 mutations.
Structural analysis of poly-SUMO chain recognition by the RNF4-SIMs domain
Authors: Kung Camy C.-H. , Naik Mandar T. , Wang Szu-Huan , Shih Hsiu-Ming , Chang Che-Chang , Lin Li-Ying , Chen Chia-Lin , Ma Che , Chang Chi-Fon , Huang Tai-Huang
Published: May 2014

The E3 ubiquitin ligase RNF4 (RING finger protein 4) contains four tandem SIM [SUMO (small ubiquitin-like modifier)-interaction motif] repeats for selective interaction with poly-SUMO-modified proteins, which it targets for degradation. We employed a multi-faceted approach to characterize the structure of the RNF4-SIMs domain and the tetra-SUMO2 chain to elucidate the interaction between them. In solution, the SIM domain was intrinsically disordered and the linkers of the tetra-SUMO2 were highly flexible. Individual SIMs of the RNF4-SIMs domains bind to SUMO2 in the groove between the β2-strand and the α1-helix parallel to the β2-strand. SIM2 and SIM3 bound to SUMO with a high affinity and together constituted the recognition module necessary for SUMO binding. SIM4 alone bound to SUMO with low affinity; however, its contribution to tetra-SUMO2 binding avidity is comparable with that of SIM3 when in the RNF4-SIMs domain. The SAXS data of the tetra-SUMO2–RNF4-SIMs domain complex indicate that it exists as an ordered structure. The HADDOCK model showed that the tandem RNF4-SIMs domain bound antiparallel to the tetra-SUMO2 chain orientation and wrapped around the SUMO protamers in a superhelical turn without imposing steric hindrance on either molecule.
Post-translational modifications of lysine in DNA-damage repair
Authors: Chatterjee Snehajyoti , Senapati Parijat , Kundu Tapas K.
Published: May 2014

DNA damage in cells is often the result of constant genotoxic insult. Nevertheless, efficient DNA repair pathways are able to maintain genomic integrity. Over the past decade it has been revealed that it is not only kinase signalling pathways which play a central role in this process, but also the different post-translational modifications at lysine residues of histone (chromatin) and non-histone proteins. These lysine modifications include acetylation, methylation, ubiquitination and SUMOylation. Genomic instability is often the major cause of different diseases, especially cancer, where lysine modifications are altered and thereby have an impact on the various DNA repair mechanisms. This chapter will discuss the recent advances in our understanding of the role of different lysine modifications in DNA repair and its physiological consequences.
Prediction of lysine post-translational modifications using bioinformatic tools
Authors: Schwartz Daniel
Published: May 2014

Our understanding of the importance of lysine post-translational modifications in mediating protein function has led to a significant improvement in the experimental tools aimed at characterizing their existence. Nevertheless, it remains likely that at present we have only experimentally detected a small fraction of all lysine modification sites across the commonly studied proteomes. As a result, online computational tools aimed at predicting lysine modification sites have the potential to provide valuable insight to researchers developing hypotheses regarding these modifications. This chapter discusses the metrics and procedures used to assess predictive tools and surveys 11 online computational tools aimed at the prediction of the four most widely studied lysine post-translational modifications (acetylation, methylation, SUMOylation and ubiquitination). Analyses using unbiased testing data sets suggest that nine of the 11 lysine post-translational modification tools perform no better than random, or have false-positive rates which make them unusable by the experimental biologist, despite self-reported sensitivity and specificity values to the contrary. The implications of these findings for those using and creating lysine post-translational modification software are discussed.
Thermoplastic Vestibuloplasty: A Novel Technique for Treatment of Lip and Cheek Adhesion
Authors: Barakat Khaled , Ali Aya
Published: May 2014

Lip and cheek adhesion to the opposing alveolus with complete or partial loss of the vestibular dimension represents a challenging problem for reconstruction. It usually occurs due to primary inadequate vestibular soft tissue repair following complicated trauma cases, burns, and lesions of the oral cavity. Surgical removal of scar tissue and creation of new vestibule is complicated by readhesion between the opposing connective tissue surfaces. Skin grafts and acellular dermal matrix represent the most dominant modalities used to treat deficient vestibule dimensions, but they are difficult to fix and lack the required stability during healing. Several devices have been created in an attempt to keep the tissues apart but their complex anchorage methods seriously reduced their reliability and usage. We devised a simple and reliable technique “thermoplastic vestibuloplasty” (TV) that benefit from the inherent reepithelialization capabilities of the oral mucosa to prevent readhesion and to resurface the created vestibule with its exact tissue color and texture. In total, 10 patients suffering from complete or partial lip or cheek adhesion with concomitant loss of vestibule were surgically treated by excising scar tissue and creating a new vestibule, followed by TV technique. Pre and posttreatment results were compared in terms of vestibular length, lip or cheek mobility, and change by time in vestibular length from 2 weeks up to 3 months. Moreover, the patient satisfaction and outcomes were measured using visual analogue scale score. All patients tolerated the procedure without complication. The mean vestibule length and mobility significantly increased from 3.8 + 0.6 mm to 11.4 + 1.4 mm ( p < 0.001) and from 0.3 to 2 ( p < 0.001), respectively. Regarding the stability of the achieved vestibular length it decreased by 14% when compared from 2 weeks to 3 months postoperatively. TV technique is a new simple and reliable technique that can effectively prevent readhesion of opposing connective tissue surfaces until intrinsic reepithelialization can resurface the newly created vestibular tissues forming a stable vestibular length with excellent color and texture.
Nuclear spin conversion of water inside fullerene cages detected by low-temperature nuclear magnetic resonance
Authors: Mamone Salvatore , Concistrè Maria , Carignani Elisa , Meier Benno , Krachmalnicoff Andrea , Johannessen Ole G. , Lei Xuegong , Li Yongjun , Denning Mark , Carravetta Marina , Goh Kelvin , Horsewill Anthony J. , Whitby Richard J. , Levitt Malcolm H.
Published: May 2014

The water-endofullerene H2O@C60 provides a unique chemical system in which freely rotating water molecules are confined inside homogeneous and symmetrical carbon cages. The spin conversion between the ortho and para species of the endohedral H2O was studied in the solid phase by low-temperature nuclear magnetic resonance. The experimental data are consistent with a second-order kinetics, indicating a bimolecular spin conversion process. Numerical simulations suggest the simultaneous presence of a spin diffusion process allowing neighbouring ortho and para molecules to exchange their angular momenta. Cross-polarization experiments found no evidence that the spin conversion of the endohedral H2O molecules is catalysed by 13C nuclei present in the cages.
Cross-correlation measurement of quantum shot noise using homemade transimpedance amplifiers
Authors: Hashisaka Masayuki , Ota Tomoaki , Yamagishi Masakazu , Fujisawa Toshimasa , Muraki Koji
Published: May 2014

We report a cross-correlation measurement system, based on a new approach, which can be used to measure shot noise in a mesoscopic conductor at milliKelvin temperatures. In contrast to other measurement systems in which high-speed low-noise voltage amplifiers are commonly used, our system employs homemade transimpedance amplifiers (TAs). The low input impedance of the TAs significantly reduces the crosstalk caused by unavoidable parasitic capacitance between wires. The TAs are designed to have a flat gain over a frequency band from 2 kHz to 1 MHz. Low-noise performance is attained by installing the TAs at a 4 K stage of a dilution refrigerator. Our system thus fulfills the technical requirements for cross-correlation measurements: low noise floor, high frequency band, and negligible crosstalk between two signal lines. Using our system, shot noise generated at a quantum point contact embedded in a quantum Hall system is measured. The good agreement between the obtained shot-noise data and theoretical predictions demonstrates the accuracy of the measurements.
Rigorous investigation of the reduced density matrix for the ideal Bose gas in harmonic traps by a loop-gas-like approach
Authors: Beau Mathieu , Savoie Baptiste
Published: May 2014

In this paper, we rigorously investigate the reduced density matrix (RDM) associated to the ideal Bose gas in harmonic traps. We present a method based on a sum-decomposition of the RDM allowing to treat not only the isotropic trap, but also general anisotropic traps. When focusing on the isotropic trap, the method is analogous to the loop-gas approach developed by Mullin [“The loop-gas approach to Bose-Einstein condensation for trapped particles,” Am. J. Phys. 68(2), 120 (2000)]. Turning to the case of anisotropic traps, we examine the RDM for some anisotropic trap models corresponding to some quasi-1D and quasi-2D regimes. For such models, we bring out an additional contribution in the local density of particles which arises from the mesoscopic loops. The close connection with the occurrence of generalized-Bose-Einstein condensation is discussed. Our loop-gas-like approach provides relevant information which can help guide numerical investigations on highly anisotropic systems based on the Path Integral Monte Carlo method.
Assessing the density functional theory-based multireference configuration interaction (DFT/MRCI) method for transition metal complexes
Authors: Escudero Daniel , Thiel Walter
Published: May 2014

We report an assessment of the performance of density functional theory-based multireference configuration interaction (DFT/MRCI) calculations for a set of 3d- and 4d-transition metal (TM) complexes. The DFT/MRCI results are compared to published reference data from reliable high-level multi-configurational ab initio studies. The assessment covers the relative energies of different ground-state minima of the highly correlated CrF6 complex, the singlet and triplet electronically excited states of seven typical TM complexes (MnO4−, Cr(CO)6, [Fe(CN)6]4−, four larger Fe and Ru complexes), and the corresponding electronic spectra (vertical excitation energies and oscillator strengths). It includes comparisons with results from different flavors of time-dependent DFT (TD-DFT) calculations using pure, hybrid, and long-range corrected functionals. The DFT/MRCI method is found to be superior to the tested TD-DFT approaches and is thus recommended for exploring the excited-state properties of TM complexes.
Conformation of polyelectrolytes in poor solvents: Variational approach and quantitative comparison with scaling predictions
Authors: Tang Haozhe , Liao Qi , Zhang Pingwen
Published: May 2014

We present the results of variational calculations of a polyelectrolyte solution with low salt in poor solvent conditions for a polymer backbone. By employing the variation method, we quantitatively determined the diagram of the state of the polyelectrolyte in poor solvents as a function of the charge density and the molecular weight. The exact structure and diagram of the polyelectrolyte were compared to the scaling predictions of the necklace model developed by Dobrynin and Rubinstein [Prog. Polym. Sci. 30, 1049–1118 (2005); Dobrynin and Rubinstein, Macromolecules 32, 915–922 (1999); Dobrynin and Rubinstein, Macromolecules 34, 1964–1972 (2001)]. We find that the scaling necklace model may be used as a rather good estimation and analytical approximation of the exact variational model. It is also pointed out that the molecular connection of polymer is crucial for ellipsoid and necklace conformation.