bluuebunny/crossref_metadata_2025 huggingface dataset:
Using social media as a tool for business improvement and certification of knowledge workers
Authors: Colomo‐Palacios Ricardo , Messnarz Richard , Siakas Kerstin , Palosi Daniel , Coakley Darragh
Published: July 2014

Business improvement is a hot topic in all business areas. In the last years, the unstoppable emergence of the use of social media by organizations and individuals alike has opened this tool for knowledge networking purposes. In this paper, the authors shed some light on how the traditional knowledge management approach has changed to a networked approach of knowledge sharing. Authors also explain how social media is used as a business tool, in particular in Information Technology industry environments. ECQA Certified Social Media Networker Skills (SIMS) is a new qualification that is available from 2013 and is meant to train and certify experts in the use of social media as a business improvement enabler and as a means for knowledge networking in organizational settings. Copyright © 2014 John Wiley & Sons, Ltd.
Normalized least mean square‐based adaptive sparse filtering algorithms for estimating multiple‐input multiple‐output channels
Authors: Gui Guan , Xu Li , Adachi Fumiyuki
Published: July 2014

This paper studies normalized least mean square‐based adaptive sparse filtering algorithms for estimating multiple‐input multiple‐output (MIMO) channels. Although the MIMO channel is often modeled as sparse, traditional normalized least mean square‐based filtering algorithm never takes the advantage of the inherent sparse structure information and thus causes some performance loss. Unlike the traditional method, the proposed two adaptive sparse channel estimation methods exploit the sparse structure information of MIMO channels. To validate the effectiveness of proposed MIMO channel estimates, theoretical analysis and simulation results are provided. We derive steady‐state mean‐square deviations of the proposed MIMO channel estimates and theoretically show that it is better than the traditional one. Moreover, their performance advantages are confirmed by computer simulations. Copyright © 2014 John Wiley & Sons, Ltd.
Interdisciplinarity as cognitive integration: auditory verbal hallucinations as a case study
Authors: Bernini Marco , Woods Angela
Published: July 2014

In this article, we advocate a bottom‐up direction for the methodological modeling of interdisciplinary research based on concrete interactions among individuals within interdisciplinary projects. Drawing on our experience in Hearing the Voice (a cross‐disciplinary project on auditory verbal hallucinations running at Durham University), we focus on the dynamic if also problematic integration of cognitive science (neuroscience, cognitive psychology, and of mind), phenomenology, and humanistic disciplines (literature, narratology, history, and theology). We propose a new model for disciplinary integration which brings to the fore an under‐investigated dynamic of interdisciplinary projects, namely their being processes of distributed cognition and cognitive integration. WIREs Cogn Sci 2014, 5:603–612. doi: 10.1002/wcs.1305

This article is categorized under:

Philosophy > Knowledge and Belief
Early development and growth in captive‐born Iberian lynx (Lynx pardinus)
Authors: Yerga Javier , Calzada Javier , Manteca Xavier , Vargas Astrid , Rivas Antonio
Published: July 2014

Knowledge on the growth and early development patterns of endangered species can become a useful conservation tool because it may allow detecting anomalous growth in newborns, both in captivity breeding and in the wild. We studied the growth and early development of 40 Iberian lynx (Lynx pardinus) cubs belonging to 21 litters born in captivity between 2005 and 2012 at “El Acebuche” Iberian Lynx Breeding Centre. This is the first study on growth in this critically endangered species. The Iberian lynx cubs were not fully developed at birth. During the first 3 weeks of life, cubs underwent many of the physical changes that allowed them to improve their interaction with the environment, such as the opening of eye and auditory channels, teeth eruptions, and the ability to walk. When the cubs were 1 month old, they were ready to leave the den and develop new behaviors such as the exploration of their environment, play, or hunt. Three different models had been fitted to the body mass growth of the Iberian lynx. The von Bertalanffy curve provided the best fit. The asymptotic adult mass was the only parameter that differed between males and females (males being 8% larger), due to the higher growth rate of males. The adult weight of hand‐reared cubs (i.e., those abandoned at born) did not differ from that of cubs reared by their mothers. Both growth and development showed differences from other lynx species. Zoo Biol. 33:381–387, 2014. © 2014 Wiley Periodicals Inc.
Lipid metabolism in mitochondrial membranes
Authors: Mayr Johannes A.
Published: July 2014

Mitochondrial membranes have a unique lipid composition necessary for proper shape and function of the organelle. Mitochondrial lipid metabolism involves biosynthesis of the phospholipids phosphatidylethanolamine, cardiolipin and phosphatidylglycerol, the latter is a precursor of the late endosomal lipid bis(monoacylglycero)phosphate. It also includes mitochondrial fatty acid synthesis necessary for the formation of the lipid cofactor lipoic acid. Furthermore the synthesis of coenzyme Q takes place in mitochondria as well as essential parts of the steroid and vitamin D metabolism. Lipid transport and remodelling, which are necessary for tailoring and maintaining specific membrane properties, are just partially unravelled. Mitochondrial lipids are involved in organelle maintenance, fission and fusion, mitophagy and cytochrome c‐mediated apoptosis. Mutations in TAZ, SERAC1 and AGK affect mitochondrial phospholipid metabolism and cause Barth syndrome, MEGDEL and Sengers syndrome, respectively. In these disorders an abnormal mitochondrial energy metabolism was found, which seems to be due to disturbed protein‐lipid interactions #Affecting especially enzymes of the oxidative phosphorylation. Since a growing number of enzymes and transport processes are recognised as parts of the mitochondrial lipid metabolism, a further increase of lipid‐related disorders can be expected.
Developing a leadership pipeline: the Cleveland Clinic experience
Authors: Hess Caryl A. , Barss Christina , Stoller James K.
Published: July 2014

The complexity of health care requires excellent leadership to address the challenges of access, quality, and cost of care. Because competencies to lead differ from clinical or research skills, there is a compelling need to develop leaders and create a talent pipeline, perhaps especially in physician-led organizations like Cleveland Clinic. In this context, we previously reported on a cohort-based physician leadership development course called Leading in Health Care and, in the current report, detail an expanded health care leadership development programme called the Cleveland Clinic Academy (CCA). CCA consists of a broad suite of offerings, including cohort-based learning and ‘a la carte’ half- or full-day courses addressing specific competencies to manage and to lead. Academy attendance is optional and is available to all physicians, nurses, and administrators with the requisite experience. Course selection is guided by competency matrices which map leadership competencies to specific courses. As of December 2012, a total of 285 course sessions have been offered to 6,050 attendees with uniformly high ratings of course quality and impact. During the past 10 years, Cleveland Clinic’s leadership and management curriculum has successfully created a pipeline of health care leaders to fill executive positions, search committees, board openings, and various other organizational leadership positions. Health care leadership can be taught and learned.
Pilot community‐mobilization program reduces maternal and perinatal mortality and prevents obstetric fistula in Niger
Authors: Seim Anders R. , Alassoum Zeidou , Bronzan Rachel N. , Mainassara Abderhamane Alou , Jacobsen Judith L. , Gali Yaroh Asma
Published: July 2014

Objective

To assess the impact of a pilot community‐mobilization program on maternal and perinatal mortality and obstetric fistula in Niger.

Methods

In the program, village volunteers identify and evacuate women with protracted labor, provide education, and collect data on pregnancies, births, and deaths. These data were used to calculate the reduction in maternal mortality, perinatal mortality, and obstetric fistula in the program area from July 2008 to June 2011.

Results

The birth‐related maternal mortality fell by 73.0% between years 1 and 3 (P < 0.001), from 630 (95% confidence interval [CI] 448–861) to 170 (95% CI 85–305) deaths per 100 000 births. Early perinatal mortality fell by 61.5% (P < 0.001), from 35 (95% CI 31–40) to 13 (95% CI 10–16) deaths per 1000 births. No deaths due to obstructed labor were reported after the lead‐in period (February to June 2008). Seven cases of community‐acquired fistula were reported between February 2008 and July 2009; from August 2009 to June 2011 (23 months; 12 254 births), no cases were recorded.

Conclusion

Community mobilization helped to prevent obstetric fistula and birth‐related deaths of women and infants in a large, remote, resource‐poor area.
On the wake dynamics of a propeller operating in drift
Authors: Di Mascio A. , Muscari R. , Dubbioso G.
Published: July 2014

The onset and the nature of dynamic instabilities experienced by the wake of a marine propeller set in oblique flow are investigated by means of detached eddy simulations. In particular, the destabilization process is inspected by a systematic comparison of the wake morphology of a propeller operating in pure axisymmetric flow and in drift with angle of 20°, under different loading conditions. The wake behaviour in oblique flow shows a markedly different character with respect to the axisymmetric condition: in the latter, the destabilization is triggered by an increasing interaction of the main vorticity confined in the tip vortex; whereas, in the former, the role of the secondary vorticity (oriented in the streamwise direction) as well as the hub vortex seems to be crucial. The features of the wake have been investigated by the$\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}\lambda _{2}$criterion (Jeong & Hussain,J. Fluid Mech., vol. 285, 1995, pp. 69–94) and typical flow variables (pressure, velocity and vorticity), for both the averaged and instantaneous flow fields. Moreover, in order to further inspect the evolution of the vortical structures, as well as their interaction and destabilization, the spectra of the kinetic energy have been considered. This investigation aims to broaden the knowledge from previous works on the subject of rotor wake instabilities, focusing on the differences between an ideal (axisymmetric) and actual operating conditions occurring in typical engineering applications.
The propagation of gravity currents in a V-shaped triangular cross-section channel: experiments and theory
Authors: Ungarish Marius , Mériaux Catherine A. , Kurz-Besson Cathy B.
Published: July 2014

We investigate the motion of high-Reynolds-number gravity currents (GCs) in a horizontal channel of V-shaped cross-section combining lock-exchange experiments and a theoretical model. While all previously published experiments in V-shaped channels were performed with the special configuration of the full-depth lock, we present the first part-depth experiment results. A fixed volume of saline, that was initially of length $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}x_0$ and height $h_0$ in a lock and embedded in water of height $H_0$ in a long tank, was released from rest and the propagation was recorded over a distance of typically $ 30 x_0$. In all of the tested cases the current displays a slumping stage of constant speed $u_N$ over a significant distance $x_S$, followed by a self-similar stage up to the distance $x_V$, where transition to the viscous regime occurs. The new data and insights of this study elucidate the influence of the height ratio $H = H_0/h_0$ and of the initial Reynolds number ${\mathit{Re}}_0 = (g^{\prime }h_0)^{{{1/2}}} h_0/ \nu $, on the motion of the triangular GC; $g^{\prime }$ and $\nu $ are the reduced gravity and kinematic viscosity coefficient, respectively. We demonstrate that the speed of propagation $u_N$ scaled with $(g^{\prime } h_0)^{{{1/2}}}$ increases with $H$, while $x_S$ decreases with $H$, and $x_V \sim [{\mathit{Re}}_0(h_0/x_0)]^{{4/9}}$. The initial propagation in the triangle is 50 % more rapid than in a standard flat-bottom channel under similar conditions. Comparisons with theoretical predictions show good qualitative agreements and fair quantitative agreement; the major discrepancy is an overpredicted $u_N$, similar to that observed in the standard flat bottom case.
Conservation assessment of the endemic plants of the Tuscan Archipelago, Italy
Authors: Foggi Bruno , Viciani Daniele , Baldini Riccardo M. , Carta Angelino , Guidi Tommaso
Published: July 2014

The Mediterranean islands support a rich diversity of flora, with a high percentage of endemic species. We used the IUCN categories and criteria to assess the conservation status of 16 endemic plant taxa (species and subspecies) of the Tuscan Archipelago, based on data collected during field surveys over 4 years. Our data were sufficient to use criteria B, C and D in our assessment. We used criterion B in the assessment of all 16 taxa, criterion C for four taxa, criterion D for 11 taxa and criteria B, C and D for three taxa, Centaurea gymnocarpa, Limonium doriae and Silene capraria. According to our results L. doriae, Romulea insularis and S. capraria are categorized as Critically Endangered and therefore require immediate conservation measures; eight taxa are categorized as Endangered, two as Vulnerable and three as Near Threatened. Compared to earlier assessments, eight species are recategorized with a higher degree of threat, two species are recategorized with a lower degree of threat, five are unchanged, and one species is assessed for the first time. Based on the IUCN categorization our results show that all the endemic species of the Tuscan Archipelago are directly and/or indirectly threatened by human activities, such as tourism and agriculture, and invasive species of plants and animals. The Tuscan Archipelago National Park is responsible for the conservation of all endemic species in the area.
Diagnosis of human fascioliasis by stool and blood techniques: update for the present global scenario
Authors: MAS-COMA S. , BARGUES M. D. , VALERO M. A.
Published: July 2014

Before the 1990s, human fascioliasis diagnosis focused on individual patients in hospitals or health centres. Case reports were mainly from developed countries and usually concerned isolated human infection in animal endemic areas. From the mid-1990s onwards, due to the progressive description of human endemic areas and human infection reports in developing countries, but also new knowledge on clinical manifestations and pathology, new situations, hitherto neglected, entered in the global scenario. Human fascioliasis has proved to be pronouncedly more heterogeneous than previously thought, including different transmission patterns and epidemiological situations. Stool and blood techniques, the main tools for diagnosis in humans, have been improved for both patient and survey diagnosis. Present availabilities for human diagnosis are reviewed focusing on advantages and weaknesses, sample management, egg differentiation, qualitative and quantitative diagnosis, antibody and antigen detection, post-treatment monitoring and post-control surveillance. Main conclusions refer to the pronounced difficulties of diagnosing fascioliasis in humans given the different infection phases and parasite migration capacities, clinical heterogeneity, immunological complexity, different epidemiological situations and transmission patterns, the lack of a diagnostic technique covering all needs and situations, and the advisability for a combined use of different techniques, at least including a stool technique and a blood technique.
HAAVELMO’S CONTRIBUTIONS TO SIMULTANEOUS-EQUATIONS ESTIMATION
Authors: Chipman John S.
Published: July 2014

This paper surveys Trygve Haavelmo’s contributions to econometrics. A brief summary of his 1944 monograph is followed by an analysis of the six important papers he contributed during 1943–47. Four of them were devoted to macroeconomic models including estimation of the Keynesian marginal propensity to consume; the first two introduced the methodology of a system of structural equations; the third marked a milestone in econometric method by deriving the reduced form of such a system; and the fourth analyzed the contrast between time-series and cross-section analysis. The fifth (joint with M.A. Girshick) on the demand for food provided a definitive treatment of estimation of demand and supply functions; it carried out the execution of a five-equation structural model of the U.S. economy. The sixth was an interesting policy model of the interrelationship between the agricultural and the rural sector of the economy, which was fitted to U.S. data and addressed to questions of policy.
TRYGVE HAAVELMO’S EXPERIMENTAL METHODOLOGY AND SCENARIO ANALYSIS IN A COINTEGRATED VECTOR AUTOREGRESSION
Authors: Hoover Kevin , Juselius Katarina
Published: July 2014

The paper provides a careful, analytical account of Trygve Haavelmo’s use of the analogy between controlled experiments common in the natural sciences and econometric techniques. The experimental analogy forms the linchpin of the methodology for passive observation that he develops in his famous monograph,The Probability Approach in Econometrics(1944). Contrary to some recent interpretations of Haavelmo’s method, the experimental analogy does not commit Haavelmo to a strong apriorism in which econometrics can only test and reject theoretical hypotheses, rather it supports the acquisition of knowledge through a two-way exchange between theory and empirical evidence. Once the details of the analogy are systematically understood, the experimental analogy can be used to shed light on theory-consistent cointegrated vector autoregression (CVAR) scenario analyses. A CVAR scenario analysis can be interpreted as a clear example of Haavelmo’s ‘experimental’ approach; and, in turn, it can be shown to extend and develop Haavelmo’s methodology and to address issues that Haavelmo regarded as unresolved.
Weddell seal foraging dives: comparison of free-ranging and isolated-hole paradigms
Authors: Madden K.M. , Fuiman L.A. , Williams T.M. , Davis R.W.
Published: July 2014

Weddell seals are polar predators that must partition their time between many behaviours, including hunting prey at depth and breathing at the surface. Although they have been well studied, little is known about how foraging behaviour changes when access to breathing holes is restricted, such as in the isolated-hole paradigm. The current study took advantage of previously gathered data for seals diving at an isolated hole to compare with foraging behaviour of free-ranging seals that had access to multiple holes. We examined dive structure, hunting tactics, and allocation of time, locomotor activity and energy based on three-dimensional dive profiles and video imagery of prey encounters for two free-ranging and six isolated-hole seals. Midsummer foraging dives of free-ranging seals were remarkably similar to those of seals diving at an isolated hole, but there were differences in two behavioural states and the frequency of several behavioural transitions. Results indicate that seals employ an energetically more conservative foraging strategy when access to breathing holes is limited and prey are less abundant. These results highlight the importance of understanding the complex interactions between breathing hole access, prey abundance and other factors that may result in different Weddell seal foraging strategies under changing future conditions.
Antiretrovirale Therapie
Authors: von Braun Amrei , Furrer Hansjakob , Battegay Manuel , Calmy Alexandra , Cavassini Matthias , Vernazza Pietro , Bernasconi Enos , Weber Rainer , Günthard Huldrych F.
Published: July 2014

Der Erfolg der antiretroviralen Therapie gegen HIV-1 ist einzigartig in der modernen Medizingeschichte. Eine zuvor fast 100 % letale Erkrankung konnte in eine chronisch behandelbare Krankheit umgewandelt werden. Wird heute gemäß internationaler Empfehlungen früh mit einer antiretroviralen Therapie begonnen, können die negativen Effekte des HIV-1 Virus auf den menschlichen Organismus minimiert werden. Dies führt bei sonst gesunden HIV-infizierten Menschen zu einer nahezu normalen Lebenserwartung. Zusätzlich sind Patienten unter erfolgreicher Therapie nicht mehr infektiös, was für die Eindämmung der Pandemie von entscheidender Bedeutung ist. Die antiretrovirale Therapie ist jedoch nach wie vor komplex. Viele Aspekte, insbesondere die langfristigen Nebenwirkungen und Medikamenteninteraktionen betreffend, sind noch offen. Behandelnde Ärzte benötigen sehr gute Kenntnisse im Bereich der HIV-Resistenz, der Immunrekonstitution sowie der Medikamententoxizität und Interaktionen. Von absoluter Wichtigkeit ist die Therapieadhärenz.
No One Likes to Lose
Authors: Schmierbach Mike , Chung Mun-Young , Wu Mu , Kim Keunyeong
Published: July 2014

Although scholars of video game enjoyment propose that games are meant to present a reasonable and appropriate challenge to players, not enough research has tested the effects of difficulty on enjoyment or the psychological mechanisms driving this relationship. In an experimental study involving college students (N = 121) playing a casual online tower defense game, we tested the relationship between difficulty and enjoyment and the possible mediating roles played by competency, as specified by self-determination theory, and challenge-skill balance, as specified by flow theory. Path analysis suggested that feelings of competency contribute to enjoyment by helping players obtain a balance between challenge and skill, and that competency is enhanced when players are assigned an easier game mode. This paper then addresses implications for theory, game design, and laboratory studies.
Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina
Authors: Pannicke T , Frommherz I , Biedermann B , Wagner L , Sauer K , Ulbricht E , Härtig W , Krügel U , Ueberham U , Arendt T , Illes P , Bringmann A , Reichenbach A , Grosche A
Published: July 2014

Gliosis of retinal Müller glial cells may have both beneficial and detrimental effects on neurons. To investigate the role of purinergic signaling in ischemia-induced reactive gliosis, transient retinal ischemia was evoked by elevation of the intraocular pressure in wild-type (Wt) mice and in mice deficient in the glia-specific nucleotide receptor P2Y1 (P2Y1 receptor-deficient (P2Y1R-KO)). While control retinae of P2Y1R-KO mice displayed reduced cell numbers in the ganglion cell and inner nuclear layers, ischemia induced apoptotic death of cells in all retinal layers in both, Wt and P2Y1R-KO mice, but the damage especially on photoreceptors was more pronounced in retinae of P2Y1R-KO mice. In contrast, gene expression profiling and histological data suggest an increased survival of amacrine cells in the postischemic retina of P2Y1R-KO mice. Interestingly, measuring the ischemia-induced downregulation of inwardly rectifying potassium channel (Kir)-mediated K+ currents as an indicator, reactive Müller cell gliosis was found to be weaker in P2Y1R-KO (current amplitude decreased by 18%) than in Wt mice (decrease by 68%). The inner retina harbors those neurons generating action potentials, which strongly rely on an intact ion homeostasis. This may explain why especially these cells appear to benefit from the preserved Kir4.1 expression in Müller cells, which should allow them to keep up their function in the context of spatial buffering of potassium. Especially under ischemic conditions, maintenance of this Müller cell function may dampen cytotoxic neuronal hyperexcitation and subsequent neuronal cell loss. In sum, we found that purinergic signaling modulates the gliotic activation pattern of Müller glia and lack of P2Y1 has janus-faced effects. In the end, the differential effects of a disrupted P2Y1 signaling onto neuronal survival in the ischemic retina call the putative therapeutical use of P2Y1-antagonists into question.
Definitions, History and Regulatory Framework for Rare Diseases and Orphan Drugs
Authors: Pryde David C. , Groft Stephen C.
Published: July 2014

The term orphan drug is a formal regulatory term used to describe a drug product that has been granted orphan status by a regulatory agency. Orphan designation is reserved for medicines that are intended to treat diseases with prevalence below the threshold set for rare diseases, which in the US is any disease or condition affecting fewer than 200 000 people. In Europe, a condition is considered rare if it affects fewer than 1 in 2000 people. There is considerable diversity among conditions defined as rare and they include neurological conditions, infectious diseases, rare cancers, autoimmune disorders, respiratory, muscle and blood disorders and a wide range of inherited genetic disorders. It has been estimated that there are more than 7000 rare diseases known but only around 5% of these have therapies available and the unmet medical need within rare diseases remains high. Across the thousands of highly heterogeneous rare diseases that are known, there is no unifying classification that links them all, with the exception that they affect a relatively small number of people, and the vast majority have no effective therapy available. Outside of the rare disease field, there is considerable misconception and misunderstanding surrounding rare diseases and orphan drugs; what these terms mean, what is classed as an orphan drug, what this designation entails and how many orphan drugs exist for which rare diseases. This chapter seeks to clear up these misconceptions and make clear to the reader what the terms orphan drug and rare disease mean, and detail the breadth of research, drugs and clinical activity taking place in this important field.
Disease Advocacy Organisations
Authors: Terry Sharon F. , Kant Caroline
Published: July 2014

Patient support groups, voluntary health organisations and disease advocacy organisations (DAOs) are just a few of the names to describe the non-profit organisations that are working to accelerate discovery and development of rare disease interventions. These organisations run the gamut from simple support for people affected by a condition to full-blown research entities that rival some pharmaceutical companies in financing and capacity. In the early years of DAOs being involved in drug development the participation was largely indirect: DAOs influenced policy and culture. In recent times DAOs have had a more direct influence on rare disease research and drug development through funding, fundamental and applied research and access to disease expertise. With the advances that new technologies, a networked age, and a mature DAO culture offer, systemic change in rare disease drug development should be possible. It is clear that DAOs connect previously disparate research, invent new models for collaboration and use social media to integrate various components of the drug discovery system. DAOs were early pioneers in forging pathways into a very technical and difficult field. In the modern age, DAOs continue to lead the way in influencing, funding and enabling research and drug development and constitute a critical element in tackling rare diseases.
Discovery and Clinical Development of Idursulfase (Elaprase®) for the Treatment of Mucopolysaccharidosis II (Hunter Syndrome)
Authors: Heartlein Michael , Kimura Alan
Published: July 2014

Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare X-linked recessive lysosomal storage disorder with an incidence of 1 in 100 000 to 160 000 live births. The clinical disease is caused by a deficiency of iduronate-2-sulfatase, which results in a chronic and progressive accumulation of glycosaminoglycans or GAGs in nearly all cell types, tissues and organs of the body. Clinical manifestations of MPS II disease include airway obstruction and compromised lung capacity, cardiomyopathy and valvular heart disease, hepatosplenomegaly, severe skeletal deformities, and neurological decline in most patients. The lack of an effective treatment and the successes of enzyme replacement therapies (ERTs) for other lysosomal storage diseases motivated the development of an ERT for MPS II. Iduronate-2-sulfatase (idursulfase) was produced by recombinant DNA technology in a fully human protein production system which, importantly, resulted in the production of idursulfase with human glycosylation. The non-clinical development of idursulfase progressed from proof-of-principle pharmacodynamic studies, to dose and dose-frequency studies, to an analysis of tissue biodistribution of the enzyme, and finally to pharmacokinetic and toxicological assessments. The clinical development of the final drug product, called Elaprase® (Shire Human Genetic Therapies, Inc., Lexington, MA), consisted of an initial Phase I/II study, followed by a Phase II/III pivotal trial. The results of the Phase II/III showed that intravenous infusions of Elaprase were generally well tolerated, and that a weekly dosing regimen provided significant clinical benefit to MPS II patients as demonstrated by improvements in walking ability and pulmonary function. Elaprase received marketing authorisation in the USA in 2006 and in Europe in 2007. During this era, the development of Elaprase as an effective therapy for MPS II patients, was part of a continuum of many important scientific and medical advances in the field of rare genetic diseases.
Small Molecules that Rescue F508del CFTR as Cystic Fibrosis Therapies
Authors: Pregel Marko J.
Published: July 2014

Cystic fibrosis (CF) is an orphan disease caused by mutations in CFTR, an epithelial ion channel. While CF is a multi-organ disorder, the primary cause of morbidity and mortality is lung disease. The F508del mutation, present in around 90% of patients, causes complex defects in folding, channel gating, endocytosis and thermal stability. The folding and gating defects can be addressed by small-molecule corrector and potentiator compounds, respectively. Combinations composed of a single corrector and a potentiator have shown positive responses in patients with the F508del mutation in ongoing clinical trials. Experiments in patient-derived airway epithelia suggest that a combination therapy of two correctors and a potentiator may provide greater efficacy. Advancement of corrector compounds has been significantly enabled by measurements of efficacy and potency in patient-derived primary airway epithelial cells. The development of biomarkers that bridge between in vitro assays and clinical responses and ‘probe’ compounds to assist in the identification of corrector targets would further empower the field. The discovery and development of CFTR modulator drugs has been accelerated by the Cystic Fibrosis Foundation, which has funded research in academia and industry and facilitated clinical trials. Because of the synergy between patient advocacy, academic research and pharmaceutical industry work, the prospect of a pharmacological therapy that addresses the root cause of disease has never been closer for most CF patients.
The Discovery and Development of Ruxolitinib for the Treatment of Myelofibrosis
Authors: Vaddi Kris
Published: July 2014

Ruxolitinib, a Janus kinase (JAK) 1 and JAK2 inhibitor, is the first FDA-approved therapy for intermediate or high-risk myelofibrosis (MF), the most serious of a group of haematological disorders known as myeloproliferative neoplasms. The idea of targeting JAKs for the treatment of cancer was first conceived in 2002, based on the biological premise that inhibition of STAT transcription factors would block tumour growth and proliferation. In 2004, discovery of a gain-of-function mutation in JAK2 known as JAK2 V617F in MPNs steered the development of ruxolitinib toward MF. MF is characterised by bone marrow fibrosis, progressive splenomegaly, debilitating constitutional symptoms, cytopenias and shortened survival. JAK2 V617F is present only in ∼50% of MF patients, while JAK dysregulation is present in all MF patients, indicating multiple mechanisms are involved in JAK dysregulation. Treatment of MF patients with ruxolitinib resulted in rapid and sustained reduction in splenomegaly and improvements in measured MF symptoms, shown first in a Phase I/II trial and later confirmed in two Phase III randomised trials, which supported its approval. Clinical benefits were observed regardless of JAK2 V617F status. Additional applications of ruxolitinib in MF and other diseases, including polycythemia vera, pancreatic cancer and other cancers, are under investigation.
Speciation of copper in agricultural soils contaminated by lead using screen-printed electrodes and square-wave anodic stripping voltammetry (SPE-SWASV)
Authors: Faucher Stéphane , Cugnet Cyril , Authier Laurent , Lespes Gaëtane
Published: July 2014

A SPE-SWASV method was developed, optimized and applied to determine total and electrolabile copper and lead concentrations in soil.
Quantification by SIFT-MS of volatile compounds emitted by Aspergillus fumigatus cultures and in co-culture with Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae
Authors: Chippendale Thomas W. E. , Gilchrist Francis J. , Španěl Patrik , Alcock Alice , Lenney Warren , Smith David
Published: July 2014

Sampling of cell culture headspace into SIFT-MS for direct analysis of volatile compounds.
Thixotropic silk nanofibril-based hydrogel with extracellular matrix-like structure
Authors: Liu Yingxin , Ling Shengjie , Wang Suhang , Chen Xin , Shao Zhengzhong
Published: July 2014

We present an injectable hydrogel based on silk fibroin (SF) nanofibrils which may offer benefits for cell encapsulation and delivery.
GeH: a novel material as a visible-light driven photocatalyst for hydrogen evolution
Authors: Liu Zhenhua , Lou Zaizhu , Li Zhujie , Wang Gang , Wang Zeyan , Liu Yuanyuan , Huang Baibiao , Xia Shengqing , Qin Xiaoyan , Zhang Xiaoyang , Dai Ying
Published: July 2014

A novel photocatalyst (GeH), with 2D layered structure, was found for the first time to exhibit photocatalytic activity in the hydrogen evolution of water splitting and decomposition of organic contaminants under irradiation of visible light.
On the origin of the high capacitance of nitrogen-containing carbon nanotubes in acidic and alkaline electrolytes
Authors: Ornelas O. , Sieben J. M. , Ruiz-Rosas R. , Morallón E. , Cazorla-Amorós D. , Geng J. , Soin N. , Siores E. , Johnson B. F. G.
Published: July 2014

The preparation of nitrogenated carbon nanotubes (N-CNT) using pyridine as a carbon precursor resulted in an eight-times increase in gravimetric capacitance.
Supramolecular polymerization at the interface: layer-by-layer assembly driven by host-enhanced π–π interaction
Authors: Yang Hui , Ma Zhan , Yuan Bin , Wang Zhiqiang , Zhang Xi
Published: July 2014

Host-enhanced π–π interaction as a new driving force was used for fabricating layer-by-layer films, which can be regarded as a sort of supramolecular polymerization at the interface.
An ab initio study of the thermoelectric enhancement potential in nano-grained TiNiSn
Authors: Kirievsky K. , Shlimovich M. , Fuks D. , Gelbstein Y.
Published: July 2014

A cross-section of the differential electron density distribution in the (001) TiNiSn plane.
The environmental profile of bioethanol produced from current and potential future poplar feedstocks in the EU
Authors: Guo Miao , Littlewood Jade , Joyce James , Murphy Richard
Published: July 2014

This study presents current and prospective environmental profiles of poplar-derived bioethanol across various potential EU supply chains.
Visualizing oil displacement with foam in a microfluidic device with permeability contrast
Authors: Conn Charles A. , Ma Kun , Hirasaki George J. , Biswal Sibani Lisa
Published: July 2014

A heterogeneous microfluidic system can be used to visualize oil displacement with foam for better understanding of EOR processes.
Microfluidic serpentine antennas with designed mechanical tunability
Authors: Huang YongAn , Wang Yezhou , Xiao Lin , Liu Huimin , Dong Wentao , Yin Zhouping
Published: July 2014

This paper describes the design and characterization of microfluidic serpentine antennas with reversible stretchability and designed mechanical frequency modulation (FM).
Preparation of europium complex-conjugated carbon dots for ratiometric fluorescence detection of copper(ii) ions
Authors: Ye Zhiqiang , Tang Rong , Wu Hao , Wang Beibei , Tan Mingqian , Yuan Jingli
Published: July 2014

A novel type of dual-emission fluorescence nanoparticle, C-dots–BHHCT–Eu3+, has been developed for the ratiometric detection of Cu2+ ions.
Nickel-catalyzed substitution reactions of propargyl halides with organotitanium reagents
Authors: Li Qing-Han , Liao Jung-Wei , Huang Yi-Ling , Chiang Ruei-Tang , Gau Han-Mou
Published: July 2014

A simple and mild catalytic coupling reaction of propargyl halides with organotitanium reagents is reported.
Divergent total synthesis of 1,6,8a-tri-epi-castanospermine and 1-deoxy-6,8a-di-epi-castanospermine from substituted azetidin-2-one (β-lactam), involving a cascade sequence of reactions as a key step
Authors: Tiwari Dipak Kumar , Bharadwaj Kishor Chandra , Puranik Vedavati G. , Tiwari Dharmendra Kumar
Published: July 2014

A divergent, short, and novel total synthesis of 1,6,8a-tri-epi-castanospermine (7) and 1-deoxy-6,8a-di-epi-castanospermine (8) has been developed.
Synthesis of aromatic 13C/2H-α-ketoacid precursors to be used in selective phenylalanine and tyrosine protein labelling
Authors: Lichtenecker R. J.
Published: July 2014

A synthetic concept to access various 13C/2H patterns of phenylalanine and tyrosine precursors for cell-based protein overexpression systems is presented. The target compounds feature isolated 13C–1H spin systems to be used in NMR probing of protein structure and dynamics.
Limonene induced chiroptical generation and inversion during aggregation of achiral polyfluorene analogs: structure-dependence and mechanism
Authors: Wang Laibing , Suzuki Nozomu , Liu Jiangfei , Matsuda Takashi , Rahim Nor Azura Abdul , Zhang Wei , Fujiki Michiya , Zhang Zhengbiao , Zhou Nianchen , Zhu Xiulin
Published: July 2014

We demonstrate an element-dependent chiroptical inversion and structural dependence of π-conjugated polymers with the help of limonene chirality in aggregation states.
Polybenzoxazines: new players in the bio-based polymer arena
Authors: Lligadas Gerard , Tüzün Alev , Ronda Juan C. , Galià Marina , Cádiz Virginia
Published: July 2014

This mini-review focuses on the recent efforts to replace petro-based feedstocks with polybenzoxazine precursors.
Edible polyelectrolyte microcapsules with water-soluble cargo assembled in organic phase
Authors: Pan Houwen Matthew , Subramanian Arjun , Ochs Christopher J. , Dewavrin Jean-Yves , Beyer Sebastian , Trau Dieter W.
Published: July 2014

Using "Generally Recognized as Safe" (GRAS) materials for assembly, edible polyelectrolytes (EPL/PGA) are coated on sugar (maltotriose)–dextran particles and crosslinked (left). Cargo-loaded hollow capsules are created by dissolution of the sugar template (right).
A green, rapid and size-controlled production of high-quality graphene sheets by hydrodynamic forces
Authors: Liu Lei , Shen Zhigang , Yi Min , Zhang Xiaojing , Ma Shulin
Published: July 2014

The synergistic enhancement of shear forces and collision effects can result in effective exfoliation of ultrathin graphene nanosheets.
Synthesis of fully alternating polycarbonate with low Tg from carbon dioxide and bio-based fatty acid
Authors: Zhang Ying-Ying , Zhang Xing-Hong , Wei Ren-Jian , Du Bin-Yang , Fan Zhi-Qiang , Qi Guo-Rong
Published: July 2014

Perfectly alternating copolymerization of CO2 with a bio-based epoxide is reported with a heterogeneous Zn–Co(iii) DMCC, affording copolymers with low Tg values of −38 to −44 °C and two end hydroxyl groups.
Feedback‐error‐resistant and reduced feedback‐rate orthogonal space‐time block coding scheme employing single transmit antenna selection
Authors: Coşkun Ahmet Faruk , Kucur Oğuz
Published: July 2014

A novel and generic transmit diversity scheme that employs combined single transmit antenna selection (TAS)/orthogonal space‐time block coding (OSTBC) scheme with reduced feedback‐rate and robust error performance in the presence of feedback errors (FEs) is introduced in this paper. Statistical expressions and performance metrics related to the post‐processing signal‐to‐noise ratio of the proposed scheme are derived for Nakagami‐m fading channels considering that the channel estimation process is error‐free and the feedback information is delivered to the transmitter side with no delay. Exact expressions for outage probability and bit/symbol error rates of M‐ary signals are presented to examine the system performance in the presence of FEs extensively. Also, the asymptotic analysis is provided to explore the asymptotic diversity order and the asymptotic coding gain of the proposed scheme that is compared with that of the conventional TAS/OSTBC scheme from different perspectives. The proposed scheme is shown to provide not only full‐diversity order as the conventional scheme for perfect feedback case but also superior error performance in the presence of FEs. Moreover, the error performances of both schemes and the superiority of the modified scheme are examined by considering an error‐correcting structure in the feedback link.
Cross‐layer capacity optimisation in WiMAX orthogonal frequency division multiple access systems with multi‐class quality of services and users queue status
Authors: Matalgah Mustafa M. , Hammouri Omar M. , Paudel Bimal
Published: July 2014

Given the broad range of applications supported, high data rate required and low latency promised; dynamic radio resource management is becoming vital for the air interface technologies such as WiMAX and LTE adopted by international standards. This study considers the OFDMA system, which has been implemented in both WiMAX and LTE technologies as their air interface multiple access mechanism. A framework for optimised resource allocation with QoS support that aims to balance between service provider's revenue and subscriber's satisfaction is proposed in this study. A cross‐layer optimisation design for subchannel and power allocations with the objective of maximising the capacity (in bits/symbol/Hz) subject to fairness parameters and QoS requirements as constraints is presented. The optimisation does not only consider users channel conditions but also queue status of each user as well as different QoS requirements. The QoS classes adopted by the IEEE 802.16e standard, for WiMAX technology, are utilised in this study. In the proposed framework, the problem of power allocation is solved analytically whereas the subchannel allocation is solved using integer programming exhaustive search. The simulation and numerical results obtained in this study have shown improved system performance as compared to other optimisation schemes known in the literature.
Optimal time allocation for two‐way relay channel using physical‐layer network coding
Authors: Cho Dae‐Soon , Shim Yeonggyu , Park Hyuncheol
Published: July 2014

This study proposes an optimal time allocation scheme for two‐way relay channel (TWRC) using the physical‐layer network coding (PNC). In other words, this study analytically determines the optimal transmit time durations for the first and the second time slot, which maximise the achievable sum rate under a sum time constraint for a given squared magnitude of the channel coefficients and transmit power values. Numerical results show that the achievable sum rate for the proposed optimal time allocation is greater than or equal to that for equal time allocation.
Langmuir probes for SPIDER (source for the production of ions of deuterium extracted from radio frequency plasma) experiment: Tests in BATMAN (Bavarian test machine for negative ions)
Authors: Brombin M. , Spolaore M. , Serianni G. , Pomaro N. , Taliercio C. , Palma M. Dalla , Pasqualotto R. , Schiesko L.
Published: July 2014

A prototype system of the Langmuir probes for SPIDER (Source for the production of Ions of Deuterium Extracted from RF plasma) was manufactured and experimentally qualified. The diagnostic was operated in RF (Radio Frequency) plasmas with cesium evaporation on the BATMAN (BAvarian Test MAchine for Negative ions) test facility, which can provide plasma conditions as expected in the SPIDER source. A RF passive compensation circuit was realised to operate the Langmuir probes in RF plasmas. The sensors’ holder, designed to better simulate the bias plate conditions in SPIDER, was exposed to a severe experimental campaign in BATMAN with cesium evaporation. No detrimental effect on the diagnostic due to cesium evaporation was found during the exposure to the BATMAN plasma and in particular the insulation of the electrodes was preserved. The paper presents the system prototype, the RF compensation circuit, the acquisition system (as foreseen in SPIDER), and the results obtained during the experimental campaigns.
Photoacoustic measurement of the Grüneisen parameter using an integrating sphere
Authors: Villanueva Yolanda , Hondebrink Erwin , Petersen Wilma , Steenbergen Wiendelt
Published: July 2014

A method that uses an integrating sphere as a platform for photoacoustic measurement of the Grüneisen parameter Γ of absorbing liquids is developed. Derivation of a simple equation for determining Γ is presented. This equation only requires the voltage peak-to-peak value of the photoacoustic signal detected by a flat transducer and the relative energy of the incident light measured by a photodetector. Absolute detector sensitivities are not required. However, a calibration procedure is necessary. An experimental setup is constructed in order to implement and verify the method. Aqueous ink solutions are used as absorbing liquids to determine the calibration (instrument) constants. Validation of the equation is done by determining Γ of ethanol at room temperature. The obtained value of Γethanol = 0.72 ± 0.06 has a 7% relative difference to the calculated value from known thermal properties reported in literature.
Gibbs ensemble Monte Carlo of nonadditive hard-sphere mixtures
Authors: Pellicane Giuseppe , Pandaram Owen D.
Published: July 2014

In this article, we perform Gibbs ensemble Monte Carlo (GEMC) simulations of liquid-liquid phase coexistence in nonadditive hard-sphere mixtures (NAHSMs) for different size ratios and non-additivity parameters. The simulation data are used to provide a benchmark to a number of theoretical and mixed theoretical/computer simulation approaches which have been adopted in the past to study phase equilibria in NAHSMs, including the method of the zero of the Residual Multi-Particle Entropy, Integral Equation Theories (IETs), and classical Density Functional Theory (DFT). We show that while the entropic criterium is quite accurate in predicting the location of phase equilibrium curves, IETs and DFT provide at best a semi-quantitative reproduction of GEMC demixing curves.