bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dangers of the Dissemination of Misinformation in Implementing the Responsibility to Protect
Authors: Foty Cherine
Published: May 2015

The creation of the responsibility to protect doctrine reformulated the historical notion of humanitarian intervention. The new doctrine was centered around the principle of nonintervention, a basic precept of the u.n. Charter system, with its initial report explicitly excluding regime change disguised as humanitarian intervention as external to the scope of the doctrine. Military intervention was only to be the means of last resort after the exhaustion of several preliminary mechanisms. In its implementation, the broad mandate of the responsibility to protect has been harshly criticized because it opens the possibility for powerful States, often seeking regime change, to interfere in the domestic affairs of weaker States. This article will first discuss (i) the chronology and evolution of the doctrine, (ii) situating it in the context of the u.n. Charter prohibition on the use of force and articulating its nonbinding nature. It will then examine (iii) the cases of Libya and Syria, focusing on the initial decision to intervene and how the dissemination of misinformation has served to promote military interventions where they would otherwise be considered illegitimate. The article will conclude with a brief discussion of (iv) how the international community can move beyond misapplication and seek to limit its abuse.
Trade Remedies in the Renewable Energy Sector: Normal Value and Double Remedies
Authors: Barthelemy Christine , Peat Daniel
Published: May 2015

Subsidies within the renewable energy (RE) sector are rife. Active government support is now advocated as a part of ‘green industrial policy’ to stimulate growth within the sector. While providing the positive externality of climate change mitigation, these policies leave certain government support measures vulnerable to countermeasures under WTO law. The same products are also often subject to simultaneous anti-dumping duties. This article aims to investigate the interaction between these trade remedies in the RE sector. It examines what lessons can be taken from recent reports of the WTO Panel and Appellate Body, and examines the 2012 US and 2013 EU investigations into the dumping of photovoltaic products from China. It concludes by reviewing outstanding issues for trade remedies in the RE sector; namely, the appropriate choice of surrogate third country and sampling technique, the accurate calculation of dumping and subsidy effects, and the burden of proof for double remedies.
A Critical Analysis of Foreign Capital Investment Law in Oman
Authors: Abdallah Amel
Published: May 2015

The Sultanate of Oman has a cluster of laws regulating the relationship between foreign investors and Omani society. Oman has tried to maintain a balance between its national and regional commitments in this regard. This article provides an in-depth analysis of the Foreign Capital Investment Law (OFCIL) as well as related laws in order to articulate standards of investment protection and to provide a road map for foreign investors in the Sultanate. A comparison with some Arab laws is undertaken in order to highlight weaknesses that can be improved in OFCIL.
Polycephalomyces yunnanensis (Hypocreales), a new species of Polycephalomyces parasitizing Ophiocordyceps nutans and stink bugs (hemipteran adults)
Authors: Wang Yuanbing , YU HONG , DAI YONG-DONG , CHEN ZI-HONG , ZENG WEN-BO , YUAN FENG , LIANG ZONG-QI
Published: May 2015

Polycephalomyces yunnanensis is described as a new species that parasitizes Ophiocordyceps nutans and stink bugs (hemipteran adults). It is characterized by the production of a viscous mass at the apex of its synnema, and it has two types of conidia (α- and β-conidia) and phialides (α- and β-phialides). A morphological and ecological investigation revealed that P. yunnanensis is distinct from any known species in the genus. Phylogenetic analyses based on the ITS and 5-locus (nrSSU, nrLSU, tef-1α, rpb1 and rpb2) data supported the treatment of this fungus as a distinct species.
Notes on Early Land Plants Today. 70. Nomenclatural notes in hornworts(Anthocerotophyta)
Authors: Villarreal Juan Carlos , Cargill Christine , Söderström Lars , Hagborg Anders , Von Konrat Matt
Published: May 2015

Prior to the publication of the world checklist of hornworts and liverworts (Söderström et al., in press) some taxa still need to be validated, transferred or synonymized. We are here dealing with the remaining nomenclatural issues among the Anthocerotophyta. Several taxa have not been typified properly and we are here suggesting several new lectotypes to stabilize the nomenclature.
Argentine Hydrellia Robineau-Desvoidy (Diptera, Ephydridae): new species and key to identification
Authors: JÚNIOR FRANCISCO DE ASSIS RODRIGUES , MATHIS WAYNE NIELSEN , HAUSER MARTIN
Published: May 2015

Hydrellia egeriae sp. nov., a new species of Hydrellia from Campana (34 14’ 04 S, 58 52’ 32 W) and Hurlingham (3435’14 S, 5838’27 W), Buenos Aires province, Argentina is described. A key to the Argentine Hydrellia species is presented.
Classification of the Polytminae (Aves: Trochilidae)
Authors: REMSEN J. V. JR. , STILES F. GARY , MCGUIRE JIMMY A.
Published: May 2015

The subfamily Polytminae, as defined by Dickinson & Remsen (2013) using the phylogeny of McGuire et al. (2009), consists of 12 genera and 27 species of hummingbirds (Trochilidae) distributed widely in the Neotropics, including the Caribbean. McGuire et al. (2014) expanded greatly on the taxon- and gene-sampling in McGuire et al. (2009), and although the phylogeny presented therein indicated the need for several changes in classification, such changes were beyond the scope of that paper.
Three new species of Anacroneuria Klapálek (Plecoptera: Perlidae) from Panama
Authors: GUTIÉRREZ-FONSECA PABLO E.
Published: May 2015

In Central America, the Plecoptera is represented by the genera Anacroneuria and Perlesta, both from the Perlidae family. A total of 45 species have been reported for the region, of which 16 have been found in Panama, all of the genus Anacroneuria. Three new species for Panama are described in this study: Anacroneuria darien, A. embera, and A. laru.
The Atmospheric Response to Weak Sea Surface Temperature Fronts*
Authors: Schneider Niklas , Qiu Bo
Published: May 2015

The response of the atmospheric boundary layer to fronts of sea surface temperature (SST) is characterized by correlations between wind stress divergence and the downwind component of the SST gradient and between the wind stress curl and the crosswind component of the SST gradient. The associated regression (or coupling) coefficients for the wind stress divergence are consistently larger than those for the wind stress curl. To explore the underlying physics, the authors introduce a linearized model of the atmospheric boundary layer response to SST-induced modulations of boundary layer hydrostatic pressure and vertical mixing in the presence of advection by a background Ekman spiral. Model solutions are a strong function of the SST scale and background advection and recover observed characteristics. The coupling coefficients for wind stress divergence and curl are governed by distinct physics. Wind stress divergence results from either large-scale winds crossing the front or from a thermally direct, cross-frontal circulation. Wind stress curl, expected to be largest when winds are parallel to SST fronts, is reduced through geostrophic spindown and thereby yields weaker coupling coefficients.
Filament Frontogenesis by Boundary Layer Turbulence
Authors: McWilliams James C. , Gula Jonathan , Molemaker M. Jeroen , Renault Lionel , Shchepetkin Alexander F.
Published: May 2015

A submesoscale filament of dense water in the oceanic surface layer can undergo frontogenesis with a secondary circulation that has a surface horizontal convergence and downwelling in its center. This occurs either because of the mesoscale straining deformation or because of the surface boundary layer turbulence that causes vertical eddy momentum flux divergence or, more briefly, vertical momentum mixing. In the latter case the circulation approximately has a linear horizontal momentum balance among the baroclinic pressure gradient, Coriolis force, and vertical momentum mixing, that is, a turbulent thermal wind. The frontogenetic evolution induced by the turbulent mixing sharpens the transverse gradient of the longitudinal velocity (i.e., it increases the vertical vorticity) through convergent advection by the secondary circulation. In an approximate model based on the turbulent thermal wind, the central vorticity approaches a finite-time singularity, and in a more general hydrostatic model, the central vorticity and horizontal convergence are amplified by shrinking the transverse scale to near the model’s resolution limit within a short advective period on the order of a day.
Beyond interdependence: Economic security and Sino-American-Australian trilateralism
Authors: Kenneth Boutin J.D.
Published: May 2015

China’s economic and politico-military development is placing considerable strain on the established framework of the trilateral relationship between itself, the United States, and Australia. Specifically, China’s rise is generating security concerns that are politicizing economic relations between the three states. A more guarded approach to economic collaboration will transform trilateralism, which up to now has been characterized by the scope allowed for the discrete pursuit of security and economic relations. This will force political authorities to carefully consider their policy priorities and further strain relations between the states, as well as supporting a more cautious approach to China on the part of the United States and Australia.
‘The New Degree?’ Constructing Internships in the Third Sector
Authors: Leonard Pauline , Halford Susan , Bruce Katie
Published: May 2015

The recent economic recession has impacted substantially on the graduate labour market, with many graduates now struggling to find secure employment in professional careers. In this context, temporary, unpaid ‘internships’ have emerged as increasingly important as a ‘way in’ to work for this group. Yet while there has been much media and policy debate on internships, academic consideration has been scant. This article begins to address this knowledge gap by drawing on a study of interns in a third sector environmental organisation. The research findings reveal that unpaid internships were rationalised through a complex mix of political motivations, career ambitions and lifestyle aims, but these intersected in important ways with social class. These findings are not only of empirical interest, contributing to our knowledge of graduate negotiations of precarity, but also of theoretical value, extending our understanding of young people’s agency and motivations in transitions into work.
Children’s trust and the development of prosocial behavior
Authors: Malti Tina , Averdijk Margit , Zuffianò Antonio , Ribeaud Denis , Betts Lucy R. , Rotenberg Ken J. , Eisner Manuel P.
Published: May 2015

This study examined the role of children’s trust beliefs and trustworthiness in the development of prosocial behavior using data from four waves of a longitudinal study in a large, ethnically-diverse sample of children in Switzerland (mean age = 8.11 years at Time 1, N = 1,028). Prosocial behavior directed towards peers was measured at all assessment points by teacher reports. Children’s trust beliefs and their trustworthiness with peers were assessed and calculated by a social relations analysis at the first assessment point using children’s reports of the extent to which classmates kept promises. In addition, teacher reports of children’s trustworthiness were assessed at all four assessment points. Latent growth curve modeling yielded a decrease in prosocial behavior over time. Peer- and teacher-reported trustworthiness predicted higher initial levels of prosocial behavior, and peer-reported trustworthiness predicted less steep decreases in prosocial behavior over time. Autoregressive cross-lagged analysis also revealed bidirectional longitudinal associations between teacher-reported trustworthiness and prosocial behavior. We discuss the implications of the findings for research on the role of trust in the development of children’s prosocial behavior.
Navigating Institutional Plurality: Organizational Governance in Hybrid Organizations
Authors: Mair Johanna , Mayer Judith , Lutz Eva
Published: May 2015

Hybrid organizations operate in a context of institutional plurality and enact elements of multiple, often conflicting institutional logics. Governance is highly relevant in navigating such an environment. This study examines how hybrid organizations set up their governance structures and practices. Building on survey data from 70 social enterprises, a subset of hybrid organizations, we identify two types of hybrid organization: conforming hybrids rely on the prioritization of a single institutional logic and dissenting hybrids use defiance, selective coupling and innovation as mechanisms to combine and balance the prescriptions of several institutional logics. We illustrate these mechanisms by drawing on the qualitative analysis of selected cases. This study refines current debates on social enterprises as hybrid organizations. Based on our findings, we speculate that some social enterprises might assume hybridity for symbolic reasons while others – genuine hybrids – do so for substantive reasons.
Characterization of Spontaneous Mammary Tumors in Domestic Djungarian Hamsters (Phodopus sungorus)
Authors: Yoshimura H. , Kimura-Tsukada N. , Ono Y. , Michishita M. , Ohkusu-Tsukada K. , Matsuda Y. , Ishiwata T. , Takahashi K.
Published: May 2015

Mammary tumors that spontaneously occurred in domestic Djungarian hamsters ( Phodopus sungorus) were histologically examined. Forty-five mammary tumors included 14 adenomas, 18 adenocarcinomas, 1 lipid-rich carcinoma, 2 adenoacanthomas, 2 malignant adenomyoepitheliomas, 1 benign mixed tumor, and 7 “balloon cell” carcinosarcomas. The latter 4 types were newly recognized neoplasms in Djungarian hamsters. The relatively high incidence of spontaneous mammary carcinosarcomas in domestic Djungarian hamsters is intriguing. Carcinosarcomas exhibited anomalous histological features made up of a mixture of glandular cells, polygonal cells (including “balloon cells”), and sarcomatous spindle cells in varying proportions. Transitional features from glandular cells to polygonal cells and subsequently to sarcomatous spindle cells were observed. Using immunohistochemistry, we observed that glandular cells exhibited an epithelial phenotype (cytokeratin(+)/vimentin(–)), spindle cells exhibited a mesenchymal phenotype (cytokeratin(–)/vimentin(+)), and polygonal cells exhibited an intermediate phenotype (cytokeratin(+)/vimentin(+)). Reduction or loss of β-catenin expression and gain of S100A4 expression were observed in polygonal and spindle cells. The polygonal cell population included a varying number of characteristic cells that were expanded by large intracytoplasmic vacuoles. Electron microscopy revealed that these “balloon cells” had large cytoplasmic lumens lined by microvilli. These observations suggest that epithelial-mesenchymal transition may account for the pathogenesis of mammary carcinosarcomas in Djungarian hamsters.
The Assessment of School Climate
Authors: Ramelow Daniela , Currie Dorothy , Felder-Puig Rosemarie
Published: May 2015

School climate measurement is a long-standing topic in educational research. This review article provides an overview and appraisal of school climate measures published between 2003 and 2013 in scientific journals. A search for published school climate instruments for secondary school students was made in three databases. Twelve articles meeting the inclusion criteria were identified and included. Each measure is described in terms of contents, and psychometric and formal quality criteria. Most of the reviewed measures showed good or acceptable results in reliability analyses but insufficient validity testing. Theory-grounding for measurement development is often missing. All instruments include items addressing the relationship among students and between students and teachers while the environmental-structural area is considered the least. This review provides a compact overview of recently published studies using school climate instruments that have also been tested psychometrically. This may be useful for schools, practitioners, and researchers.
The Lethality Screen
Authors: Messing Jill Theresa , Campbell Jacquelyn , Sullivan Wilson Janet , Brown Sheryll , Patchell Beverly
Published: May 2015

This research is an examination of the predictive validity of the Lethality Screen, a tool used in conjunction with the Lethality Assessment Program (LAP). This intimate partner violence (IPV) risk assessment is an 11-item version of the Danger Assessment (DA) that was designed to be user-friendly for first responders and to maximize sensitivity. Participants ( N = 254) were recruited into the study at the scene of police-involved IPV incidents in one Southwestern state and subsequently participated in two structured telephone interviews approximately 7 months apart. These analyses provide evidence that the Lethality Screen has considerable sensitivity (92%-93%) and a high negative predictive value (93%-96%) for near lethal and severe violence. However, specificity was low (21%). The Lethality Screen also has good agreement with the DA and IPV survivors’ perception of risk. The high sensitivity and low specificity should be considered carefully when determining whether the Lethality Screen is appropriate for particular areas of practice with IPV survivors and/or perpetrators.
Palaeoenvironment, palaeoclimate and sea-level changes in the Shuaiba Lagoon during the late Holocene (last 3.6 ka), eastern Red Sea coast, Saudi Arabia
Authors: Abu-Zied Ramadan H , Bantan Rashad A
Published: May 2015

Multi-proxy investigations of sediment lithology, geochemistry, benthic foraminifera, and δ18O and δ13C of Elphidium striatopunctatum were carried out on a sediment core SHUA3 (2.2 m long) spanning the last 3.6 ka and recovered from Shuaiba Lagoon, eastern Red Sea coast. Results showed that the interval before 1500 BC was deposited under supratidal to sabkha environments as indicated by the absence of benthic foraminifera and predominance of clastics enriched in terrestrial materials due to a relative lowering of sea level accompanied with arid conditions. From 1550 BC to the top of the core, the benthic species variations showed progressive depositional environmental changes from subtidal to intertidal conditions. Relative abundance of Sorites orbiculus co-varied with the reconstructed palaeo-tidal elevation, δ18O and δ13C values suggesting its sensitivity to climatic changes in the lagoon. δ18O and δ13C showed intervals of depletion at 350 BC, the beginning of the 1st millennium, AD 400 and AD 700 due likely to arid conditions that led to low evaporation and rapid water circulation. These are interleaved with intervals of enrichment at 150 BC, AD 200 and AD 600, due likely to warm conditions that led to high evaporation as testified also by changes in both palaeo-tidal elevation and Sorites orbiculus abundance. These proxies reached their highest and most prolonged levels during the AD 800–1550 interval, indicating warm conditions corresponding to the world ‘Medieval Warm Period’. Immediately after this period, the arid conditions of the ‘Little Ice Age’ prevailed throughout the AD 1550–1850 interval, and this was succeeded by the present warming conditions.
The Incremental Validity of Narrative Identity in Predicting Well-Being
Authors: Adler Jonathan M. , Lodi-Smith Jennifer , Philippe Frederick L. , Houle Iliane
Published: May 2015

Grounded in four theoretical positions—structural, cognitive, phenomenological, and ethical—the present review demonstrates the empirical evidence for the incremental validity of narrative identity as a cross-sectional indicator and prospective predictor of well-being, compared with other individual difference and situational variables. In doing so, we develop an organizational framework of four categories of narrative variables: (a) motivational themes, (b) affective themes, (c) themes of integrative meaning, and (d) structural elements. Using this framework, we detail empirical evidence supporting the incremental association between narrative identity and well-being, a case that is strongest for motivational, affective, and integrative meaning themes. These categories of themes serve as vital complimentary correlates and predictors of well-being, alongside commonly assessed variables such as dispositional personality traits. We then use the theoretically grounded review of the empirical literature to develop concrete areas of future research for the field.
Views That Are Shared With Others Are Expressed With Greater Confidence and Greater Fluency Independent of Any Social Influence
Authors: Koriat Asher , Adiv Shiri , Schwarz Norbert
Published: May 2015

Research on group influence has yielded a prototypical majority effect (PME): Majority views are endorsed faster and with greater confidence than minority views, with the difference increasing with majority size. The PME was attributed to conformity pressure enhancing confidence in consensual views and causing inhibition in venturing deviant opinions. Our results, however, indicate that PME for binary choices can arise from the process underlying confidence and latency independent of social influence. PME was demonstrated for tasks and conditions that are stripped of social relevance; it was observed in within-individual analyses in contrasting the individual’s more frequent and less frequent responses to the same item, and was found for the predictions of others’ responses. A self-consistency model, which assumes that choice and confidence are based on the sampling of representations from a commonly shared pool of representations, yielded a PME for confidence and latency. Behavioral implications of the results are discussed.
Still blaming the victim of intimate partner violence? Women’s narratives of victim desistance and redemption when seeking support
Authors: Meyer Silke
Published: May 2015

This article presents a theoretical examination of victims’ ( N = 28) experiences when trying to rebuild a victimization-free identity after having experienced multiple years of severe intimate partner violence (IPV). Narratives reveal experiences of victim-blaming attitudes when seeking help from informal and general formal support sources, which suggest that victims of IPV do not meet the criteria of the ‘ideal’, innocent victim worthy of ongoing formal and informal support. Drawing on criminological theories of redemption and desistance, in combination with victimological theories around social stigma and construction of the ‘ideal victim’, the study finds that victims often feel they have to redeem themselves as worthy of empathy in order to access ongoing support. These misplaced expectations of ‘desistance’ with the victim rather than the perpetrator highlight that the social stigma associated with IPV goes beyond the private nature of this type of violence and extends to victim behavior and decision making.
Enhancing the Impact of Family Justice Centers via Motivational Interviewing
Authors: Simmons Catherine A. , Howell Kathryn H. , Duke Michael R. , Beck J. Gayle
Published: May 2015

The Family Justice Center (FJC) model is an approach to assisting survivors of intimate partner violence (IPV) that focuses on integration of services under one roof and co-location of staff members from a range of multidisciplinary agencies. Even though the FJC model is touted as a best practice strategy to help IPV survivors, empirical support for the effectiveness of this approach is scarce. The current article consolidates this small yet promising body of empirically based literature in a clinically focused review. Findings point to the importance of integrating additional resources into the FJC model to engage IPV survivors who have ambivalent feelings about whether to accept help, leave the abusive relationship, and/or participate in criminal justice processes to hold the offender accountable. One such resource, motivational interviewing (MI), holds promise in aiding IPV survivors with these decisions, but empirical investigation into how MI can be incorporated into the FJC model has yet to be published. This article, therefore, also integrates the body of literature supporting the FJC model with the body of literature supporting MI with IPV survivors. Implications for practice, policy, and research are incorporated throughout this review.
Adenosine A2Breceptor stimulates angiogenesis by inducing VEGF and eNOS in human microvascular endothelial cells
Authors: Du Xiaolong , Ou Xuehai , Song Tao , Zhang Wentao , Cong Fei , Zhang Shihui , Xiong Yongmin
Published: May 2015

Angiogenesis is critical to wound repair due to its role in providing oxygen and nutrients that are required to support the growth and function of reparative cells in damaged tissues. Adenosine receptors are claimed to be of paramount importance in driving wound angiogenesis by inducing VEGF. However, the underlying mechanisms for the regulation of adenosine receptors in VEGF as well as eNOS remain poorly understood. In the present study, we found that adenosine and the non-selective adenosine receptor agonists (NECA) induced tube formation in HMEC-1 in a dose-dependent manner. Adenosine or NECA (10 µmol/L) significantly augmented the number and length of the segments in comparison with the control. Simultaneously, VEGF and eNOS were significantly upregulated following the administration of 10 µmol/L NECA, while they were suppressed after A2BAR genetic silencing and pharmacological inhibition by MRS1754. In addition, VEGF expression and eNOS bioavailability elimination significantly reduced the formation of capillary-like structures. Furthermore, the activation of A2BAR by NECA significantly increased the intracellular cAMP levels and concomitant CREB phosphorylation, eventually leading to the production of VEGF in HMEC-1. However, the activated PKA-CREB pathway seemed to be invalidated in the induction of eNOS. Moreover, we found that the elicited PI3K/AKT signaling in response to the induction of NECA assisted in regulating eNOS but failed to impact on VEGF generation. In conclusion, the A2BAR activation-driven angiogenesis via cAMP-PKA-CREB mediated VEGF production and PI3K/AKT-dependent upregulation of eNOS in HMEC-1.
Noninvasive Neuromodulation in Poststroke Gait Disorders
Authors: Chieffo Raffaella , Comi Giancarlo , Leocani Letizia
Published: May 2015

Walking rehabilitation is one of the primary goals in stroke survivors because of its great potential for recovery and its functional relevance in daily living activities. Although 70% to 80% of people in the chronic poststroke phases are able to walk, impairment of gait often persists, involving speed, endurance, and stability. Walking involves several brain regions, such as the sensorimotor cortex, supplementary motor area, cerebellum, and brainstem, which are approachable by the application of noninvasive brain stimulation (NIBS). NIBS techniques, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation, have been reported to modulate neural activity beyond the period of stimulation, facilitating neuroplasticity. NIBS methods have been largely applied for improving paretic hand motor function and stroke-associated cognitive deficits. Recent studies suggest a possible effectiveness of these techniques also in the recovery of poststroke gait disturbance. This article is a selective review about functional investigations addressing the mechanisms of lower-limb motor system reorganization after stroke and the application of NIBS for neurorehabilitation.
Subcutaneous immunoglobulin in treating inflammatory neuromuscular disorders
Authors: Yoon Min-Suk , Gold Ralf , Kerasnoudis Antonios
Published: May 2015

Objective:

Intravenous immunoglobulin administration has long been used in the treatment of autoimmune neuromuscular disorders. Immunoglobulins may be administered by intramuscular, intravenous or subcutaneous routes.

Methods:

This is a report on the long-term clinical follow up of six patients with inflammatory neuromuscular disorders, that is, three chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy (MMN), one inclusion body myositis (IBM) and one myasthenia gravis (MG), treated with subcutaneous immunoglobulins for a mean of 3.25 years.

Results:

One MMN and two CIDP patients received a weekly dose of subcutaneous immunoglobulins equivalent to intravenous immunoglobulin. One CIDP patient received a 50% dose reduction, the IBM patient received a 30% reduction and the MG patient a 20% reduction. The lower dose chosen in the majority of patients was based not only on clinical effects, but also on studies of primary immunodeficiency syndromes. One patient with CIDP showed clinical fluctuation, which was successfully treated with an adaptation of the dose of subcutaneous immunoglobulins, while the remaining patients with neuromuscular disorders had a stable clinical course for 2 years. No serious side effects were observed.

Conclusions:

Our results suggest that subcutaneous immunoglobulins can be an attractive alternative therapy in autoimmune neuromuscular disorders.
Safety, tolerability and pharmacodynamics of a novel immunomodulator, MIS416, in patients with chronic progressive multiple sclerosis
Authors: Luckey Alison M , Anderson Tim , Silverman Michael H , Webster Gill
Published: May 2015

Background

Preclinical studies have demonstrated that MIS416, a bacterially derived immune modulator, targets myeloid cells following systemic delivery. MIS416 stimulated myeloid cells have the capacity to regulate innate inflammation, a potential therapeutic target for progressive multiple sclerosis.

Objectives

To determine the safety, tolerability, pharmacodynamics and maximum tolerated dose and/or recommended Phase 2 dose of MIS416.

Methods

An open-label, non-randomized, phase II, dose-escalation study, in patients with progressive multiple sclerosis: dose-escalation phase, with MIS416 administered once weekly for four weeks to determine maximum tolerated dose; and dose-confirmation phase, administered once weekly for up to 12 weeks.

Results

The safety profile indicates the majority of adverse events were mild or moderate, tolerable, self-limiting and consistent with the known bioactivity of MIS416 (acute flu-like symptoms). Maximum tolerated dose was not reached. A dose of 500 µg/week was recommended for the Phase 2 dose.

Conclusion

MIS416 is well tolerated at a dose of 500 µg/week. The adverse event profile is consistent with the mechanism of action of MIS416, indicating bioactivity within the signal transduction pathways and supported by induction of a known MIS416 pharmacodynamic marker. It is recommended that safety and efficacy of MIS416 is investigated further in a larger randomized controlled trial. http://clinicaltrials.gov reference NCT01191996
Hashtags Functions in the Protests Across Brazil
Authors: Recuero Raquel , Zago Gabriela , Bastos Marco T. , Araújo Ricardo
Published: May 2015

In this article, we discuss the communicative functions of hashtags during a period of major social protests in Brazil. Drawing from a theoretical background of the use of Twitter and hashtags in protests and the functions of language, we extracted a sample of 46,090 hashtags from 2,321,249 tweets related to Brazilian protests in June 2013. We analyzed the hashtags through content analysis, focusing on functions, and co-occurrences. We also qualitatively analyzed a group of 500 most retweeted tweets to understand the users’ tagging behavior. Our results show how users appropriate tags to accomplish different effects on the narrative of the protests.
Hypermorphic mutation of phospholipase C, γ2 acquired in ibrutinib-resistant CLL confers BTK independency upon B-cell receptor activation
Authors: Liu Ta-Ming , Woyach Jennifer A. , Zhong Yiming , Lozanski Arletta , Lozanski Gerard , Dong Shuai , Strattan Ethan , Lehman Amy , Zhang Xiaoli , Jones Jeffrey A. , Flynn Joseph , Andritsos Leslie A. , Maddocks Kami , Jaglowski Samantha M. , Blum Kristie A. , Byrd John C. , Dubovsky Jason A. , Johnson Amy J.
Published: May 2015

Key Points

Hypermorphic PLCγ2 is independent of BTK activation. SYK or LYN inhibition antagonizes mutant PLCγ2-mediated signaling events.
A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4)
Authors: Choi Philip Young-Ill , Roncolato Fernando , Badoux Xavier , Ramanathan Sundra , Ho Shir-Jing , Chong Beng H.
Published: May 2015

Key Points

Triple therapy is well tolerated and effective in patients with chronic ITP. Relapse free survival was 92% for responders after 12 months and 76% after 24 months.
Efficient treatment of breast cancer xenografts with multifunctionalized iron oxide nanoparticles combining magnetic hyperthermia and anti-cancer drug delivery
Authors: Kossatz Susanne , Grandke Julia , Couleaud Pierre , Latorre Alfonso , Aires Antonio , Crosbie-Staunton Kieran , Ludwig Robert , Dähring Heidi , Ettelt Volker , Lazaro-Carrillo Ana , Calero Macarena , Sader Maha , Courty José , Volkov Yuri , Prina-Mello Adriele , Villanueva Angeles , Somoza Álvaro , Cortajarena Aitziber L , Miranda Rodolfo , Hilger Ingrid
Published: May 2015

Introduction

Tumor cells can effectively be killed by heat, e.g. by using magnetic hyperthermia. The main challenge in the field, however, is the generation of therapeutic temperatures selectively in the whole tumor region. We aimed to improve magnetic hyperthermia of breast cancer by using innovative nanoparticles which display a high heating potential and are functionalized with a cell internalization and a chemotherapeutic agent to increase cell death.

Methods

The superparamagnetic iron oxide nanoparticles (MF66) were electrostatically functionalized with either Nucant multivalent pseudopeptide (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6LDOX). Their cytotoxic potential was assessed in a breast adenocarcinoma cell line MDA-MB-231. Therapeutic efficacy was analyzed on subcutaneous MDA-MB-231 tumor bearing female athymic nude mice.

Results

All nanoparticle variants showed an excellent heating potential around 500 W/g Fe in the alternating magnetic field (AMF, conditions: H = 15.4 kA/m, f = 435 kHz). We could show a gradual inter- and intracellular release of the ligands, and nanoparticle uptake in cells was increased by the N6L functionalization. MF66-DOX and MF66-N6LDOX in combination with hyperthermia were more cytotoxic to breast cancer cells than the respective free ligands. We observed a substantial tumor growth inhibition (to 40% of the initial tumor volume, complete tumor regression in many cases) after intratumoral injection of the nanoparticles in vivo. The proliferative activity of the remaining tumor tissue was distinctly reduced.

Conclusion

The therapeutic effects of breast cancer magnetic hyperthermia could be strongly enhanced by the combination of MF66 functionalized with N6L and DOX and magnetic hyperthermia. Our approach combines two ways of tumor cell killing (magnetic hyperthermia and chemotherapy) and represents a straightforward strategy for translation into the clinical practice when injecting nanoparticles intratumorally.
Alzheimer’s disease progression by geographical region in a clinical trial setting
Authors: Henley David B , Dowsett Sherie A , Chen Yun-Fei , Liu-Seifert Hong , Grill Joshua D , Doody Rachelle S , Aisen Paul , Raman Rema , Miller David S , Hake Ann M , Cummings Jeffrey
Published: May 2015

Introduction

To facilitate enrollment and meet local registration requirements, sponsors have increasingly implemented multi-national Alzheimer’s disease (AD) studies. Geographic regions vary on many dimensions that may affect disease progression or its measurement. To aid researchers designing and implementing Phase 3 AD trials, we assessed disease progression across geographic regions using placebo data from four large, multi-national clinical trials of investigational compounds developed to target AD pathophysiology.

Methods

Four similarly-designed 76 to 80 week, randomized, double-blind placebo-controlled trials with nearly identical entry criteria enrolled patients aged ≥55 years with mild or moderate NINCDS/ADRDA probable AD. Descriptive analyses were performed for observed mean score and observed mean change in score from baseline at each scheduled visit. Data included in the analyses were pooled from the intent-to-treat placebo-assigned overall (mild and moderate) AD dementia populations from all four studies. Disease progression was assessed as change from baseline for each of 5 scales - the AD Assessment Scale-cognitive subscale (ADAS-cog11), the AD Cooperative Study- Activities of Daily Living Scale (ADCS-ADL), Mini-Mental State Examination (MMSE), the Clinical Dementia Rating scored by the sum of boxes method (CDR-SB), and the Neuropsychiatric Inventory (NPI).

Results

Regions were heterogeneous at baseline. At baseline, disease severity as measured by ADAS-cog11, ADCS-ADL, and CDR-SB was numerically worse for Eastern Europe/Russia compared with other regions. Of all regional populations, Eastern Europe/Russia showed the greatest cognitive and functional decline from baseline; Japan, Asia and/or S. America/Mexico showed the least cognitive and functional decline.

Conclusions

These data suggest that in multi-national clinical trials, AD progression or its measurement may differ across geographic regions; this may be in part due to heterogeneity across populations at baseline. The observed differences in AD progression between outcome measures across geographic regions may generalize to 'real-world' clinic populations, where heterogeneity is the norm.

Trial registrations

ClinicalTrials.gov NCT00594568 – IDENTITY. Registered 11 January 2008.

ClinicalTrials.gov NCT00762411 – IDENTITY2. Registered 26 September 2008

ClinicalTrials.gov NCT00905372 – EXPEDITION. Registered 18 May 2009

ClinicalTrials.gov NCT00904683 – EXPEDITION2. Registered 18 May 2009
Once an entrepreneur, always an entrepreneur? The impacts of skills developed before, during and after college on firm start-ups
Authors: Orazem Peter F , Jolly Robert , Yu Li
Published: May 2015

By allowing agents to switch from entrepreneurship to wage work and vice versa over the life cycle, this study proposes a dynamic Jacks-of-All-Trades (JAT) model where entrepreneurs invest in highly varied skills to manage their business. We simultaneously endogenize human capital investment and occupational decisions. Using the survey data of Iowa State alumni graduating between 1982 and 2006, we find that the probability of selecting a broad curriculum, having a more varied career, and becoming an entrepreneur are jointly positively correlated. Academic diversity is found to be initially important in starting a business shortly after completing schooling, but its importance declines over time.
Wage returns to mid-career investments in job training through employer supported course enrollment: evidence for Canada
Authors: Ci Wen , Galdo Jose , Voia Marcel , Worswick Christopher
Published: May 2015

Using longitudinal data for Canada, we analyze the incidence and wage returns to employer supported course enrollment for men and women. Availability of confidential data, along with a relatively rich set of observable covariates, lead us to the estimation of difference-in-differences matching models of the effect of employer supported course enrolment on wages. The estimated average treatment effects on the treated range from 5.5 to 7.2 percent for men and 7.1 to 9.0 for women. While high-skilled workers show disproportionately higher rates of participation in employer-supported training, we observe no wage premiums for these types of workers. Statistically significant positive wage returns are found, on the other hand, for low-skilled workers.

JEL codes:C14, I20, J24, J31, M53
Extraction methods for uncertain inference rules by ant colony optimization
Authors: Chen Ling , Sun Yun , Zhu Yuanguo
Published: May 2015

In recent years, the research on data mining methods has received increasing attention. In this paper, we design an uncertain system with the extracted uncertain inference rules to solve the classification problems in data mining. And then, two extraction methods integrated with ant colony optimization are proposed for the generation of the uncertain inference rules. Finally, two applications are given to verify the effectiveness and superiority of the proposed methods.
α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons
Authors: Zaltieri Michela , Grigoletto Jessica , Longhena Francesca , Navarria Laura , Favero Gaia , Castrezzati Stefania , Colivicchi Maria Alessandra , Della Corte Laura , Rezzani Rita , Pizzi Marina , Benfenati Fabio , Spillantini Maria Grazia , Missale Cristina , Spano PierFranco , Bellucci Arianna
Published: May 2015

The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain α-synuclein (α-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that α-syn interacts with and modulates synapsin III. The absence of α-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In α-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in α-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of α-syn and synapsin III in the regulation of dopamine neuron synaptic function.
The MAL protein is crucial for proper membrane condensation at the ciliary base, which is required for primary cilium elongation
Authors: Reales Elena , Bernabé-Rubio Miguel , Casares-Arias Javier , Rentero Carles , Fernández-Barrera Jaime , Rangel Laura , Correas Isabel , Enrich Carlos , Andrés Germán , Alonso Miguel A.
Published: May 2015

The base of the primary cilium contains a zone of condensed membranes whose importance is not known. Here, we have studied the involvement of MAL, a tetraspanning protein that exclusively partitions into condensed membrane fractions, in the condensation of membranes at the ciliary base and investigated the importance of these membranes in primary cilium formation. We show that MAL accumulates at the ciliary base of epithelial MDCK cells. Knockdown of MAL expression resulted in a drastic reduction in the condensation of membranes at the ciliary base, the percentage of ciliated cells and the length of the cilia, but did not affect the docking of the centrosome to the plasma membrane or produce missorting of proteins to the pericentriolar zone or to the membrane of the remaining cilia. Rab8 (for which there are two isoforms, Rab8A and Rab8b), IFT88 and IFT20, which are important components of the machinery of ciliary growth, were recruited normally to the ciliary base of MAL-knockdown cells but were unable to elongate the primary cilium correctly. MAL, therefore, is crucial for the proper condensation of membranes at the ciliary base, which is required for efficient primary cilium extension.
Two New Sesquiterpenoids from the Root of Strophanthus divaricatus
Authors: Chen Neng-Hua , Zhang Yu-Bo , Li Zhen-Hua , Jiang Jian-Wei , Li Guo-Qiang , Wang Guo-Cai , Li Yao-Lan
Published: May 2015

Two new sesquiterpenoids, strophanthoids A and B (1 and 2), along with seven known cardiac glycosides were isolated from the roots of Strophanthus divaricatus. Their structures were elucidated on the basis of extensive analyses by IR, HR-ESI-MS, NMR, and single-crystal X-ray diffraction. And the new compounds were tested cytotoxic activities on the tumor cells SK-MEL-110 and SK-MEL-28.
Dehydrogenation of Alcohols and Hydrocarbons by Atomic Metal Anions
Authors: Halvachizadeh Jaleh , Mungham Alex , Mayer Paul M.
Published: May 2015

The reactivity of anionic metal–carbonyl systems toward hydrocarbons, alcohols, and a variety of other classes of molecules is well established in the literature. In this study we explored the reactions of atomic metal anions M−, notably K−, Cs−, Co−, Fe−, Cu−, and Ag−, with alcohols, alkanes, alkenes, and alkynes. All of the metal anions deprotonated the alcohols and alkynes. Also observed were the subsequent reactions of the resulting organic anions. Fe− and Cu− consistently displayed mono- and bis-dehydrogenation of primary and secondary alcohols, and alkanes, alkenes, and alkynes to form MH− and MH2−. Mechanisms for the dehydrogenation reactions are proposed and substantiated with isotopically-labelled reagents and thermochemical arguments.
Automated Quantum Chemistry Based Molecular Dynamics Simulations of Electron Ionization Induced Fragmentations of the Nucleobases Uracil, Thymine, Cytosine, and Guanine
Authors: Bauer Christoph Alexander , Grimme Stefan
Published: May 2015

The gas-phase decomposition pathways of electron ionization (EI)-induced radical cations of the nucleobases uracil, thymine, cytosine, and guanine are investigated by means of mixed quantum-classical molecular dynamics. No preconceived fragmentation channels are used in the calculations. The results compare well to a plethora of experimental and theoretical data for these important biomolecules. With our combined stochastic and dynamic approach, one can access in an unbiased way the energetically available decomposition mechanisms. Additionally, we are able to separate the EI mass spectra of different tautomers of cytosine and guanine. Our method (previously termed quantum chemistry electron ionization mass spectra) reproduces free nucleobase experimental mass spectra well and provides detailed mechanistic in-sight into high-energy unimolecular decomposition processes.