bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a novel orally administered calpain inhibitor SNJ‐1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis
Authors: Trager Nicole , Smith Amena , Wallace IV Gerald , Azuma Mitsuyoshi , Inoue Jun , Beeson Craig , Haque Azizul , Banik Naren L. 
Published: January 2014

AbstractMultiple sclerosis (MS) pathology is marked by the massive infiltration of myelin‐specific T cells into the CNS. Hallmarks of T helper (Th) cells during active disease are pro‐inflammatory Th1/Th17 cells that predominate over immunoregulatory Th2/Treg cells. Neurodegeneration, a major factor in progressive MS, is often overlooked when considering drug prescription. Here, we show that oral dosing with SNJ‐1945, a novel water‐soluble calpain inhibitor, reduces experimental autoimmune encephalomyelitis clinical scores in vivo and has a two pronged effect via anti‐inflammation and protection against neurodegeneration. We also show that SNJ‐1945 treatment down‐regulates Th1/Th17 inflammatory responses, and promotes regulatory T cells (Tregs) and myeloid‐derived suppressor cells in vivo, which are known to have the capacity to suppress helper as well as cytotoxic T cell functions. Through analysis of spinal cord samples, we show a reduction in calpain expression, decreased infiltration of inflammatory cells, and signs of inhibition of neurodegeneration. We also show a marked reduction in neuronal cell death in spinal cord (SC) sections. These results suggest that calpain inhibition attenuates experimental autoimmune encephalomyelitis pathology by reducing both inflammation and neurodegeneration, and could be used in clinical settings to augment the efficacy of standard immunomodulatory agents used to treat MS.
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Multiple sclerosis (MS) pathology is marked by inflammation and infiltration of myelin‐specific T cells into the central nervous system. Inflammation leads to neurodegeneration in progressive MS which also leads to epitope spreading, feedback looping to more inflammation. Calpain can play a role in both arms of the disease. Here, oral dosing with SNJ‐1945, a novel water‐soluble calpain inhibitor, reduces experimental autoimmune encephalomyelitis clinical scores in vivo and has a two‐pronged effect via anti‐inflammation and protection against neurodegeneration.
Association between mid‐ to late life physical fitness and dementia: evidence from the CAIDE study
Authors: Kulmala J. , Solomon A. , Kåreholt I. , Ngandu T. , Rantanen T. , Laatikainen T. , Soininen H. , Tuomilehto J. , Kivipelto M. 
Published: January 2014

AbstractObjectivesThis study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid‐ to late life and dementia risk.DesignProspective cohort study.SettingCardiovascular risk factors, ageing and incidence of dementia (CAIDE) study.SubjectsSubjects were selected from four independent, random samples of population‐based cardiovascular surveys and were first examined in 1972, 1977, 1982 or 1987, when they were on average 50 years old. The CAIDE target population included 3559 individuals. A random sample of 2000 individuals still alive in 1997 was drawn for re‐examinations (performed in 1998 and 2005–2008) that consisted of cognitive assessments, with 1511 subjects participating in at least one re‐examination. Dementia diagnoses were also confirmed from national registers for the entire target population.Main outcome measureAll‐cause dementia.ResultsPoor physical fitness at midlife was associated with increased dementia risk in the entire target population [hazard ratio (HR), 1.5; 95% confidence interval (CI), 1.1–2.0]. In participants, odds ratio (OR) was 2.0 (95% CI, 0.9–4.0). This association was significant in apolipoprotein E ε4 allele (APOEε4) noncarriers (OR, 4.3; 95% CI, 1.4–13.3), men (HR, 1.8; 95% CI, 1.1–3.0) and people with chronic conditions (HR, 2.9; 95% CI, 1.3–6.6). A decline in fitness after midlife was also associated with dementia (OR, 3.0; 95% CI, 1.7–5.1), which was significant amongst both men and women and more pronounced in APOEε4 carriers (OR, 4.4; 95% CI, 2.1–9.1).ConclusionsPerceived poor physical fitness reflects a combination of biological and lifestyle‐related factors that can increase dementia risk. A simple question about perceived physical fitness may reveal at‐risk individuals who could benefit from preventive interventions.
Established and novel disease‐modifying treatments in multiple sclerosis
Authors: Cross A. H. , Naismith R. T. 
Published: January 2014

AbstractMultiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of MS. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of MS, which allow individualized treatment based upon the benefits and risks. Disease‐modifying therapies introduced in the 1990s, the beta‐interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha‐4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for MS treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long‐term postmarketing efficacy and safety data in a general MS population. Because of this lack of long‐term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with MS who present with highly inflammatory and potentially aggressive disease, the benefit‐to‐risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e.g. fingolimod or natalizumab if JC virus antibody‐negative). The aim of this review is to discuss the clinical benefits, mechanisms of action, safety profiles and monitoring strategies of current MS disease‐modifying therapies in clinical practice and of those expected to enter the market in the near future.
Confucian Cosmopolitanism
Authors: Ivanhoe Philip J 
Published: January 2014

AbstractScholars in the humanities and social sciences are keenly aware of and often deeply engaged with more global or cosmopolitan approaches to their respective fields; nevertheless, theories of cosmopolitanism remain exceedingly controversial and arise exclusively from Western philosophical sources. Recently,MarthaNussbaum presented a contemporary Western liberal cosmopolitan theory and sought to integrate it with a call for multicultural education. In this essay, I describe, analyze, and criticizeNussbaum's conception of cosmopolitanism and argue that it does not sit comfortably with her laudable advocacy of multicultural education. I then draw upon resources within the Confucian tradition to sketch two alternative conceptions of cosmopolitanism, which I argue are both more powerful than whatNussbaum proposes and better support the kind of multicultural education she so eloquently advocates.
The Impact of a Creativity‐supporting Work Environment on a Firm's Product Innovation Performance
Authors: Dul Jan , Ceylan Canan 
Published: January 2014

Many scholars and practitioners have suggested that a creativity‐supporting work environment contributes to a firm's product innovation performance. Although there is evidence that such an environment enhances innovative behavior at individual level, very few studies address the effect of a creativity‐supporting work environment on product innovation performance at firm level, and the results are inconsistent.This paper examines the relationship between a firm's creativity‐supporting work environment and a firm's product innovation performance in a sample of 103 firms. For measuring a firm's creativity‐supporting work environment, a comprehensive and creativity‐focused framework is used. The framework consists of 9 social‐organizational and 12 physical work environment characteristics that are likely to enhance employee creativity. These characteristics contribute to the firm's overall work environment that supports creativity. The firm's product innovation performance is defined by two distinct concepts: new product productivity (NP productivity), which is the extent to which the firm introduces new products to the market, and new product success (NP success), which is the percentage of the firm's sales from new products. In most firms, different knowledgeable informants provided the data for the variables.The results show that firms with creativity‐supporting work environments introduce more new products to the market (NP productivity), and have more NP success in terms of new product sales (NP success). NP productivity partly mediates the relationship between creativity‐supporting work environment and NP success. The mediation model shows that the two paths from a creativity‐supporting work environment to NP success are about equally important: the direct path between creativity‐supporting work environment and NP success has a coefficient of .22, and the coefficient of the indirect path via NP productivity is .23.The creativity‐supporting work environment framework can be used in managerial practice to enhance employee creativity for product innovation. It allows applying a flexible and broad approach by influencing both social‐organizational and physical characteristics of the work environment.
PORTMANTEAU AUTOCORRELATION TESTS UNDERQ‐DEPENDENCE AND HETEROSKEDASTICITY
Authors: Harris David , Kew Hsein 
Published: January 2014

AbstractWe propose extensions of the Box–Pierce () portmanteau autocorrelation test to allow for two generalizations: (i) time series that exhibit unconditional heteroskedasticity and (ii) to test for the presence of autocorrelation only after a fixed lagq. These extensions involve a generalized quadratic form of the Box–Pierce test that uses the heteroskedasticity autocorrelation consistent‐type estimator. While we show that this modified test is robust to unconditional heteroskedasticity, the resulting power loss may be substantial. We therefore develop feasible weighted tests that make use of nonparametric estimates of the unobserved variance process. Simulation experiments show that the weighted tests have good size and superior power properties over the unweighted tests.
Reproductive interference between honeybee species in artificial sympatry
Authors: Remnant Emily J. , Koetz Anna , Tan Ken , Hinson Eloise , Beekman Madeleine , Oldroyd Benjamin P. 
Published: January 2014

AbstractReproductive isolation between closely related species is often incomplete. The Western honeybee, Apis mellifera, and the Eastern hive bee, Apis cerana, have been allopatric for millions of years, but are nonetheless similar in morphology and behaviour. During the last century, the two species were brought into contact anthropogenically, providing potential opportunities for interspecific matings. Hybrids between A. mellifera and A. cerana are inviable, so natural interspecific matings are of concern because they may reduce the viability of A. cerana and A. mellifera populations – two of the world's most important pollinators. We examined the mating behaviour of A. mellifera and A. cerana queens and drones from Caoba Basin, China and Cairns, Australia. Drone mating flight times overlap in both areas. Analysis of the spermathecal contents of queens with species‐specific genetic markers indicated that in Caoba Basin, 14% of A. mellifera queens mated with at least one A. cerana male, but we detected no A. cerana queens that had mated with A. mellifera males. Similarly, in Cairns, no A. cerana queens carried A. mellifera sperm, but one‐third of A. mellifera queens had mated with at least one A. cerana male. No hybrid embryos were detected in eggs laid by interspecifically mated A. mellifera queens in either location. However, A. mellifera queens artificially inseminated with A. cerana sperm produced inviable hybrid eggs or unfertilized drones. This suggests that reproductive interference will impact the viability of honeybee populations wherever A. cerana and A. mellifera are in contact.
Molecular epidemiology and antifungal susceptibility of Serbian Cryptococcus neoformans isolates
Authors: Arsic Arsenijevic Valentina , Pekmezovic Marina G. , Meis Jacques F. , Hagen Ferry 
Published: January 2014

SummaryMolecular typing and antifungal susceptibility testing of 34 clinical Serbian Cryptococcus neoformans isolates from 25 patients was retrospectively performed. Amplified fragment length polymorphism (AFLP) fingerprinting was used for genotyping, whereas a novel real‐time PCR was used to determine the mating‐ and serotype. The antifungals amphotericin B, 5‐fluorocytosine, fluconazole, voriconazole, itraconazole and posaconazole were used to determine the antifungal susceptibility profiles. The majority of isolates belonged to genotype AFLP1/VNI (n = 20; 58.8%), followed by AFLP2/VNIV (n = 10; 29.4%), AFLP3/VNIII (n = 3; 8.8%) and AFLP1B/VNII (n = 1; 2.9%). All AFLP1/VNI isolates were mating–serotype αA, the sole AFLP1B/VNII isolate was found to be aA, whereas AFLP2/VNIV harboured serotype D isolates with either the a (n = 2; 5.9%) or α (n = 8; 23.5%) mating‐type allele. The isolates (n = 3; 8.8%) that were found to be genotype AFLP3/VNIII had the hybrid mating‐ and serotype combination aA‐αD. In vitro antifungal susceptibility testing showed that all isolates were susceptible to amphotericin B, voriconazole and posaconazole. Low resistance level was observed for fluconazole (n = 1; 2.9%) and 5‐fluorocytosine. (n = 2; 5.8%). A large percentage of isolates was found to be susceptible dose dependent to itraconazole (n = 16; 47.1%). AFLP1/VNI was the most common genotype among clinical C. neoformans isolates from immunocompromised patients in Serbia. C. neoformans from HIV‐negative patients were significantly less susceptible to 5‐fluorocytosine (P < 0.01). Correlation between genotypes and antifungal susceptibility was not observed.
The Influence of Emotional Intelligence on Negotiation Outcomes and the Mediating Effect of Rapport: A Structural Equation Modeling Approach
Authors: Kim Kihwan , Cundiff Nicole L. A. , Choi Suk Bong 
Published: January 2014

Although early research on negotiation focused on cognition and decision‐making processes, recently, negotiation scholars have started to pay attention to the importance of emotion in negotiation and have suggested that emotional intelligence is likely to improve negotiation performance. Few studies, however, have tested the relationship between emotional intelligence and negotiation outcomes. This study contributes by empirically testing the influence of emotional intelligence on specific negotiation outcomes (joint gain, trust between parties, and the desire of parties to work together again) and also examines the mediating effects of rapport.We used a laboratory experimental design with 202 participants to test the hypotheses. We found that a negotiator's emotional intelligence was correlated with his or her counterpart's trust level and desire to work again but had no effect on joint gain. In addition, rapport fully mediated the relationship between emotional intelligence and desire to work again, and between emotional intelligence and trust.
Civil Society and Peace Negotiations: Beyond the Inclusion–Exclusion Dichotomy
Authors: Paffenholz Thania 
Published: January 2014

Civil society is generally seen as an important actor in peace processes. But when it comes to reaching an agreement during peace negotiations, much of the current debate is centered on the question of including or excluding civil society. Although most researchers argue that civil society participation makes the process more sustainable and democratic, most practitioners emphasize that enhanced civil society participation makes it more difficult to reach a peace agreement.I argue that practitioners and theorists must both move beyond this dichotomy and, instead, focus on the variety of ways in which civil society actors can be included in a given negotiation process. To this end, I present in this article a comprehensive overview of nine models of inclusion, from most to least direct involvement of civil society, supported by illustrative case studies. Analysis of these models suggests that it will be possible to broaden the participation of civil society in peace negotiations without decreasing the negotiations' effectiveness.
The Beginning of a New History
Authors: FUKUYAMA FRANCIS , ATTALI JACQUES 
Published: January 2014

If the 20th Century was the century of physics, the 21st Century is the century of cybernetics, biology and ecology. Technological advance has both crossed new frontiers and discovered old limits.Nobel laureate Ilya Prigogine broke new ground with his understanding that nature, including its human component, seeks to establish order out of chaos by “self‐organizing,” not only according to pre‐determined laws, but through random creative choices as well that are responsible for the endless novelty and potentiality of being.The technologically‐armed purposive role of humans in the Anthropocentric Age thus takes on a new significance: “What we do today depends on our image of the future rather than the future depending on what we do today” as Prigogine puts it. “The equations of the future are written in our actions as well as in nature. Time becomes construction.”Nowhere is this truer than in the new science of genomics, which touches the soul, and in the effort to preserve the ecological balance that has enabled humanity to flourish within the narrow band of earth's livable climate.In this section we bring together leading thinkers, scientists and technologists of our age to address these issues of mankind's fate.
The Limits of Cloning
Authors: WILMUT IAN 
Published: January 2014

If the 20th Century was the century of physics, the 21st Century is the century of cybernetics, biology and ecology. Technological advance has both crossed new frontiers and discovered old limits.Nobel laureate Ilya Prigogine broke new ground with his understanding that nature, including its human component, seeks to establish order out of chaos by “self‐organizing,” not only according to pre‐determined laws, but through random creative choices as well that are responsible for the endless novelty and potentiality of being.The technologically‐armed purposive role of humans in the Anthropocentric Age thus takes on a new significance: “What we do today depends on our image of the future rather than the future depending on what we do today” as Prigogine puts it. “The equations of the future are written in our actions as well as in nature. Time becomes construction.”Nowhere is this truer than in the new science of genomics, which touches the soul, and in the effort to preserve the ecological balance that has enabled humanity to flourish within the narrow band of earth's livable climate.In this section we bring together leading thinkers, scientists and technologists of our age to address these issues of mankind's fate.
Longitudinal study of spherical refractive error in infantile nystagmus syndrome
Authors: Healey Natasha , McClelland Julie F. , Saunders Kathryn J. , Jackson A. Jonathan 
Published: January 2014

AbstractPurposeTo explore the onset and progression of spherical refractive error in a population with infantile nystagmus syndrome.MethodsRetrospective refractive error data were obtained from 147 medical records of children with infantile nystagmus syndrome (albinism n = 98; idiopathic infantile nystagmus n = 49), attending a low vision clinic in Northern Ireland, over a 24 year period (1986–2010). Data were categorised by age to allow for comparisons with published studies. A prospective group of participants with Infantile nystagmus syndrome (INS) [n = 22 (albinism n = 18, idiopathic infantile nystagmus n = 4)] (aged 0–4) were also recruited. Cycloplegic streak retinoscopy was performed biannually, over a 3 year period. Spherical equivalent refractive error and most ametropic meridian were analysed.ResultsThe mean spherical equivalent refractive errors for albinism and idiopathic infantile nystagmus groups (across all age categories) were hypermetropic, with highest levels demonstrated by the participants with albinism aged 1 ≤ 4 years (Mann‐Whitney U test, p = 0.013). Mean most ametropic meridian was highest in the albinism group aged 1 ≤ 12 years (Mann‐Whitney U test, p < 0.05). Individual data demonstrated relatively static spherical equivalent refractive errors over time. Prospective participants were hypermetropic at all visits and those with albinism had, on average, higher refractive errors than those with idiopathic infantile nystagmus (IIN). No significant correlations were noted between visual acuity and spherical equivalent refractive errors or most ametropic meridian.ConclusionsHypermetropia is the most prevalent spherical refractive error in the INS population, irrespective of level of visual acuity. Individuals with infantile nystagmus syndrome fail to demonstrate typical patterns of emmetropisation, particularly in the presence of albinism.
Performance on the Wechsler Adult Intelligence Scale‐III in Japanese patients with schizophrenia
Authors: Fujino Haruo , Sumiyoshi Chika , Sumiyoshi Tomiki , Yasuda Yuka , Yamamori Hidenaga , Ohi Kazutaka , Fujimoto Michiko , Umeda‐Yano Satomi , Higuchi Arisa , Hibi Yumiko , Matsuura Yukako , Hashimoto Ryota , Takeda Masatoshi , Imura Osamu 
Published: January 2014

AimPatients with schizophrenia have been reported to perform worse than non‐schizophrenic populations on neuropsychological tests, which may be affected by cultural factors. The aim of this study was to examine the performance of a sizable number of patients with schizophrenia on the Japanese version of the Wechsler Adult Intelligence Scale‐III (WAIS‐III) compared with healthy controls.MethodsPerformance on the WAIS‐III was evaluated in 157 Japanese patients with schizophrenia and in 264 healthy control subjects.ResultsAll IQ scores and four indices from the WAIS‐III were impaired for patients with schizophrenia compared with healthy controls. Processing Speed was markedly disturbed, approximately 2 SD below that of the healthy control group. Among the 13 subtests, Comprehension (z = −1.70, d = 1.55), Digit Symbol Coding (z = −1.84, d = 1.88), and Symbol Search (z = −1.85, d = 1.77) were profoundly impaired relative to the healthy controls.ConclusionThese results indicate that the pattern and degree of impairment, as evaluated by the WAIS‐III, in Japanese patients are similar to those previously reported in English‐speaking patients and that the deficits of some neuropsychological domains relevant to functional outcomes are universally characteristic of schizophrenia.