bluuebunny/crossref_metadata_2025 huggingface dataset:
Antecedents of Innovativeness in Technology‐Based Services (TBS): Peering into the Black Box of Entrepreneurial Orientation
Authors: Joshi Maheshkumar P. , Das Sidhartha R. , Mouri Nacef
Published: April 2015

Innovativeness is the organization's capability for developing and introducing innovations. We argue that new combinations and recombinations of prior and new knowledge (by way of creating, assembling, and transforming knowledge) result in innovativeness in an organization. We further assert that a knowledge‐based focus on innovativeness is particularly important for firms that are technology‐based. The majority of studies focusing on innovativeness are in the entrepreneurship arena, and a large number of studies consider innovativeness as one of three dimensions of the entrepreneurial orientation (EO) construct, the other two dimensions being proactiveness and risk‐taking. However, recent research has suggested peering into the black box of EO by disaggregating the EO construct and examining the interrelationships among its three components. Hence, using the knowledge‐based view and drawing from multiple disciplines, our study conceptualizes innovativeness as a criterion variable and investigates the antecedent role of proactiveness and risk‐taking propensity on innovativeness in the context of technology‐based services (TBS). We hypothesize that both proactiveness and risk‐taking propensity exhibit a curvilinear relationship with innovativeness and introduce organizational structure formality as a moderator to further explicate these relationships. Our results show that proactiveness has a curvilinear (inverted U relationship) with innovativeness, and that this relationship is attenuated by organizational structure formality. Additional analysis indicates that in TBS firms, risk‐taking propensity has a positive linear relationship with innovativeness, and this relationship is accentuated by organizational structure formality. Finally, we discuss important conceptual and practical implications of our study and provide suggestions for future research.
Effects of luseogliflozin, a sodium–glucose co‐transporter 2 inhibitor, on 24‐h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double‐blind, placebo‐controlled, crossover study
Authors: Nishimura R. , Osonoi T. , Kanada S. , Jinnouchi H. , Sugio K. , Omiya H. , Ubukata M. , Sakai S. , Samukawa Y.
Published: April 2015

The aim of the present study was to determine the effects of luseogliflozin on 24‐h glucose levels, assessed by continuous glucose monitoring, and on pharmacodynamic variables measured throughout the day. In this double‐blind, placebo‐controlled, crossover study, 37 patients with type 2 diabetes mellitus inadequately controlled with diet and exercise were randomized into two groups. Patients in each group first received luseogliflozin then placebo for 7 days each, or vice versa. After 7 days of treatment, the mean 24‐h glucose level was significantly lower with luseogliflozin than with placebo [mean (95% confidence interval) 145.9 (134.4–157.5) mg/dl vs 168.5 (156.9–180.0) mg/dl; p < 0.001]. The proportion of time spent with glucose levels ≥70 to ≤180 mg/dl was significantly greater with luseogliflozin than with placebo [median (interquartile range) 83.2 (67.7–96.5)% vs 71.9 (46.9–83.3)%; p < 0.001] without inducing hypoglycaemia. The decrease in glucose levels was accompanied by reductions in serum insulin levels throughout the day.
Pharmacological characterization and antidiabetic activity of a long‐acting glucagon‐like peptide‐1 analogue conjugated to an antithrombin III‐binding pentasaccharide
Authors: Patterson S. , de Kort M. , Irwin N. , Moffett R. C. , Dokter W. H. A. , Bos E. S. , Miltenburg A. M. M. , Flatt P. R.
Published: April 2015

Aims

To examine the biological characteristics of a novel glucagon‐like peptide‐1 (GLP‐1) conjugate, in which an antithrombin III (ATIII)‐binding pentasaccharide is conjugated to d‐Ala8GLP‐1 using a tetraethylene glycol linker.

Methods

We assessed GLP‐1 receptor binding, cAMP generation and insulin secretory activity of the GLP‐1 conjugate in vitro. Circulating half‐life, glucose homeostatic and subchronic therapeutic effectiveness were then examined in vivo.

Results

The half‐life of the GLP‐1 conjugate in mice was ∼11 h. In vitro insulin secretion from clonal β cells and islets was increased (p < 0.001) by the conjugate. The conjugate had half maximum effective concentration values of 1.3 × 10−7 and 9.9 × 10−8 M for displacement of 125I‐GLP‐1 in competitive GLP‐1 receptor binding and cAMP generation, respectively. Glucose tolerance in normal mice, immediately and 4 h after conjugate injection, resulted in significant (p < 0.001) improvements in blood glucose. These effects persisted for >48 h after administration. Daily treatment (21 days) of high‐fat‐fed and ob/ob mice with 25 nmol/kg conjugate resulted in significant improvement in glucose tolerance (p < 0.001) and reductions in glycated haemoglobin (HbA1c; p < 0.01) equivalent to or better than with exenatide or liraglutide. Treatment of C57BL/KsJ db/db mice for 15 days with 100 nmol/kg conjugate significantly (p < 0.001) reduced glucose and raised plasma insulin. Oral glucose tolerance was significantly (p < 0.001) improved and both 24‐h glucose profile (p < 0.001) and HbA1c levels (p < 0.001) were reduced. Islet size (p < 0.001) and pancreatic insulin content were increased without change of islet cell proliferation or apoptosis.

Conclusion

These data show that d‐Ala8GLP‐1(Lys37) pentasaccharide exerts significant antidiabetic actions and has a projected pharmacokinetic/pharmacodynamic profile that merits further evaluation in humans for a possible once‐weekly dosing regimen.
Climate change overruns resilience conferred by temperature‐dependent sex determination in sea turtles and threatens their survival
Authors: Santidrián Tomillo Pilar , Genovart Meritxell , Paladino Frank V. , Spotila James R. , Oro Daniel
Published: April 2015

Temperature‐dependent sex determination (TSD) is the predominant form of environmental sex determination (ESD) in reptiles, but the adaptive significance of TSD in this group remains unclear. Additionally, the viability of species with TSD may be compromised as climate gets warmer. We simulated population responses in a turtle with TSD to increasing nest temperatures and compared the results to those of a virtual population with genotypic sex determination (GSD) and fixed sex ratios. Then, we assessed the effectiveness of TSD as a mechanism to maintain populations under climate change scenarios. TSD populations were more resilient to increased nest temperatures and mitigated the negative effects of high temperatures by increasing production of female offspring and therefore, future fecundity. That buffered the negative effect of temperature on the population growth. TSD provides an evolutionary advantage to sea turtles. However, this mechanism was only effective over a range of temperatures and will become inefficient as temperatures rise to levels projected by current climate change models. Projected global warming threatens survival of sea turtles, and the IPCC high gas concentration scenario may result in extirpation of the studied population in 50 years.
Potential impact of large ungulate grazers on African vegetation, carbon storage and fire regimes
Authors: Pachzelt Adrian , Forrest Matthew , Rammig Anja , Higgins Steven I. , Hickler Thomas
Published: April 2015

Aim

Large ungulate grazers have been a fundamental component of African savannas since the spread of the savanna ecosystem in the Miocene. The magnitude of the impact of ungulates on vegetation has been debated for a long time, but quantifying such effects at the continental scale has been difficult. This study presents an attempt to estimate for the first time the potential impact of large natural ungulate grazer herds on African ecosystems.

Location

The African continent (excluding Madagascar).

Method

The potential impacts of grazing on grass biomass, competition between grasses and trees, the occurrence and effects of wildfire and biome distribution were simulated with a model that couples a physiological grazer population model with a physiological dynamic vegetation one (not including the effects of browsing). This model has previously been shown to reproduce grazer densities across African wildlife reserves.

Results

Modelled grazer densities corresponded reasonably well with the continental distribution of African grazers represented by the herbivore functional types in the model. The coupled model predicted a hump‐shaped relationship between annual precipitation and grazer biomass densities within a range of estimates from independent studies. In accordance with other studies, net primary productivity and the length of the dry season were the strongest predictors of grazer densities in the model. The inclusion of grazers in the model did not substantially alter an already (without grazers) reasonable fit between simulated vegetation biomass and burned area and estimates of these derived from remote sensing data. Nevertheless, the grazer–vegetation model predicted substantial impacts on grass biomass, tree biomass and burned area, particularly in areas with high grazer densities. The biome distribution at the continental scale, however, was similar with and without grazers.

Main conclusion

The results suggest that natural large ungulate grazers have been important drivers of ecosystem functioning in some savanna ecosystems, but also that they do not have a large effect on the continental‐scale biome distribution and carbon stocks.
A comparison of conventional and automatic milking system pasture utilization and pre‐ and post‐grazing pasture mass
Authors: Clark C. E. F. , Farina S. R. , Garcia S. C. , Islam M. R. , Kerrisk K. L. , Fulkerson W. J.
Published: April 2015

Automatic milking systems (AMS) present an opportunity for dairy farmers to not only improve their lifestyle and conditions of work, but also save on labour costs and/or increase the time available to focus on overall farm management. However, the viability of AMS will rely on achieving high levels of pasture utilization. Well‐established pasture management principles are implemented on many conventional milking system (CMS) farms and high levels of pasture utilization are achieved; however, the ability to follow these same principles on AMS is unknown. This study compared levels of pasture utilization and pre‐ and post‐grazing pasture mass between AMS and CMS farms at the same site when managed by the same pasture management principles. From 1 March 2007 to 29 February 2008, pre‐ and post‐grazing compressed height, milk yield and milk composition data were collected for two CMS farms and one AMS farm at the Elizabeth Macarthur Agricultural Institute, Camden, Australia. Despite differences in pre‐ and post‐ grazing pasture mass between milking systems, pre‐grazing mass was predominantly maintained within the bounds of 2200 and 2500 kg DM ha−1 and post‐grazing mass between 1400 and 1500 kg DM ha−1 (5–6 cm height). Similar levels of pasture utilization (mean 13 500 kg DM ha−1 year−1) were recorded between AMS and CMS farms. These findings highlight the ability to follow established grazing management principles and achieve high levels of pasture utilization on pasture‐based AMS farms.
Organized sports participation and the association with injury in paediatric patients with haemophilia
Authors: McGee S. , Raffini L. , Witmer C.
Published: April 2015

Introduction

With the wide availability of factor and the routine use of prophylaxis boys with haemophilia are now able to participate in regular physical activity, including organized sports. Current guidelines vary regarding specific recommendations for sports participation and concerns remain regarding safety.

Aim

To determine if participation in organized sports is associated with an increased risk for injury in paediatric subjects with haemophilia.

Methods

Retrospective single‐centre cohort study from January 1, 2008 to December 31, 2010 in male subjects ages 10–18 years with a factor VIII (FVIII) or FIX level <40%. The number of injuries per subject and participation in organized sports was recorded.

Results

48 male subjects with a mean age of 14.3 ± 2.6 years (range: 10–18.8) were included; 64.6% (31/48) FVIII deficiency, 54.2% (26/48) severe haemophilia, 18.8% (9/48) moderate and 27.1% (13/48) mild. The majority [62.5% (30/48)] of subjects participated in at least one season of organized sport. There were 77 injuries in 36/48 (75%) subjects. The mean number of injuries per subject was 1.6 ± 1.5. There was no statistical difference in the mean number of injuries (P = 0.44) or target joint formation (P = 0.52) between the subjects who participated in organized sports compared to those who did not.

Conclusion

In this study, participation in organized sports by boys with haemophilia, ages 10–18 years, is common and not associated with an increased number of injuries or the development of a target joint. As injuries occurred equally in both groups, concerted efforts should be directed at reducing injuries in all patients.
Workforce development and models of care in home hemodialysis
Authors: Mitra Sandip , Cress Cheryl , Goovaerts Tony
Published: April 2015

Creating and maintaining a successful home hemodialysis (HD) program is highly dependent on the workforce model and quality of staff. We describe the minimum staff required to start a home HD program (e.g., a clinical champion and lead nurse) and detail what additional workforce (e.g., renal technician, dietitian, psychologist, and others) may be necessary as the program evolves and expands. The goal of the program and allied staff should be to provide a seamless patient journey, a process that requires consideration of a patient recruitment strategy, a patient training pathway, thoughtful initiation of home HD, and development of support systems for routine care and emergencies at home. This module describes how care models are implemented at centers of excellence in various locations around the world, highlights the importance of an integrated care pathway, and describes workforce challenges that programs may encounter.
The Global Forum for Home Hemodialysis: a new open‐source practical manual
Authors: Marshall Mark R. , Chan Christopher T. ,   The Global Forum for Home Hemodialysis
Published: April 2015

Encouraging clinical outcomes from observational and randomized controlled data in the forms of frequent hemodialysis (HD) has renewed interest in home HD. However, given its benefits, home HD is relatively underutilized throughout the world. The Global Forum for Home Hemodialysis, an independent panel comprised of internationally recognized nephrologists, home HD nurses, administrators, patient advocates, and a long‐time home HD patient, has convened with the intention of creating an open‐source, comprehensive, practical manual that provides useful information to clinicians who are interested in implementing home HD.
Consent revisited: the impact of return of results on participants' views and expectations about trial participation
Authors: Tarrant Carolyn , Jackson Clare , Dixon‐Woods Mary , McNicol Sarah , Kenyon Sara , Armstrong Natalie
Published: April 2015

Background

Increasingly, the sharing of study results with participants is advocated as an element of good research practice. Yet little is known about how receiving the results of trials may impact on participants' perceptions of their original decision to consent.

Objective

We explored participants' views of their decision to consent to a clinical trial after they received results showing adverse outcomes in some arms of the trial.

Method

Semi‐structured interviews were conducted with a purposive sample of 38 women in the UK who participated in a trial of antibiotics in pregnancy. All had received results from a follow‐up study that reported increased risk of adverse outcomes for children of participants in some of the trial intervention arms. Data analysis was based on the constant comparative method.

Results

Participants' original decisions to consent to the trial had been based on hope of personal benefit and assumptions of safety. On receiving the results, most made sense of their experience in ways that enabled them to remain content with their decision to take part. But for some, the results provoked recognition that their original expectations might have been mistaken or that they had not understood the implications of their decision to participate. These participants experienced guilt, a sense of betrayal by the maternity staff and researchers involved in the trial, and damage to trust.

Conclusions

Sharing of study results is not a wholly benign practice, and requires careful development of suitable approaches for further evaluation before widespread adoption.
ESTIMATION OF DYNAMIC DISCRETE CHOICE MODELS BY MAXIMUM LIKELIHOOD AND THE SIMULATED METHOD OF MOMENTS
Authors: Eisenhauer Philipp , Heckman James J. , Mosso Stefano
Published: April 2015

We compare the performance of maximum likelihood (ML) and simulated method of moments (SMM) estimators for dynamic discrete choice models. We construct and estimate a simplified dynamic structural model of education that captures some basic features of educational choices in the United States in the 1980s and early 1990s. We use estimates from our model to simulate a synthetic data set and assess the ability of ML and SMM to recover the model parameters on this sample. We investigate the performance of alternative tuning parameters for SMM.
DOES IT PAY FOR WOMEN TO VOLUNTEER?
Authors: Sauer Robert M.
Published: April 2015

This article estimates the economic and noneconomic returns to volunteering for prime‐aged women. Estimates of a DCDP model indicate that an extra year of volunteer experience increases wage offers by 8.5% in future part‐time work and by 2.6% in future full‐time work. On average, working for free increases lifetime earnings by 16.7%. The economic returns to volunteering are more important than the noneconomic returns in increasing lifetime utility. The model also reveals an adverse selection mechanism into volunteering that helps explain why reduced‐form regressions of the returns to working for free will likely be downward biased.
Six mathematical gems from the history of distance geometry
Authors: Liberti Leo , Lavor Carlile
Published: April 2015

This is a partial account of the fascinating history of distance geometry. We make no claim to completeness, but we do promise a dazzling display of beautiful, elementary mathematics. We prove Heron's formula, Cauchy's theorem on the rigidity of polyhedra, Cayley's generalization of Heron's formula to higher dimensions, Menger's characterization of abstract semimetric spaces, a result of Gödel on metric spaces on the sphere, and Schoenberg's equivalence of distance and positive semidefinite matrices, which is at the basis of multidimensional scaling.
A simulation model of a coordinated decentralized supply chain
Authors: Cannella Salvatore , López‐Campos Mónica , Dominguez Roberto , Ashayeri Jalal , Miranda Pablo A.
Published: April 2015

This paper presents a simulation‐based study of a coordinated, decentralized linear supply chain (SC) system. In the proposed model, any supply tier considers its successors as part of its inventory system and generates replenishment orders on the basis of its partners’ operational information. We show that the proposed coordinated decision‐making process creates a reduction in information distortion along an SC compared with a traditional, noncoordinated strategy. A novel result is that we show how a coordinated SC can avoid the detrimental consequences of demand amplification in terms of penalty costs due to the stockout phenomenon in upstream stages.
The Differential Diagnosis of Dementia
Authors: Gershon Samuel , Herman Stephen P.
Published: April 2015

Contrary to prevailing medical belief, dementia is generally not caused by arteriosclerosis of cerebral vessels. There may be, in fact, as many as 50 different causes. While the two major types of dementia, Alzheimer's disease and multi‐infarct dementia, are irreversible, perhaps 20 per cent of dementias are secondary to treatable causes, and are reversible. The most important of these is the pseudodementia of depression, which can be easily missed without a high degree of suspicion. Tips on the differential diagnosis of Alzheimer's disease, multi‐infarct dementia, and pseudodementia are discussed, as are other causes of dementia secondary to various diseases or therapy.
Working Group Recommendations: Research on Content and Efficacy of Geriatric Evaluation and Management Interventions
Authors: Jahnigen Dennis W. , Applegate William B. , Cohen Harvey Jay , Epstein Arnold , Granger Carl , Hogan David , Kennedy Robert , Lazaroff Alan
Published: April 2015

Methods of conducting comprehensive geriatric evaluation and management (GEM) are proliferating in a variety of clinical settings. However, rigorous evaluations of efficacy for this new approach to care of older patients have demonstrated a favorable impact on patient outcome in only a few studies. All of these have been controlled single site studies, and replication is needed. If replication studies show similar results, further studies should be undertaken to define the minimum necessary intervention to achieve the desired outcome.

Controlled trials are needed to determine if consultative geriatric evaluation and/or primary patient management is effective. Further innovative work is needed in model development for geriatric assessment and management in outpatient settings. Finally, studies of geriatric evaluation and management in other environments, such as home care or the nursing home, are recommended.
Surface Crystallization and Water Diffusion of Silica Glass Fibers: Causes of Mechanical Strength Degradation
Authors: Lezzi Peter J. , Evke Erin E. , Aaldenberg Emily M. , Tomozawa Minoru
Published: April 2015

Pristine silica glass fiber is well‐known to become mechanically weaker when heat‐treated in air but the cause of such weakening is not presently known. The time dependence of mechanical degradation of various silica glass fibers containing varying impurity contents were studied in the range from 500°C to 1000°C. Two possible sources of strength degradation were considered: surface crystallization and water diffusion. Surface crystallization kinetics of silica glass fibers were investigated in a wide temperature range, including nanoscale surface nucleation at low temperatures via scanning electron microscopy. From the comparison of the strength degradation, surface crystallization, and water diffusion data in literature, it was concluded that surface crystallization may be responsible for the mechanical weakening observed in silica glass fiber surface during heat‐treatment at temperatures above ~800°C, whereas water diffusion into the glass surface may be responsible for the strength degradation at lower temperatures.
Human intrabony defect regeneration with rhFGF‐2 and hyaluronic acid – a randomized controlled clinical trial
Authors: de Santana Ronaldo Barcellos , de Santana Carolina Miller Mattos
Published: April 2015

Aim

The goal of this study was to evaluate if a biological hydrogel of recombinant human Fibroblast Growth Factor type 2 (rhFGF‐2) in a hyaluronic acid (HA) carrier applied in periodontal intrabony defects would enhance the clinical parameters of regeneration of the periodontal attachment apparatus

Materials and Methods

Thirty adult patients were evaluated. Two intrabony defects present in contra‐lateral quadrants in each patient were randomly allocated for each of the treatment methods employed. Control group (n = 30) were treated by open debridement with the papilla preservation flaps, while the test group (n = 30) also received a topical application of rhFGF‐2/HA in the intrabony defect. The parameters evaluated, at baseline and after one year, were, were probing depth (PD), gingival recession (REC), probing attachment level (PAL) and probing bone level (PBL). The primary outcome measures was PAL gain

Results

Test sites exhibited significantly more PD reduction (5.5 versus 2.9 mm), PAL gains (4.8 versus 2.2 mm) and shallower residual PD (4.2 versus 6.6 mm) than controls. Moreover, residual PD smaller than 5 mm (100 versus 0%) and PAL gain > 4 mm (60 versus 20%) was significantly more frequent in the test group

Conclusion

Application of rhFGF‐2/HA significantly improved clinical parameters of periodontal wound healing one year after treatment.
Stability of root coverage outcomes at single maxillary gingival recession with loss of interdental attachment: 3‐year extension results from a randomized, controlled, clinical trial
Authors: Cairo Francesco , Cortellini Pierpaolo , Tonetti Maurizio , Nieri Michele , Mervelt Jana , Pagavino Gabriella , Pini‐Prato Giovan Paolo
Published: April 2015

Background

The aim of this study was to assess the stability of root coverage outcomes 3 years after Connective Tissue Graft (CTG) plus Coronally Advanced Flap (CAF) or CAF alone at single maxillary gingival recession with minimal inter‐dental clinical attachment loss.

Material and Methods

Twenty‐four of the original 29 patients, 13 treated with CAF + CTG and 11 with CAF, were available for the 3‐year follow‐up. Measurements were performed by a blind and calibrated examiner. Outcome measures included complete root coverage (CRC), recession reduction (RecRed), Root coverage Esthetic Score (RES) and Keratinized Tissue (KT) Gain. Visual Analogue Scale (VAS) was used to evaluate patient satisfaction.

Results

After 3 years, CAF + CTG resulted in better outcomes in terms of CRC (p = 0.0054) than CAF alone. No difference was detected in terms of RecRed, RES score and VAS values. Furthermore, CAF + CTG was associated with higher KT gain than CAF at the last follow‐up (p < 0.0001).

Conclusion

Root coverage outcomes in single gingival recession with inter‐dental CAL loss are stable after 3 years. The application of CTG under CAF was associated with increased probability to obtain CRC than CAF alone at the final follow‐up.
Simulated environmental transport distances of Lepeophtheirus salmonis in Loch Linnhe, Scotland, for informing aquaculture area management structures
Authors: Salama N K G , Murray A G , Rabe B
Published: April 2015

In the majority of salmon farming countries, production occurs in zones where practices are coordinated to manage disease agents such as Lepeophtheirus salmonis. To inform the structure of zones in specific systems, models have been developed accounting for parasite biology and system hydrodynamics. These models provide individual system farm relationships, and as such, it may be beneficial to produce more generalized principles for informing structures. Here, we use six different forcing scenarios to provide simulations from a previously described model of the Loch Linnhe system, Scotland, to assess the maximum dispersal distance of lice particles released from 12 sites transported over 19 day. Results indicate that the median distance travelled is 6.1 km from release site with <2.5% transported beyond 15 km, which occurs from particles originating from half of the release sites, with an absolute simulated distance of 36 km observed. This provides information suggesting that the disease management areas developed for infectious salmon anaemia control may also have properties appropriate for salmon lice management in Scottish coastal waters. Additionally, general numerical descriptors of the simulated relative lice abundance reduction with increased distance from release location are proposed.
A central role for the acid sphingomyelinase/ceramide system in neurogenesis and major depression
Authors: Gulbins Erich , Walter Silke , Becker Katrin Anne , Halmer Ramona , Liu Yang , Reichel Martin , Edwards Michael J. , Müller Christian P. , Fassbender Klaus , Kornhuber Johannes
Published: April 2015

Major depressive disorder is a severe and chronic illness with high lifetime prevalence and a high incidence of suicide as the cause of death for patients with this diagnosis. Major depressive disorder is often treated with anti‐depressants. Although these drugs have been used for many years, their exact mode of action is still unknown. It has been suggested that many anti‐depressants act by increasing the concentrations of serotonergic transmitters in the synaptic space. However, recent studies have examined the effects of anti‐depressants on neurogenesis in the hippocampus, the restoration of hippocampal neuronal networks that may be affected by major depression, and the regulation of the hypothalamic–pituitary–adrenal axis by immature neurons in the hippocampus. Here, we present and discuss a novel hypothesis suggesting that these events are regulated by the concentrations of sphingolipids, in particular ceramide, in the hippocampus. These concepts suggest that the acid sphingomyelinase/ceramide system plays a central role in the pathogenesis of major depression and may be a novel target for anti‐depressants.

image

Major depressive disorder is a severe and chronic illness with high lifetime prevalence and high incidence of suicide. Major depression is caused in part by an imbalance between factors that positively and negatively control neurogenesis. Anti‐depressants inhibit the acid sphingomyelinase/ceramide system and thereby reduce the sum of negative factors restoring neurogenesis, neuronal survival, and improved mood.
Revisiting theIberian honey bee (Apis mellifera iberiensis) contact zone: maternal and genome‐wide nuclear variations provide support for secondary contact from historical refugia
Authors: Chávez‐Galarza Julio , Henriques Dora , Johnston J. Spencer , Carneiro Miguel , Rufino José , Patton John C. , Pinto M. Alice
Published: April 2015

Dissecting diversity patterns of organisms endemic to Iberia has been truly challenging for a variety of taxa, and the Iberian honey bee is no exception. Surveys of genetic variation in the Iberian honey bee are among the most extensive for any honey bee subspecies. From these, differential and complex patterns of diversity have emerged, which have yet to be fully resolved. Here, we used a genome‐wide data set of 309 neutrally tested single nucleotide polymorphisms (SNPs), scattered across the 16 honey bee chromosomes, which were genotyped in 711 haploid males. These SNPs were analysed along with an intergenic locus of the mtDNA, to reveal historical patterns of population structure across the entire range of the Iberian honey bee. Overall, patterns of population structure inferred from nuclear loci by multiple clustering approaches and geographic cline analysis were consistent with two major clusters forming a well‐defined cline that bisects Iberia along a northeastern–southwestern axis, a pattern that remarkably parallels that of the mtDNA. While a mechanism of primary intergradation or isolation by distance could explain the observed clinal variation, our results are more consistent with an alternative model of secondary contact between divergent populations previously isolated in glacial refugia, as proposed for a growing list of other Iberian taxa. Despite current intense honey bee management, human‐mediated processes have seemingly played a minor role in shaping Iberian honey bee genetic structure. This study highlights the complexity of the Iberian honey bee patterns and reinforces the importance of Iberia as a reservoir ofApis melliferadiversity.
NextGen nuclear DNA sequencing in cyclic vomiting syndrome reveals a significant association with the stress‐induced calcium channel (RYR2)
Authors: Lee J. , Wong S. A. , Li B. U. K. , Boles R. G.
Published: April 2015

Background

Cyclic vomiting syndrome (CVS) is a common, frequently disabling, ‘functional’ condition characterized by recurring, stereotypical attacks of intense nausea, vomiting, and lethargy, with the essential absence of these symptoms between episodes. Although the pathogenesis of CVS is yet unexplained, evidence has accumulated which suggest pathogenic roles for stress‐related, autonomic, neuroendocrine, and mitochondrial factors. The objective of this pilot study was to elucidate mechanism(s) by identifying genes involved in the presumed multifactorial pathogenesis of CVS.

Methods

In this pilot study, DNA from 75 unrelated CVS cases and 60 healthy controls were assayed by Courtagen Life Science's next‐generation sequencing platform (nucSEEK™), including over 1100 nuclear‐encoded genes involved with mitochondria, metabolism, or ion channels. Significant sequence variants were defined as evolutionary conservation at least to Xenopus (frog) per the UCSC Genome Browser.

Key Results

The RYR2 gene, encoding a stress‐induced calcium channel present in many neurons, was the only gene demonstrating a statistically significant difference in the proportion of conserved sequence variants among the groups (18/75 CVS, 24%, vs 3/60 controls, 5%; p = 0.0018, OR = 6.0, 95% CI = 1.7–22).

Conclusions & Inferences

We propose a mechanism in which RYR2 sequence variants result in aberrant stress‐induced calcium release into the mitochondria of autonomic neurons, resulting in an increased risk to develop autonomic/functional disease such as CVS, and related conditions such as migraine and gut dysmotility. This model incorporates the existing hypotheses regarding CVS pathogenesis into a cohesive mechanism, and might have treatment implications.
Toll‐like receptor signaling in primary immune deficiencies
Authors: Maglione Paul J. , Simchoni Noa , Cunningham‐Rundles Charlotte
Published: April 2015

Toll‐like receptors (TLRs) recognize common microbial or host‐derived macromolecules and have important roles in early activation of the immune system. Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins to the human immune system. Defects in interleukin‐1 receptor‐associated kinase‐4 and myeloid differentiation factor 88 (MyD88) lead to susceptibility to infections with bacteria, while mutations in nuclear factor‐κB essential modulator (NEMO) and other downstream mediators generally induce broader susceptibility to bacteria, viruses, and fungi. In contrast, TLR3 signaling defects are specific for susceptibility to herpes simplex virus type 1 encephalitis. Other PIDs induce functional alterations of TLR signaling pathways, such as common variable immunodeficiency in which plasmacytoid dendritic cell defects enhance defective responses of B cells to shared TLR agonists. Dampening of TLR responses is seen for TLRs 2 and 4 in chronic granulomatous disease (CGD) and X‐linked agammaglobulinemia (XLA). Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome, and for most TLRs in adenosine deaminase deficiency.
A developmental switch between fetal and adult B lymphopoiesis
Authors: Li Yue‐Sheng , Zhou Yan , Tang Lingjuan , Shinton Susan A. , Hayakawa Kyoko , Hardy Richard R.
Published: April 2015

Fluorescence‐activated cell sorting (FACS)–purified pro‐B cells from fetal liver and adult bone marrow generate B cells with distinct phenotypes: fetal cells generate few IgDhigh B cells and half express CD5, whereas adult cells generate mostly IgDhigh cells and few express CD5. These results led us to propose a model of a developmental switch in B lymphopoiesis, similar to the well‐known switch in fetal to adult erythropoiesis. More recent global analysis of mRNA and microRNA expression comparing these two types of pro‐B cells revealed differential expression of Lin28b and microRNAs from the Let‐7 family, indicating that this regulatory axis plays a role in the switch. Further analysis has provided data supporting this model, implicating Arid3a as a key transcription factor in mediating fetal‐type B cell development. Function of this regulatory axis in human B lineage precursors may also explain the predominance of CD5+ B cells in cord blood. We suggest that Lin28b‐promoted B cell development generates many cells expressing CD5 as a consequence of positively selected self‐reactivity. While such cells serve a useful role in clearance of senescent cells and in certain immune responses, they also carry the risk of progression to leukemia/lymphoma later in life.
The Land Question in Amazonia: Cadastral Knowledge and Ignorance in Brazil's Tenure Regularization Program
Authors: Campbell Jeremy M.
Published: April 2015

In the Brazilian Amazon, a questão fundiária (the land question) has been asked and answered in a variety of ways since the region was opened up to large‐scale migration and development projects in the 1960s. The question of who is entitled to land and under what conditions is at the heart of most debates concerning the region's future, but recent attempts to reform and simplify rural land tenure in Amazonia confront a history of contradictory land‐use policies and a legacy of impunity. In response to economic and demographic pressures, the Brazilian state aims to combat the illicit occupation, sale, and transformation of lands. This article presents an ethnographic approach to the land question in Amazonia by studying the knowledge‐making practices associated with the Programa Terra Legal (Legal Land Program), Brazil's effort to create a cadastral registry for rural holdings in the region. It argues that tenure regularization dedicated to securing smallholders’ rights and to instituting environmental regulations is being used by rural elites as a mechanism to accumulate land and power. By showing how a reform program gets remade in the thrall of local interests and vernacular dispositions of property, this article reveals how knowledge both illuminates and obscures subjects of governance.
Soft Transport Policies and Ground‐Level Ozone: An Evaluation of the “Clear the Air Challenge” in Salt Lake City
Authors: Teague William Seth , Zick Cathleen D. , Smith Ken R.
Published: April 2015

In recent years, communities have begun to implement both “soft” and mandatory policies designed to address worsening air quality. Voluntary or soft transportation policies have included air quality alert systems that encourage people not to drive on days when the air quality index is above a specified threshold and public education/action campaigns that focus on reducing automobile related travel. In this article, we evaluate the effectiveness of one such soft policy, the Clear the Air Challenge (CAC), in reducing ground‐level ozone during the Wasatch Front's summer ozone season. Using daily ozone data and color‐coded daily air quality designations from 2006 through 2012, we estimate a range of nonequivalent control group models. In only one of the models does the CAC generate a statistically significant but small reduction in ground‐level ozone. Future research should assess the full range of costs and benefits to the public associated with such soft transport policies.
Impact of prolonged sitting on lower and upper limb micro‐ and macrovascular dilator function
Authors: Restaino Robert M. , Holwerda Seth W. , Credeur Daniel P. , Fadel Paul J. , Padilla Jaume
Published: April 2015

New Findings

What is the central question of this study?

The prevalence of sedentary behaviour in the workplace and increased daily sitting time have been associated with the development of cardiovascular disease; however, studies investigating the impact of sitting on vascular function remain limited.

What is the main finding and its importance?

We demonstrate that there is a marked vulnerability of the vasculature in the lower and upper limbs to prolonged sitting and highlight the importance of physical activity in restoring vascular function in a limb‐specific manner.

Sedentary behaviour in the workplace and increased daily sitting time are on the rise; however, studies investigating the impact of sitting on vascular function remain limited. Herein, we hypothesized that 6 h of uninterrupted sitting would impair limb micro‐ and macrovascular dilator function and that this impairment could be improved with a bout of walking. Resting blood flow, reactive hyperaemia to 5 min cuff occlusion (microvascular reactivity) and associated flow‐mediated dilatation (FMD; macrovascular reactivity) were assessed in popliteal and brachial arteries of young men at baseline (Pre Sit) and after 6 h of uninterrupted sitting (Post Sit). Measures were then repeated after a 10 min walk (∼1000 steps). Sitting resulted in a marked reduction of resting popliteal artery mean blood flow and mean shear rate (6 h mean shear rate, −52 ± 8 s−1 versus Pre Sit, P < 0.05). Interestingly, reductions were also found in the brachial artery (6 h mean shear rate, −169 ± 41 s−1 versus Pre Sit, P < 0.05). Likewise, after 6 h of sitting, cuff‐induced reactive hyperaemia was reduced in both the lower leg (−43 ± 7% versus Pre Sit, P < 0.05) and forearm (−31 ± 11% versus Pre Sit, P < 0.05). In contrast, popliteal but not brachial artery FMD was blunted with sitting. Notably, lower leg reactive hyperaemia and FMD were restored after walking. Collectively, these data suggest that prolonged sitting markedly reduces lower leg micro‐ and macrovascular dilator function, but these impairments can be fully normalized with a short bout of walking. In contrast, upper arm microvascular reactivity is selectively impaired with prolonged sitting, and walking does not influence this effect.
Reversing motor adaptation deficits in the ageing brain using non‐invasive stimulation
Authors: Panouillères Muriel T. N. , Joundi Raed A. , Brittain John‐Stuart , Jenkinson Ned
Published: April 2015

Key points

Healthy ageing in man is associated with a decline in motor adaptation.

Transcranial direct current stimulation (TDCS) over the primary motor cortex (M1) or the lateral cerebellum can improve motor adaptation in young and older adults, but as yet no direct comparisons of TDCS effects exist between the two age groups and the two stimulation sites.

TDCS over M1 enhanced the motor adaptation in both age groups by ∼30% relative to their respective non‐stimulated groups and improved the performance of older adults to the extent that it compared with that of young adults without stimulation.

The study suggests that the plastic mechanisms activated by TDCS that underpin improvements in motor behaviour in young adults remain available in older adults.

The results indicate that TDCS may be a useful tool to help combat the normal decline in motor performance seen in normal healthy ageing.

Healthy ageing is characterised by deterioration of motor performance. In normal circumstances motor adaptation corrects for movements’ inaccuracies and as such, it is critical in maintaining optimal motor control. However, motor adaptation performance is also known to decline with age. Anodal transcranial direct current stimulation (TDCS) of the cerebellum and the primary motor cortex (M1) have been found to improve visuomotor adaptation in healthy young and older adults. However, no study has directly compared the effect of TDCS on motor adaptation between the two age populations. The aim of our study was to investigate whether the application of anodal TDCS over the lateral cerebellum and M1 affected motor adaptation in young and older adults similarly. Young and older participants performed a visuomotor rotation task and concurrently received TDCS over the left M1, the right cerebellum or received sham stimulation. Our results replicated the finding that older adults are impaired compared to the young adults in visuomotor adaptation. At the end of the adaptation session, older adults displayed a larger error (−17 deg) than the young adults (−10 deg). The stimulation of the lateral cerebellum did not change the adaptation in both age groups. In contrast, anodal TDCS over M1 improved initial adaptation in both age groups by around 30% compared to sham and this improvement lasted up to 40 min after the end of the stimulation. These results demonstrate that TDCS of M1 can enhance visuomotor adaptation, via mechanisms that remain available in the ageing population.
Visualization of Multiscale Processes - Bubble Dynamics in Surface Active Colloids
Authors: Manoharan S. , Kalaikadal D. , Manglik R. M. , Iskrenova-Ekiert E. , Patnaik S. S.
Published: April 2015

The growth dynamics of isolated gas bubbles from a submerged capillary-tube orifice in a pool of aqueous solution of Cetyl Trimethyl Ammonium Bromide (CTAB) was studied by multi-scale modeling. The macro-scale bubble ebullience is controlled by the molecular scale surfactant adsorption/desorption on the liquid-gas interface. Molecular dynamics simulations were carried out to predict the interfacial adsorption/desorption kinetics. The results of the molecular dynamics simulations were input to the volume-of-fluid based macro-scale computations. The size and shape of bubbles from incipience to departure were measured using high speed videography for model validation. Predictions of the multi-scale model agree with the experimental measurements of bubble size evolution and bubble diameter at departure. The surfactant mass transfer and adsorption on the liquid gas interface gives rise to dynamic surface tension. As a result of the surfactant presence, the bubble departure diameters were smaller in CTAB solution compared to pure water. Furthermore, dynamic surface tension behavior of CTAB makes the bubble departure diameter a function of bubble Reynolds number (Re based on the orifice diameter and air flow rate). At low flow rates or low Re, the bubble departure diameters are smaller than those in water. As the air flow rate increases, the bubble departure diameters tend towards those in pure water. The authors gratefully acknowledge funding from AFOSR Thermal Science Program and AFRL DoD Supercomputing Resource Center for computing time and resources.
Gas-Turbine, Extended-Surface, Heat Exchanger: Modern Design and Performance
Authors: Howitt I. , Thurner R. P.
Published: April 2015

The gas turbine-regenerator design being offered by the authors’ companies is a result of fifteen years of activity in this field. Design modifications as well as surface configuration changes have been made to keep pace with the dictates of field experiences. These changes are considered with special emphasis on field performance and problem areas that have resulted in a redesign of the heat exchanger.
Combustion-System Design for Industrial Gas Turbines
Authors: Strong R. E. , Hussey C. E.
Published: April 2015

Some of the problems encountered in combustion-system design are discussed with particular attention to combustor discharge-temperature patterns. The results of extensive laboratory and field tests that culminated in improved temperature patterns are presented.
Design and Test of a Large Two-Shaft Gas Turbine
Authors: Starkey N. E. , Gilbert K. E.
Published: April 2015

The largest two-shaft gas turbine in the United States has been operated in combined cycle service at the Oklahoma Gas and Electric Company Horseshoe Lake Station since May 1963. The same design unit has been operated in peaking and stand-by service at Public Service Electric and Gas (Essex, N. J.) station since December 1963. The O.G & E. unit has a NEMA rating of 25 Mw base load. The PSEG unit has a NEMA peaking rating of 29 Mw. The paper describes the design features of this unit and a method of testing the high-pressure set and variable second-stage nozzle under full-load conditions without actually loading the load turbine.
A 31/42 Mw Gas Turbine for Power Generation
Authors: Congiu A.
Published: April 2015

This paper presents a 37/42 Mw compound open-cycle-type TG3000 gas turbine, designed by the author’s company, which is one of the most powerful gas turbines ever built and in industrial operation. The first unit started industrial operation in September 1962 in Italy at Chivasso Power Plant; three more units, destined for a power plant in Belgrade, are being bench-tested or under assembly. The paper illustrates the considerations which led the author’s company to choose the power and the cycle arrangement of the gas turbine, the main construction and design features of the single components as well as the initial operating results.