bluuebunny/crossref_metadata_2025 huggingface dataset:
Green Service: Construct Development and Measurement Validation
Authors: Chan Ting‐Yan , Wong Christina W. Y. , Lai Kee‐Hung , Lun Venus Y. H. , Ng Chi To , Ngai Eric W. T.
Published: June 2015

Facing the growing concern of environmental impact, green service (GS) has emerged as an important research topic in production and operations management. However, empirical research on GS is hindered by the lack of theoretically developed and empirically validated measurement scales covering various practices in service operations of a supply chain. GS indicates the strategic orientation of firms in developing a combination of practices and routines to reduce environmental impact in service operations that span from product development to servicing customers. Grounded in the natural resource‐based view (NRBV), this study conceptualizes GS from the supply chain perspective and in the consumer‐product context to develop a GS measurement model. Collecting secondary and primary data in both qualitative and quantitative forms, this study reports the development of GS multi‐item measurement scales using a multi‐method research design that combines interviews, content analysis, and mass survey. GS is operationalized as a multi‐dimensional construct reflecting three complementary dimensions, namely pollution prevention‐, product‐, and long‐term development‐oriented GS practices, where each of them comprises three sub‐dimensions, resulting in a total of 34 measurement items. The empirically validated scales can be used to advance theory and practices of GS, while providing a useful reference for firms to evaluate their GS efforts, and identify areas for improvement.
Economic Manufacturing Quantity and Its Integrating Implications
Authors: Moily Jaya P.
Published: June 2015

Several contradictions are noted among the Economic Order Quantity (EOQ), Just‐In‐Time (JIT), and Optimized Production Technology (OPT) approaches and the economic framework for profit maximization. A fundamental model referred to as the Economic Manufacturing Quantity (EMO) is developed and examined for its integrating implications for the three approaches. An implication for the classic EOQ approach is that the balance between setup and inventory carrying costs is valid when a production facility is operating at or below a certain critical level but not when operating above that level. An implication for the JIT approach is that one must reduce setup cost at non‐bottlenecks and setup time at bottlenecks to reduce inventory. An implication for the OPT approach is that trade‐offs between setup and inventory carrying costs may indeed be ignored while determining process batch sizes, provided each facility in a production system is operating at or above Its critical level. Economic theoretic analysis of the EMO model provides a basis for unification of JIT which advocates stability in operating level as a key to improved productivity and quality, and OPT that advocates maximizing operating level with resultant emphasis on bottlenecks as a key to increased profits. This unifying basis states that a profit‐maximizing production facility or system will operate at the full and stable level as long as market demand remains relatively sensitive to price and operating at the full (maximum) level provides positive unit contribution.
Eukaryotic picophytoplankton community response to copper enrichment in a metal‐perturbed coastal environment
Authors: Henríquez‐Castillo Carlos , Rodríguez‐Marconi Susana , Rubio Francisca , Trefault Nicole , Andrade Santiago , De la Iglesia Rodrigo
Published: June 2015

Copper is an essential micronutrient, especially for photosynthetic organisms, but can be toxic at high concentrations. In the past years, coastal waters have been exposed to an increase in copper concentration due to anthropogenic inputs. One well known case is the Chañaral area (Easter South Pacific coast), where a long term coastal copper enrichment event has occurred. That event strongly affected benthic marine diversity, including microbial communities. In this work, microcosm experiments were carried out to address the changes on picophytoplankton community composition of the disturbed area, when challenged to copper additions. Eukaryotic picophytoplankton communities from two areas were analyzed: one in the most copper‐perturbed area and another at the north edge of the perturbed area. Flow cytometry data showed that 25 μg L−1 of copper addition exerted a positive effect in the growth kinetics on part of the eukaryotic picophytoplankton communities, independently of the site. 16S‐plastid terminal restriction fragment length polymorphisms analysis suggested that eukaryotic picophytoplankton display a short and directional response to high copper levels. Members of the Prasinophyceae class, a Coscinodiscophyceae diatom, as well as Phaeocystis, respond in a short time to the environmental disturbance, making them excellent candidates for further studies to evaluate phytoplanktonic species as sentinels for copper disturbances in coastal marine ecosystems.
Gauging the Effects of Social Accountability on Services, Governance, and Citizen Empowerment
Authors: Brinkerhoff Derick W. , Wetterberg Anna
Published: June 2015

Engaging citizens in holding public officials and service providers accountable, referred to as social accountability, is a popular remedy for public sector performance weaknesses, figuring prominently in many international donor‐funded projects and leading to widespread replication. However, the contextual factors that influence the successful transfer of social accountability are debated. Demand‐side factors (civil society and citizens) are overemphasized in much of the literature. Yet supply‐side factors (state structures and processes) and the nature of state–society relations are also important. This article examines four projects in developing countries to explore how these contextual factors influenced social accountability aims and outcomes. The salience of supply factors in enabling social accountability for service delivery and government performance stands out, particularly the degree of decentralization and the availability of space for citizen engagement. The capacity and motivation of citizens to occupy the available space, aggregate and voice their concerns, and participate with state actors in assessing service delivery performance and problems are critical.
Comparison of in vivo probe‐based confocal laser endomicroscopy with histopathology in lung cancer: A move toward optical biopsy
Authors: Wellikoff Adam S. , Holladay Robert C. , Downie Gordon H. , Chaudoir Catherine S. , Brandi Luis , Turbat‐Herrera Elba A.
Published: June 2015

Background and objective

The development of novel technologies has increased the yield from transbronchial biopsies while preserving patient safety by guiding biopsies to the area of interest. Other technologies have helped identify pre‐cancerous or sessile lesions in the endobronchial space by utilizing interactions between tissue and light at varying wavelengths. Probe‐based confocal laser endomicroscopy (pCLE) is a new technology that encompasses the benefits of both guided biopsies and novel optical imaging in one device. This project compares pCLE images to the findings of light microscopy in non‐small cell lung cancer (NSCLC).

Methods

Patients who underwent bronchoscopies between July 2012 and January 2013 for evaluation of pulmonary lesions (transbronchial and endobronchial) were recruited. Histopathological images from malignant lesions were compared with the pCLE images obtained from the same area. The microscopic and pCLE images were reviewed side by side with the microscopic findings.

Results

Images from pCLE correlate with some histopathological findings. pCLE changes seen in NSCLC consist of mottled elastin, septal studding and disorganization/fragmentation with increased friability. These changes also seem to correlate with degrees of differentiation.

Conclusions

pCLE can identify changes to the elastin composition of the airways and alveoli in lung cancer. These changes correlate with histopathology and may help indicate the presence of malignant changes in vivo.
Application of the World Health Organization Programmatic Assessment Tool for Risk of Measles Virus Transmission—Lessons Learned from a Measles Outbreak in Senegal
Authors: Harris Jennifer B. , Badiane Ousseynou , Lam Eugene , Nicholson Jennifer , Oumar Ba Ibrahim , Diallo Aliou , Fall Amadou , Masresha Balcha G. , Goodson James L.
Published: June 2015

The World Health Organization (WHO) African Region set a goal for regional measles elimination by 2020; however, regional measles incidence was 125/1,000,000 in 2012. To support elimination efforts, the WHO and U.S. Centers for Disease Control and Prevention developed a tool to assess performance of measles control activities and identify high‐risk areas at the subnational level. The tool uses routinely collected data to generate district‐level risk scores across four categories: population immunity, surveillance quality, program performance, and threat assessment. To pilot test this tool, we used retrospective data from 2006 to 2008 to identify high‐risk districts in Senegal; results were compared with measles case‐based surveillance data from 2009 when Senegal experienced a large measles outbreak. Seventeen (25%) of 69 districts in Senegal were classified as high or very high risk. The tool highlighted how each of the four categories contributed to the total risk scores for high or very high risk districts. Measles case‐based surveillance reported 986 cases during 2009, including 368 laboratory‐confirmed, 540 epidemiologically linked, and 78 clinically compatible cases. The seven districts with the highest numbers of laboratory‐confirmed or epidemiologically linked cases were within the capital region of Dakar. All except one of these seven districts were estimated to be high or very high risk, suggesting that districts identified as high risk by the tool have the potential for measles outbreaks. Prospective use of this tool is recommended to help immunization and surveillance program managers identify high‐risk areas in which to strengthen specific programmatic weaknesses and mitigate risk for potential measles outbreaks.
Dimensionality of stress experiences: Factorial structure of the Perceived Stress Questionnaire (PSQ) in a population‐based Swedish sample
Authors: Rönnlund Michael , Vestergren Peter , Stenling Andreas , Nilsson Lars‐Göran , Bergdahl Maud , Bergdahl Jan
Published: June 2015

We investigated the factorial structure of the Perceived Stress Questionnaire (PSQ‐recent; Levenstein, Prantera, Varvo et al., 1993) in a large (N = 1516; 35–95 years) population‐based Swedish sample (Nilsson, Adolfsson, Bäckman et al., 2004; Nilsson, Bäckman, Erngrund et al., 1997). Exploratory principal components analysis (PCA) was conducted on a first, randomly drawn subsample (n = 506). Next, the model based on the PCA was tested in a second sample (n = 505). Finally, a third sample (n = 505) was used to cross‐validate the model. Five components were extracted in the PCA (eigenvalue > 1) and labeled “Demands,” “Worries/Tension,” “Lack of joy,” “Conflict,” and “Fatigue,” respectively. Twenty‐one out of the 30 original PSQ items were retained in a confirmatory factor analysis (CFA) model that included the five (first‐order) factors and, additionally, a general (second‐order) stress factor, not considered in prior models. The model showed reasonable goodness of fit [χ2(184) = 511.2, p < 0.001; CFI = 0.904; RMSEA = 0.059; and SRMR = 0.063]. Multigroup confirmatory factor analyses supported the validity of the established model. The results are discussed in relation to prior investigations of the factorial structure of the PSQ.
Antisocial behavior reduces the association between subdimensions of ADHDsymptoms and alcohol use in a large population‐based sample of adolescents
Authors: Lövenhag Sara , Larm Peter , Åslund Cecilia , Nilsson Kent W.
Published: June 2015

The aim of this study was to investigate possible effects of antisocial behavior on reducing the association between subdimensions ofADHDsymptoms (inattention, hyperactivity and impulsivity) and alcohol use. Boys and girls were analyzed separately using a population‐based Swedish adolescent sample. A randomly selected cross‐sectional survey was performed in secondary and upper secondary schools in Västmanland County during 2010. Participants were a population of 2,439 15–16 year‐olds and 1,425 17–18 year‐olds (1,947 girls and 1,917 boys). Psychosocial adversity, antisocial behaviors, symptoms ofADHDand alcohol use were assessed by questionnaires. Except for girls' inattention, subdimensions ofADHDsymptoms were not associated with alcohol use when variance due to antisocial behavior was accounted for. Among boys, instead of an indirect effect of antisocial behavior on the association between impulsivity and alcohol use, a moderating effect was found. Among girls, the inattention component ofADHDwas independently associated with alcohol use even when adjusted for antisocial behavior. The reduced associations between symptoms of hyperactivity, impulsivity, and alcohol use for boys and girls after adjusting for antisocial behavior suggest a considerable overlap between hyperactivity, impulsivity, and antisocial behavior. The direct pathway between inattention and alcohol use among girls suggests that girls with inattention symptoms are at risk of alcohol use regardless of antisocial behavior. Special attention should be given to these girls. Accounting for antisocial behavior reduced the relation between subdimensions ofADHDsymptoms and alcohol use, and antisocial behaviors should therefore be screened for when symptoms ofADHDare present.
Asymmetric Behaviour of Inflation around the Target in Inflation‐Targeting Countries
Authors: Akdoğan Kurmaş
Published: June 2015

We explore the asymmetric behaviour of inflation around the target level for inflation‐targeting countries. The first rationale behind this asymmetry is the asymmetric policy response of the central bank around the target. Central banks could have a stronger bias towards overshooting rather than undershooting the inflation target. Consequently, the policy response would be stronger once the inflation jumps above the target, compared to a negative deviation. Second rationale is the asymmetric inflation persistence. We suggest that recently developed Asymmetric Exponential Smooth Transition Autoregressive (AESTAR) model provides a convenient framework to capture the asymmetric behaviour of inflation driven by these two effects. We further conduct an out‐of‐sample forecasting exercise and show that the predictive power ofAESTARmodel for inflation is high for some countries in our sample, especially at long‐horizons.
Superiority in English and German: Cross‐Language Grammatical Differences?
Authors: Häussler Jana , Grant Margaret , Fanselow Gisbert , Frazier Lyn
Published: June 2015

Do the grammars of English and German contain a ban on moving the lower of two wh‐phrases (Superiority), or is the lower acceptability due simply to the complexity of processing the longer dependency that results when the lower wh‐phrase is moved? The results of four acceptability‐judgment studies suggest that a pure processing account is inadequate. Crossing wh‐dependencies lower the acceptability of both German and English questions but with a significantly larger penalty in English than in German (experiment 1). The larger penalty in English cannot be attributed to greater sensitivity to violations in English, because relative clause island violations result in similar effects in the two languages (experiment 2). A pure processing account might claim long dependencies are easier to process in German than in English because of richer case, but a control experiment did not support this possibility (experiment 4). We suggest that moving the lower of two wh‐phrases is banned in the grammar of English but not in the grammar of German. This predicts that there should be a penalty for crossing dependencies in English even in helpful (Bolinger) contexts, as confirmed in experiment 3, and even in short easy‐to‐process sentences, as confirmed by simple six‐word sentences in Clifton, Fanselow & Frazier 2006. Finally, if German grammar does not contain a ban on crossing, it is not surprising that the penalty in German is smaller than in English or that like animacy of the two wh‐phrases plays a larger role in German than in English because feature similarity generally gives rise to difficulty in processing, whereas in English a grammatical ban on crossing will reduce acceptability regardless of whether there is processing difficulty.
A metamorphic perspective on foreland flexure during intraplate orogeny: evidence for the involvement of weak lithosphere
Authors: Walsh Alec K. , Hand Martin , Kelsey David E.
Published: June 2015

Constraining depth–temperature conditions of syn‐orogenic burial metamorphism of syn‐orogenic sediments in a foreland basin provides an innovative way to investigate the thermomechanical state of the lithosphere. In central Australia, major intraplate deformation resulted in 10 km of syn‐orogenic sedimentation in a basin approximately 70 km wide. The deep level of burial in the foreland of the intraplate orogen requires the involvement of weak lithosphere with an elastic thickness of ≤20 km. The profound flexural response of the foreland region indicates that major intraplate deformation in central Australia was localised into a region of dramatically weakened lithosphere.
Readiness of Ugandan health services for the management of outpatients with chronic diseases
Authors: Katende David , Mutungi Gerald , Baisley Kathy , Biraro Samuel , Ikoona Eric , Peck Robert , Smeeth Liam , Hayes Richard , Munderi Paula , Grosskurth Heiner
Published: June 2015

Objective

Traditionally, health systems in sub‐Saharan Africa have focused on acute conditions. Few data exist on the readiness of African health facilities (HFs) to address the growing burden of chronic diseases (CDs), specifically chronic, non‐communicable diseases (NCDs).

Methods

A stratified random sample of 28 urban and rural Ugandan HFs was surveyed to document the burden of selected CDs by analysing the service statistics, service availability and service readiness using a modified WHO Service Availability and Readiness Assessment questionnaire. Knowledge, skills and practice in the management of CDs of 222 health workers were assessed through a self‐completed questionnaire.

Results

Among adult outpatient visits at hospitals, 33% were for CDs including HIV vs. 14% and 4% at medium‐sized and small health centres, respectively. Many HFs lacked guidelines, diagnostic equipment and essential medicines for the primary management of CDs; training and reporting systems were weak. Lower‐level facilities routinely referred patients with hypertension and diabetes. HIV services accounted for most CD visits and were stronger than NCD services. Systems were weaker in lower‐level HFs. Non‐doctor clinicians and nurses lacked knowledge and experience in NCD care.

Conclusion

Compared with higher level HFs, lower‐level ones are less prepared and little used for CD care. Health systems in Uganda, particularly lower‐level HFs, urgently need improvement in managing common NCDs to cope with the growing burden. This should include the provision of standard guidelines, essential diagnostic equipment and drugs, training of health workers, supportive supervision and improved referral systems. Substantially better HIV basic service readiness demonstrates that improved NCD care is feasible.
PAY1 improves plant architecture and enhances grain yield in rice
Authors: Zhao Lei , Tan Lubin , Zhu Zuofeng , Xiao Langtao , Xie Daoxin , Sun Chuanqing
Published: June 2015

Plant architecture, a complex of the important agronomic traits that determine grain yield, is a primary target of artificial selection of rice domestication and improvement. Some important genes affecting plant architecture and grain yield have been isolated and characterized in recent decades; however, their underlying mechanism remains to be elucidated. Here, we report genetic identification and functional analysis of the PLANT ARCHITECTURE AND YIELD 1 (PAY1) gene in rice, which affects plant architecture and grain yield in rice. Transgenic plants over‐expressing PAY1 had twice the number of grains per panicle and consequently produced nearly 38% more grain yield per plant than control plants. Mechanistically, PAY1 could improve plant architecture via affecting polar auxin transport activity and altering endogenous indole‐3‐acetic acid distribution. Furthermore, introgression of PAY1 into elite rice cultivars, using marker‐assisted background selection, dramatically increased grain yield compared with the recipient parents. Overall, these results demonstrated that PAY1 could be a new beneficial genetic resource for shaping ideal plant architecture and breeding high‐yielding rice varieties.
Arabidopsis dynamin‐related protein 1E in sphingolipid‐enriched plasma membrane domains is associated with the development of freezing tolerance
Authors: Minami Anzu , Tominaga Yoko , Furuto Akari , Kondo Mariko , Kawamura Yukio , Uemura Matsuo
Published: June 2015

The freezing tolerance of Arabidopsis thaliana is enhanced by cold acclimation, resulting in changes in the compositions and function of the plasma membrane. Here, we show that a dynamin‐related protein 1E (DRP1E), which is thought to function in the vesicle trafficking pathway in cells, is related to an increase in freezing tolerance during cold acclimation. DRP1E accumulated in sphingolipid and sterol‐enriched plasma membrane domains after cold acclimation. Analysis of drp1e mutants clearly showed that DRP1E is required for full development of freezing tolerance after cold acclimation. DRP1E fused with green fluorescent protein was visible as small foci that overlapped with fluorescent dye‐labelled plasma membrane, providing evidence that DRP1E localizes non‐uniformly in specific areas of the plasma membrane. These results suggest that DRP1E accumulates in sphingolipid and sterol‐enriched plasma membrane domains and plays a role in freezing tolerance development during cold acclimation.
Arabidopsis ACT11 modifies actin turnover to promote pollen germination and maintain the normal rate of tube growth
Authors: Chang Ming , Huang Shanjin
Published: June 2015

Actin is an ancient conserved protein that is encoded by multiple isovariants in multicellular organisms. There are eight functional actin genes in the Arabidopsis genome, and the precise function and mechanism of action of each isovariant remain poorly understood. Here, we report the characterization of ACT11, a reproductive actin isovariant. Our studies reveal that loss of function of ACT11 causes a delay in pollen germination, but enhances pollen tube growth. Cytological analysis revealed that the amount of filamentous actin decreased, and the rate of actin turnover increased in act11 pollen. Convergence of actin filaments upon the germination aperture was impaired in act11 pollen, consistent with the observed delay of germination. Reduction of actin dynamics with jasplakinolide suppressed the germination and tube growth phenotypes in act11 pollen, suggesting that the underlying mechanisms involve an increase in actin dynamics. Thus, we demonstrate that ACT11 is required to maintain the rate of actin turnover in order to promote pollen germination and maintain the normal rate of pollen tube growth.
Optimization of an ex vivo wound healing model in the adult human skin: Functional evaluation using photodynamic therapy
Authors: Mendoza‐Garcia Jenifer , Sebastian Anil , Alonso‐Rasgado Teresa , Bayat Ardeshir
Published: June 2015

Limited utility of in vitro tests and animal models of human repair, create a demand for alternative models of cutaneous healing capable of functional testing. The adult human skin Wound Healing Organ Culture (WHOC) provides a useful model, to study repair and enable evaluation of therapies such as the photodynamic therapy (PDT). Thus, the aim here was to identify the optimal WHOC model and to evaluate the role of PDT in repair. Wound geometry, system of support, and growth media, cellular and matrix biomarkers were investigated in WHOC models. Subsequently, cellular activity, extracellular matrix remodeling, and oxidative stress plus gene and protein levels of makers of wound repair measured the effect of PDT on the optimized WHOC. WHOCs embedded in collagen and supplemented DMEM were better organized showing stratified epidermis and compact dermis with developing neo‐epidermis. Post‐PDT, the advancing reepithelialization tongue was 3.5 folds longer, and was highly proliferative with CK‐14 plus p16 increased (p < 0.05) compared to controls. The neo‐epidermis was fully differentiated forming neo‐collagen. Proliferating nuclear antigen, p16, COLI, COLIII, MMP3, MMP19, and α‐SMA were significantly more expressed (p < 0.05) in dermis surrounding the healing wound. In conclusion, an optimal model of WHOC treated with PDT shows increased reepithelialization and extracellular matrix reconstruction and remodeling, supporting evidence toward development of an optimal ex vivo wound healing model.
Early life exposure to chronic intermittent hypoxia causes upper airway dilator muscle weakness, which persists into young adulthood
Authors: McDonald Fiona B. , Williams Robert , Sheehan David , O'Halloran Ken D.
Published: June 2015

New Findings

What is the central question of this study?

Chronic intermittent hypoxia (CIH) is a dominant feature of respiratory control disorders, which are common. We sought to examine the effects of exposure to CIH during neonatal development on respiratory muscle form and function in male and female rats.

What is the main finding and its importance?

Exposure to CIH during neonatal development caused sternohyoid muscle weakness in both sexes; an effect that persisted into young adult life upon return to normoxia. Upper airway dilator muscle dysfunction in vivo could predispose to airway collapse, leading to impaired respiratory homeostasis.

Chronic intermittent hypoxia (CIH) is a feature of sleep‐disordered breathing, which is very common. Exposure to CIH is associated with aberrant plasticity in the respiratory control system including the final effector organs, the striated muscles of breathing. We reasoned that developmental age and sex are key factors determining the functional response of respiratory muscle to CIH. We tested the hypothesis that exposure to CIH causes persistent impairment of sternohyoid muscle function due to oxidative stress and that males are more susceptible to CIH‐induced muscle impairment than females. Wistar rat litters (with respective dams) were exposed to intermittent hypoxia for 12 cycles per hour, 8 h per day for 3 weeks from the first day of life [postnatal day (P) 0]. Sham experiments were run in parallel. Half of each litter was studied on P22; the other half was returned to normoxia and studied on P42. Functional properties of the sternohyoid muscle were determined ex vivo. Exposure to CIH significantly decreased sternohyoid muscle force in both sexes; an effect that persisted into young adult life. Chronic intermittent hypoxia had no effect on sternohyoid muscle endurance. Chronic intermittent hypoxia did not affect sternohyoid myosin fibre type, succinate dehydrogenase or glycerol‐3‐phosphate dehydrogenase activities, or protein free thiol and carbonyl content. Muscles exposed to CIH had smaller cross‐sectional areas, consistent with the observation of muscle weakness. In human infants with disordered breathing, CIH‐induced upper airway dilator muscle weakness could increase the propensity for airway narrowing or collapse, which could serve to perpetuate impaired respiratory homeostasis.
Interleukin‐1 as a pharmacological target in acute brain injury
Authors: Brough David , Rothwell Nancy J. , Allan Stuart M.
Published: June 2015

New Findings

What is the topic of this review?

This review discusses the latest findings on the contribution of inflammation to brain injury, how inflammation is a therapeutic target, and details of recent and forthcoming clinical studies.

What advances does it highlight?

Here we highlight recent advances on the role and regulation of inflammasomes, and the latest clinical progress in targeting inflammation.

Acute brain injury is one of the leading causes of mortality and disability worldwide. Despite this, treatments for acute brain injuries are limited, and there remains a massive unmet clinical need. Inflammation has emerged as a major contributor to non‐communicable diseases, and there is now substantial and growing evidence that inflammation, driven by the cytokine interleukin‐1 (IL‐1), worsens acute brain injury. Interleukin‐1 is regulated by large, multimolecular complexes called inflammasomes. Here, we discuss the latest research on the regulation of inflammasomes and IL‐1 in the brain, preclinical efforts to establish the IL‐1 system as a therapeutic target, and the promise of recent and future clinical studies on blocking the action of IL‐1 for the treatment of brain injury.
Tissue and sex specificities in Ca2+ handling by isolated mitochondria in conditions avoiding the permeability transition
Authors: Chweih Hanan , Castilho Roger F. , Figueira Tiago R.
Published: June 2015

New Findings

What is the central question of this study?

The assessment of Ca2+ handling by isolated mitochondria can be biased by dysfunctions secondary to Ca2+‐induced mitochondrial permeability transition (MPT). As a result of this uncertainty and the differing experimental conditions between studies, the tissue and sex diversities in mitochondrial Ca2+ transport are still unsettled questions.

What is the main finding and its importance?

If MPT is not prevented during Ca2+ transport assays, some measured variables are biased. Accounting for the implied importance of preventing MPT, we observed substantial tissue specificities in the mitochondrial Ca2+ handling, particularly in the Ca2+ efflux pathways.

The characteristics of mitochondria, including their Ca2+ transport functions, may exhibit tissue specificity and sexual dimorphism. Given that measurements of Ca2+ handling by isolated mitochondria may be biased by dysfunction secondary to Ca2+‐induced mitochondrial permeability transition (MPT) pore opening, this study evaluated the extent to which MPT inhibition by ciclosporin affected the measurement of Ca2+ transport in isolated rat liver mitochondria. The results indicate that the steady‐state levels of external Ca2+ and the rates of mitochondrial Ca2+ efflux through the selective pathways can be overestimated by up to fourfold if MPT pore opening is not prevented. We analysed Ca2+ transport in isolated mitochondria from the liver, skeletal muscle, heart and brain of male and female rats in incubation conditions containing MPT inhibitors, NAD‐linked substrates and relevant levels of free Ca2+, Mg2+ and Na+. The Ca2+ influx rates were similar among the samples, except that the liver mitochondria displayed values fourfold higher. In contrast, the Ca2+ efflux rates exhibited more tissue diversity, especially in the presence of Na+. Interestingly, the Na+‐independent Ca2+ efflux was highest in the heart mitochondria (∼4 nmol mg−1 min−1), thus challenging the view that cardiac mitochondrial Ca2+ efflux relies almost exclusively on a Na+‐dependent pathway. Sex specificity was observed in only two kinetic indexes of heart mitochondrial Ca2+ homeostasis and in the ADP‐stimulated respiration of liver mitochondria (∼20% higher in females). The present study shows the methodological importance of preventing MPT when measuring the properties and the physiological variability of the Ca2+ handling by isolated mitochondria.
Fluid restriction during exercise in the heat reduces tolerance to progressive central hypovolaemia
Authors: Schlader Zachary J. , Gagnon Daniel , Rivas Eric , Convertino Victor A. , Crandall Craig G.
Published: June 2015

New Findings

What is the central question of this study?

Interactions between dehydration, as occurs during exercise in the heat without fluid replacement, and hyperthermia on the ability to tolerate central hypovolaemia are unknown.

What is the main finding and its importance?

We show that inadequate fluid intake during exercise in the heat can impair tolerance to central hypovolaemia even when it elicits only mild dehydration. These findings suggest that hydration during physical work in the heat has important military and occupational relevance for protection against the adverse effects of a subsequent haemorrhagic injury.

This study tested the hypothesis that dehydration induced via exercise in the heat impairs tolerance to central hypovolaemia. Eleven male subjects (32 ± 7 years old, 81.5 ± 11.1 kg) walked (O2 uptake 1.7 ± 0.4 l min−1) in a 40°C, 30% relative humidity environment on three occasions, as follows: (i) subjects walked for 90 min, drinking water to offset sweat loss (Hydrated, n = 11); (ii) water intake was restricted, and exercise was terminated when intestinal temperature increased to the same level as in the Hydrated trial (Isothermic Dehydrated, n = 11); and (iii) water intake was restricted, and exercise duration was 90 min (Time Match Dehydrated, n = 9). For each trial, tolerance to central hypovolaemia was determined following exercise via progressive lower body negative pressure and quantified as time to presyncope. Increases in intestinal temperature prior to lower body negative pressure were not different (P = 0.91) between Hydrated (1.1 ± 0.4°C) and Isothermic Dehydrated trials (1.1 ± 0.4°C), but both were lower than in the Time Match Dehydrated trial (1.7 ± 0.5°C, P < 0.01). Prior to lower body negative pressure, body weight was unchanged in the Hydrated trial (−0.1 ± 0.2%), but was reduced in Isothermic Dehydrated (−0.9 ± 0.4%) and further so in Time Match Dehydrated trial (−1.9 ± 0.6%, all P < 0.01). Time to presyncope was greater in Hydrated (14.7 ± 3.2 min) compared with Isothermic Dehydrated (11.9 ± 3.3 min, P < 0.01) and Time Match Dehydrated trials (10.2 ± 1.6 min, P = 0.03), which were not different (P = 0.19). These data indicate that inadequate fluid intake during exercise in the heat reduces tolerance to central hypovolaemia independent of increases in body temperature.
Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness
Authors: Sequeira Vasco , Najafi Aref , McConnell Mark , Fowler Ewan D. , Bollen Ilse A. E. , Wüst Rob C. I. , dos Remedios Cris , Helmes Michiel , White Ed , Stienen Ger J. M. , Tardiff Jil , Kuster Diederik W. D. , van der Velden Jolanda
Published: June 2015

Key points

Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall.

Increased actomyosin interactions may significantly limit diastolic capacity, however, direct evidence is absent.

From experiments at the cellular and whole organ level, in humans and rats, we show that actomyosin‐related force development contributes significantly to high diastolic stiffness in environments where high ADP and increased diastolic [Ca2+] are present, such as the failing myocardium.

Our basal study provides a mechanical mechanism which may partly underlie diastolic dysfunction.

Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross‐bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross‐bridge interactions are dependent on cytosolic [Ca2+] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca2+ handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca2+] promotes diastolic cross‐bridge formation and force generation and thereby increases diastolic stiffness. ADP dose‐dependently increased force production in the absence of Ca2+ in membrane‐permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca2+ both in human and rat membrane‐permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca2+] revealed a 76 ± 1% contribution of cross‐bridge interaction to total diastolic stress in rat membrane‐permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme‐isolated intact rat cardiomyocytes impaired diastolic re‐lengthening associated with diastolic Ca2+ overload. In isolated Langendorff‐perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca2+]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross‐bridges, even at low Ca2+, and thereby increase myocardial stiffness.
Enhanced BDNF signalling following chronic hypoxia potentiates catecholamine release from cultured rat adrenal chromaffin cells
Authors: Scott Angela L. , Zhang Min , Nurse Colin A.
Published: June 2015

Key points

We investigated the role of the neurotrophin BDNF signalling via the TrkB receptor in rat adrenomedullary chromaffin cells (AMCs) exposed to normoxia (Nox; 21% O2) and chronic hypoxia (CHox; 2% O2) in vitro for ∼48 h.

TrkB receptor expression was upregulated in primary AMCs and in immortalized chromaffin (MAH) cells exposed to CHox; this effect was absent in MAH cells deficient in the transcription factor, hypoxia inducible factor (HIF)‐2α.

Relative to normoxic controls, activation of the TrkB receptor in chronically hypoxic AMCs led to a marked increase in membrane excitability, intracellular [Ca2+], and catecholamine secretion.

The BDNF‐induced rise of intracellular [Ca2+] in CHox cells was sensitive to the selective T‐type Ca2+ channel blocker TTA‐P2 and tetrodotoxin (TTX), suggesting key roles of low threshold T‐type Ca2+ and voltage‐gated Na+ channels in the signalling pathway.

Environmental stressors, including chronic hypoxia, enhance the ability of adrenomedullary chromaffin cells (AMCs) to secrete catecholamines; however, the underlying molecular mechanisms remain unclear. Here, we investigated the role of brain‐derived neurotrophic factor (BDNF) signalling in rat AMCs exposed to chronic hypoxia. In rat adrenal glands, BDNF and its tropomyosin‐related kinase B (TrkB) receptor are highly expressed in the cortex and medulla, respectively. Exposure of AMCs to chronic hypoxia (2% O2; 48 h) in vitro caused a significant increase to TrkB mRNA expression. A similar increase was observed in an immortalized chromaffin cell line (MAH cells); however, it was absent in MAH cells deficient in the transcription factor HIF‐2α. A specific TrkB agonist, 7,8‐dihydroxyflavone (7,8‐DHF), stimulated quantal catecholamine secretion from chronically hypoxic (CHox; 2% O2) AMCs to a greater extent than normoxic (Nox; 21% O2) controls. Activation of TrkB by BDNF or 7,8‐DHF increased intracellular Ca2+ ([Ca2+]i), an effect that was significantly larger in CHox cells. The 7,8‐DHF‐induced [Ca2+]i rise was sensitive to the tyrosine kinase inhibitor K252a and nickel (2 mm), but not the Ca2+ store‐depleting agent cyclopiazonic acid. Blockade of T‐type calcium channels with TTA‐P2 (1 μm) or voltage‐gated Na+ channels with TTX inhibited BDNF‐induced [Ca2+]i increases. BDNF also induced a dose‐dependent enhancement of action potential firing in CHox cells. These data demonstrate that during chronic hypoxia, enhancement of BDNF‐TrkB signalling increases voltage‐dependent Ca2+ influx and catecholamine secretion in chromaffin cells, and that T‐type Ca2+ channels play a key role in the signalling pathway.
Two key temporally distinguishable molecular and cellular components of white adipose tissue browning during cold acclimation
Authors: Jankovic Aleksandra , Golic Igor , Markelic Milica , Stancic Ana , Otasevic Vesna , Buzadzic Biljana , Korac Aleksandra , Korac Bato
Published: June 2015

Key points

White to brown adipose tissue conversion and thermogenesis can be ignited by different conditions or agents and its sustainability over the long term is still unclear.

Browning of rat retroperitoneal white adipose tissue (rpWAT) during cold acclimation involves two temporally apparent components: (1) a predominant non‐selective browning of most adipocytes and an initial sharp but transient induction of uncoupling protein 1, peroxisome proliferator‐activated receptor (PPAR) coactivator‐1α, PPARγ and PPARα expression, and (2) the subsistence of relatively few thermogenically competent adipocytes after 45 days of cold acclimation.

The different behaviours of two rpWAT beige/brown adipocyte subsets control temporal aspects of the browning process, and thus regulation of both components may influence body weight and the potential successfulness of anti‐obesity therapies.

Conversion of white into brown adipose tissue may have important implications in obesity resistance and treatment. Several browning agents or conditions ignite thermogenesis in white adipose tissue (WAT). To reveal the capacity of WAT to function in a brownish/burning mode over the long term, we investigated the progression of the rat retroperitoneal WAT (rpWAT) browning during 45 days of cold acclimation. During the early stages of cold acclimation, the majority of rpWAT adipocytes underwent multilocularization and thermogenic‐profile induction, as demonstrated by the presence of a multitude of uncoupling protein 1 (UCP1)‐immunopositive paucilocular adipocytes containing peroxisome proliferator‐activated receptor (PPAR) coactivator‐1α (PGC‐1α) and PR domain‐containing 16 (PRDM16) in their nuclei. After 45 days, all adipocytes remained PRDM16 immunopositive, but only a few multilocular adipocytes rich in mitochondria remained UCP1/PGC‐1α immunopositive. Molecular evidence showed that thermogenic recruitment of rpWAT occurred following cold exposure, but returned to starting levels after cold acclimation. Compared with controls (22 ± 1°C), levels of UCP1 mRNA increased in parallel with PPARγ (PPARα from days 1 to 7 and PGC‐1α on day 1). Transcriptional recruitment of rpWAT was followed by an increase in UCP1 protein content (from days 1 to 21). Results clearly showed that most of the adipocytes within rpWAT underwent transient brown‐fat‐like thermogenic recruitment upon stimulation, but only a minority of cells retained a brown adipose tissue‐like phenotype after the attainment of cold acclimation. Therefore, browning of WAT is dependent on both maintaining the thermogenic response and retaining enough brown‐like thermogenically competent adipocytes in the long‐term. Both aspects of browning could be important for long‐term energy homeostasis and body‐weight regulation.
Microstructure Stability During Creep of Friction Stir Welded AZ31B Magnesium Alloy
Authors: Regev Michael , Spigarelli Stefano , Cabibbo Marcello
Published: June 2015

Friction stir welding (FSW) was applied in the current study in order to butt weld AZ31B-H24 alloy plates. Creep tests were conducted both on the parent material and on the friction stir welded specimens. The microstructure of the AZ31B alloy was found to be unstable under creep conditions. In the case of friction stir welded AZ31B, the material undergoes during FSW both recrystallization and grain growth, then the exposure to temperature during creep yields an extensive additional grain growth. On the other hand, twinning and twin-induced recrystallization occur as well during creep so that ultrafine grains are being created concurrently.
Thermal Modeling of Temperature Rise for Bone Drilling With Experimental Validation
Authors: Sui Jianbo , Sugita Naohiko , Mitsuishi Mamoru
Published: June 2015

This paper provides a methodology to develop a thermal model for predicting the temperature rise during surgical drilling of bone. The thermal model consists of heat generation calculation based on classical machining theory and development of governing equations of heat transfer individually for drill bit and bone. These two governing equations are coupled by shared boundary conditions. Finite-difference method is utilized to approximate the thermal model and effects of drill bit geometry and process parameters on temperature rise are evaluated by comparison with experiments. The simulated results fit well with experiments with respect to different drill bit geometry (<3.02 °C) and process parameters (<4.32 °C).
Comparison of breast specific gamma imaging and molecular breast tomosynthesis in breast cancer detection: Evaluation in phantoms
Authors: Gong Zongyi , Williams Mark B.
Published: June 2015

Purpose:

Breast specific gamma imaging or molecular breast imaging (BSGI) obtains 2D images of 99mTc sestamibi distribution in the breast. Molecular breast tomosynthesis (MBT) maps the tracer distribution in 3D by acquiring multiple projections over a limited angular range. Here, the authors compare the performance of the two technologies in terms of spatial resolution, lesion contrast, and contrast‐to‐noise ratio (CNR) in phantom studies under conditions of clinically relevant sestamibi dose and imaging time.

Methods:

The systems tested were a Dilon 6800 and a MBT prototype developed at the University of Virginia. Both systems comprise a pixelated sodium iodide scintillator, an array of position sensitive photomultipliers, and a parallel hole collimator. The active areas and energy resolution of the systems are similar. System sensitivity, spatial resolution, lesion contrast, and CNR were measured using a Petri dish, a point source phantom, and a breast phantom containing simulated lesions at two depths, respectively. A single BSGI projection was acquired. Five MBT projections were acquired over ±20°. For both modalities, the total scan count density was comparable to that observed for each in typical 10 min human scans following injection of 22 mCi (814 MBq) of 99mTc‐sestamibi. To assess the impact of reducing the tracer dose, the pixel counts of projection images were later binomially subsampled by a factor of 2 to give images corresponding to an injected activity of approximately 11 mCi (407 MBq). Both unprocessed (pixelated) BSGI projections and interpolated (smoothed) BSGI images displayed by default on the Dilon 6800 workstation were analyzed. Volumetric images were reconstructed from the MBT projections using a maximum likelihood expectation maximization algorithm and extracted slices were analyzed.

Results:

Over a depth range of 1.5–7.5 cm, BSGI spatial resolution was 5.6–11.5 mm in unprocessed projections and 5.7–12.0 mm in interpolated images. Over the same range, the in‐slice MBT spatial resolution was 6.7–9.4 mm. Lesion contrast was significantly improved with MBT relative to BSGI for five out of eight lesions imaged at either the 22 mCi or the 11 mCi dose level (p < 0.05). At both dose levels, significant improvements in CNR with MBT were also found for five out of eight lesions (9.8, 7.8, 6.2 mm lesions at water depth of 1.7 cm and 9.8, 7.8 mm lesions at water depth of 4.5 cm, p < 0.05). The 6.2 and 4.9 mm lesions located at 4.5 cm below the water surface were not visible in either modality at either activity level.

Conclusions:

Under conditions of equal dose, imaging time and similar detectors, compared to BSGI, MBT provided higher lesion contrast, higher CNR, and spatial resolution that was less depth dependent.