bluuebunny/crossref_metadata_2025 huggingface dataset:
A voltammetric and mathematical analysis of histaminergic modulation of serotonin in the mouse hypothalamus
Authors: Samaranayake Srimal , Abdalla Aya , Robke Rhiannon , Nijhout H. Frederik , Reed Michael C. , Best Janet , Hashemi Parastoo
Published: May 2016

Histamine and serotonin are neuromodulators which facilitate numerous, diverse neurological functions. Being co‐localized in many brain regions, these two neurotransmitters are thought to modulate one another's chemistry and are often implicated in the etiology of disease. Thus, it is desirable to interpret the in vivo chemistry underlying neurotransmission of these two molecules to better define their roles in health and disease. In this work, we describe a voltammetric approach to monitoring serotonin and histamine simultaneously in real time. Via electrical stimulation of the axonal bundles in the medial forebrain bundle, histamine release was evoked in the mouse premammillary nucleus. We found that histamine release was accompanied by a rapid, potent inhibition of serotonin in a concentration‐dependent manner. We developed mathematical models to capture the experimental time courses of histamine and serotonin, which necessitated incorporation of an inhibitory receptor on serotonin neurons. We employed pharmacological experiments to verify that this serotonin inhibition was mediated by H3 receptors. Our novel approach provides fundamental mechanistic insights that can be used to examine the full extent of interconnectivity between histamine and serotonin in the brain.

image

Histamine and serotonin are co‐implicated in many of the brain's functions. In this paper, we develop a novel voltammetric method for simultaneous real‐time monitoring of histamine and serotonin in the mouse premammillary nucleus. Electrical stimulation of the medial forebrain bundle evokes histamine and inhibits serotonin release. We show voltammetrically, mathematically, and pharmacologically that this serotonin inhibition is H3 receptor mediated.
The effect of a classroom activity break on physical activity levels and adiposity in primary school children
Authors: Drummy Clare , Murtagh Elaine M , McKee David P , Breslin Gavin , Davison Gareth W , Murphy Marie H
Published: May 2016

Aim

Despite recognition that regular physical activity is essential for good health, many children do not accumulate sufficient daily physical activity. The aim of this study was to examine the effect of a classroom‐based activity break on accelerometer‐determined moderate‐to‐vigorous intensity physical activity (MVPA) and adiposity in primary school children.

Methods

One hundred twenty children from seven primary schools in Northern Ireland participated in the study. In each school, one class of children was randomly assigned to an intervention group and another class to a control group. Teachers of the intervention classes led a 5‐min activity break three times per day for 12 weeks. Accelerometer‐determined MVPA, height, weight and four skinfolds were measured at baseline and post‐intervention.

Results

Compared with the control group, the intervention group significantly increased weekday MVPA (+9.5 min) from baseline to post‐intervention. There were no significant changes in BMI; however, an increase in sum‐of‐skinfolds of the intervention group was observed.

Conclusions

Classroom‐based activity breaks led by the teacher are successful in increasing children's physical activity levels. The programme shows a positive step in improving overall physical activity levels and contributing to the goal of 60 min daily MVPA.
Parent and teacher perceptions of emerging special health care needs
Authors: O'Connor Meredith , Rosema Stefanie , Quach Jon , Kvalsvig Amanda , Goldfeld Sharon
Published: May 2016

Aim

A fifth of children enter school with special health care needs (SHCN) impacting on their physical, psychosocial or educational development, including many with emerging SHCN who often do not qualify for additional supports. This study aimed to compare the perceptions of parents and teachers on children's emerging SHCN, and explore correlates of conflicting reports.

Methods

The Longitudinal Study of Australian Children (LSAC) is a nationally representative study of Australian children, which includes the abbreviated Children with Special Health Care Needs Screener. Data were analysed from a subsample of n = 720 children from the LSAC Kindergarten cohort (n = 4983) for whom teachers also completed the Australian Early Development Index checklist, a measure of early childhood development that includes teacher reported SHCN.

Results

Teachers (n = 120, 17.34%) identified more emerging SHCN than parents (n = 74, 10.74%), and reports were often discrepant. Children were more likely to have consistent reports of emerging SHCN when their parents had high levels of involvement at school (OR 4.86; 95% CI 1.08–21.80; P < 0.05), whereas children who came from disadvantaged family backgrounds were more likely to have teacher‐only identified difficulties (OR 3.66; 95% CI 1.17–11.50; P < 0.05).

Conclusion

Parents and teachers bring different perspectives to children's development and additional support needs, each of which is valuable. Greater attention should be given to ensuring that common understandings about a child's needs at school are established early in children's educational pathways.
Effect of quercetin on the uptake and efflux of aristolochic acid I from Caco-2 cell monolayers
Authors: Kimura Osamu , Fujii Yukiko , Haraguchi Koichi , Ohta Chiho , Koga Nobuyuki , Kato Yoshihisa , Endo Tetsuya
Published: May 2016

Objective

The purpose of this study was to determine whether quercetin decreases the uptake of aristolochic acid I (AAI) from the apical membranes of Caco-2 cells via H+-linked MCTs at neutral pH as well as to confirm the secretion of AAI through the Caco-2 cell monolayers via ABC transporters.

Methods

Caco-2 cells cultured on the dishes or permeable membranes were incubated with AAI in the absence or presence of quercetin or transporter inhibitors.

Key findings

Coincubation with quercetin decreased the uptake of AAI by Caco-2 cells cultured on the dishes at pH 7.4, and a similar decrease in AAI uptake was found when the cells were coincubated with acetic acid or benzoic acid. In contrast, the basolateral-to-apical transport of AAI was higher than the apical-to-basolateral transport of AAI at pH 7.4, and the former transport was decreased by quercetin and the BCRP inhibitors of Ko-143 and mitoxantrone, but not by P-gp or MRP2 inhibitors.

Conclusions

AAI appears to be secreted from the apical membranes of Caco-2 cells via BCRP at neutral pH, although a small amount of AAI is taken up from the apical membranes via H+-linked MCTs, and quercetin may decrease both the BCRP-mediated efflux and the MCT-mediated influx of AAI.
Development and optimization of ketoconazole oral strips by means of continuous hot-melt extrusion processing
Authors: Maniruzzaman Mohammed , Farias Smirna , Slipper Ian J , Boateng Joshua S , Chowdhry Babur Z , Nair Arun , Douroumis Dennis
Published: May 2016

Objectives

The aim of this study was to develop mucoadhesive oral strips using hot-melt extrusion as a continuous manufacturing process.

Methods

Powder blends of ketoconazole, a water-insoluble drug – either hydroxypropyl methylcellulose (HPMC) or soluplus (SOL), sorbitol (SRB) and magnesium aluminometasilicate (MAS) were extruded to manufacture thin strips with 0.5-mm thickness. The presence of the inorganic metasilicate facilitated smooth processing of the extruded strips as it worked as an absorbent directly impacting on the extensive mixing of the drug/excipients inside the extruder barrel.

Key findings

The use of MAS also favoured the rapid hydration, swelling and eventual disintegration of the strips. Differential scanning calorimetry and transmission X-ray diffraction analysis revealed the existence of the amorphous drug within the extruded strips. Scanning electron microscopy and energy dispersive X-ray undertaken on the formulations showed a homogeneous drug distribution within the extruded strips.

Conclusion

The strips produced via continuous hot-melt extrusion processing showed significantly faster release of ketoconazole compared to the bulk drug substance.
Is psychosocial and cognitive dysfunction misattributed to the virus in hepatitis C infection? Select psychosocial contributors identified
Authors: Lowry D. , Burke T. , Galvin Z. , Ryan J. D. , Russell J. , Murphy A. , Hegarty J. , Stewart S. , Crowe J.
Published: May 2016

Chronic hepatitis C is associated with health‐related quality of life and cognitive impairments, even in mild disease. Recent evidence demonstrating hepatitis C virus (HCV) neurotropism has strengthened a neuropathophysiological hypothesis. However, sample heterogeneity confounds study outcomes. A uniquely homogeneous cohort of Irish women, following an iatrogenic HCV outbreak, offers a rare opportunity to control for HCV chronicity and the virus’ purported impact on quality of life and cognition. A multi site, three‐group, cross‐sectional design was employed. Noncirrhotic, iatrogenically infected women, developing either acute or chronic infection, were recruited from prospective tertiary‐care liver clinics and the community. Well‐matched healthy controls were also recruited. All participants completed a psychosocial survey and were invited to undergo a comprehensive neuropsychological test battery. Significantly distressed psychosocial symptom profiles were observed in those with an iatrogenic HCV exposure history, which was independent of viral chronicity. Chronic and cleared HCV cohorts were not differentiated from each other. Two distinct subgroups, demarcated along ‘impaired’ vs ‘nonimpaired’ quality‐of‐life reports, were clearly identified and logistic regression analysis identified depressed mood and cognitive fatigue, rather than viral status, as statistically significant predictors of group membership. Compared with matched controls, significant cognitive impairments were not observed in either HCV cohort. Our findings provide strong evidence of nonviral factors accounting for quality of life impairment in chronic HCV and they also appear to question existing reports of cognitive dysfunction in mild disease. Depressed mood and cognitive fatigue appear to be critical psychosocial mediators of reduced quality‐of‐life and we hypothesize that metabolite abnormalities reported in HCV samples may also be confounded by these factors, given the associated literature.
The Digitization of Literary Reading
Authors: Mangen Anne
Published: May 2016

With the growing popularity of e‐readers such as Kindle, literary reading is increasingly digitized. The transition from paper‐based to screen‐based literature invites theoretical and empirical reconsiderations of a number of basic research questions which might at first glance seem trivial: does it make a difference for aspects of the literary reading experience if the text is read on a screen‐based device rather than on paper? Findings from a recent experiment suggest that affordances of surf tablets such asiPad might negatively affect emotional aspects of reading. Referring to empirical research on emotional aspects of literary reading, the article aims to demonstrate the usefulness of more interdisciplinary approaches in studies of the literary reading experience.
Vibrationally Resolved Absorption and Fluorescence Spectra of Firefly Luciferin: A Theoretical Simulation in the Gas Phase and in Solution
Authors: Cheng Yuan‐Yuan , Liu Ya‐Jun
Published: May 2016

Firefly bioluminescence has been applied in several fields. However, the absorption and fluorescence spectra of the substrate, luciferin, have not been observed at the vibrational level. In this study, the vibrationally resolved absorption and fluorescence spectra of firefly luciferin (neutral form LH2, phenolate ion form LH− and dianion form L2−) are simulated using the density functional method and convoluted by a Gaussian function, with displacement, distortion and Duschinsky effects in the framework of the Franck–Condon approximation. Both neutral and anionic forms of the luciferin are considered in the gas phase and in solution. The simulated spectra have desired band maxima with the experimental ones. The vibronic structure analysis reveals that the features of the most contributive vibrational modes coincide with the key geometry‐changing region during transition between the ground state and the first singlet excited state.
Stakeholder integration in new product development: a systematic analysis of drivers and firm capabilities
Authors: Vaquero Martín María , Reinhardt Ronny , Gurtner Sebastian
Published: May 2016

In this article, we develop a conceptual model of stakeholder integration in new product development (NPD) that (i) explains the drivers of the process and (ii) proposes a framework of capabilities that firms need for successful stakeholder integration. The focus lies on external stakeholders that directly influence the adoption of new products. We conduct a systematic literature review and content analyze a sample of 96 peer‐reviewed journal articles. The study is restricted to the medical device industry to enable the use of specific search terms and the consistent categorization of information. We dedicate a section to showing how the framework applies to other settings. The drivers of stakeholder integration are classified into push factors (i.e., expected benefits for the focal firm) and pull factors (i.e., expected benefits for the stakeholders). This study provides an initial model of how stakeholder integration works based on its drivers. In addition, three related stakeholder integration capabilities emerge: stakeholder identification capability, stakeholder interaction capability and stakeholder input integration capability. The paper proposes a description of these capabilities for stakeholder integration in NPD and, thus, contributes to stakeholder theory and research on the management of NPD. The results open new paths for empirical testing and offer practical guidance on how to successfully integrate stakeholders in NPD processes.
Of Quantiles and Expectiles: Consistent Scoring Functions, Choquet Representations and Forecast Rankings
Authors: Ehm Werner , Gneiting Tilmann , Jordan Alexander , Krüger Fabian
Published: May 2016

In the practice of point prediction, it is desirable that forecasters receive a directive in the form of a statistical functional. For example, forecasters might be asked to report the mean or a quantile of their predictive distributions. When evaluating and comparing competing forecasts, it is then critical that the scoring function used for these purposes be consistent for the functional at hand, in the sense that the expected score is minimized when following the directive. We show that any scoring function that is consistent for a quantile or an expectile functional can be represented as a mixture of elementary or extremal scoring functions that form a linearly parameterized family. Scoring functions for the mean value and probability forecasts of binary events constitute important examples. The extremal scoring functions admit appealing economic interpretations of quantiles and expectiles in the context of betting and investment problems. The Choquet-type mixture representations give rise to simple checks of whether a forecast dominates another in the sense that it is preferable under any consistent scoring function. In empirical settings it suffices to compare the average scores for only a finite number of extremal elements. Plots of the average scores with respect to the extremal scoring functions, which we call Murphy diagrams, permit detailed comparisons of the relative merits of competing forecasts.
Oracally Efficient Estimation and Consistent Model Selection for Auto-Regressive Moving Average Time Series with Trend
Authors: Shao Qin , Yang Lijian
Published: May 2016

Most time series that are encountered in practice contain non-zero trend, yet textbook approaches to time series analysis are typically focused on zero-mean stationary auto-regressive moving average (ARMA) processes. Trend is often estimated by ad hoc methods and subtracted from time series, and the residuals are used as the true ARMA noise for data analysis and inference, including parameter estimation, lag selection and prediction. We propose a theoretically justified two-step method to analyse time series consisting of a smooth trend function and ARMA error term, which is computationally efficient and easy for practitioners to implement. The trend is estimated by B-spline regression, and the maximum likelihood estimator based on residuals is shown to be oracally efficient in the sense that it is asymptotically as efficient as if the true trend function were known and then removed to obtain the ARMA errors. In addition, consistency of the Bayesian information criterion for model selection is established for the detrended residual sequence. Finite sample performance of the procedure is illustrated by simulation studies and real data analysis.
“A Grain of Salt in a Pepper Shaker”: Interviewing Whites, Blacks, and Latinos about Their Neighborhood Preferences
Authors: Meyerhoffer Cassi A.
Published: May 2016

Several perspectives dominate as explanations for neighborhood preferences: pure race, racial proxy, race‐based neighborhood stereotyping, and race‐associated neighborhood factors. This analysis extends and supports the pure race and race‐associated neighborhood factors arguments by showing that these theories are applied differently depending on respondents' social class, race and ethnicity, and whether they are talking about white, black, or Latino neighborhoods. Race‐associated factors are emphasized for white and black neighborhoods, but pure race serves as a better theoretical framework for understanding people's preferences for Latino neighborhoods. I analyze qualitative interview data, using maps of real neighborhoods and hypothetical neighborhood show cards, to examine the neighborhood preferences of 65 white, black, and Latino residents in Ogden, Utah, and Buffalo, New York.
Identification of a novel HLA‐C allele, HLA‐C*07:477 in a Drung Chinese individual
Authors: Wang J. , Yao F. Z. , Ji X. , Zhu X. M. , Su P. C.
Published: May 2016

HLA‐C*07:477 has one nonsynonymous nucleotide change from HLA‐C*07:02:01:01 in codon 176, exon 3 (AAG>GAG).
Transport Supply and Demand Changes in Relation to Unemployment: Empirical Evidence from the Czech Republic in a Time of Crisis
Authors: Marada Miroslav , Květoň Viktor
Published: May 2016

The continuing European recession underlines the urgency of the unemployment and labour force mobility issue. Therefore, the objective of this study is to scrutinise the relationship between changes in unemployment rate and transport indicators in the intercensal period 2001–2011. Both primary and secondary data are used in the analysis. Rate of car ownership and commuting data were taken from national censuses in 2001 and 2011 which surrounded the 2008 crisis. Primary data came from 1,023 interviews. The relationships among indicators are identified with the help of several statistical techniques whose results are analysed. Further, analyses have confirmed the dominant importance of passenger car ownership and car use in relation to decreased unemployment. It is particularly important in economically weaker areas with a poor access, that are endangered by social exclusions. Furthermore, it is necessary to emphasise the importance of public transport as a means of preventing social exclusion.
Hematopoietic progenitor cell mobilization is more robust in healthy African American compared to Caucasian donors and is not affected by the presence of sickle cell trait
Authors: Panch Sandhya R. , Yau Yu Ying , Fitzhugh Courtney D. , Hsieh Matthew M. , Tisdale John F. , Leitman Susan F.
Published: May 2016

BACKGROUND

Granulocyte–colony‐stimulating factor (G‐CSF)‐stimulated hematopoietic progenitor cells (HPCs) collected by apheresis have become the predominant graft source for HPC transplantation in adults. Among healthy allogeneic donors, demographic characteristics (age, sex, body mass index [BMI]) and baseline hematologic counts affect HPC mobilization, leading to variability in CD34+ apheresis yields. Racial differences in HPC mobilization are less well characterized.

STUDY DESIGN AND METHODS

We retrospectively analyzed data from 1096 consecutive G‐CSF–stimulated leukapheresis procedures in healthy allogeneic African American (AA) or Caucasian donors.

RESULTS

In a multivariate analysis, after adjusting for age, sex, BMI, baseline platelet and mononuclear cell counts, and daily G‐CSF dose, peak CD34+ cell mobilization was significantly higher among AAs (n = 215) than Caucasians (n = 881; 123 ± 87 × 106 cells/L vs. 75 ± 47 × 106 cells/L; p < 0.0001). A ceiling effect was observed with increasing G‐CSF dose (10 µg/kg/day vs. 16 µg/kg/day) in AAs (123 ± 88 × 106 cells/L vs. 123 ± 87 × 106 cells/L) but not in Caucasians (74 ± 46 × 106 cells/L vs. 93 ± 53 × 106 cells/L; p < 0.001). In AA donors, the presence of sickle cell trait (SCT; n = 41) did not affect CD34+ mobilization (peak CD34+ 123 ± 91 × 106 cells/L vs. 107 ± 72 × 106 cells/L, HbAS vs. HbAA; p = 0.34). Adverse events were minimal and similar across race.

CONCLUSIONS

AAs demonstrated significantly better CD34 mobilization responses to G‐CSF than Caucasians. This was independent of other demographic and hematologic variables. Studying race‐associated pharmacogenomics in relation to G‐CSF may improve dosing strategies. Adverse event profile and CD34 mobilization were similar in AA donors with and without SCT. Our findings suggest that it would be safe to include healthy AA donors with SCT in unrelated donor registries.
Effect of increased agitation speed on pathogen inactivation efficacy and in vitro quality in UVC‐treated platelet concentrates
Authors: van der Meer P. F. , Gravemann U. , de Korte D. , Sumian C. , Tolksdorf F. , Müller T. H. , Seltsam A.
Published: May 2016

Background and Objectives

Pathogen inactivation technologies require continuous development for adjustment to different blood components and products. With Theraflex UV‐Platelets, a system using shortwave ultraviolet C (UVC) light (254 nm), efficient mixing of platelet concentrates (PCs) during UVC treatment is essential to ensure homogeneous illumination of the blood components. In this study, we investigated the impact of increasing the agitation speed during UVC treatment on pathogen inactivation capacity and platelet quality.

Material and Methods

The pathogen inactivation efficacy of UVC treatment was evaluated at two agitation speeds (110 vs. 180 rpm) using four different transfusion‐relevant bacteria strains and three model viruses. Using a pool‐and‐split design, the in vitro quality of buffy coat‐derived PCs stored in SSP+ additive solution for up to 7 days was assessed in UVC‐treated PCs agitated at either 110 rpm (standard speed) or 180 rpm (increased speed) and in untreated controls.

Results

The higher agitation speed improved bacterial inactivation but did not influence viral inactivation. Metabolic activity (glucose consumption and lactate accumulation) in UVC‐treated platelets was slightly higher than in untreated controls. Increases in parameters such as CD62P expression and annexin A5 binding indicated moderate activation of UVC‐treated platelets. Quality variables for UVC‐treated platelets agitated at standard vs. increased agitation speed were comparable.

Conclusion

The mixing rate during illumination may be a process parameter for further development of UVC‐based pathogen inactivation procedures for PLT concentrates.
Prevalence of blood donor iron deficiency and feasibility ferritin‐based iron replacement: a blood collection agency‐based study
Authors: Gorlin J. , Katz L. , Elsmore D. , Kirbach K. , Erickson Y. , Hove A. , Black C. , Walsh‐Jahnke R.
Published: May 2016

Iron depletion is high in frequent whole‐blood donors. It is of interest to blood centres to develop ways to mitigate this risk while maintaining the current blood supply. Our feasibility study shows that blood collection agencies can measure iron stores and safely offer iron replacement in frequent blood donors with low ferritin to reduce the risk of iron depletion and future donor deferrals for low haemoglobin.
International Expansion of Colombian Firms: Understanding their emergence in foreign markets
Authors: Veléz Ocampo Juan Fernando , Gonzalez-Perez Maria Alejandra
Published: May 2016

En este estudio se muestra que aunque no hay evidencia de un patrón generalizable en el proceso de internacionalización de compañías colombianas, hay algunos rasgos comunes en la mayoría de las empresas observadas: la elección de exportaciones como el modo de entrada inicial, el ingreso a países con baja distancia psicológica y geográfica, y el desarrollo de ventajas estratégicas locales que eventualmente se replican en el exterior. Se utilizaron una encuesta y una entrevista estructurada que incluyen variables numéricas y categóricas seguido de un análisis cruzado de casos. También se encontró que las decisiones de internacionalización operan bajo una base ad-hoc y dependen de la experiencia y la intuición de los altos ejecutivos de las empresas
Intención emprendedora de estudiantes de educación media: extendiendo la teoría de comportamiento planificado mediante el efecto exposición
Authors: Osorio Fabian , Londoño Roldán Juan Carlos
Published: May 2016

El modelo de intención basado en la teoría del comportamiento planificado
(TCP) ha sido evaluado empíricamente en la formación de intenciones
emprendedoras, más que todo, en estudiantes universitarios de diferentes
orígenes culturales. Este artículo prueba la TCP en una muestra de
estudiantes de colegios de la ciudad de Cali, Colombia, a través de un
modelo con cuadrados mínimos parciales y se encontró que la exposición
previa en actividades de emprendimiento tiene un efecto positivo sobre los
determinantes de la intención emprendedora. Esta línea de investigación
se puede continuar con un estudio longitudinal que brindará resultados
más sólidos y con mayor extensión de cara a las diferencias culturales..
Comparison of Numerical and Experimental Assessment of a Latent Heat Energy Storage Module for a High-Temperature Phase-Change Material
Authors: Ramos Archibold Antonio , Bhardwaj Abhinav , Rahman Muhammad M. , Yogi Goswami D. , Stefanakos Elias L.
Published: May 2016

This paper presents a comprehensive analysis of the heat transfer during the melting process of a high-temperature (>800 °C) phase-change material (PCM) encapsulated in a vertical cylindrical container. The energy contributions from radiation, natural convection, and conduction have been included in the mathematical model in order to capture most of the physics that describe and characterize the problem and quantify the role that each mechanism plays during the phase-change process. Numerical predictions based on the finite-volume method have been obtained by solving the mass, momentum, and energy conservation principles along with the enthalpy porosity method to track the liquid/solid interface. Experiments were conducted to obtain the temperature response of the thermal energy storage (TES) cell during the sensible heating and phase-change regions of the PCM. Continuous temperature measurements of porcelain crucibles filled with ACS grade NaCl were recorded. The temperature readings were recorded at the center of the sample and at the wall of the crucible as the samples were heated in a furnace over a temperature range of 700–850 °C. The numerical predictions have been validated by the experimental results, and the effect of the controlling parameters of the system on the melt fraction rate has been evaluated. The results showed that the natural convection is the dominant heat transfer mechanism. In all the experimental study cases, the measured temperature response captured the PCM melting trend with acceptable repeatability. The uncertainty analysis of the experimental data yielded an approximate error of ±5.81 °C.
Cooling of Turbine Blade Surface With Expanded Exit Holes: Computational Suction-Side Analysis
Authors: Forghan Fariborz , Askari Omid , Narusawa Uichiro , Metghalchi Hameed
Published: May 2016

Turbine blade surfaces are cooled by jet flow from expanded exit holes (EEHs) against the prevailing hot gas flow. The flow through EEH must be designed to form a film of cool air over the blade. Computational analyses are performed to examine the cooling effectiveness of flow from EEH over the suction side of a blade by solving conservation equations and the ideal gas equation of state for turbulent and compressible flow. For a sufficiently high coolant mass flow rate, the flow through EEH, which acts as a converging–diverging nozzle, is choked at the nozzle throat, resulting in a supersonic flow, a shock, and then a subsonic flow downstream. The location of the shock relative to the high-temperature gas flow determines the temperature distribution along the blade surface; which is analyzed in detail when the following conditions are varied: coolant mass flow rate, the temperature difference between gas-and coolant-flow, EEH location on the blade surface, EEH inclination angle to the blade surface, and exit-to-inlet area ratio (AR) of EEH. The film cooling effectiveness is calculated along the surface of the blade. The results show (1) increasing the coolant flow rate improves the effectiveness, (2) change in temperature difference between the mainstream and the coolant slightly affects the effectiveness, (3) inclination angle of EEH has a pronounced effect on film cooling and the corresponding effectiveness, (4) both the location of the EEH on a blade and the AR of the EEH slightly change the effectiveness.
Experimental validation of a nonlinear derating technique based upon Gaussian-modal representation of focused ultrasound beams
Authors: Dibaji Seyed Ahmad Reza , Banerjee Rupak K. , Liu Yunbo , Soneson Joshua E. , Myers Matthew R.
Published: May 2016

A technique useful for performing derating at acoustic powers where significant harmonic generation occurs is illustrated and validated with experimental measurements. The technique was previously presented using data from simulations. The method is based upon a Gaussian representation of the propagation modes, resulting in simple expressions for the modal quantities, but a Gaussian source is not required. The nonlinear interaction of modes within tissue is estimated from the nonlinear interaction in water, using appropriate amounts of source reduction and focal-point reduction derived from numerical simulations. An important feature of this nonlinear derating method is that focal temperatures can be estimated with little additional effort beyond that required to determine the focal pressure waveforms. Hydrophone measurements made in water were used to inform the derating algorithm, and the resulting pressure waveforms and increases in temperature were compared with values directly measured in tissue phantoms. For a 1.05 MHz focused transducer operated at 80 W and 128 W, the derated pressures (peak positive, peak negative) agreed with the directly measured values to within 11%. Focal temperature rises determined by the derating method agreed with values measured using a remote thermocouple technique with a difference of 17%.
Effects of Aerobic Exercise Applied Early After Coronary Artery Bypass Grafting on Pulmonary Function, Respiratory Muscle Strength, and Functional Capacity: A Randomized Controlled Trial
Authors: Borges Daniel L. , Silva Mayara Gabrielle , Silva Luan Nascimento , Fortes João Vyctor , Costa Erika Thalita , Assunção Rebeca Pessoa , Lima Carlos Magno , da Silva Nina Vinícius José , Bernardo-Filho Mário , Caputo Danúbia Sá
Published: May 2016

Background:

Physical activity is beneficial in several clinical situations and recommended for patients with ischemic heart disease, as well as for those undergoing cardiac surgery.

Methods:

In a randomized controlled trial, 34 patients underwent coronary artery bypass grafting. A randomized control group (n = 15) submitted to conventional physiotherapy. The intervention group (n = 19) received the same protocol plus additional aerobic exercise with cycle ergometer. Pulmonary function by spirometry, respiratory muscle strength by manovacuometry, and functional capacity through 6-minute walking test was assessed before surgery and at hospital discharge.

Results:

There was significant reduction in pulmonary function in both groups. In both groups, inspiratory muscle strength was maintained while expiratory muscle strength significantly decreased. Functional capacity was maintained in the intervention group (364.5 [324.5 to 428] vs. 348 [300.7 to 413.7] meters, P = .06), but it decreased significantly in control group patients (320 [288.5 to 393.0] vs. 292 [237.0 to 336.0] meters, P = .01). A significant difference in functional capacity was also found in intergroup analyses at hospital discharge (P = .03).

Conclusion:

Aerobic exercise applied early on coronary artery bypass grafting patients may promote maintenance of functional capacity, with no impact on pulmonary function and respiratory muscle strength when compared with conventional physiotherapy.
Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease
Authors: Brier Matthew R. , Gordon Brian , Friedrichsen Karl , McCarthy John , Stern Ari , Christensen Jon , Owen Christopher , Aldea Patricia , Su Yi , Hassenstab Jason , Cairns Nigel J. , Holtzman David M. , Fagan Anne M. , Morris John C. , Benzinger Tammie L. S. , Ances Beau M.
Published: May 2016

PET imaging of pathological tau correlates more closely with Alzheimer’s disease–related cognitive impairment than does imaging of β-amyloid.
Science Sound Bites, a Podcast for STEM Curriculum Supplementation
Authors: Johnson Michael D. L. , Ayers Kate A.
Published: May 2016

First hand accounts of research are a valuable part of students’ understanding and integration of scientific material, yet it is often difficult to access scientists to discuss ongoing research projects. To address this issue, we offer details of a podcast called Science Sound Bites; a tool designed to supplement STEM and biology curricula at the middle and high school grade levels. Roughly 20 minutes in length, each episode consists of a candid interview of a PhD- or MD-level researcher about their current research, while infusing and defining field-specific scientific terminology. Additionally, each Science Sound Bites podcast comes with a short biography of the interviewee and a list of terms that are defined within the episode, which serves to help teachers find relevant podcasts for a given lesson plan. The goal of this podcast is to provide real world applications of science in an attempt to bridge the gap between scientists in the field and students in the classroom.
ImmuneQuest: Assessment of a Video Game as a Supplement to an Undergraduate Immunology Course
Authors: Raimondi Stacey L.
Published: May 2016

The study of immunology, particularly in this day and age, is an integral aspect of the training of future biologists, especially health professionals. Unfortunately, many students lose interest in or lack true comprehension of immunology due to the jargon of the field, preventing them from gaining a true conceptual understanding that is essential to all biological learning. To that end, a new video game, ImmuneQuest, has been developed that allows undergraduate students to “be” cells in the immune system, finding and attacking pathogens, while answering questions to earn additional abilities. The ultimate goal of ImmuneQuest is to allow students to understand how the major cells in the immune system work together to fight disease, rather than focusing on them as separate entities as is more commonly done in lecture material. This work provides the first assessment of ImmuneQuest in an upper-level immunology course. Students had significant gains in learning of information presented in ImmuneQuest compared with information discussed in lecture only. Furthermore, while students found the game “frustrating” at times, they agreed that the game aided their learning and recommended it for future courses. Taken together, these results suggest that ImmuneQuest appears to be a useful tool to supplement lecture material and increase student learning and comprehension.
Sexual Health—Get Involved: A Kinesthetic Learning Experience of STI Transmission and Prevention
Authors: Patel Selina , Krachler Anne Marie
Published: May 2016

OFSTED repeatedly finds the teaching of sexually transmitted infections in secondary schools ‘inadequate’ across the UK (3). This is thought to be due to a number of reasons, including the fact that staff teaching this topic feel inadequately prepared and not knowledgeable enough to do so (4).

In 2010, over half of newly diagnosed sexually transmitted infections (STIs) in England were within patients aged 16-24 years (2). This could be the result of a lack of mandatory, quality sexual health education in schools, combined with larger scale social issues. Young females, in particular, reported feelings of shame when visiting sexual health clinics which on occasion may compel them to lie about their sexual history to a practitioner in order to protect a ‘fragile sexual reputation’(1).

In response to the recommendations of FPA and the aforementioned public health statistics, this session was developed to improve student understanding of sexual health and of the risks associated with different sexual behaviors. Another aim was, by integrating information about the importance of regular sexual health check-ups into sexual health education in schools, to reduce the associated feelings of shame across the young female population. The activity was carried out with two classes of Year 12 students (16-17 years) in an independent school in the London borough of Lewisham. The session builds on education about STIs, which is part of the national science curriculum, and extends concepts about transmission to the most common STIs prevalent within the population aged 16-24.
Dual Transcriptome Profiling ofLeishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures
Authors: Fernandes Maria Cecilia , Dillon Laura A. L. , Belew Ashton Trey , Bravo Hector Corrada , Mosser David M. , El-Sayed Najib M.
Published: May 2016

Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells ofLeishmaniaspp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of twoLeishmaniaspecies and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected byLeishmaniaspp. points toward a general signature of theLeishmania-macrophage infectome.

IMPORTANCELittle is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures ofLeishmaniaspp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in infection that was reduced at later time points. A similar expression pattern was observed in the parasites. Our analyses provide specific insights into the interplay between human macrophages andLeishmaniaparasites and constitute an important general resource for the study of how pathogens evade host defenses and modulate the functions of the cell to survive intracellularly.
Lipid Flippase Subunit Cdc50 Mediates Drug Resistance and Virulence in Cryptococcus neoformans
Authors: Huang Wei , Liao Guojian , Baker Gregory M. , Wang Yina , Lau Richard , Paderu Padmaja , Perlin David S. , Xue Chaoyang
Published: May 2016

Cryptococcus neoformans
is a human fungal pathogen and a major cause of fungal meningitis in immunocompromised individuals. Treatment options for cryptococcosis are limited. Of the two major antifungal drug classes, azoles are active against
C. neoformans
but exert a fungistatic effect, necessitating long treatment regimens and leaving open an avenue for emergence of azole resistance. Drugs of the echinocandin class, which target the glucan synthase and are fungicidal against a number of other fungal pathogens, such as
Candida
species, are ineffective against
C. neoformans
. Despite the sensitivity of the target enzyme to the drug, the reasons for the innate resistance of
C. neoformans
to echinocandins remain unknown. To understand the mechanism of echinocandin resistance in
C. neoformans
, we screened gene disruption and gene deletion libraries for mutants sensitive to the echinocandin-class drug caspofungin and identified a mutation of
CDC50
, which encodes the β-subunit of membrane lipid flippase. We found that the Cdc50 protein localized to membranes and that its absence led to plasma membrane defects and enhanced caspofungin penetration into the cell, potentially explaining the increased caspofungin sensitivity. Loss of
CDC50
also led to hypersensitivity to the azole-class drug fluconazole. Interestingly, in addition to functioning in drug resistance,
CDC50
was also essential for fungal resistance to macrophage killing and for virulence in a murine model of cryptococcosis. Furthermore, the surface of
cdc50Δ
cells contained increased levels of phosphatidylserine, which has been proposed to act as a macrophage recognition signal. Together, these results reveal a previously unappreciated role of membrane lipid flippase in
C. neoformans
drug resistance and virulence.

IMPORTANCE
Cryptococcus neoformans
is a fungal pathogen that is the most common cause of fungal meningitis, causing over 620,000 deaths annually. The treatment options for cryptococcosis are very limited. The most commonly used drugs are either fungistatic (azoles) or highly toxic (amphotericin B). Echinocandins are the newest fungicidal drug class that works well in treating candidiasis and aspergillosis, yet they are ineffective in treating cryptococcosis. In this study, we showed that the regulatory subunit of the lipid translocase (flippase), a protein that regulates the asymmetrical orientation of membrane lipids, is required for
C. neoformans
resistance to caspofungin, as well as for virulence during infection. This discovery identifies lipid flippase as a potential
C. neoformans
drug target, which plays an important role in the innate resistance of
C. neoformans
to echinocandins and in fungal virulence.
Induction of Protective Immunity to Cryptococcal Infection in Mice by a Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans
Authors: Upadhya Rajendra , Lam Woei C. , Maybruck Brian , Specht Charles A. , Levitz Stuart M. , Lodge Jennifer K.
Published: May 2016

Cryptococcus neoformansis a major opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised individuals and is responsible for a large proportion of AIDS-related deaths. The fungal cell wall is an essential organelle which undergoes constant modification during various stages of growth and is critical for fungal pathogenesis. One critical component of the fungal cell wall is chitin, which inC. neoformansis predominantly deacetylated to chitosan. We previously reported that three chitin deacetylase (CDA) genes have to be deleted to generate a chitosan-deficientC. neoformansstrain. Thiscda1Δ2Δ3Δstrain was avirulent in mice, as it was rapidly cleared from the lungs of infected mice. Here, we report that clearance of thecda1Δ2Δ3Δstrain was associated with sharply spiked concentrations of proinflammatory molecules that are known to be critical mediators of the orchestration of a protective Th1-type adaptive immune response. This was followed by the selective enrichment of the Th1-type T cell population in thecda1Δ2Δ3Δstrain-infected mouse lung. Importantly, this response resulted in the development of robust protective immunity to a subsequent lethal challenge with a virulent wild-typeC. neoformansstrain. Moreover, protective immunity was also induced in mice vaccinated with heat-killedcda1Δ2Δ3Δcells and was effective in multiple mouse strains. The results presented here provide a strong framework to develop thecda1Δ2Δ3Δstrain as a potential vaccine candidate forC. neoformansinfection.

IMPORTANCEThe most commonly used anticryptococcal therapies include amphotericin B, 5-fluorocytosine, and fluconazole alone or in combination. Major drawbacks of these treatment options are their limited efficacy, poor availability in limited resource areas, and potential toxicity. The development of antifungal vaccines and immune-based therapeutic interventions is promising and an attractive alternative to chemotherapeutics. Currently, there are no fungal vaccines in clinical use. This is the first report of aC. neoformansdeletion strain with an avirulent phenotype in mice exhibiting protective immunity when used as a vaccine after heat inactivation, although other strains that overexpress fungal or murine proteins have recently been shown to induce a protective response. The data presented here demonstrate the potential for developing the avirulentcda1Δ2Δ3Δstrain into a vaccine-based therapy to treatC. neoformansinfection.
Geologic and anthropogenic history of the Palouse Falls area
Authors: Pritchard Chad J. , Cebula Larry
Published: May 2016

This one-day field trip of geologic and historical significance goes from Washtucna, Washington, through Palouse Falls State Park, Lyons Ferry State Park, and Starbuck, and ends in the Tucannon River valley. At Palouse Falls, it is readily apparent why Native Americans crafted stories about the origins of this spectacular area and why geologic debates regarding the role of Pleistocene glacial Lake Missoula floods during the formation of this natural wonderland have been centered here. This field trip focuses on structural geology and the Palouse Falls fracture zone, Columbia River Basalt Group stratigraphy at the falls, and subsequent erosion by glacial outburst floods. Discussion of the falls will include human history and the formation of Palouse Falls State Park. The main stop at Palouse Falls will explore the stratigraphy of the Columbia River Basalt Group, Vantage Member, loess islands, fracture zones, and human history dating back at least 12,000 yr. Driving south through Lyons Ferry State Park and the Tucannon Valley, we will discuss topics ranging from the Palouse Indians to sheep herding and from clastic dikes to terracettes.