bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-Scale Methodology for URANS/Large Eddy Simulation Solutions of Unsteady Turbomachinery Flows
Authors: He L. , Yi J.
Published: May 2017

A general issue in turbomachinery flow computations is how to capture and resolve two kinds of unsteadiness efficiently and accurately: (a) deterministic disturbances with temporal and spatial periodicities linked to blade count and rotational speed and (b) nondeterministic disturbances including turbulence and self-excited coherent patterns (e.g., vortex shedding, shear layer instabilities, etc.) with temporal and spatial wave lengths unrelated to blade count and rotational speed. In particular, the high cost of large eddy simulations (LES) is further compounded by the need to capture the deterministic unsteadiness of bladerow interactions in computational domains with large number of blade passages. This work addresses this challenge by developing a multiscale solution approach. The framework is based on an ensemble-averaging to split deterministic and nondeterministic disturbances. The two types of disturbances can be solved in suitably selected computational domains and solvers, respectively. The local fine mesh is used for nondeterministic turbulence eddies and vortex shedding, while the global coarse mesh is for deterministic unsteadiness. A key enabler is that the unsteady stress terms (UST) of the nondeterministic disturbances are obtained only in a small set of blade passages and propagated to the whole domain with many more passages by a block spectral mapping. This distinctive multiscale treatment makes it possible to achieve a high-resolution unsteady Reynolds-averaged Navier–Stokes (URANS)/LES solution in a multipassage/whole annulus domain very efficiently. The method description will be followed by test cases demonstrating the validity and potential of the proposed methodology.
Performance of a Diesel Engine at High Coolant Temperatures
Authors: Adler Jonas , Bandhauer Todd
Published: May 2017

The current state of the art in waste heat recovery (WHR) from internal combustion engines (ICEs) is limited in part by the low temperature of the engine coolant. In the present study, the effects of operating a diesel engine at elevated coolant temperatures to improve utilization of engine coolant waste heat are investigated. An energy balance was performed on a modified three-cylinder diesel engine at six different coolant temperatures (90 °C, 100 °C, 125 °C, 150 °C, 175 °C, and 200 °C) and 15 different engine loads to determine the impact on waste heat as the coolant temperature increased. The relative brake efficiency of the engine alone decreased between 4.5% and 7.3% as the coolant temperature was increased from 90 °C to 150 °C. However, the engine coolant exergy increased between 20% and 40% over the same interval. The exhaust exergy also increased between 14% and 28% for a total waste heat exergy increase between 19% and 25%. The engine condition was evaluated after testing and problem areas were identified such as overexpansion of pistons, oil breakdown at the piston rings, and head gasket seal failure.
Computing the Exergy of Solar Radiation From Real Radiation Data
Authors: Neri Manuela , Luscietti Davide , Pilotelli Mariagrazia
Published: May 2017

The decrease of fossil fuels availability and the consequent increase of their price have led to a rapid evolution of renewable market and policy frameworks in recent years. Renewable resources include solar radiation, which is of considerable interest as it is inexhaustible, free, and clean. In order to calculate how much work can be obtained from solar radiation, several methods have been proposed in the literature and are here reviewed. In this paper, a single exergy factor to be applied to the total radiation measured on horizontal surface in a given place is proposed. The factor is estimated from both direct and diffuse radiation.
Effect of Flow Area to Fluid Power and Turbine Pressure Drop Factor of Solar Chimney Power Plants
Authors: Zhou Xinping , Xu Yangyang , Hou Yaxiong
Published: May 2017

In this paper, a theoretical model of solar chimney power plants (SCPPs) is presented based on compressible ideal gas law assumptions. The theoretical optimal turbine pressure drop factors (TPDFs) for constant and nonconstant densities (CD and NCD) are studied, and the effects of flow area parameters examined. Results show that the theoretical optimal TPDF for CD is equal to 2/3 and is independent of the flow area parameters. Results also show that the theoretical optimal TPDF for NCD is close to 1 and is affected by the flow area parameters. However, the theoretical maximum fluid power (MFP) obtained for NCD is never attained in real life. For the actual states, the theoretical optimal TPDF for NCD is still effectively high enough. The TPDF and the fluid power for NCD increase with the reduction of the collector inlet area, and more precisely with the reduction of the chimney inlet area. The TPDF and the fluid power definitely increase with larger chimney flow area. The increase in the fluid power due to shape optimization of the SCPP is limited compared to that due to higher input heat flux of collector. Divergent-top and upward slanting roof shapes are recommended for the solar chimney and the solar collector, respectively, for better SCPP performance. Additionally, locations exposed to strong solar radiation are preferred for SCPPs.
Bio-Inspired Heuristic Network Configuration in Air Transportation System-of-Systems Design Optimization
Authors: Chamseddine Ibrahim M. , Kokkolaras Michael
Published: May 2017

Previous work in air transportation system-of-systems (ATSoSs) design optimization considered integrated aircraft sizing, fleet allocation, and route network configuration. The associated nested multidisciplinary formulation posed a numerically challenging blackbox optimization problem; therefore, direct search methods with convergence properties were used to solve it. However, the complexity of the blackbox impedes greatly the solution of larger-scale problems, where the number of considered nodes in the route network is high. The research presented here adopts a rule-based route network design inspired by biological transfer principles. This bio-inspired approach decouples the network configuration problem from the optimization loop, leading to significant numerical simplifications. The usefulness of the bio-inspired approach is demonstrated by comparing its results to those obtained using the nested formulation for a 15 city network. We then consider introduction of new aircraft as well as a larger problem with 20 cities.
Chinchilla middle ear transmission matrix model and middle-ear flexibility
Authors: Ravicz Michael E. , Rosowski John J.
Published: May 2017

The function of the middle ear (ME) in transforming ME acoustic inputs and outputs (sound pressures and volume velocities) can be described with an acoustic two-port transmission matrix. This description is independent of the load on the ME (cochlea or ear canal) and holds in either direction: forward (from ear canal to cochlea) or reverse (from cochlea to ear canal). A transmission matrix describing ME function in chinchilla, an animal commonly used in auditory research, is presented, computed from measurements of forward ME function: input admittance YTM, ME pressure gain GMEP, ME velocity transfer function HV, and cochlear input admittance YC, in the same set of ears [Ravicz and Rosowski (2012b). J. Acoust. Soc. Am. 132, 2437–2454; (2013a). J. Acoust. Soc. Am. 133, 2208–2223; (2013b). J. Acoust. Soc. Am. 134, 2852–2865]. Unlike previous estimates, these computations require no assumptions about the state of the inner ear, effectiveness of ME manipulations, or measurements of sound transmission in the reverse direction. These element values are generally consistent with physical constraints and the anatomical ME “transformer ratio.” Differences from a previous estimate in chinchilla [Songer and Rosowski (2007). J. Acoust. Soc. Am. 122, 932–942] may be due to a difference in ME flexibility between the two subject groups.
Sound-field measurement with moving microphones
Authors: Katzberg Fabrice , Mazur Radoslaw , Maass Marco , Koch Philipp , Mertins Alfred
Published: May 2017

Closed-room scenarios are characterized by reverberation, which decreases the performance of applications such as hands-free teleconferencing and multichannel sound reproduction. However, exact knowledge of the sound field inside a volume of interest enables the compensation of room effects and allows for a performance improvement within a wide range of applications. The sampling of sound fields involves the measurement of spatially dependent room impulse responses, where the Nyquist-Shannon sampling theorem applies in the temporal and spatial domains. The spatial measurement often requires a huge number of sampling points and entails other difficulties, such as the need for exact calibration of a large number of microphones. In this paper, a method for measuring sound fields using moving microphones is presented. The number of microphones is customizable, allowing for a tradeoff between hardware effort and measurement time. The goal is to reconstruct room impulse responses on a regular grid from data acquired with microphones between grid positions, in general. For this, the sound field at equidistant positions is related to the measurements taken along the microphone trajectories via spatial interpolation. The benefits of using perfect sequences for excitation, a multigrid recovery, and the prospects for reconstruction by compressed sensing are presented.
Zero-group velocity modes in plates with continuous material variation through the thickness
Authors: Tofeldt Oskar , Ryden Nils
Published: May 2017

Lamb modes with zero group velocity at nonzero wave numbers correspond to local and stationary resonances in isotropic plates. Lamb modes can be utilized for nondestructive evaluation of the elastic properties and thickness. One example of an application is the testing of plate-like concrete structures. In this example, continuous variation in the material velocity through the thickness may occur. This is usually not accounted for in analyses, and with this as starting point, two inhomogeneous and nonsymmetric cases with continuous material variations are investigated using a semi-analytical finite element technique and a simulated measurement application. In a numerical study limited to the lowest zero-group velocity mode, results show that these modes for the inhomogeneous cases are generated with similar behavior and the same detectability as in the case of an isotropic plate. However, a complex relationship between mode frequency and material velocity exists for the inhomogeneous cases. This hinders the evaluation and interpretation of representative estimations such as those for a cross-sectional mean value of the plate properties. This may lead to errors or uncertainties in practical applications.
Physiological effects of railway vibration and noise on sleep
Authors: Smith Michael G. , Croy Ilona , Ögren Mikael , Hammar Oscar , Lindberg Eva , Persson Waye Kerstin
Published: May 2017

This paper evaluates the relative contribution of vibration and noise from railway on physiological sleep outcomes. Vibration from railway freight often accompanies airborne noise, yet is almost totally absent in the existing literature. In an experimental investigation, 23 participants, each sleeping for six nights in the laboratory, were exposed to 36 simulated railway freight pass-bys per night with vibration alone (aWd,max = 0.0204 ms−2), noise alone (LAF,max = 49.8 dB), or both vibration and noise simultaneously. A fourth exposure night involved 52 pass-bys with concurrent vibration and noise. Sleep was measured with polysomnography. Cardiac activity was measured with electrocardiography. The probability of cortical arousals or awakenings was greater following all exposures, including vibration alone, than spontaneous reaction probability (p < 0.05). The effects of vibration exposure and noise exposure on changes of sleep stage and arousals were directly additive. Vibration and noise exposure both induced heart rate acceleration above spontaneously expected fluctuations at baseline. The results indicate that vibration and noise are processed in the brain separately yet in parallel, with both contributing towards the likelihood of sleep disruption. The findings show that vibration is of importance when considering the impact of railway freight on sleep.
Visualizing the movement of the contact between vocal folds during vibration by using array-based transmission ultrasonic glottography
Authors: Jing Bowen , Chigan Pengju , Ge Zhengtong , Wu Liang , Wang Supin , Wan Mingxi
Published: May 2017

For the purpose of noninvasively visualizing the dynamics of the contact between vibrating vocal fold medial surfaces, an ultrasonic imaging method which is referred to as array-based transmission ultrasonic glottography is proposed. An array of ultrasound transducers is used to detect the ultrasound wave transmitted from one side of the vocal folds to the other side through the small-sized contact between the vocal folds. A passive acoustic mapping method is employed to visualize and locate the contact. The results of the investigation using tissue-mimicking phantoms indicate that it is feasible to use the proposed method to visualize and locate the contact between soft tissues. Furthermore, the proposed method was used for investigating the movement of the contact between the vibrating vocal folds of excised canine larynges. The results indicate that the vertical movement of the contact can be visualized as a vertical movement of a high-intensity stripe in a series of images obtained by using the proposed method. Moreover, a visualization and analysis method, which is referred to as array-based ultrasonic kymography, is presented. The velocity of the vertical movement of the contact, which is estimated from the array-based ultrasonic kymogram, could reach 0.8 m/s during the vocal fold vibration.
Exercise and Dementia in Nursing Homes: Views of Staff and Family Carers
Authors: Brett Lindsey , Traynor Victoria , Stapley Paul , Meedya Shahla
Published: May 2017

This paper reports the qualitative component of a randomized controlled trial which evaluated the impact and feasibility of a physical exercise intervention on individuals living with dementia in nursing homes. Interviews were conducted with 10 staff and nine family carers about their views and opinions of physical exercise (n = 19). Thematic content analysis revealed both benefits and barriers to physical exercise for individuals living with dementia in nursing homes. Another theme was the influences of knowledge and understanding on individuals’ views of physical exercise. The involvement of staff and family carers in research encourage their involvement in the implementation of research into clinical practice. This can help to improve provisions of meaningful and beneficial activities for individuals living with dementia in nursing homes. The views and opinions of individuals living with dementia in nursing homes were not considered, though it would be beneficial to include them in future research.
Active Travel to and From School Among School-Age Children During 1997–2011 and Associated Factors in China
Authors: Yang Yong , Hong Xue , Gurney James G. , Wang Youfa
Published: May 2017

Background:

Active travel to school (ATS) is positively associated with various health indicators. The rapid social, economic, and environmental changes in China provide a unique setting to study changes and predictors of ATS over time.

Methods:

Using logistic regression modeling, we analyzed data from the China Health and Nutrition Survey during 1997 to 2011 (N = 9487, ages 6 to 17 years) to estimate the change over time in ATS and to identify associated factors.

Results:

The prevalence of reported ATS among children dropped from 95.8% in 1997 to 69.3% in 2011. ATS was common in children living closer to school, in middle school, from low-income households, with low parental education status, and those without a private vehicle. Children who were living in a metropolitan area and who had more than 40 minutes of total PA per day were less likely to report ATS.

Conclusions:

The decrease of ATS had been concurrent with the increase of the children living at a longer distance from school and the increase of household owning private vehicles which were associated with the rapid urbanization and economic growth in China. Factors associated with the decreased ATS in China are similar to other countries but the underlying reasons may be different.
Development of Physical Activity–Related Parenting Practices Scales for Urban Chinese Parents of Preschoolers: Confirmatory Factor Analysis and Reliability
Authors: Suen Yi-nam , Cerin Ester , Barnett Anthony , Huang Wendy Y.J. , Mellecker Robin R.
Published: May 2017

Background:

Valid instruments of parenting practices related to children’s physical activity (PA) are essential to understand how parents affect preschoolers’ PA. This study developed and validated a questionnaire of PA-related parenting practices for Chinese-speaking parents of preschoolers in Hong Kong.

Methods:

Parents (n = 394) completed a questionnaire developed using findings from formative qualitative research and literature searches. Test-retest reliability was determined on a subsample (n = 61). Factorial validity was assessed using confirmatory factor analysis. Subscale internal consistency was determined.

Results:

The scale of parenting practices encouraging PA comprised 2 latent factors: Modeling, structure and participatory engagement in PA (23 items), and Provision of appropriate places for child’s PA (4 items). The scale of parenting practices discouraging PA scale encompassed 4 latent factors: Safety concern/overprotection (6 items), Psychological/behavioral control (5 items), Promoting inactivity (4 items), and Promoting screen time (2 items). Test-retest reliabilities were moderate to excellent (0.58 to 0.82), and internal subscale reliabilities were acceptable (0.63 to 0.89).

Conclusion:

We developed a theory-based questionnaire for assessing PA-related parenting practices among Chinese-speaking parents of Hong Kong preschoolers. While some items were context and culture specific, many were similar to those previously found in other populations, indicating a degree of construct generalizability across cultures.
Do Sitting, Standing, or Treadmill Desks Impact Psychobiological Indicators of Work Productivity?
Authors: Gilson Nicholas D. , Hall Caitlin , Renton Angela , Ng Norman , von Hippel William
Published: May 2017

Background:

This pilot study investigated the links between psychobiological indicators of work productivity, prolonged desk sitting, and conditions whereby office workers were able to interrupt sitting using a sit–stand or treadmill desk.

Methods:

Twenty participants visited our laboratory and completed their own desk work in counterbalanced sit-only, sit–stand (Varidesk Pro Plus 48™), and sit–walk conditions (Infiniti TR1200-DTS™). Steady-state visually evoked potentials calculated from electroencephalography recordings during a set task at the end of the workday assessed attentional resource. Salivary cortisol samples were taken during the morning and afternoon to measure stress response. Within-subject analyses were used to compare work productivity indicators relative to condition.

Results:

No significant differences in mean steady-state visually evoked potential amplitude were observed, although attentional resource allocation was found to be the most effective following the sit–stand [1.01 (0.46) μV] compared with the sit–walk [0.9 (0.28) μV] and sit-only [0.91 (0.32) μV] conditions. The mean magnitude of decrease in cortisol was most apparent when workers used treadmill (1.5 nmol/L; P = .007) and sit–stand (1.6 nmol/L; P = .001) desks, and least evident in the sit-only condition (1.0 nmol/L; P = .146).

Conclusions:

The findings highlight the potential benefits of standing or active deskwork to the allocation of attentional resources and the regulation of stress.
Infraspinatus Isolation During External Rotation Exercise at Varying Degrees of Abduction
Authors: Ryan Gareth , Johnston Heather , Moreside Janice
Published: May 2017

Context: External rotation (ER) strengthening exercises are a common component of shoulder injury prevention and rehabilitation programs. They are primarily intended to target the infraspinatus muscle, based on its role in glenohumeral stabilization and inferior humeral glide. ER also recruits the posterior deltoid, which can be undesirable due to its role in subacromial space narrowing. Objective: To determine the angle of humeral abduction that maximizes the infraspinatus to posterior deltoid activation ratio (INFRA/PD) during ER. Design: Within-subjects repeated-measures controlled lab trial. Participants: A total of 10 healthy participants (5 males, 5 females) aged 21 (0.67) years participated in the study. Intervention: 7 consecutive repetitions of ER at 7 different abduction angles ranging from 0° to 90°, with resistance normalized to 3% body mass. Main Outcome Measures: Surface electromyography was performed on the infraspinatus, middle deltoid, and posterior deltoid. Surface electromyography data were processed to determine absolute muscle activation as well as INFRA/PD at each abduction angle. Group means were compared between abduction angles using 1-way analysis of variance. Results: Abduction significantly reduced overall infraspinatus activity but increased posterior deltoid activity (P < .01). Average and peak INFRA/PD decreased as the angle of abduction increased (P < .001 and P < .01, respectively). Conclusion: Our findings suggest that ER should be performed in 0° of abduction to maximize infraspinatus isolation. Slight abduction, such as placing a towel under the humerus, as recommended by some clinicians, may improve patient comfort, but did not increase infraspinatus isolation in this study.
Biomechanical Comparison of Countermovement Jumps Performed on Land and in Water: Age Effects
Authors: Louder Talin , Dolny Dennis , Bressel Eadric
Published: May 2017

Context: The aquatic environment provides a low-impact alternative to land-based exercise and rehabilitation in older adults. Objective: Evaluate the biomechanics of older adults and young adults performing jumping movements on land and in water. Design and Setting: Cross-sectional, mixed-factorial experiment; adjustable-depth pool at sports medicine research facility. Participants: Fifty-six young adults (age = 22.0 [3.9] y) and 12 healthy older adults (age = 57.3 [4.4] y). Interventions: Each participant performed 6 maximal effort countermovement jumps: 3 jumps were performed on land, and 3 other jumps were performed with participants immersed in chest-deep water. Main Outcome Measures: Using data from the amortization and propulsive phases of jumping, the authors computed the following kinetic and kinematic measures: peak and mean mechanical power, peak force, amortization time and rate, unweighting and propulsive times, and lower-extremity segment kinematics. Results: Mechanical power outputs were greater in younger adults (peak: 7322 [4035] W) versus older adults (peak: 5661.65 [2639.86] W) and for jumps performed in water (peak: 9387 [3981] W) versus on land (peak: 4545.84 [1356.53] W). Peak dorsiflexion velocities were greater for jumps performed in water (66 [34] deg/s) versus on land (4 [7] deg/s). The amortization rate was 26% greater in water versus on land. The amortization time was 20% longer in older adults versus young adults. Conclusions: Countermovement jumps performed in water are mechanically specific from those performed on land. Older adults jumped with longer unweighting times and increased mechanical power in water. These results suggest that aquatic-based exercise and rehabilitation programs that feature jumping movements may benefit older adults.
Application of Acoustic Radiation Force Impulse Elastography in Imaging of Delayed Onset Muscle Soreness: A Comparative Analysis With 3T MRI
Authors: Hotfiel Thilo , Kellermann Marion , Swoboda Bernd , Wildner Dane , Golditz Tobias , Grim Casper , Raithel Martin , Uder Michael , Heiss Rafael
Published: May 2017

Context: Delayed onset muscle soreness is one of the most common reasons for impaired muscle performance in sports and is associated with reduced muscle strength and frequently observed both in professional and recreational athletes. Objective: To emphasize the diagnostic value of acoustic radiation force impulse (ARFI) in imaging of delayed onset muscle soreness by comparing findings with high-resolution 3T magnetic resonance imaging T2-weighted sequences. Design: Case series. Setting: Laboratory environment. Participants: Fifteen healthy students (7 females and 8 males; mean [SD]: age 24 [4] y, height 178 [10] cm, body weight 67 [12] kg). Main Outcome Measures: ARFI values, represented as shear wave velocities of the gastrocnemius muscle and soleus muscle, as well as conventional ultrasound, high-resolution 3T magnetic resonance imaging, creatine kinase activity, extension range of the ankle joint, calf circumference, and muscle soreness were assessed before (baseline) and 60 hours after (postintervention) a standardized eccentric exercise. Results: ARFI shear wave velocity values of the gastrocnemius muscle revealed a statistically significant decrease of 19.1% between baseline (2.2 [0.26] m/s) and postintervention (1.78 [0.24] m/s); P = .01. At follow-up, the magnetic resonance imaging investigations showed intramuscular edema for the gastrocnemius muscle in all participants corresponding to a significant raise in T2 signal intensity (P = .001) and in T2-time values (P = .004). Conclusions: ARFI elastography seems to be an additional sensitive diagnostic modality in the diagnostic workup of delayed onset muscle soreness. Intramuscular shear wave velocities could represent an additional imaging marker for the assessment and monitoring of ultrastructural muscle injuries and therefore be helpful for individual training composition in elite sports.
Short-Term Effects of Kinesio Taping on Muscle Recruitment Order During a Vertical Jump: A Pilot Study
Authors: Mendez-Rebolledo Guillermo , Ramirez-Campillo Rodrigo , Guzman-Muñoz Eduardo , Gatica-Rojas Valeska , Dabanch-Santis Alexis , Diaz-Valenzuela Francisco
Published: May 2017

Context: Kinesio taping is commonly used in sports and rehabilitation settings with the aim of prevention and treatment of musculoskeletal injuries. However, limited evidence exists regarding the effects of 24 and 72 hours of kinesio taping on trunk and lower limb neuromuscular and kinetic performance during a vertical jump. Objective: The purpose of this study was to analyze the short-term effects of kinesio taping on height and ground reaction force during a vertical jump, in addition to trunk and lower limb muscle latency and recruitment order. Design: Single-group pretest–posttest. Setting: University laboratory. Participants: Twelve male athletes from different sports (track and field, basketball, and soccer). Interventions: They completed a single squat and countermovement jump at basal time (no kinesio taping), 24, and 72 hours of kinesio taping application on the gluteus maximus, biceps femoris, rectus femoris, gastrocnemius medialis, and longissimus. Main Outcome Measures: Muscle onset latencies were assessed by electromyography during a squat and countermovement jump, in addition to measurements of the jump height and normalized ground reaction force. Results: The kinesio taping had no effect after 24 hours on either the countermovement or squat jump. However, at 72 hours, the kinesio taping increased the jump height (P = .02; d = 0.36) and normalized ground reaction force (P = .001; d = 0.45) during the countermovement jump. In addition, 72-hour kinesio taping reduced longissimus onset latency (P = .03; d = 1.34) and improved muscle recruitment order during a countermovement jump. Conclusions: These findings suggest that kinesio taping may improve neuromuscular and kinetic performance during a countermovement jump only after 72 hours of application on healthy and uninjured male athletes. However, no changes were observed on a squat jump. Future studies should incorporate a control group to verify kinesio taping’s effects and its influence on injured athletes.
Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis
Authors: Rizzuto Gabrielle , Tagliani Elisa , Manandhar Priyanka , Erlebacher Adrian , Bakardjiev Anna I.
Published: May 2017

The bacterial pathogenListeria monocytogenescauses foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics ofL. monocytogenesinfection in primary human decidual organ cultures and in the murine deciduain vivo. A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses againstL. monocytogenesin the spleen, as well as a decrease in the tissue density of inflammatory Ly6Chimonocytesin vivo. These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment ofL. monocytogenesto the gestational uterus but rather is due to compromised local innate cellular immune responses.
Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C Virus Glycoprotein E2
Authors: Vasiliauskaite Ieva , Owsianka Ania , England Patrick , Khan Abdul Ghafoor , Cole Sarah , Bankwitz Dorothea , Foung Steven K. H. , Pietschmann Thomas , Marcotrigiano Joseph , Rey Felix A. , Patel Arvind H. , Krey Thomas
Published: May 2017

The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site. A detailed interaction analysis of DAO5 and cross-competing neutralizing antibodies with soluble E2 revealed that the Ig-like domain is trapped by different antibodies in at least two distinct conformations. DAO5 specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5-captured HCVpp can be blocked by a cross-competing neutralizing antibody, indicating that a single virus particle simultaneously displays E2 molecules in more than one conformation on its surface. Such conformational plasticity of the HCV E2 receptor binding site has important implications for immunogen design.

IMPORTANCE
Recent advances in the treatment of hepatitis C virus (HCV) infection with direct-acting antiviral drugs have enabled the control of this major human pathogen. However, due to their high costs and limited accessibility in combination with the lack of awareness of the mostly asymptomatic infection, there is an unchanged urgent need for an effective vaccine. The viral glycoprotein E2 contains regions that are crucial for virus entry into the host cell, and antibodies that bind to these regions can neutralize infection. One of the major targets of neutralizing antibodies is the central immunoglobulin (Ig)-like domain within E2. We show here that this Ig-like domain is conformationally flexible at the surface of infectious HCV particles and pseudoparticles. Our study provides novel insights into the interactions of HCV E2 with the humoral immune system that should aid future vaccine development.
Glutathionylation of
Yersinia pestis
LcrV and Its Effects on Plague Pathogenesis
Authors: Mitchell Anthony , Tam Christina , Elli Derek , Charlton Thomas , Osei-Owusu Patrick , Fazlollahi Farbod , Faull Kym F. , Schneewind Olaf
Published: May 2017

Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that
Yersinia pestis
LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys
273
and that this modification promotes association with host ribosomal protein S3 (RPS3), moderates
Y. pestis
type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys
273
Ala in
lcrV
. Moreover, the
lcrV

C273A

mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys
273
Ala substitution. Furthermore, macrophages infected by the
lcrV

C273A

variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of
gshB
, which encodes glutathione synthetase of
Y. pestis
, resulted in undetectable levels of intracellular glutathione, and we used a
Y. pestis
Δ
gshB
mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione.

IMPORTANCE
Yersinia pestis
, the causative agent of plague, has killed large segments of the human population; however, the molecular bases for the extraordinary virulence attributes of this pathogen are not well understood. We show here that LcrV, the cap protein of bacterial type III secretion needles, is modified by host glutathione and that this modification contributes to the high virulence of
Y. pestis
in mouse and rat models for bubonic plague. These data suggest that
Y. pestis
exploits glutathione in host tissues to activate a virulence strategy, thereby accelerating plague pathogenesis.
The Fungal Cell Wall: Structure, Biosynthesis, and Function
Authors: Gow Neil A. R. , Latge Jean-Paul , Munro Carol A.
Published: May 2017

The molecular composition of the cell wall is critical for the biology and ecology of each fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major cell wall components of fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of fungal walls. For similar reasons the enzymes that assemble fungal cell wall components are excellent targets for antifungal chemotherapies and fungicides. However, for fungal pathogens, the cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on fungal cell walls are moving from a descriptive phase defining the underlying genes and component parts of fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of cell walls and how the cell wall is targeted by immune recognition systems and the design of antifungal diagnostics and therapeutics.
The Role of ESX-1 in
Mycobacterium tuberculosis
Pathogenesis
Authors: Wong Ka-Wing
Published: May 2017

In this article, we have described several cellular pathological effects caused by the
Mycobacterium tuberculosis
ESX-1. The effects include induction of necrosis, NOD2 signaling, type I interferon production, and autophagy. We then attempted to suggest that these pathological effects are mediated by the cytosolic access of
M. tuberculosis
-derived materials as a result of the phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity of ESAT-6 is most likely due to its pore-forming activity at the membrane. The amyloidogenic characteristic of ESAT-6 is reviewed here as a potential mechanism of membrane pore formation. In addition to ESAT-6, the ESX-1 substrate EspB interferes with membrane-mediated innate immune mechanisms such as efferocytosis and autophagy, most likely through its ability to bind phospholipids. Overall, the
M. tuberculosis
ESX-1 secretion system appears to be a specialized system for the deployment of host membrane-targeting proteins, whose primary function is to interrupt key steps in innate immune mechanisms against pathogens. Inhibitors that block the ESX-1 system or block host factors critical for ESX-1 toxicity have been identified and should represent attractive potential new antituberculosis drugs.
Duodenal biopsies for the diagnosis of coeliac disease: are we adhering to current guidance?
Authors: Husnoo Nilofer , Ahmed Wafaa , Shiwani Muhammad Hanif
Published: May 2017

Background

The British Society of Gastroenterology guidelines recommend taking at least four duodenal biopsy specimens at the time of upper gastrointestinal (UGI) endoscopy if coeliac disease (CD) is suspected and it has been shown to increase the diagnostic yield of CD. We assessed the compliance to these guidelines within our institution. We then applied measures to improve our compliance rate and assessed the resulting impact on our diagnostic rate of CD.

Methods

We performed a retrospective audit of electronic records for all patients, with no prior diagnosis of CD, who underwent UGI endoscopy with duodenal biopsies between August 2014 and May 2015. We implemented measures to raise awareness among endoscopy users at our institution and carried out a reaudit between February and May 2016.

Results

924 patients were found to be eligible in the first part of the study and 278 in the second part. The proportion of patients who had ≥4 biopsy specimens submitted increased from 21.9% to 60.8% (p<0.001). The diagnostic rate of CD increased from 3.5% in the audit group to 7.6% in the reaudit group (p=0.004). A positive serology result and suspected CD as an indication for biopsy were found to be independent predictors of the likelihood of complying with guidelines.

Conclusions

Our study suggests that taking <4 duodenal biopsy specimens to assess for the presence of CD may lead to the diagnosis of CD being missed. Simple measures can improve the local compliance rate to current guidelines.
Risk and outcomes of aortic valve endocarditis among patients with bicuspid and tricuspid aortic valves
Authors: Kiyota Yuka , Della Corte Alessandro , Montiero Vieira Vanessa , Habchi Karam , Huang Chuan-Chin , Della Ratta Ester E , Sundt Thoralf M , Shekar Prem , Muehlschlegel Jochen D , Body Simon C
Published: May 2017

Objective

Patients with structural abnormalities of cardiac valves, including bicuspid aortic valve (BAV), are said to be at higher risk of infective endocarditis (IE). We sought to determine the risk of IE of the BAV compared with the tricuspid aortic valve (TAV) and to determine the risk of aortic valve replacement and mortality after IE.

Methods

From medical records of two US and one Italian hospitals, patients with their first episode of IE of any native valve were identified. In the US cohort 42 patients with BAV and 393 patients with TAV with IE occurring between 1 January 2000 and 30 June 2014 were identified. In the Italian cohort 48 patients with BAV and 341 patients with TAV with IE underwent valve replacement surgery between 1 January 2000 and1 November 2015. The risk of IE for BAV and TAV and subsequent outcomes were determined after matching to patients without IE.

Results

After adjustment for risk factors, the risk of IE in the US cohort was 23.1 (95% CI 8.1 to 100, p <0.0001) times greater for BAV than TAV. Patients with BAV with IE were more likely to have an aortic root abscess. Within the subsequent 5 years, BAV patients with IE were more likely to undergo valve replacement (85%) than TAV patients with IE (46%). Patients with IE were at increased risk of death. The findings were similar in the Italian cohort.

Conclusions

Patients with BAV are at markedly increased risk of IE and aortic root abscess than patients with TAV. Increased risk of IE in patients with BAV indicates they may be a candidate group for long-term trials of antibiotic prophylaxis of IE.
Syndromes of orthostatic intolerance and syncope in young adults
Authors: Hamrefors Viktor , Spahic Jasmina Medic , Nilsson David , Senneby Martin , Sutton Richard , Melander Olle , Fedorowski Artur
Published: May 2017

Objective

To explore the clinical and neuroendocrine characteristics of syndromes of orthostatic intolerance and syncope in young adults.

Methods

Two hundred and thirty-six patients aged 18–40 years with orthostatic intolerance and/or syncope were examined by head-up tilt test (HUT). Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1 and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were analysed. Patients’ history, haemodynamic parameters and plasma biomarkers were related to main diagnoses such as vasovagal syncope (VVS), postural tachycardia syndrome (POTS), orthostatic hypotension (OH) and negative HUT.

Results

No self-reported symptom of orthostatic intolerance was highly specific for any diagnosis. Patients with VVS (n=103) were more likely to be men (p=0.011) and had lower resting heart rate (HR; 66±11) compared with POTS (73±11; n=72; p=0.001) and negative HUT (74±11; n=39; p=0.001). Patients with POTS demonstrated greater rise in norepinephrine (p=0.008) and CT-proAVP (p=0.033) on standing compared with negative HUT, and lower resting MR-proANP compared with VVS (p=0.04) and OH (p=0.03). Patients with OH had lower resting renin (p=0.03). Subjects with a resting HR <70 and MR-proANP >45 pm/L had an OR of 3.99 (95 % CI 1.68 to 9.52; p=0.002) for VVS compared with subjects without any of these criteria; if male sex was added the OR was 21.8 (95% CI 3.99 to 119; p<0.001).

Conclusions

Syndromes of orthostatic intolerance and syncope share many characteristics in younger persons. However, patients with VVS are more likely to be men, have lower HR and higher MR-proANP at rest compared with POTS, which might be taken into account at an early stage of evaluation.
Survey on antimicrobial prescribing patterns in small animal veterinary practice in Emilia Romagna, Italy
Authors: Barbarossa A. , Rambaldi J. , Miraglia V. , Giunti M. , Diegoli G. , Zaghini A.
Published: May 2017

This investigation provides for the first time a general view of the prescribing patterns of antimicrobials in small animal practice in Emilia Romagna, Italy. In the context of a project on antimicrobial resistance managed by the Regional Veterinary Service, veterinary clinicians were invited to voluntarily complete an online questionnaire. This was designed to gather information on antimicrobial prescribing practices and biosecurity measures and to understand the perception of the issue specific to this region of Italy. In total, 266 questionnaires correctly completed were collected. Although clinicians seemed to follow different approaches when using antimicrobials, the data analysis revealed a general awareness on resistance. Penicillins were the most commonly prescribed class, followed by (fluoro)quinolones and cephalosporins. Among those who use laboratory testing more or less frequently (microbiological analysis and susceptibility testing) to support their prescribing habits, only 7 per cent make a habit of always waiting for the results before starting the treatment. Seventy‐eight per cent of the respondents declared the use of antimicrobials licensed for human beings. Biosecurity measures were carefully taken into account by the majority of the veterinarians. The results identified the antimicrobial classes that are commonly prescribed and highlighted that perioperative hygiene measures and the use of laboratory diagnosis are critical aspects that need to be emphasised in drawing up guidelines on the prudent use of these drugs in pets.
Identification, assessment and management of new and re‐emerging animal‐related risks: UK perspective
Authors: Kosmider R. , Gibbens J. , Avigad R.
Published: May 2017

Veterinary surveillance programmes aim to reduce the burden to the public, livestock and wider society posed by animal‐related ‘risks’ (referred to as ‘threats’ later in the paper in line with a definition used by the European Food Safety Authority) including the re‐emergence of diseases believed absent or eradicated. To achieve this, it is important to have a systematic approach to identifying and dealing with such threats rapidly and effectively. This paper describes the transparent, systematic and auditable process used for identifying, assessing, escalating and prioritising new and re‐emerging animal‐related threats in the UK. This has been achieved through the establishment of a Veterinary Risk Group in late 2009.
A bioenergetics systems evaluation of ketogenic diet liver effects
Authors: Hutfles Lewis J. , Wilkins Heather M. , Koppel Scott J. , Weidling Ian W. , Selfridge J. Eva , Tan Eephie , Thyfault John P. , Slawson Chad , Fenton Aron W. , Zhu Hao , Swerdlow Russell H.
Published: May 2017

Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.
Cholic acid dimers as invertible amphiphilic pockets: synthesis, molecular modeling, and inclusion studies
Authors: Zhang Meng , Levaray Nicolas , Daniel Josée R. , Waldron Karen C. , Zhu X.X.
Published: May 2017

Two dimers of cholic acid were synthesized through simple covalent linkers. The dimers form invertible molecular pockets in media of different polarity; hydrophobic pockets are formed in water and hydrophilic pockets are formed in organic media. Fluorescence studies show that pockets formed by these dimers can serve as invertible hosts for the hydrophobic guest pyrene and the hydrophilic guest coumarin 343. The molecular pocket also enhances dissolution of the weakly soluble cresol red sodium salt in organic media. Molecular modeling was performed to better understand the host–guest complexation process of the invertible amphiphilic pockets. The calculated free energy changes indicate that the two dimers form the most stable complexes with coumarin 343 at a host to guest ratio of 2:2, whereas the host to guest ratio differs in the formation of complexes with pyrene for the two dimers. The dimer with the shorter, less flexible linker seems to form host–guest complexes that are more stable in both water and organic solvents.