bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Hot Electron Scattering and Electron–Phonon Interactions on Thermal Boundary Conductance at Metal/Nonmetal Interfaces
Authors: Giri Ashutosh , Foley Brian M. , Hopkins Patrick E.
Published: May 2014

It has recently been demonstrated that under certain conditions of electron nonequilibrium, electron to substrate energy coupling could represent a unique mechanism to enhance heat flow across interfaces. In this work, we present a coupled thermodynamic and quantum mechanical derivation of electron–phonon scattering at free electron metal/nonmetal substrate interfaces. A simplified approach to the Fermi's Golden Rule with electron energy transitions between only three energy levels is adopted to derive an electron–phonon diffuse mismatch model, that account for the electron–phonon thermal boundary conductance at metal/insulator interfaces increases with electron temperature. Our approach demonstrates that the metal-electron/nonmetal phonon conductance at interfaces can be an order of magnitude larger than purely phonon driven processes when the electrons are driven out of equilibrium with the phonons, consistent with recent experimental observations.
Asymmetrical Heating in Rarefied Flows Through Circular Microchannels
Authors: Pamela Vocale , Marco Spiga
Published: May 2014

This work is aimed at contributing to the thermal analysis of slip flow through circular microducts, providing an analytical solution to the energy conservation equation for partially heated walls. A uniform wall heat flux (H2 boundary conditions) is considered on the heated perimeter of the cross section while the remaining arc length is assumed to be adiabatic. The gaseous flow is considered laminar, fully developed, in steady state condition, and forced convection. The temperature profile, wall temperature distribution, and Nusselt number are presented as functions of both the heated perimeter of the cross section and the Knudsen number, resorting to simple converging series of trigonometric functions. The proposed solution can be useful for the design of the microfluidic devices such as micro heat sinks and micro heat exchangers.
Investigation on the Stability of Parallel and Oblique Plates as Suppressors of Vortex-Induced Vibration of a Circular Cylinder
Authors: Assi Gustavo R. S. , Franco Guilherme S. , Vestri Michaelli S.
Published: May 2014

Experiments have been carried out with models of free-to-rotate parallel and oblique plates fitted to a rigid section of circular cylinder to investigate the effect of plate length and oblique angle on the stability of this type of vortex-induced vibration (VIV) suppressor. Measurements of the dynamic response and trajectories of motion are presented for models with low mass and damping which are free to respond in the cross-flow and streamwise directions. It is shown that, depending on a combination of some geometric parameters, the devices might not be able to completely suppress VIV for the whole range of reduced velocities investigated. Plates with larger oblique angles turned to be less stable than parallel plates and induced high-amplitude vibrations for specific reduced velocities. Systems may present streamwise vibration due to strong flow separation and reattachment on the outer surface of plates with large oblique angles. Large angles may also increase drag. Experiments with a plain cylinder in the Reynolds number range from 3000 to 20,000 have been performed to serve as reference. Reduced velocity was varied between 2 and 13. Two-dimensional numerical simulation of static systems at Re = 10,000 revealed that complex and fully separated flow regimes exist for almost all investigated cases. There is a good chance that systems with such geometric characteristics will be unstable unless other structural parameters are positively verified.
Attenuation of Gas Pulsation in the Valve Chamber of a Reciprocating Compressor Using the Helmholtz Resonator
Authors: Jia Xiaohan , Liu Boxiang , Feng Jianmei , Peng Xueyuan
Published: June 2014

This paper presents testing and analysis results associated with a new control method based on the Helmholtz resonator to suppress the pressure pulsations in the valve chamber and cylinder nozzle of a reciprocating compressor. The characteristic response of the designed Helmholtz resonator was analyzed and its attenuation characteristics on the gas pulsation were investigated. A three-dimensional acoustic model of the gas pulsation was established by means of the finite element method (FEM) for a compressor discharge piping system with and without the resonator. The gas column natural frequencies of the piping system and the pressure wave profiles were predicted using the presented model and validated by comparing the simulated results with the experimental data. The results showed that the pressure pulsating amplitude in the valve chamber was reduced by 40.4% when the resonator was installed. If the resonance frequency of the resonator shifted from the cylinder nozzle characteristic frequency by a range of ±13%, the reduction in the pressure fluctuations within the valve chamber was about 24%. The best attenuation effectiveness on the valve chamber, a reduction of 47%, was obtained when two resonators were installed on the valve covers of both the head and crank ends. Two new frequencies of 40.4 Hz and 66.9 Hz appeared to replace the original cylinder nozzle characteristic frequency of 53.9 Hz with the Helmholtz resonator installation, and the corresponding resonance region was transferred from the valve chamber to the resonator.
Development of an Apparatus for Bilateral Rhythmical Training of Arm Movement Via Linear and Elliptical Trajectories of Various Directions
Authors: Matjačić Zlatko , Zadravec Matjaž , Oblak Jakob
Published: June 2014

Clinical rehabilitation of individuals with various neurological disorders requires a significant number of movement repetitions in order to improve coordination and restoration of appropriate muscle activation patterns. Arm reaching movement is frequently practiced via motorized arm cycling ergometers where the trajectory of movement is circular thus providing means for practicing a single and rather nonfunctional set of muscle activation patterns, which is a significant limitation. We have developed a novel mechanism that in the combination with an existing arm ergometer device enables nine different movement modalities/trajectories ranging from purely circular trajectory to four elliptical and four linear trajectories where the direction of movement may be varied. The main objective of this study was to test a hypothesis stating that different movement modalities facilitate differences in muscle activation patterns as a result of varying shape and direction of movement. Muscle activation patterns in all movement modalities were assessed in a group of neurologically intact individuals in the form of recording the electromyographic (EMG) activity of four selected muscle groups of the shoulder and the elbow. Statistical analysis of the root mean square (RMS) values of resulting EMG signals have shown that muscle activation patterns corresponding to each of the nine movement modalities significantly differ in order to accommodate to variation of the trajectories shape and direction. Further, we assessed muscle activation patterns following the same protocol in a selected clinical case of hemiparesis. These results have shown the ability of the selected case subject to produce different muscle activation patterns as a response to different movement modalities which show some resemblance to those assessed in the group of neurologically intact individuals. The results of the study indicate that the developed device may significantly extend the scope of strength and coordination training in stroke rehabilitation which is in current clinical rehabilitation practice done through arm cycling.
A Simple Empirical Model for Tube–Support Normal Impact Interaction
Authors: Azizian Reza , Mureithi Njuki
Published: June 2014

Flow-induced vibration in a steam generator may cause tube–support interaction. This long term interaction is a challenging problem as it may lead to tube fretting-wear and possibly tube failure. An estimation of the normal impact force during tube–support interaction is important to precisely quantify material removal. A precise study of the interaction presents several challenges as a result of the many parameters involved during the interaction, including fluid forces, number and type of supports, and geometry of contact. The present study investigates tube–support interaction using a simple experimental rig, consisting of a tube interacting with a flat support positioned at the tube midspan. The work investigates the normal force–displacement relationship and arrives at an estimation of empirical parameters, associated with the nonlinearity in this relationship. The resulting empirical model is used to simulate tube–support interaction for various gap sizes and excitation forces. Comparison with experiments indicates that using the nonlinear spring–damper model significantly reduces the predicted impact force error, to less than 20%, when compared to experimental tests. Various energy dissipation mechanisms during tube–support interaction, including impact and structural damping are also studied. The effect of impact damping on the tube response is investigated, using the Hunt and Crossley model. Investigation on structural damping suggests that using a higher effective structural damping during tube–support contact, depending upon tube–support gap size, improves the accuracy of the estimation of the tube response, at least for moderate gap sizes.
MicroRNAs as Therapeutic Targets and Biomarkers of Cardiovascular Disease
Authors: Olson Eric N.
Published: June 2014

MicroRNAs play central roles in cardiovascular disease, and their therapeutic manipulation raises exciting opportunities as well as challenges in the path toward clinical development.
Exposure of Bacillus subtilis to Low Pressure (5 Kilopascals) Induces Several Global Regulons, Including Those Involved in the SigB-Mediated General Stress Response
Authors: Waters Samantha M. , Robles-Martínez José A. , Nicholson Wayne L.
Published: May 2014

Studies of how microorganisms respond to pressure have been limited mostly to the extreme high pressures of the deep sea (i.e., the piezosphere). In contrast, despite the fact that the growth of most bacteria is inhibited at pressures below ∼2.5 kPa, little is known of microbial responses to low pressure (LP). To study the global LP response, we performed transcription microarrays on
Bacillus subtilis
cells grown under normal atmospheric pressure (∼101 kPa) and a nearly inhibitory LP (5 kPa), equivalent to the pressure found at an altitude of ∼20 km. Microarray analysis revealed altered levels of 363 transcripts belonging to several global regulons (AbrB, CcpA, CodY, Fur, IolR, ResD, Rok, SigH, Spo0A). Notably, the highest number of upregulated genes, 86, belonged to the SigB-mediated general stress response (GSR) regulon. Upregulation of the GSR by LP was confirmed by monitoring the expression of the SigB-dependent
ctc-lacZ
reporter fusion. Measuring transcriptome changes resulting from exposure of bacterial cells to LP reveals insights into cellular processes that may respond to LP exposure.
Plant-Pathogenic Oomycetes, Escherichia coli Strains, and Salmonella spp. Frequently Found in Surface Water Used for Irrigation of Fruit and Vegetable Crops in New York State
Authors: Jones Lisa A. , Worobo Randy W. , Smart Christine D.
Published: May 2014

In the United States, surface water is commonly used to irrigate a variety of produce crops and can harbor pathogens responsible for food-borne illnesses and plant diseases. Understanding when pathogens infest water sources is valuable information for produce growers to improve the food safety and production of these crops. In this study, prevalence data along with regression tree analyses were used to correlate water quality parameters (pH, temperature, turbidity), irrigation site properties (source, the presence of livestock or fowl nearby), and precipitation data to the presence and concentrations of
Escherichia coli
,
Salmonella
spp., and hymexazol-insensitive (HIS) oomycetes (
Phytophthora
and
Pythium
spp.) in New York State surface waters. A total of 123 samples from 18 sites across New York State were tested for
E. coli
and
Salmonella
spp., of which 33% and 43% were positive, respectively. Additionally, 210 samples from 38 sites were tested for HIS oomycetes, and 88% were found to be positive, with 10 species of
Phytophthora
and 11 species of
Pythium
being identified from the samples. Regression analysis found no strong correlations between water quality parameters, site factors, or precipitation to the presence or concentration of
E. coli
in irrigation sources. For
Salmonella
, precipitation (≤0.64 cm) 3 days before sampling was correlated to both presence and the highest counts. Analyses for oomycetes found creeks to have higher average counts than ponds, and higher turbidity levels were associated with higher oomycete counts. Overall, information gathered from this study can be used to better understand the food safety and plant pathogen risks of using surface water for irrigation.
Adult-onset Still's disease presenting as myopericarditis
Authors: Gonzalez Filipe André , Beirão Pedro , Adrião Joana , Coelho Margarida Lopes
Published: June 2014

A 24-year-old man presented to the emergency department with fever, maculopapular rash, myalgia and polyarthralgia, thoracic pain and dry cough, which had been present for 24 h. At the time of observation he had high fever (39°C), maculopapular rash on the torso, arms and legs proximally, axillary adenopathies and pharyngitis. Laboratorial data showed elevated inflammation markers (leukocytosis, C reactive protein of 44 mg/dL, erythrocyte sedimentation rate of 120 mm), elevated transaminases, lactate dehydrogenase, ferritin levels (>2000 ng/mL) and rising troponin. ECG had sinus rhythm and ST elevation in leads V1–V5. Thoracic radiography revealed bilateral interstitial infiltrate confirmed by CT scan. Echocardiographic findings included diffuse hypokinesia of the left ventricle and impaired systolic function. After the investigation of an infectious or autoimmune aetiology was negative, the diagnosis of adult-onset Still's disease was considered. The patient was put on a 60 mg/day prednisolone regimen with remission of symptoms and normalisation of systolic function and ECG.
Cluster-like headache responsive to phlebotomy
Authors: Khalil Modar , Yoga Bindu , Ahmed Fayyaz
Published: June 2014

We report the first case of cluster-like headache secondary to polycythaemia vera (PV) that responded to phlebotomy as part of PV treatment.
Prevention of head louse infestation: a randomised, double-blind, cross-over study of a novel concept product, 1% 1,2-octanediol spray versus placebo
Authors: Burgess Ian F , Brunton Elizabeth R , French Rebecca , Burgess Nazma A
Published: May 2014

Objectives

To determine whether regular use of a spray containing 1,2-octanediol 1%, which has been shown to inhibit survival of head lice, is able to work as a preventive against establishment of new infestations.

Setting

Randomised, double-blind, cross-over, community study in Cambridgeshire, UK.

Participants

63 male and female schoolchildren aged 4–16 years judged to have a high risk of recurrent infestation. Only the youngest member of a household attending school participated.

Interventions

Participants were treated to eliminate lice, randomised between 1% octanediol or placebo sprays for 6 weeks then crossed-over to the other spray for 6 weeks. Parents applied the sprays at least twice weekly or more frequently if the hair was washed. Investigators monitored weekly for infestation and replenished supplies of spray.

Primary and secondary outcome measures

The primary endpoint was the time taken until the first infestation event occurred. The secondary measure was safety of the product in regular use.

Results

Intention-to-treat analysis found a total of 32 confirmed infestations in 20 participants, with 9 of them infested while using both products. In these nine participants the time to first infestation showed a significant advantage to 1% octanediol (p=0.0129). Per-protocol analysis showed only trends because the population included was not large enough to demonstrate significance. There were no serious adverse events and only two adverse events possibly related to treatment, one was a case of transient erythema and another of a rash that resolved after 5 days.

Conclusions

Routine use of 1% octanediol spray provided a significant level of protection from infestation. It was concluded that this product is effective if applied regularly and thoroughly.

Trial registration number

ISRCTN09524995.
Patient evaluation of hospital outcomes: an analysis of open-ended comments from extreme clusters in a national survey
Authors: Iversen Hilde Hestad , Bjertnæs Øyvind Andresen , Skudal Kjersti Eeg
Published: May 2014

Objectives

A recent study identified patients in six distinct response groups based on their evaluations of outcomes related to overall satisfaction, malpractice and benefit of treatment. This study validates the response clusters by analysing and comparing open-ended comments from the extreme positive and extreme negative response groups.

Design

Qualitative content analysis.

Setting

Data from open-ended comment fields provided by patients who completed a national patient-experience survey carried out in Norway in 2011. 10 514 patients responded to the questionnaire and 3233 provided comments. A random sample of 50 open-ended comments from respondents representing cluster 1 (‘excellent services’), cluster 5 (‘services have clear improvement needs’) and outliers (‘very poor services’) was reviewed.

Results

3 distinct patient profiles were identified. More than half of the comments in cluster 1 included descriptions of positive healthcare experiences, one addressed patient safety issues. Only 1 of the comments in cluster 5 was positive, and 12 were related to safety. All comments from the outliers were negative, and more than three-quarters reported experiences related to malpractice or adverse events. Recurring themes did not differ significantly between the three respondent groups, but significant differences were found for the descriptions and severity of the experiences.

Conclusions

Patients in negative response groups had distinct and much poorer healthcare descriptions than those in the extreme positive group, supporting the interpretation of quality differences between these groups. Further research should assess ways of combining statistical cluster information and qualitative comments, which could be used for local quality improvement and public reporting.
Comparison of the ultra-low-doseVeoalgorithm with the gold standard filtered back projection for detecting pulmonary asbestos-related conditions: a clinical observational study
Authors: Tekath Marielle , Dutheil Frédéric , Bellini Romain , Roche Antoine , Pereira Bruno , Naughton Geraldine , Chamoux Alain , Michel Jean-Luc
Published: May 2014

Objectives

Radiation delivered during CT is a major concern, especially for individuals undergoing repeated screening. We aimed to compare a new ultra-low-dose algorithm calledVeowith the gold standard filtered back projection (FBP) for detecting pulmonary asbestos-related conditions.

Setting

University Hospital CHU G. Montpied, Clermont-Ferrand, France

Participants

Asbestos-exposed workers were recruited following referral to screening for asbestos-related conditions. Two acquisitions were performed on a 64-slice CT: the gold standard FBP followed byVeoreconstruction.

Outcome measures

Two radiologists independently assessed asbestos-related abnormalities, pulmonary nodules, radiation doses and image quality (noise).

Results

We included 27 asbestos-exposed workers (63.3±6.5 years with 11.9±9.7 years of asbestos exposure). We observed 297 pleural plaques in 20 participants (74%). All patients (100%) had pulmonary nodules, totalling 167 nodules. Detection rates did not differ for pleural plaques (Veo87% vs FBP 97%, NS), pleural thickening (100% for both) and pulmonary nodules (80% for both). Interstitial abnormalities were depicted less frequently withVeothan FBP. False negative and false positive did not exceed 2.7%. Compared with FBP,Veodecreased the radiation dose up to 87% (Veo0.23±0.07 vs FBP 1.83±0.88 mSv, p<0.001). The objective image noise also decreased withVeoas much as 23% and signal-to-noise ratio increased up to 33%.

Conclusions

A low-dose CT withVeoreconstruction substantially reduced radiation.Veocompared favourably with FBP in detecting pleural plaques, pleural thickening and pulmonary nodules. These results should be confirmed on a larger sample size before the use ofVeoin clinical routine practice in asbestos-related conditions, especially regarding the low prevalence of interstitial abnormalities in this study.

Trial registration number

NCT01955018.
Population, sex, and ontogenetic differences in the procurrent rays of the caudal fin in threespine sticklebacks (Gasterosteusaculeatus)
Authors: Reimchen T.E. , MacAdams J.C.
Published: June 2014

The procurrent rays occur at the leading edge of the caudal fin in bony fishes and are taxonomically variable and possibly important to caudal motion. Using radiographs, as well as stained and cleared specimens, of threespine sticklebacks (Gasterosteus aculeatus L., 1758) from lakes on Haida Gwaii, British Columbia, we examined the extent of individual and population variabilities in these rays. Among 1113 fish from Drizzle Lake, 53% of individuals were dorsoventrally asymmetric in number of rays of which 95% had greater number of rays on the dorsal lobe. On 274 fish, we also quantified dorsal to ventral (D/V) ratios of the width of the most posterior procurrent rays and found ontogenetic shifts with symmetrical D/V ratios in subadults shifting to significant dorsal biases on the larger fish (60–90 mm standard length (SL)). Males have proportionally greater dorsal bias than females of equivalent size in both number and width of procurrent rays. We examined D/V width ratios in 105 stained and cleared specimens from 13 additional allopatric lake populations on Haida Gwaii. Eight populations were symmetrical for width of dorsal and ventral rays, while three populations were ventrally biased and two populations were dorsally biased. D/V ratios were best predicted by positive associations with adult body size and negative associations with total number of gill rakers.
The nylon scintillator containment vessels for the Borexino solar neutrino experiment
Authors: Cadonati L. , Calaprice F. , Galbiati C. , Pocar A. , Shutt T.
Published: June 2014

The neutrino event rate in the Borexino scintillator is very low (~ 0.5 events per day per ton) and concentrated in an energy region well below the 2.6 MeV threshold of natural radioactivity. The intrinsic radioactive contaminants in the photomultipliers (PMTs), in the Stainless Steel Sphere, and in other detector components, play special requirements on the system required to contain the scintillator. The liquid scintillator must be shielded from the Stainless Steel Sphere and from the PMTs by a thick barrier of buffer fluid. The fluid barrier, in addition, needs to be segmented in order to contain migration of radon and daughters emanated by the Stainless Steel Sphere and by the PMTs. These requirements were met by designing and building two spherical vessel made of thin nylon film. The inner vessel contains the scintillator, separating it from the surrounding buffer. The buffer region itself is divided into two concentric shells by the second, outer nylon vessel. In addition, the two nylon vessels must satisfy stringent requirements for radioactivity and for mechanical, optical and chemical properties. This paper describes the requirements of the the nylon vessels for the Borexino experiment and offers a brief overview of the construction methods adopted to meet those requirements.
Analysis of radioactive trace impurities with μBq-sensitivity in Borexino
Authors: Simgen Hardy , Heusser Gerd , Laubenstein Matthias , Zuzel Grzegorz
Published: June 2014

BOREXINO has set new standards in the field of ultra-low background experiments. Such a success was only possible by a strict quality control program during the construction phase of the experiment. In this paper, we describe how construction materials and auxiliary systems of the BOREXINO detector were screened for their residual radioactivity with unprecedented high sensitivity. The highly sensitive assay techniques developed for this purpose were also used to validate the purity of water and nitrogen used in the experiment. Moreover, we report on the production of 222 Rn -free nitrogen and synthetic air with very low 222 Rn concentration as well as on the successful search for commercial nitrogen with a particularly low concentration of argon and krypton.
Data analysis in Borexino
Authors: Testera Gemma
Published: June 2014

The signal produced in Borexino by solar neutrinos interacting in the liquid scintillator has no particular signatures that allow to distinguish it from the background on a event-by-event basis. I recall the main features of the analysis method and, in particular, I describe three procedures that have been particularly implemented in Borexino and that are essential to extract the signal from the background: the reconstruction of the event position, the pulse shape discrimination and the three fold coincidence.
A family of polycyclic groups over which the uniform conjugacy problem is NP-complete
Authors: Cavallo Bren , Kahrobaei Delaram
Published: June 2014

In this paper, we study the conjugacy problem in polycyclic groups. Our main result is that we construct polycyclic groups Gn whose conjugacy problem is at least as hard as the subset sum problem with n indeterminates. As such, the uniform conjugacy problem over the groups Gn is NP-complete where the parameters of the problem are taken in terms of n and the length of the elements given on input.
Spherically symmetric solutions of multidimensional zero-pressure gas dynamics system
Authors: Choudhury Anupam Pal , Joseph K. T. , Sahoo Manas R.
Published: June 2014

We derive explicit formulae for spherically symmetric solutions to the system of multidimensional zero-pressure gas dynamics and its adhesion approximation. The asymptotic behavior of the explicit solutions of the adhesion approximation is studied here. We observe that the radial components of the velocity and density satisfy a simpler equation, which enables us to get explicit formulae for different types of domains and study its asymptotic behavior. A class of solutions to the inviscid system with conditions on the mass instead of conditions at origin is also analyzed here.
THE NEUROPROTECTIVE EFFECTS ON RETINAL STRUCTURE BY MINOCYCLINE IN A RAT MODEL OF HIGH IOP INDUCED RETINAL ISCHEMIA INJURY
Authors: Huang Pei-Yun , Lin Chung-Tien
Published: June 2014

The present study investigated the neuroprotective effect of minocycline, a microglial inhibitor, against the retinal ischemia–reperfusion (IR) injury in the rat. The retinal IR injury was induced in Sprague–Dawley (SD) rats by infusing normal saline into anterior chamber of eye to create a higher intraocular pressure (IOP) than blood pressure for 45 min. Minocycline (45 and 90 mg/kg/day) was administered intraperitoneally to rats receiving IR injury. The neuroprotective effects were evaluated by morphometrical histology analysis 7 days after ischemia. The data was compared with the groups treated with saline and methylprenisolone (MP, 30 mg/kg, IV). The results showed that the retinal inner plexiform layer/outer nuclear layer (IPL/ONL) ratio was reduced following IR damage compared with that in the normal control. The IPL/ONL ratio was reduced to 43.5% in the IR-control group, 93.3% and 93.6% in the Mino-45 and Mino-90 group. The IPL/ONL ratio was preserved to 95.7% in the MP group. These results suggest that minocycline and methylprednisolone showed significantly good neuroprotective effects demonstrated in retinal histology of the rats under retinal IR injury.
Balance and Stealth: The Role of Noncoding RNAs in the Regulation of Virus Gene Expression
Authors: Cox Jennifer E. , Sullivan Christopher S.
Published: June 2014

In the past two decades, our knowledge of gene regulation has been greatly expanded by the discovery of microRNAs (miRNAs). miRNAs are small (19–24 nt) noncoding RNAs (ncRNAs) found in metazoans, plants, and some viruses. They have been shown to regulate many cellular processes, including differentiation, maintenance of homeostasis, apoptosis, and the immune response. At present, there are over 300 known viral miRNAs encoded by diverse virus families. One well-characterized function of some viral miRNAs is the regulation of viral transcripts. Host miRNAs can also regulate viral gene expression. We propose that viruses take advantage of both host and viral ncRNA regulation to balance replication and infectious state (for example, latent versus lytic infection). As miRNA regulation can be reversed upon certain cellular stresses, we hypothesize that ncRNAs can serve viruses as barometers for cellular stress.
Kinetics and utilization of lipid sources during acute exercise and acipimox
Authors: Nellemann Birgitte , Søndergaard Esben , Jensen Jørgen , Pedersen Steen Bønløkke , Jessen Niels , Jørgensen Jens Otto Lunde , Nielsen Søren
Published: June 2014

Overweight is associated with abnormalities of lipid metabolism, many of which are reversed by exercise. We investigated the impact of experimental antilipolysis and acute exercise on lipid kinetics and oxidation from VLDL-TG, plasma FFA, and “residual lipids” in overweight men ( n = 8) using VLDL-TG and palmitate tracers in combination with muscle biopsies in a randomized, placebo-controlled design. Participants received placebo or acipimox on each study day (4 h of rest, 90 min of exercise at 50% V̇o2 max). Exercise suppressed VLDL-TG secretion significantly during placebo but not acipimox (placebo-rest: 64.2 ± 9.4; placebo-exercise: 48.3 ± 8.0; acipimox-rest: 55.2 ± 13.4; acipimox-exercise: 52.0 ± 10.9). Resting oxidation of VLDL-TG FA and FFA was significantly reduced during acipimox compared with placebo, whereas “residual lipid oxidation” increased significantly [VLDL-TG oxidation (placebo: 18 ± 3 kcal/h; acipimox: 11 ± 2 kcal/h), FFA oxidation (placebo: 14 ± 2 kcal/h; acipimox: 4 ± 0.5 kcal/h), and residual lipid oxidation (placebo: 3 ± 5 kcal/h; acipimox: 14 ± 5 kcal/h)]. Additionally, during exercise on both placebo and acipimox, oxidation of VLDL-TG and FFA increased, but the relative contribution to total lipid oxidation diminished, except for FFA, which remained unchanged during acipimox. Residual lipid oxidation increased significantly during exercise in both absolute and relative terms. Changes in selected cellular enzymes and proteins provided no explanations for kinetic changes. In conclusion, suppressed FFA availability blunts the effect of exercise on VLDL-TG secretion and modifies the contribution of lipid sources for oxidation.
Extranuclear estrogen receptor's roles in physiology: lessons from mouse models
Authors: Levin Ellis R.
Published: June 2014

Steroid receptors exist and function in multiple compartments of cells in most organs. Although the functions and nature of some of these receptors is being defined, important aspects of receptor localization and signaling to physiology and pathophysiology have been identified. In particular, extranuclear sex steroid receptors have been found in many normal cells and in epithelial tumors, where they enact signal transduction that impacts both nongenomic and genomic functions. Here, I focus on the progress made in understanding the roles of extranuclear estrogen receptors (ER) in physiology and pathophysiology. Extranuclear ER serve as a model to selectively intervene with novel receptor reagents to prevent or limit disease progression. Recent novel mouse models and membrane ER-selective agonists also provide a better understanding of receptor pool cross-talk that results in the overall integrative actions of sex steroids.
Distinct mechanisms of induction of hepatic growth hormone resistance by endogenous IL-6, TNF-α, and IL-1β
Authors: Zhao Yueshui , Xiao Xiaoqiu , Frank Stuart J. , Lin Herbert Y. , Xia Yin
Published: June 2014

During inflammation, the liver becomes resistant to growth hormone (GH) actions, leading to downregulation of the GH target gene IGF-I and activation of catabolism. Proinflammatory cytokines IL-6, TNF-α, and IL-1β are critically involved in the pathogenesis of hepatic GH resistance. However, the mechanisms used by endogenous IL-6, TNF-α, and IL-1β to inhibit the hepatic GH-IGF-I pathway during inflammation are not fully understood. Here, we show that TNF-α and IL-1β inhibited GH receptor (GHR) expression but had minor effects on the downstream suppressor of cytokine signaling (SOCS)3, while IL-6 induced SOCS3 expression but had no effect on GHR expression in Huh-7 cells. Consistent with the in vitro observations, neutralization of TNF-α and IL-1β in mouse models of inflammation did not significantly alter SOCS3 expression stimulated by inflammation but restored GHR and IGF-I expression suppressed by inflammation. Neutralization of IL-6 did not alter inflammation-suppressed GHR expression but drastically reduced the inflammation-stimulated SOCS3 expression and restored IGF-I expression. Interestingly, when the GH-IGF-I pathway was turned off by maximal inhibition of GHR expression, IL-6 and SOCS3 were no longer able to regulate IGF-I expression. Taken together, our results suggest that TNF-α/IL-1β and IL-6 use distinct mechanisms to induce hepatic GH resistance, with TNF-α and IL-1β acting primarily on GHR and IL-6 acting primarily on SOCS3. IL-6 action may be superseded by factors such as TNF-α and IL-1β that inhibit GHR expression.
Vasoconstrictor role of cyclooxygenase-1-mediated prostacyclin synthesis in non-insulin-dependent diabetic mice induced by high-fat diet and streptozotocin
Authors: Zhu Ningxia , Liu Bin , Luo Wenhong , Zhang Yingzhan , Li Hui , Li Shasha , Zhou Yingbi
Published: May 2014

This study tested the hypothesis that in diabetic arteries, cyclooxygenase (COX)-1 mediates endothelial prostacyclin (PGI2) synthesis, which evokes vasoconstrictor activity under the pathological condition. Non-insulin-dependent diabetes was induced to C57BL/6 mice and those with COX-1 deficiency (COX-1−/−mice) using a high-fat diet in combination with streptozotocin injection. In vitro analyses were performed 3 mo after. Results showed that in diabetic aortas, the endothelial muscarinic receptor agonist ACh evoked an endothelium-dependent production of the PGI2metabolite 6-keto-PGF1α, which was abolished in COX-1−/−mice. Meanwhile, COX-1 deficiency or COX-1 inhibition prevented vasoconstrictor activity in diabetic abdominal aortas, resulting in enhanced relaxation evoked by ACh. In a similar manner, COX-1 deficiency increased the relaxation evoked by ACh in nitric oxide synthase-inhibited diabetic renal arteries. Also, in diabetic abdominal aortas and/or renal arteries, both PGI2and the COX substrate arachidonic acid evoked contractions similar to those of nondiabetic mice. However, the contraction to arachidonic acid, but not that to PGI2, was abolished in vessels from COX-1−/−mice. Moreover, we found that 3 mo after streptozotocin injection, systemic blood pressure increased in diabetic C57BL/6 mice but not in diabetic COX-1−/−mice. These results explicitly demonstrate that in the given arteries from non-insulin-dependent diabetic mice, COX-1 remains a major contributor to the endothelial PGI2synthesis that evokes vasoconstrictor activity under the pathological condition. Also, our data suggest that COX-1 deficiency prevents or attenuates diabetic hypertension in mice, although this could be related to the loss of COX-1-mediated activities derived from both vascular and nonvascular tissues.
Wave potential and the one-dimensional windkessel as a wave-based paradigm of diastolic arterial hemodynamics
Authors: Mynard Jonathan P. , Smolich Joseph J.
Published: May 2014

Controversy exists about whether one-dimensional wave theory can explain the “self-canceling” waves that accompany the diastolic pressure decay and discharge of the arterial reservoir. Although it has been proposed that reservoir and wave effects be treated as separate phenomena, thus avoiding the issue of self-canceling waves, we have argued that reservoir effects are a phenomenological and mathematical subset of wave effects. However, a complete wave-based explanation of self-canceling diastolic expansion (pressure-decreasing) waves has not yet been advanced. These waves are present in the forward and backward components of arterial pressure and flow (P±and Q±, respectively), which are calculated by integrating incremental pressure and flow changes (dP±and dQ±, respectively). While the integration constants for this calculation have previously been considered arbitrary, we showed that physiologically meaningful constants can be obtained by identifying “undisturbed pressure” as mean circulatory pressure. Using a series of numeric experiments, absolute P±and Q±values were shown to represent “wave potential,” gradients of which produce propagating wavefronts. With the aid of a “one-dimensional windkessel,” we showed how wave theory predicts discharge of the arterial reservoir. Simulated data, along with hemodynamic recordings in seven sheep, suggested that self-canceling diastolic waves arise from repeated and diffuse reflection of the late systolic forward expansion wave throughout the arterial system and at the closed aortic valve, along with progressive leakage of wave potential from the conduit arteries. The combination of wave and wave potential concepts leads to a comprehensive one-dimensional (i.e., wave-based) explanation of arterial hemodynamics, including the diastolic pressure decay.
Airway collagen and elastic fiber content correlates with lung function in equine heaves
Authors: Setlakwe Emilie L. , Lemos Karen R. , Lavoie-Lamoureux Anouk , Duguay Jean-David , Lavoie Jean-Pierre
Published: May 2014

The consequences on lung function and inflammation of alterations in the extracellular matrix affecting the peripheral airway wall in asthma are largely unknown. We hypothesized that remodeling of collagen and elastic fibers in the peripheral airway wall leads to airway obstruction and contributes to neutrophilic airway inflammation. Animals used were six heaves-affected horses and five controls. Large peripheral lung biopsies were obtained from horses with heaves in clinical remission (Baseline) and during disease exacerbation and from age-matched controls. The area of collagen and elastic fiber content in the lamina propria was measured by histological staining techniques and corrected for airway size. Collagen type 1 and type 3 content was further assessed from additional horses after postmortem lung samples by immunohistochemistry. The collagen breakdown products proline-glycine-proline (PGP) and N-acetylated-PGP ( N-α-PGP) were also measured in bronchoalveolar lavage fluids (BALF) by mass spectrometry. Compared with controls, heaves-affected horses had an increase in collagen ( P = 0.05) and elastic fiber contents ( P = 0.04) at baseline. Collagen types 1 and 3 content was also significantly increased in diseased horses ( P = 0.015) when both collagen types were combined. No further change in collagen content was observed after a 30-day antigenic challenge. Airway collagen at baseline was positively correlated with pulmonary resistance in asthmatic horses ( r2= 0.78, P = 0.03) and elastic fiber content was positively associated with pulmonary elastance in controls ( r2= 0.95, P = 0.02). No difference between groups was appreciated in PGP and N-α-PGP peptides in BALF. Increased airway wall collagen and elastic fiber content may contribute to residual obstruction in the asthmatic airways.
γ-Herpes virus-68, but notPseudomonas aeruginosaor influenza A (H1N1), exacerbates established murine lung fibrosis
Authors: Ashley Shanna L. , Jegal Yangjin , Moore Thomas A. , van Dyk Linda F. , Laouar Yasmina , Moore Bethany B.
Published: May 2014

Patients with idiopathic pulmonary fibrosis (IPF) often do worse following infection, but the cause of the decline is not fully understood. We previously demonstrated that infection with a murine gamma herpes virus (γHV-68) could exacerbate established lung fibrosis following administration of fluorescein isothiocyanate (McMillan et al. Am J Respir Crit Care Med 177: 771–780, 2008). In the present study, we anesthetized mice and injected saline or bleomycin intratracheally on day 0. On day 14, mice were anesthetized again and infected with either a Gram-negative bacteria ( Pseudomonas aeruginosa), or with H1N1 or γHV-68 viruses. Measurements were then made on days 15, 21, or 35. We demonstrate that infection with P. aeruginosa does not exacerbate extracellular matrix deposition post-bleomycin. Furthermore, fibrotic mice are effectively able to clear P. aeruginosa infection. In contrast, bleomycin-treated mice develop worse lung fibrosis when infected with γHV-68, but not when infected with H1N1. The differential ability of γHV-68 to cause increased collagen deposition could not be explained by differences in inflammatory cell recruitment or whole lung chemokine and cytokine responses. Alveolar epithelial cells from γHV-68-infected mice displayed increased expression of TGFβ receptor 1, increased SMAD3 phosphorylation, and evidence of apoptosis measured by cleaved poly-ADP ribose polymerase (PARP). The ability of γHV-68 to augment fibrosis required the ability of the virus to reactivate from latency. This property appears unique to γHV-68, as the β-herpes virus, cytomegalovirus, did not have the same effect.
Food intake and energy expenditure are increased in high-fat-sensitive but not in high-carbohydrate-sensitive obesity-prone rats
Authors: Azzout-Marniche Dalila , Chaumontet Catherine , Nadkarni Nachiket A. , Piedcoq Julien , Fromentin Gilles , Tomé Daniel , Even Patrick C.
Published: June 2014

Obesity-prone (OP) rodents are used as models of human obesity predisposition. The goal of the present study was to identify preexisting defects in energy expenditure components in OP rats. Two studies were performed. In the first one, male Wistar rats ( n = 48) were fed a high-carbohydrate diet (HCD) for 3 wk and then a high-fat diet (HFD) for the next 3 wk. This study showed that adiposity gain under HCD was 2.9-fold larger in carbohydrate-sensitive (CS) than in carbohydrate-resistant (CR) rats, confirming the concept of “carbohydrate-sensitive” rats. Energy expenditure (EE), respiratory quotient (RQ), caloric intake (CI), and locomotor activity measured during HFD identified no differences in EE and RQ between fat-resistant (FR) and fat-sensitive (FS) rats, and indicated that obesity developed in FS rats only as the result of a larger CI not fully compensated by a parallel increase in EE. A specific pattern of spontaneous activity, characterized by reduced activity burst intensity, was identified in FS rats but not in CS ones. This mirrors a previous observation that under HCD, CS but not FS rats, exhibited bursts of activity of reduced intensity. In a second study, rats were fed a HFD for 3 wk, and the components of energy expenditure were examined by indirect calorimetry in 10 FR and 10 FS rats. This study confirmed that a low basal EE, reduced thermic effect of feeding, defective postprandial energy partitioning, or a defective substrate utilization by the working muscle are not involved in the FS phenotype.
Prostaglandin E2 regulation of amnion cell vascular endothelial growth factor expression: relationship with intramembranous absorption rate in fetal sheep
Authors: Cheung Cecilia Y. , Beardall Michael K. , Anderson Debra F. , Brace Robert A.
Published: June 2014

We hypothesized that prostaglandin E2 (PGE2) stimulates amniotic fluid transport across the amnion by upregulating vascular endothelial growth factor (VEGF) expression in amnion cells and that amniotic PGE2 concentration correlates positively with intramembranous (IM) absorption rate in fetal sheep. The effects of PGE2 at a range of concentrations on VEGF164 and caveolin-1 gene expressions were analyzed in cultured ovine amnion cells. IM absorption rate, amniotic fluid (AF) volume, and PGE2 concentration in AF were determined in late-gestation fetal sheep during control conditions, isovolumic fetal urine replacement (low IM absorption rate), or intra-amniotic fluid infusion (high IM absorption rate). In ovine amnion cells, PGE2 induced dose- and time-dependent increases in VEGF164 mRNA levels and reduced caveolin-1 mRNA and protein levels. VEGF receptor blockade abolished the caveolin-1 response, while minimally affecting the VEGF response to PGE2. In sheep fetuses, urine replacement reduced amniotic PGE2 concentration by 58%, decreased IM absorption rate by half, and doubled AF volume ( P < 0.01). Intra-amniotic fluid infusion increased IM absorption rate and AF volume ( P < 0.01), while amniotic PGE2 concentration was unchanged. Neither IM absorption rate nor AF volume correlated with amniotic PGE2 concentration under each experimental condition. Although PGE2 at micromolar concentrations induced dose-dependent responses in VEGF and caveolin-1 gene expression in cultured amnion cells consistent with a role of PGE2 in activating VEGF to mediate AF transport across the amnion, amniotic PGE2 at physiological nanomolar concentrations does not appear to regulate IM absorption rate or AF volume.
Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells
Authors: Voisin Grégory , Bouvet Guillaume F. , Legendre Pierre , Dagenais André , Massé Chantal , Berthiaume Yves
Published: June 2014

Although cystic fibrosis (CF) pathophysiology is explained by a defect in CF transmembrane conductance regulator (CFTR) protein, the broad spectrum of disease severity is the consequence of environmental and genetic factors. Among them, oxidative stress has been demonstrated to play an important role in the evolution of this disease, with susceptibility to oxidative damage, decline of pulmonary function, and impaired lung antioxidant defense. Although oxidative stress has been implicated in the regulation of inflammation, its molecular outcomes in CF cells remain to be evaluated. To address the question, we compared the gene expression profile in NuLi-1 cells with wild-type CFTR and CuFi-1 cells homozygous for ΔF508 mutation cultured at air-liquid interface. We analyzed the transcriptomic response of these cell lines with microarray technology, under basal culture conditions and after 24 h oxidative stress induced by 15 μM 2,3-dimethoxy-1,4-naphtoquinone. In the absence of oxidative conditions, CuFi-1 gene profiling showed typical dysregulated inflammatory responses compared with NuLi-1. In the presence of oxidative conditions, the transcriptome of CuFi-1 cells reflected apoptotic transcript modulation. These results were confirmed in the CFBE41o- and corrCFBE41o- cell lines as well as in primary culture of human CF airway epithelial cells. Altogether, our data point to the influence of oxidative stress on cell survival functions in CF and identify several genes that could be implicated in the inflammation response observed in CF patients.