bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta‐analysis in medicine: an introduction
Authors: MAK Anselm , CHEUNG Mike W.L. , FU Erin H.Y. , HO Roger C.M.
Published: April 2010

Meta‐analysis, a complex statistical method which involves synthesis of data from relevant studies to devise an effect size or a conclusion, has increasingly been recognized and impacts on evidence‐based medicine, especially in the field of health science. Thanks to the advent and unmet need of evidence‐based medicine, since the first recordable publication of a meta‐analysis in 1904 addressing the effectiveness of typhoid vaccine, both the number and quality of meta‐analyses published relating to healthcare science have been on a steep rise. If properly conducted, based on answering relevant clinical questions, strict selection criteria of participating studies, appropriate analytical methods, and proper presentation of results, coupled with critical and faithful discussion on the strength and weakness of the analysis, meta‐analysis will definitely be an invaluable tool for clinicians and researchers in understanding epidemiology, justifying and refining hypotheses of various diseases, for medical practitioners to implement sound management decisions based on evidence‐based medicine, and ultimately, for policy‐makers to formulate cost‐efficient treatment strategies, guidelines and legislation. In this first paper of a mini‐series, the current trend of meta‐analysis publications in the medical literature, examples of important meta‐analyses relevant to rheumatology and the pros and cons of meta‐analysis, will be discussed. Important terminology related to meta‐analysis, the systematic ways to critically appraise, and finally the preferred methodology of conducting meta‐analysis will be covered in the subsequent three reviews of this mini‐series.
Breast lymphoma in Sjögren’s syndrome complicated by acute monocular blindness
Authors: SOLDEVILLA Helmar F. , MOLINA Ramon Miguel M. , NAVARRA Sandra V.
Published: April 2010

A 69‐year‐old hypertensive woman presented with eye and mouth dryness, bilateral parotid gland enlargement, associated with anasarca and proteinuria. Family history was notable for malignancies including breast, nasopharyngeal and colon cancers. Physical exam disclosed hypertension, bilaterally enlarged, firm, non‐tender parotid glands, fine bibasilar crackles and bipedal edema. Anti Ro/Sjögren’s syndrome antigen A antibody was positive, with negative tests for anti La/Sjögren’s syndrome antigen B and anti‐nuclear antibody (ANA). Chest radiographs showed basal infiltrates. Sjögren’s syndrome associated with glomerulonephritis and interstitial lung disease was diagnosed, and she received pulse methylprednisololone followed by oral prednisone with dramatic improvement. Two months later, while on prednisone 5 mg/day, she returned to the clinic with an enlarging fixed non‐tender right breast mass. She underwent modified radical mastectomy of the right breast, and pathologic report revealed diffuse, small cell, non‐Hodgkin’s lymphoma of the breast; axillary lymph nodes were negative for tumor. She opted for alternative therapy and did not return to the clinic until 7 months later when she developed sudden monocular blindness in the right eye with no other systemic manifestations. Magnetic resonance imaging (MRI) revealed swelling and enhancement of intracanalicular and pre‐chiasmatic segments of the right optic nerve and right side of the optic chiasm. Considerations were Devic’s disease versus metastases. She received pulse methylprednisolone therapy (1 g/day for 3 days) with partial recovery of vision. She is scheduled for lymphoma chemotherapy to include rituximab.
The effects of hyperoxic ventilation on tissue oxygenation
Authors: MEIER JENS , LAUSCHER PATRICK , KERTSCHO HARRY , HABLER OLIVER
Published: April 2010

Application of high inspiratory oxygen concentrations is an established method to improve arterial oxygen content, oxygen transport and tissue oxygenation. However, in the past years a considerable amount of data have emerged challenging this approach: hyperoxic ventilation (ventilation with pure oxygen, HV) and subsequent hyperoxemia have been accused of inducing unfavorable effects on microcirculation and tissue perfusion, resulting in regional tissue hypoxia. Interestingly, these disadvantegous properties of HV seem to occur predominantly in patients with physiological hemoglobin concentrations and probably play a minor role in anemic patients. In animal experiments the effect of HV on tissue oxygenation and on outcome of several severe pathologic conditions essentially depends on the hemoglobin concentration: HV failed to have a considerable impact on survival of severe hypovolemia or methemoglobinemia (physiological hemoglobin concentration), whereas it convincingly improves outcome of severe normovolemic anemia. The present review discusses a perspective on the effects of HV at different hemoglobin concentrations and its potential to improve oxygen transport and tissue oxygenation especially during moderate and severe anemia.
Neurotransmitter and neuromodulatory mechanisms at peripheral arterial chemoreceptors
Authors: Nurse Colin A.
Published: April 2010

The control of breathing depends critically on sensory inputs to the central pattern generator of the brainstem, arising from peripheral arterial chemoreceptors located principally in the carotid bodies (CBs). The CB receptors, i.e. glomus or type I cells, are excited by chemical stimuli in arterial blood, particularly hypoxia, hypercapnia, acidosis and low glucose, which initiate corrective reflex cardiorespiratory and cardiovascular adjustments. Type I cells occur in clusters and are innervated by petrosal afferent fibres. Synaptic specializations (both chemical and electrical) occur between type I cells and petrosal terminals, and between neighbouring type I cells. This, together with the presence of a wide array of neurotransmitters and neuromodulators linked to both ionotropic and metabotropic receptors, allows for a complex modulation of CB sensory output. Studies in several laboratories over the last ∼20 years have provided much insight into the transduction mechanisms. More recent studies, aided by the development of a co‐culture model of the rat CB, have shed light on the role of neurotransmitters and neuromodulators in shaping the afferent response. This review highlights some of these developments, which have contributed to our current understanding of information processing at CB chemoreceptors.
Monitoring and Control of Electrochemical Machining (ECM)
Authors: Rajurkar K. P. , Wei B. , Schnacker C. L.
Published: April 2010

The main advantages of the electrochemical machining (ECM) process, such as high material removal rates and smooth, damage-free machined surface, are often offset by the poor dimensional control and process stability resulting from the complex and stochastic nature of the interelectrode gap (IEG) states. Full economic utilization of ECM will be realized only when reliable dimensional and process control systems are developed. This paper presents an ECM control model based on the basic ECM dynamics that accounts for the dynamic nature of the ECM process. The state space methodology is applied to transform it into the control model applicable to an ECM control system based on a digital computer. The simulations have been made for the model verification and controller design. A new approach is introduced to develop an indicator that detects or predicts the onset of random sparks based on ECM current signal analysis. ECM current and voltage signals have been acquired using a specially-built data acquisition circuit. The signals are digitized and analyzed with an IBM PC. The frequency analysis of the signal leads to a better insight of the physical mechanism of the ECM process. A comprehensive review of the state-of-the-art ECM research and development efforts in the areas of spark and short circuit detection and IEG control is also included in the paper.
On the Mechanism of Pool Boiling Critical Heat Flux Enhancement in Nanofluids
Authors: Kim Hyungdae , Ahn Ho Seon , Kim Moo Hwan
Published: April 2010

The pool boiling characteristics of water-based nanofluids with alumina and titania nanoparticles of 0.01 vol % were investigated on a thermally heated disk heater at saturated temperature and atmospheric pressure. The results confirmed the findings of previous studies that nanofluids can significantly enhance the critical heat flux (CHF), resulting in a large increase in the wall superheat. It was found that some nanoparticles deposit on the heater surface during nucleate boiling, and the surface modification due to the deposition results in the same magnitude of CHF enhancement in pure water as for nanofluids. Subsequent to the boiling experiments, the interfacial properties of the heater surfaces were examined using dynamic wetting of an evaporating water droplet. As the surface temperature increased, the evaporating meniscus on the clean surface suddenly receded toward the liquid due to the evaporation recoil force on the liquid-vapor interface, but the nanoparticle-fouled surface exhibited stable wetting of the liquid meniscus even at a remarkably higher wall superheat. The heat flux gain attainable due to the improved wetting of the evaporating meniscus on the fouled surface showed good agreement with the CHF enhancement during nanofluid boiling. It is supposed that the nanoparticle layer increases the stability of the evaporating microlayer underneath a bubble growing on a heated surface and thus the irreversible growth of a hot/dry spot is inhibited even at a high wall superheat, resulting in the CHF enhancement observed when boiling nanofluids.
Melting of Phase Change Materials With Volume Change in Metal Foams
Authors: Yang Zhen , Garimella Suresh V.
Published: April 2010

Melting of phase change materials (PCMs) embedded in metal foams is investigated. The two-temperature model developed accounts for volume change in the PCM upon melting. Volume-averaged mass and momentum equations are solved, with the Brinkman–Forchheimer extension to Darcy’s law employed to model the porous-medium resistance. Local thermal equilibrium does not hold due to the large difference in thermal diffusivity between the metal foam and the PCM. Therefore, a two-temperature approach is adopted, with the heat transfer between the metal foam and the PCM being coupled by means of an interstitial Nusselt number. The enthalpy method is applied to account for phase change. The governing equations are solved using a finite-volume approach. Effects of volume shrinkage/expansion are considered for different interstitial heat transfer rates between the foam and PCM. The detailed behavior of the melting region as a function of buoyancy-driven convection and interstitial Nusselt number is analyzed. For strong interstitial heat transfer, the melting region is significantly reduced in extent and the melting process is greatly enhanced as is heat transfer from the wall; the converse applies for weak interstitial heat transfer. The melting process at a low interstitial Nusselt number is significantly influenced by melt convection, while the behavior is dominated by conduction at high interstitial Nusselt numbers. Volume shrinkage/expansion due to phase change induces an added flow, which affects the PCM melting rate.
Increased Conformity Offers Diminishing Returns for Reducing Total Knee Replacement Wear
Authors: Fregly Benjamin J. , Marquez-Barrientos Carlos , Banks Scott A. , DesJardins John D.
Published: April 2010

Wear remains a significant problem limiting the lifespan of total knee replacements (TKRs). Though increased conformity between TKR components has the potential to decrease wear, the optimal amount and planes of conformity have not been investigated. Furthermore, differing conformities in the medial and lateral compartments may provide designers the opportunity to address both wear and kinematic design goals simultaneously. This study used a computational model of a Stanmore knee simulator machine and a previously validated wear model to investigate this issue for simulated gait. TKR geometries with different amounts and planes of conformity on the medial and lateral sides were created and tested in two phases. The first phase utilized a wide range of sagittal and coronal conformity combinations to blanket a physically realistic design space. The second phase performed a focused investigation of the conformity conditions from the first phase to which predicted wear volume was sensitive. For the first phase, sagittal but not coronal conformity was found to have a significant effect on predicted wear volume. For the second phase, increased sagittal conformity was found to decrease predicted wear volume in a nonlinear fashion, with reductions gradually diminishing as conformity increased. These results suggest that TKR geometric design efforts aimed at minimizing wear should focus on sagittal rather than coronal conformity and that at least moderate sagittal conformity is desirable in both compartments.
Dynamic Hemodynamic Energy Loss in Normal and Stenosed Aortic Valves
Authors: Yap Choon-Hwai , Dasi Lakshmi P. , Yoganathan Ajit P.
Published: April 2010

Aortic valve (AV) stenosis, if untreated, leads to heart failure. From a mechanics standpoint, heart failure can be interpreted as the failure of the heart to generate sufficient power to overcome energy losses in the circulation. Thus, energy efficiency-based measures for evaluating AV performance and disease severity have the advantage of being a direct measure of the contribution of the AV hydrodynamic characteristics toward heart failure. We present a new method for computing the rate of energy dissipation as a function of systolic time, by modifying the Navier–Stokes momentum equation. This method preserves the dynamic term of the Navier–Stokes momentum equation, and allows the investigation of the trend of the rate of energy dissipation over time. This method is applied to a series of in vitro experiments, where a trimmed porcine valve is exposed to various conditions: varying stroke volumes (50 ml to 90 ml) at the fixed heart rate; varying heart rates (60–80 beats/min) at fixed stroke volume; and varying stenosis levels (normal, mild stenosis, moderate stenosis). The results are: (1) energy dissipation waveform has a distinctive pattern of being skewed toward late systole, due to flow instabilities during deceleration phases; (2) increasing heart rate and stroke volume increases energy dissipation, but the normalized shape of the energy dissipation waveform is preserved across heart rates and stroke volumes; (3) increasing stenosis level increases energy dissipation, and also alters the normalized shape of the energy dissipation waveform. Since stenosis produces a signature energy dissipation waveform shape, dynamic energy dissipation analysis can potentially be extended into a clinical tool for AV evaluation.
Study of the synthesis of tungsten trioxide nanostructured arrays by tungsten hot filament chemical vapor deposition method and their field emission properties
Authors: Lu Di , Liang Bo , Ogino Akihisa , Nagatsu Masaaki
Published: April 2010

Tungsten trioxides (WO3) nanorod arrays had been fabricated at different substrate temperatures by hot filament chemical vapor deposition. The morphology of the WO3 nanorod array is significantly dependent on the substrate temperature in a relatively narrow range (600–800 °C). Through the x-ray diffraction pattern, different preference growth directions of WO3 nanorods at different substrate temperatures were observed. A discussion of the possible growth mechanism is given. Furthermore, the substrate temperature during the growth was also found to be closely related with the morphologies of the nanorod arrays and their field emission properties.
Backing collisions: a study of drivers' eye and backing behaviour using combined rear-view camera and sensor systems
Authors: Hurwitz David S , Pradhan Anuj , Fisher Donald L , Knodler Michael A , Muttart Jeffrey W , Menon Rajiv , Meissner Uwe
Published: April 2010

Context

Backing crash injures can be severe; approximately 200 of the 2,500 reported injuries of this type per year to children under the age of 15 years result in death. Technology for assisting drivers when backing has limited success in preventing backing crashes.

Objectives

Two questions are addressed: Why is the reduction in backing crashes moderate when rear-view cameras are deployed? Could rear-view cameras augment sensor systems?

Design

46 drivers (36 experimental, 10 control) completed 16 parking trials over 2  days (eight trials per day). Experimental participants were provided with a sensor camera system, controls were not. Three crash scenarios were introduced.

Setting

Parking facility at UMass Amherst, USA.

Subjects

46 drivers (33 men, 13 women) average age 29 years, who were Massachusetts residents licensed within the USA for an average of 9.3  years.

Interventions

Vehicles equipped with a rear-view camera and sensor system-based parking aid.

Main Outcome Measures

Subject's eye fixations while driving and researcher's observation of collision with objects during backing.

Results

Only 20% of drivers looked at the rear-view camera before backing, and 88% of those did not crash. Of those who did not look at the rear-view camera before backing, 46% looked after the sensor warned the driver.

Conclusions

This study indicates that drivers not only attend to an audible warning, but will look at a rear-view camera if available. Evidence suggests that when used appropriately, rear-view cameras can mitigate the occurrence of backing crashes, particularly when paired with an appropriate sensor system.
Evaluation of skiing and snowboarding injuries sustained in terrain parks versus traditional slopes
Authors: Brooks M Alison , Evans Michael D , Rivara Frederick P
Published: April 2010

This study compares skiing and snowboarding injuries in terrain parks versus slopes at two ski areas, 2000–05. A total of 3953 (26.7%) injuries occurred in terrain parks, predominantly among young male snowboarders. Terrain park injuries were more likely to be severe, involving head (RR 1.31, 95% CI 1.16 to 1.48) or back (RR 1.96, 95% CI 1.67 to 2.29).
THE BLOCK GAUSS–SEIDEL METHOD IN SOUND TRANSMISSION PROBLEMS
Authors: POBLET-PUIG J. , RODRÍGUEZ-FERRAN A.
Published: April 2010

Sound transmission through partitions can be modeled as an acoustic fluid–elastic structure interaction problem. The block Gauss–Seidel iterative method is used in order to solve the finite element linear system of equations. The blocks are defined, respecting the fluid and structural domains. The convergence criterion is analyzed and interpreted in physical terms by means of simple one-dimensional problems. This analysis highlights the negative influence on the convergence of a strong degree of coupling between the acoustic domains and the structure. A selective coupling strategy has been developed and applied to problems with strong coupling (e.g. double walls).
Comparison of Matrix Dimensionality Reduction Methods in Uncovering Latent Structures in the Data
Authors: Aswani Kumar Ch. , Palanisamy Ramaraj
Published: April 2010

Matrix decomposition methods: Singular Value Decomposition (SVD) and Semi Discrete Decomposition (SDD) are proved to be successful in dimensionality reduction. However, to the best of our knowledge, no empirical results are presented and no comparison between these methods is done to uncover latent structures in the data. In this paper, we present how these methods can be used to identify and visualise latent structures in the time series data. Results on a high dimensional dataset demonstrate that SVD is more successful in uncovering the latent structures.
The Impact of KM on Small and Medium Sized Organisations in Sudan
Authors: Mohamed Elshaiekh Nour-Eldin , Woods Peter Charles , Raman Murali
Published: April 2010

This paper explains the impacts of knowledge management (KM) on organisational levels in Sudanese small and medium sized organisations. Based on the processes and methods of organisational learning, this paper presents the impact of KM on organisational levels, namely processes, product, workers, and general performance. The paper is based on a questionnaire and the data is collected from 255 people within a medium size company case study in Sudan. There are various kinds of impacts that KM have on organisations and organisational levels; these effects appear in different sectors, including processes, product, workers, and general performance. The paper finds that the interrelated impacts of KM on organisations are positive at several sectors. The impact on one element might lead to synergistic impacts on another element as well. These findings tend to corroborate, in line with the global KM goals.
HOPF BIFURCATION AND STABILITY ANALYSIS FOR A STAGE-STRUCTURED SYSTEM
Authors: LIU JUNLI , ZHANG TAILEI
Published: April 2010

In this paper, we considered a time-delay predator–prey system, in which the prey has two life stages, juvenile and mature. Delay was regarded as the bifurcation parameter, we analyzed the characteristic equation of the system at the positive equilibrium, stability of the positive equilibrium and existence of Hopf bifurcation with delay τ in the term of degree are investigated. The explicit formulae which determine the direction of the bifurcations, stability, and other properties of the bifurcating periodic solutions are given by using the normal form theory and center manifold theorem. To verify our theoretical results, a numerical example is also included.
A STUDY ON THE MATHEMATICAL MODEL FOR THE POPULATION AGE REPLACEMENT OF PINUS KORAIENSIS IN NATURAL FOREST
Authors: WANG XIAOJING , SONG GUOHUA
Published: April 2010

In this paper, a mathematical model for the population age replacement of Pinus koraiensis (Korean pine) in natural forest is developed. Using the stability and qualitative theory of ordinary differential equations, the sufficient conditions of existence of limit cycle and globally asymptotic stability of the positive equilibrium for the model are given. Furthermore, the stability of limit cycle is determined. At last we validate the result by plotting with Maple and conclude that young trees and mother trees of Pinus koraiensis in natural forest will change in a periodic undulation.
JET-RICCI GEOMETRY OF TIME-DEPENDENT HUMAN BIOMECHANICS
Authors: IVANCEVIC TIJANA T.
Published: April 2010

We propose the time-dependent generalization of an "ordinary" autonomous human biomechanics, in which total mechanical + biochemical energy is not conserved. We introduce a general framework for time-dependent biomechanics in terms of jet manifolds derived from the extended musculo-skeletal configuration manifold. The corresponding Riemannian geometrical evolution follows the Ricci flow diffusion. In particular, we show that the exponential-like decay of total biomechanical energy (due to exhaustion of biochemical resources) is closely related to the Ricci flow on the biomechanical configuration manifold.
ON EXPLORING EFFECTS OF MOLECULAR NOISE IN A SIMPLE VIRAL INFECTION MODEL
Authors: XIE ZHI , KULASIRI DON
Published: April 2010

Intrinsic and extrinsic noises are all believed to be important in the development and function of many living organisms. In this study, we investigate the sources of the intrinsic noise and the influence of the extrinsic noise on an intracellular viral infection system. The contribution of the intrinsic noise from each reaction is measured by means of a special form of stochastic differential equations (SDEs), chemical Langevin equation. The intrinsic noise of the system is a linear sum of the noise in each of the reactions. The intrinsic noise mainly arises from the degradation of mRNA and the transcription processes. We then study the effects of extrinsic noise by the means of a general form of SDE. It is found that the noise of the viral components grows logarithmically with the increasing noise intensities. The system is most susceptible to the noise in the virus assembly process. A high level of noise in this process can even inhibit the growth of the viruses. This study also demonstrates the utility of SDEs in analyzing genetic regulatory networks perturbed by either inherent or parametric stochasticity.
USING FIELD-PROGRAMMABLE GATE ARRAYS FOR HIGH-SPEED REAL-TIME SIMULATION
Authors: CROSBIE ROY
Published: April 2010

Some applications of real-time simulation now require frame times that are shorter in duration than can be delivered by traditional methods such as real-time versions of Linux (RT-Linux). RT-Linux can be satisfactory for frames as short as 10μS, but there is now a need, for example in the simulation of power-electronic systems, for frame times as short as 1 μS or even less. Techniques based on the interfacing of digital signal processors (DSPs) to a Windows PC have achieved a 2 μS frame time for a typical power electronics application and less than 1 μS is shown to be possible using field-programmable gate arrays (FPGAs). Combining these high-speed techniques with simulations of the rest of the system necessitates the use of multi-rate techniques. Software tools, interfacing issues, and system architecture for a high-speed, real-time, distributed, multi-rate (HRDM) simulator are discussed.
QUALITY ASSURANCE OF MODELS AND SIMULATION APPLICATIONS
Authors: WANG ZHONGSHI , LEHMANN AXEL
Published: April 2010

As a consequence of the permanently increasing complexity of modeling and simulation (M&S) applications, the demand for controlling and demonstrating the quality of a model and its applications by introducing adequate quality measures, techniques, and tools is obvious. Since efforts toward quality assurance such as model documentation and verification and validation (V&V) are time consuming and costly, a reasonable balance between quality and efficiency should be achieved in all practical applications. In the context of an integrated quality assurance strategy, several quality- and efficiency-related concepts have been developed and combined, including a model documentation guideline, a generalized V&V concept (the V&V Triangle), a graph-based V&V, and a multistage tailoring process. This article describes the proposed concepts and their applications in two selected simulation development projects. While the primary objective of the first project was introduction and application of the documentation guideline and the tailoring concept; the second project focused more on applying the V&V Triangle and the graph-based V&V. Based on the findings achieved by the case studies, some relevant lessons learned are summarized, which serve as expertise for both theoretical concept refinement and practical applications.
Oxford stone revisited: causes and consequences of diversity in building limestone used in the historic centre of Oxford, England
Authors: Gomez-Heras Miguel , Smith Bernard J. , Viles Heather A.
Published: April 2010

Stone decay is the result of the interaction of stone with its environment. It is therefore important to understand why certain materials, sometimes not the most suitable, were used to shape the built heritage of specific areas. The historical evolution of these areas conditioned many of the combinations of materials we see today, which in some cases can interact to accelerate decay. These combinations were driven by availability during construction, architectural fashion or the simultaneous utilization of materials that are aesthetically similar but differ significantly in their physical and chemical properties. A microcosm of the complex decisions that determine stone selection and subsequent interactions is provided by the City of Oxford, which is an excellent example of how such historic evolution can work with material characteristics to accelerate decay.
Contribution to the technological characterization of two widely used Portuguese dimension stones: the ‘Semi-rijo’ and ‘Moca Creme’ stones
Authors: Figueiredo Carlos , Folha Rita , Maurício António , Alves Carlos , Aires-Barros Luís
Published: April 2010

Stone weathering and durability are two major concerns widely recognized within construction, cultural heritage and monument stone decay assessment and conservation works. This paper aims to complement the technological data on the two commercial varieties of Portuguese dimension stones (‘Semi-rijo’ and ‘Moca Creme’), widely used in pavement and cladding inside and outside buildings. New data on the pore structures (fluid transport–related properties) and the durability (salt crystallization tests) of these limestones are presented. The pore structure was studied by a combined application of optical microscopy, scanning electron microscopy and mercury injection porosimetry. Fluid migration physical tests (open and free porosity, capillary imbibition and Hirschwald coefficient) were also performed, according to Portuguese and French standards. The resistance to salt crystallization was determined using the Portuguese standard NP EN 12370. An integrated analysis of all data has allowed a comparison of the results of the durability tests with characteristics of the pore network and properties related to fluid transport as well as petrographical features of the stones. The open porosity and freely-interconnected pores accessible to water after 48 hours (N48) seem to be the main features controlling their durability.
Raman spectra of reduced carbonaceous matter as a tool for determining the provenance of marbles: examples of ‘graphitic’ marbles from Czech quarries
Authors: Šťastná Aneta , Jehlička Jan , Přikryl Richard
Published: April 2010

This study reports the Raman data for reduced carbonaceous matter (CM) in crystalline marbles, related to a determination of their provenance. Raman microspectrometry was tested on ‘graphitic’ marbles formed under different metamorphic conditions (regional v. contact) with various geological ages, and with distinct types of CM from the Bohemian Massif (Czech Republic). First, various modes of occurrence of CM were examined by optical microscopy (OM). The Raman results exhibited spectral variations of CM with different metamorphic grades and types. Several marble groups could be distinguished: (1) well-ordered CM/graphite of higher grade regional metamorphosed marbles; less graphitized metamorphosed organic matter (‘disordered’ CM); (2) low-grade regional metamorphosed rocks, and (3) contact metamorphosed marbles.
Transgenic mice expressing an intracellular fluorescent fusion of angiotensin II demonstrate renal thrombotic microangiopathy and elevated blood pressure
Authors: Redding K. M. , Chen B. L. , Singh A. , Re R. N. , Navar L. G. , Seth D. M. , Sigmund C. D. , Tang W. W. , Cook J. L.
Published: April 2010

We have generated transgenic mice that express angiotensin II (ANG II) fused downstream of enhanced cyan fluorescent protein, expression of which is regulated by the mouse metallothionein promoter. The fusion protein, which lacks a secretory signal, is retained intracellularly. In the present study, RT-PCR, immunoblot analyses, whole-animal fluorescent imaging, and fluorescent microscopy of murine embryonic fibroblasts confirm expression of the fusion protein in vivo and in vitro. The transgene is expressed in all tissues tested (including brain, heart, kidney, liver, lung, and testes), and radioimmunoassay of plasma samples obtained from transgenic mice indicate no increase in circulating ANG II over wild-type levels, consistent with intracellular retention of the transgene product. Kidneys from transgenic and corresponding wild-type littermates were histologically evaluated, and abnormalities in transgenic mice consistent with thrombotic microangiopathy were observed; microthrombosis was frequently observed within the glomerular capillaries and small vessels. In addition, systolic and diastolic blood pressures, measured by telemetry ( n = 8 for each group), were significantly higher in transgenic mice compared with wild-type littermates. Blood pressure of line A male transgenic mice was 125 ± 1.7 over 97 ± 1.6 compared with 109 ± 1.7 over 83 ± 1.4 mmHg in wild-type littermates (systolic over diastolic). In summary, overexpression of an intracellular fluorescent fusion protein of ANG II correlates with elevated blood pressure and kidney pathology. This transgenic model may be useful to further explore the intracellular renin-angiotensin system and its implication in abnormal kidney function and hypertension.
Akt1 genetic deficiency limits hypothermia cardioprotection following murine cardiac arrest
Authors: Beiser David G. , Wojcik Kimberly R. , Zhao Danhong , Orbelyan Gerasim A. , Hamann Kimm J. , Vanden Hoek Terry L.
Published: April 2010

Therapeutic hypothermia (TH) cardioprotection has recently been associated with increased Akt signaling in a rat model of cardiac arrest. However, it is not known whether Akt is required for this beneficial effect of TH. We used a mouse model of cardiac arrest demonstrating TH cardioprotection to study the response of mice deficient in an Akt1 allele. We hypothesized that Akt1 mediates TH cardioprotection and that decreases in Akt1 content would diminish such protection. Adult C57BL/6 wild-type (WT) mice underwent an 8-min cardiac arrest. After 6 min, the mice were randomized to normothermia (WTNT, 37°C) or TH (WTTH, 30°C). Following cardiopulmonary resuscitation and the return of spontaneous circulation (ROSC), the animals were hemodynamically monitored for 240 min (R240). At R240, cardiac tissue Akt content and phosphorylation were assayed. Studies were repeated in Akt1 heterozygous (Akt1+/−) mice. As a result, baseline characteristics and ROSC rates were equivalent across groups. At R240, WTTH mice exhibited lower heart rate, larger stroke volume, and higher cardiac output than WTNT animals ( P < 0.05). Cardioprotection in WTTH at R240 was associated with increased cardiac Akt phosphorylation at Ser473 and Thr308 compared with that in WTNT ( P < 0.05). TH-associated alterations in Akt phosphorylation, stroke volume, heart rate, and cardiac output were abrogated in Akt1+/− animals. In conclusion, TH improves post-ROSC cardiac function and increases Akt phosphorylation in WT, but not Akt1+/−, mice. The Akt1 isoform appears necessary for TH-mediated cardioprotection.
Sensitivity of NOS-dependent vascular relaxation pathway to mineralocorticoid receptor blockade in caveolin-1-deficient mice
Authors: Pojoga Luminita H. , Adamová Zuzana , Kumar Abhinav , Stennett Amanda K. , Romero Jose R. , Adler Gail K. , Williams Gordon H. , Khalil Raouf A.
Published: April 2010

Endothelial caveolin-1 (cav-1) is an anchoring protein in plasma membrane caveolae where it binds endothelial nitric oxide synthase (eNOS) and limits its activation, particularly in animals fed a high salt (HS) diet. Cav-1 also interacts with steroid receptors such as the mineralocorticoid receptor (MR). To test the hypothesis that vascular reactivity is influenced by an interplay between MR and cav-1 during HS diet, we examined the effects of MR blockade on NOS-mediated vascular relaxation in normal and cav-1-deficient mice. Wild-type (WT) and cav-1 knockout mice (cav-1−/−) were fed for 14 days a HS (4% NaCl) diet with and without the MR antagonist eplerenone (Epl; 100 mg·kg−1·day−1). After systolic blood pressure (BP) was measured, the thoracic aorta was isolated for measurement of vascular reactivity, and the aorta and heart were used for measurement of eNOS and MR expression. BP was not different between WT + Epl and WT, but was higher in cav-1−/− + Epl than in cav-1−/− mice. Phenylephrine (Phe)-induced vascular contraction was less in cav-1−/− than WT, and significantly enhanced in cav-1−/− + Epl than in cav-1−/−, but not in WT + Epl compared with WT. Endothelium removal and NOS blockade by Nω-nitro-l-arginine methyl ester (l-NAME) enhanced Phe contraction in cav-1−/−, but not cav-1−/− + Epl. ACh-induced aortic relaxation was reduced in cav-1−/− + Epl versus cav-1−/−, but not in WT + Epl compared with WT. Endothelium removal, l-NAME, and the guanylate cyclase inhibitor ODQ abolished the large ACh-induced relaxation in cav-1−/− and the remaining relaxation in the cav-1−/− + Epl but had similar inhibitory effect in WT and WT + Epl. Real-time RT-PCR indicated decreased eNOS mRNA expression in the aorta and heart, and Western blots revealed decreased total eNOS in the heart of cav-1−/− + Epl compared with cav-1−/−. Vascular and cardiac MR expression was less in cav-1−/− than WT, but not in cav-1−/− + Epl compared with cav-1−/−. Plasma aldosterone (Aldo) was not different between WT and cav-1−/− mice nontreated or treated with Epl. Thus in cav-1 deficiency states and HS diet MR blockade is associated with increased BP, enhanced vasoconstriction, and decreased NOS-mediated vascular relaxation and eNOS expression. The data suggest that, in the absence of cav-1, MR activation plays a beneficial role in regulating eNOS expression/activity and, consequently, the vascular function during HS diet.
Roles of hyperpolarization-activated current If in sinoatrial node pacemaking: insights from bifurcation analysis of mathematical models
Authors: Kurata Yasutaka , Matsuda Hiroyuki , Hisatome Ichiro , Shibamoto Toshishige
Published: April 2010

To elucidate the roles of hyperpolarization-activated current ( If) in sinoatrial node (SAN) pacemaking, we theoretically investigated 1) the effects of If on stability and bifurcation during hyperpolarization of SAN cells; 2) combined effects of If and the sustained inward current ( Ist) or Na+ channel current ( INa) on robustness of pacemaking against hyperpolarization; and 3) whether blocking If abolishes pacemaker activity under certain conditions. Bifurcation analyses were performed for mathematical models of rabbit SAN cells; equilibrium points (EPs), periodic orbits, and their stability were determined as functions of parameters. Unstable steady-state potential region determined with applications of constant bias currents shrunk as If density increased. In the central SAN cell, the critical acetylcholine concentration at which bifurcations, to yield a stable EP and quiescence, occur was increased by smaller If, but decreased by larger If. In contrast, the critical acetylcholine concentration and conductance of gap junctions between SAN and atrial cells at bifurcations progressively increased with enhancing If in the peripheral SAN cell. These effects of If were significantly attenuated by eliminating Ist or INa, or by accelerating their inactivation. Under hyperpolarized conditions, blocking If abolished SAN pacemaking via bifurcations. These results suggest that 1) If itself cannot destabilize EPs; 2) If improves SAN cell robustness against parasympathetic stimulation via preventing bifurcations in the presence of Ist or INa; 3) If dramatically enhances peripheral cell robustness against electrotonic loads of the atrium in combination with INa; and 4) pacemaker activity of hyperpolarized SAN cells could be abolished by blocking If.
Effects of exercise training on cellular mechanisms of endothelial nitric oxide synthase regulation in coronary arteries after chronic occlusion
Authors: Zhou Minglong , Widmer R. Jay , Xie Wei , Jimmy Widmer A. , Miller Matthew W. , Schroeder Friedhelm , Parker Janet L. , Heaps Cristine L.
Published: April 2010

Exercise training enhances agonist-mediated relaxation in both control and collateral-dependent coronary arteries of hearts subjected to chronic occlusion, an enhancement that is mediated in part by nitric oxide. The purpose of the present study was to elucidate exercise training-induced adaptations in specific cellular mechanisms involved in the regulation of endothelial nitric oxide synthase (eNOS) in coronary arteries of ischemic hearts. Ameroid constrictors were surgically placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniature swine. Eight weeks postoperatively, animals were randomized into sedentary (pen-confined) or exercise training (treadmill run; 5 days/wk; 14 wk) protocols. Coronary artery segments (∼1.0 mm luminal diameter) were isolated from collateral-dependent (LCX) and control (nonoccluded left anterior descending) arteries 22 wk after ameroid placement. Endothelial cells were enzymatically dissociated, and intracellular Ca2+ responses (fura 2) to bradykinin stimulation were studied. Immunofluorescence and laser scanning confocal microscopy were used to quantify endothelial cell eNOS and caveolin-1 cellular distribution under basal and bradykinin-stimulated conditions. Immunoblot analysis was used to determine eNOS, phosphorylated (p)-eNOS, protein kinase B (Akt), pAkt, and caveolin-1 protein levels. Bradykinin-stimulated nitrite plus nitrate (NOx; nitric oxide metabolites) levels were assessed via HPLC. Exercise training resulted in significantly enhanced bradykinin-mediated increases in endothelial Ca2+ levels, NOx levels, and the distribution of eNOS-to-caveolin-1 ratio at the plasma membrane in endothelial cells of control and collateral-dependent arteries. Exercise training also significantly increased total eNOS and phosphorylated levels of eNOS (pSer1179) in collateral-dependent arteries. Total eNOS protein levels were also significantly increased in collateral-dependent arteries of sedentary animals. These data provide new insights into exercise training-induced adaptations in cellular mechanisms of nitric oxide regulation in collateral-dependent coronary arteries of chronically occluded hearts that contribute to enhanced nitric oxide production.
A biophysical model for cardiac microimpedance measurements
Authors: Pollard Andrew E. , Barr Roger C.
Published: April 2010

Alterations to cell-to-cell electrical conductance and to the structural arrangement of the collagen network in cardiac tissue are recognized contributors to arrhythmia development, yet no present method allows direct in vivo measurements of these conductances at their true microscopic scale. The present report documents such a plan, which involves interstitial multisite stimulation at a subcellular to cellular size scale, and verifies the performance of the method through biophysical modeling. Although elements of the plan have been analyzed previously, their performance as a whole is considered here in a comprehensive way. Our analyses take advantage of a three-dimensional structural framework in which interstitial, intracellular, and membrane components are coupled to one another on the fine size scale, and electrodes are separated from one another as in arrays we fabricate routinely. With this arrangement, determination of passive tissue resistances can be made from measurements taken on top of the currents flowing in active tissue. In particular, our results show that measurements taken at multiple frequencies and electrode separations provide powerful predictions of the underlying tissue resistances in all geometric dimensions. Because of the small electrode size, separation of interstitial from intracellular compartment contributions is readily achieved.
Properties of WT and mutant hERG K+ channels expressed in neonatal mouse cardiomyocytes
Authors: Lin Eric C. , Holzem Katherine M. , Anson Blake D. , Moungey Brooke M. , Balijepalli Sadguna Y. , Tester David J. , Ackerman Michael J. , Delisle Brian P. , Balijepalli Ravi C. , January Craig T.
Published: April 2010

Mutations in human ether-a-go-go-related gene 1 ( hERG) are linked to long QT syndrome type 2 (LQT2). hERG encodes the pore-forming α-subunits that coassemble to form rapidly activating delayed rectifier K+ current in the heart. LQT2-linked missense mutations have been extensively studied in noncardiac heterologous expression systems, where biogenic (protein trafficking) and biophysical (gating and permeation) abnormalities have been postulated to underlie the loss-of-function phenotype associated with LQT2 channels. Little is known about the properties of LQT2-linked hERG channel proteins in native cardiomyocyte systems. In this study, we expressed wild-type (WT) hERG and three LQT2-linked mutations in neonatal mouse cardiomyocytes and studied their electrophysiological and biochemical properties. Compared with WT hERG channels, the LQT2 missense mutations G601S and N470D hERG exhibited altered protein trafficking and underwent pharmacological correction, and N470D hERG channels gated at more negative voltages. The ΔY475 hERG deletion mutation trafficked similar to WT hERG channels, gated at more negative voltages, and had rapid deactivation kinetics, and these properties were confirmed in both neonatal mouse cardiomyocyte and human embryonic kidney (HEK)-293 cell expression systems. Differences between the cardiomyocytes and HEK-293 cell expression systems were that hERG current densities were reduced 10-fold and deactivation kinetics were accelerated 1.5- to 2-fold in neonatal mouse cardiomyocytes. An important finding of this work is that pharmacological correction of trafficking-deficient LQT2 mutations, as a potential innovative approach to therapy, is possible in native cardiac tissue.
Effects of Granulocyte-Colony Stimulating Factor After Stroke in Aged Rats
Authors: Popa-Wagner Aurel , Stöcker Kai , Balseanu Adrian Tudor , Rogalewski Andreas , Diederich Kai , Minnerup Jens , Margaritescu Claudiu , Schäbitz Wolf-Rüdiger
Published: April 2010

Background and Purpose—

In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. Granulocyte-colony stimulating factor (G-CSF), a member of the cytokine family of growth factors, promotes brain neurogenesis and improves functional outcome after stroke in young animals. We tested the hypothesis that G-CSF provides a restorative therapeutic benefit in aged animals.

Methods—

Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 19- to 20-month-old male Sprague-Dawley rats. One hour after reperfusion, the aged rats were treated daily with 15 μg/kg G-CSF and for 15 days total. Rats were behaviorally tested and the brains removed for analysis at 28 days poststroke.

Results—

G-CSF treatment after stroke exerted a robust and sustained beneficial effect on survival rate and running function. Transient improvement after G-CSF treatment could be observed for coordinative motor function on the inclined plane test and for working memory in the radial-arm maze test. At the cellular level, G-CSF treatment increased the number of proliferating cells in the subventricular zone and dentate gyrus and also increased the number of newborn neurons in the subventricular zone ipsilateral to the lesion.

Conclusions—

These results suggest that G-CSF treatment in aged rats has a survival-enhancing capacity and a beneficial effect on functional outcome, most likely through supportive cellular processes such as neurogenesis.
Gender Differences in Cardiovascular Risk Factors and Risk Perception Among Individuals With Diabetes
Authors: Homko Carol J. , Zamora Linda , Santamore William P. , Kashem Abul , McConnell Timothy , Bove Alfred A.
Published: April 2010

Purpose

The purpose of this study was to examine gender-based differences in cardiovascular risk factors and risk perception among individuals with diabetes.

Methods

The sample consisted of patients with an established history of diabetes who were enrolled in a telemedicine trial to reduce cardiovascular disease (CVD) risk. All subjects had a 10% or greater risk on the Framingham risk index. Assessments included blood pressure, A1C, lipid profile, medication history, and knowledge and risk perception surveys.

Results

Data were available for 211 individuals with type 2 diabetes (88 men and 123 women). The women and men did not differ in age, body mass index, or Framingham risk. Only 37.4% of women and 40.9% of men were at an A1C target of <7%. Total cholesterol levels were significantly higher among women, and fewer women were at low-density lipoprotein or blood pressure targets. Knowledge of CVD was similar between the 2 sexes. However, women perceived their risk for CVD to be significantly higher than did men.

Conclusion

Less favorable cardiovascular risk profiles are observed among women with diabetes as compared with their male counterparts. Multifaceted approaches to both diabetes management and education are needed to target CVD risk reduction among individuals with diabetes.