bluuebunny/crossref_metadata_2025 huggingface dataset:
A clinicopathological analysis of 26 patients with infection-associated haemophagocytic lymphohistiocytosis and the importance of bone marrow phagocytosis for the early initiation of immunomodulatory treatment
Authors: Nair Velu , Das Satyaranjan , Sharma Ajay , Sharma Sanjeevan , Sharma Prafull , Ray Sougat , Bhattacharya Shilajit
Published: December 2012

Objective

To analyse the clinicopathological presentation, outcome and importance of bone marrow haemophagocytosis in patients with infection-associated haemophagocytic lymphohistiocytosis (IA-HLH) in a tertiary care hospital in Northern India.

Study design

Between January 2007 and December 2009, 26 consecutive patients meeting the diagnostic criteria for IA-HLH, based on the HLH2004 protocol of the Histiocyte Society, were followed up for between 12 and 34 months (median 20 months).

Results

IA-HLH was diagnosed in three of the five patients who died 5–6 weeks after the onset of the illness, whereas diagnosis in the remaining group was made a median of 2 weeks after the onset of the illness. The predominant presenting features were fever (100%), hepatomegaly (69%), splenomegaly (58%) and anaemia (96%). All patients showed >3% haemophagocytosis on bone marrow studies—in four cases after serial aspiration/biopsies. Twenty-one (80.8%) cases were non-fatal and five (19.2%) patients died. The non-fatal cases included eight (38.1%) cases of viral infection, seven (33.3%) bacterial infections, two (9.6%) fungal and four (19.0%) protozoal infections; whereas four (80%) bacterial infections and one (20%) viral infection were associated with the fatal cases. The mean of the nadir blood counts of white blood cells, absolute neutrophil counts and platelets; the mean of all the peak biochemical parameters of liver function tests, lactate dehydrogenase and ferritin and the lowest fibrinogen values before treatment, differed significantly (p<0.05) between the non-fatal and the fatal group, being worse in the latter.

Conclusions

IA-HLH is important because it can obscure the typical clinical features of the underlying primary disease, thus delaying the diagnosis and having a negative effect on the outcome. Although bone marrow haemophagocytosis is not a mandatory diagnostic criterion, we found it to be a useful tool together with biochemical parameters for early recognition of HLH, especially in developing countries lacking molecular and flow laboratories. The severity of pancytopenia and derangement in biochemical markers were significantly higher in the patients who died.
Informal confidential voting interviewing in a sexual risk assessment of men who have sex with men (MSM) and transgenders (hijra) in Bangalore, India
Authors: Phillips Anna Elizabeth , Molitor John , Boily Marie Claude , Lowndes Catherine M , Gurav Kaveri , Blanchard James , Alary Michel
Published: December 2012

Objective

The accuracy of self-reporting sensitive sexual risk behaviours is highly susceptible to misreporting. Informal confidential voting interviews (ICVIs) may minimise social desirability bias by increasing the privacy of the interview setting. The objective was to investigate determinants of risky behaviour among men who have sex with men (MSM) and ‘hijra’ (transgenders) reported through two interviewing tools: ICVIs and face-to-face interviews (FTFIs).

Methods

Cluster random sampling was used to recruit MSM in 85 cruising sites in Bangalore, including eight hammams (bath houses) and 77 public locations where MSM and hijra cruise for sex. Individuals were randomly allocated to one of the data collection methods(5 : 2 FTFI : ICVI). Data were analysed using standard regression and a profile regression approach that associates clusters of behaviours with our outcome (FTFI vs ICVI).

Results

A total of 372 MSM and hijra were interviewed for the FTFIs and 153 respondents completed ICVIs. Participants were more likely to report injecting drug use (4% vs 1%; p=0.008) and paying to have sex with a female sex worker (FSW) in the last year (28% vs 8%; p=0.001) in the ICVIs. There were no differences to questions on sociodemographics, sexual debut with another male, non-condom use (12% vs 14%), ever selling sex to men (58% vs 56%), current female partner (26% vs 20%) and non-condom use with a main female partner (17% vs 19%).

Conclusions

The significant differences between interview modes for certain outcomes, such as intravenous drug use and sex with a FSW, demonstrate how certain behaviour is stigmatised among the MSM community. Nevertheless, the lack of effect of the interviewing tool in other outcomes may indicate either less reporting bias in reporting this behaviour or environmental factors such as the interviewers not adequately screening themselves from the respondent or a potential disadvantage of using other MSM as interviewers.
Bringing it home: community survey of HIV risks to primary sex partners of men and women in alcohol-serving establishments in Cape Town, South Africa
Authors: Kalichman Seth C , Pitpitan Eileen , Eaton Lisa , Cain Demetria , Carey Kate B , Carey Michael P , Harel Ofer , Mehlomakhulu Vuyelwa , Simbayi Leickness Chisamu , Mwaba Kelvin
Published: December 2012

Background

Concurrent sexual relationships facilitate the spread of HIV infection, and sex with non-primary partners may pose particularly high risks for HIV transmission to primary partners.

Objective

We examined the sexual and alcohol-related risks associated with sex partners outside of primary relationships among South African men and women in informal drinking establishments.

Methods

Men (n=4959) and women (n=2367) with primary sex partners residing in a Xhosa-speaking South African township completed anonymous surveys. Logistic regressions tested associations between having outside partners and risks for sexually transmitted infections (STI)/HIV.

Results

Forty-four percent of men and 26% women with primary sex partners reported also having outside sex partners in the previous month. Condom use with outside partners was inconsistent for men and women; only 19% of men and 12% of women used condoms consistently with outside sex partners. Multivariable regressions for men and women showed that having outside partners was significantly associated with having been diagnosed with an STI, consuming alcohol in greater frequency and quantity, alcohol use during sex, meeting sex partners in alcohol-serving venues, and higher rates of unprotected sex.

Conclusions

Having outside sex partners was associated with multiple risk factors for HIV infection among South African shebeen patrons. Social and structural interventions that encourage condom use are needed for men and women with outside partners who patronise alcohol-serving venues.
Forces applied with a hoof tester to cadaver feet vary widely between users
Authors: Arndt J. L. , Pfau T. , Day P. , Pardoe C. , Bolt D. M. , Weller R.
Published: December 2012

Hoof testers are commonly used in equine practice. In this study, we determined the intraoperator and interoperator reliability of force application with hoof testers for different groups: experienced veterinarians, novices and farriers. For this purpose, we have developed and validated an instrumented hoof tester. Forces varied significantly between the different regions of the foot for experienced operators applying the highest forces to the heels, then the frog, then the toe, and the lowest forces to the quarters. Novices applied significantly more force to the toe versus the frog. Intraoperator reliability varied significantly between regions and operators. Novices had the narrowest width of limits of agreement for the frog and heel, but the widest for the toe and the quarters, whereas farriers had the narrowest width of agreement for the toe and quarter. Force application differed significantly between groups for the frog and heel regions, but not the toe and quarters. Veterinarians applied higher forces to the frog compared with farriers and novices, and higher forces to the heel compared with novices. This study showed that hoof tester forces vary widely within and between operators, and standardisation of hoof tester use is needed to make this diagnostic test more reliable.
Habitat variation and invasive species as factors influencing the distribution of native fishes in the lower Fraser River Valley, British Columbia, with an emphasis on brassy minnow (Hybognathus hankinsoni)
Authors: Nowosad Damon M. , Taylor Eric B.
Published: December 2012

Brassy minnow (Hybognathus hankinsoni Hubbs, 1929) have disjunct distributions in western Canada, making them a species of conservation concern. We assessed changes in the distribution of invasive species as factors influencing the distribution of brassy minnow and other native species by comparing historical and current distributions in the lower Fraser River in British Columbia. We tested effects of physical habitat parameters on local distributions of brassy minnow and for evidence of negative interactions between brassy minnow and invasive brown bullhead (Ameiurus nebulosus (Lesueur, 1819)). Comparison of contemporary and historical (1956 and 1959) fish distributions indicated significant declines in native cypriniform (minnows and suckers) species, including brassy minnow, but no change in the number of invasive species, although there was some faunal turnover. Logistic regression suggested that conductivity, turbidity, and water temperature were important predictors of brassy minnow presence. Appearances of adult-sized brown bullhead at one site corresponded with reduced abundance of native fishes. In growth experiments with brassy minnow, brown bullhead, and redside shiner (Richardsonius balteatus (Richardson, 1836)), brassy minnow exhibited mass loss and mortalities, suggesting that they were poor competitors. Our results contribute to a better understanding of abiotic and biotic factors affecting distribution and persistence of brassy minnow.
Is Canada fulfilling its obligations to sustain marine biodiversity? A summary review, conclusions, and recommendations1This manuscript is a companion paper to Hutchings et al. (doi:10.1139/a2012-011) and VanderZwaag et al. (doi:10.1139/a2012-013) also appearing in this issue. These three papers comprise an edited version of a February 2012 Royal Society of Canada Expert Panel Report.
Authors: Hutchings Jeffrey A. , Côté Isabelle M. , Dodson Julian J. , Fleming Ian A. , Jennings S. , Mantua Nathan J. , Peterman Randall M. , Riddell Brian E. , Weaver Andrew J. , VanderZwaag David L.
Published: December 2012

Canada has made numerous national and international commitments to sustain marine biodiversity. Given current and potential threats to biodiversity from climate change, fisheries, and aquaculture, we provide a summary review of Canada’s progress in fulfilling its obligations to protect, conserve, recover, and responsibly exploit marine biodiversity. We conclude that Canada has made little substantive progress, when compared to most developed nations, in meeting its biodiversity commitments. Much of Canada’s policy and rhetoric has not been operationalised, leaving many of the country’s national and international obligations unfulfilled in some key areas, such as the establishment of marine protected areas and incorporation of the precautionary approach to fisheries management. We conclude that regulatory conflict within Canada’s Department of Fisheries and Oceans (DFO) and the absolute discretion exercised by the national Minister of Fisheries and Oceans contribute significantly to an unduly slow rate of policy and statute implementation. We recommend new approaches and measures to sustain Canadian marine biodiversity and new research initiatives to support scientific advice to decision-makers. Many recommendations focus on management actions required to meet existing commitments to biodiversity conservation. Overall, we conclude that the most effective strategy is to protect existing biological diversity and to rebuild depleted populations and species to restore natural diversity. By improving and protecting the biodiversity in Canada’s oceans, such a strategy will restore the natural resilience of Canada’s ocean ecosystems to adapt to the challenges posed by climate change and other anthropogenic activities with consequent long-term benefits for food security and social and economic well-being.
RECESSED-GATE NORMALLY-OFF GaN MOSFET TECHNOLOGIES
Authors: IM KI-SIK , KIM KI-WON , KIM DONG-SEOK , KANG HEE-SUNG , KIM DO-KYWN , CHANG SUNG-JAE , BAE YOUNG-HO , HAHM SUNG-HO , CRISTOLOVEANU SORIN , LEE JUNG-HEE
Published: December 2012

We have fabricated and investigated several types of GaN MOSFETs with normally-off operation. The recessed-gate GaN MOSFET is preferred for normally-off operation, because the threshold voltage (Vth) of the device can be easily controlled, but it suffers from relatively modest current drivability which must be improved by adopting appropriate device structure and/or process. Enhanced performances have been achieved in this work by combining the recessed-gate technology with additional processes, such as: the post-recess tetramethylammonium hydroxide (TMAH) treatment to remove the plasma damage, the post-deposition annealing of gate oxide to decrease the gate leakage current, the re-growth of n+ GaN layer for source/drain to improve the access resistance and Vth uniformity, the stress control technology to achieve extremely high 2-D electron-gas density (2DEG) on source/drain and decrease the series resistance, and the use of the p- GaN back-barrier to decrease the buffer leakage current. The GaN -based FinFET with very narrow fin was also investigated as a possible candidate for high performance normally-off GaN MOSFETs.
SILICON-ON-INSULATOR MESFETS AT THE 45NM NODE
Authors: LEPKOWSKI WILLIAM , WILK SETH J. , GHAJAR M. REZA , PARSI ANURADHA , THORNTON TREVOR J.
Published: December 2012

Metal-semiconductor field-effect-transistors (MESFETs) have been fabricated using a commercially available 45nm silicon-on-insulator (SOI) CMOS foundry with no changes to the process flow. Depending upon the layout dimensions, these n-channel, depletion mode devices can be designed for high current drive (IDSAT≥ 100mA/mm ), high operating frequency (fmax> 35 GHz ) or enhanced breakdown voltage (VBD> 25 V ). The design flexibility provided by the SOI MESFETs, coupled with the high performance of ULSI CMOS at the 45nm node will enable a variety of analog, RF and mixed signal applications.
InAs1-xSbx ALLOYS WITH NATIVE LATTICE PARAMETERS GROWN ON COMPOSITIONALLY GRADED BUFFERS: STRUCTURAL AND OPTICAL PROPERTIES
Authors: WANG D. , DONETSKY D. , LIN Y. , KIPSHIDZE G. , SHTERENGAS L. , BELENKY G. , SARNEY W. L. , SVENSSON S. P.
Published: December 2012

GaInSb and AlGaInSb compositionally graded buffer layers grown on GaSb by MBE were used to develop unrelaxed InAs1-xSbx epitaxial alloys with strain-free native lattice constants up to 2.1% larger than that of GaSb . The in-plane lattice constant of the strained top buffer layer was grown to be equal to the native, unstrained lattice constant of InAs1-xSbx with given x. The InAs0.56Sb0.44 layers demonstrated a photoluminescence (PL) peak at 9.4 μm at T = 150 K. The minority carrier lifetime measured at 77 K for InAs0.8Sb0.2 was 250 ns.
EXPRESSIVENESS OF ELEMENTARY CELLULAR AUTOMATA
Authors: REDEKER MARKUS , ADAMATZKY ANDREW , MARTÍNEZ GENARO J.
Published: December 2012

We investigate expressiveness, a parameter of one-dimensional cellular automata, in the context of simulated biological systems. The development of elementary cellular automata is interpreted in terms of biological systems, and biologically inspired parameters for biodiversity are applied to the configurations of cellular automata. This paper contains a survey of the Elementary Cellular Automata in terms of their expressiveness and an evaluation whether expressiveness is a meaningful term in the context of simulated biology.
AN AREA DEFUZZIFICATION TECHNIQUE TO ASSESS NUCLEAR EVENT RELIABILITY DATA FROM FAILURE POSSIBILITIES
Authors: PURBA JULWAN HENDRY , LU JIE , ZHANG GUANGQUAN , RUAN DA
Published: December 2012

Reliability data is essential for a nuclear power plant probabilistic safety assessment by fault tree analysis to assess the performance of the safety-related systems. The limitation of conventional reliability data arises from insufficient historical data for probabilistic calculation. This study describes a new approach to calculate nuclear event reliability data by utilizing the concept of failure possibilities, which are expressed in qualitative natural languages, mathematically represented by membership functions of fuzzy numbers, and subjectively justified by a group of experts based on their working experience and expertise. We also propose an area defuzzification technique to convert the membership function into nuclear event reliability data. The actual event reliability data, which are collected from the operational experiences of the reactor protection system in Babcock & Wilcox pressurized water reactor between 1984 and 1998, are then compared with the reliability data calculated from the new approach. The results show that fuzzy failure rates can be used as alternatives for probabilistic failure rates when nuclear event historical data are insufficient or unavailable for probabilistic calculation. This study also confirms that our proposed area defuzzification technique is a suitable technique to defuzzify failure possibilities into nuclear event reliability data.
NONLINEAR FREE VIBRATION ANALYSIS OF AN EMBEDDED DOUBLE LAYER GRAPHENE SHEET IN POLYMER MEDIUM
Authors: MAHDAVI MOHAMMAD HADI , JIANG LIYING , SUN XUELIANG
Published: December 2012

This paper investigates the nonlinear free vibration of a double layer graphene sheet (DLGS) embedded in a polymer matrix aroused by the nonlinear van der Waals (vdW) interactions based on the classic Kirchhoff plate theory. Harmonic balance method is used to predict the nonlinear relation between deflection amplitudes and resonant frequencies of the DLGS. The embedded DLGS presents a hardening nonlinearity in both in-phase vibration (IPV) and anti-phase vibration (APV) modes. The surrounding polymer medium is found to have significant effect on the resonant frequency, especially for the IPV mode. For example, the variation of the resonant frequencies of an embedded DLGS is less dependent on the graphene aspect ratio and mode numbers as compared with a free-standing one. Uni-axial and bi-axial in-plane load effects upon the vibrational behavior of DLGS are also investigated. It is concluded that due to the influence of the nonlinear interlayer and interfacial vdW forces on the DLGS, prediction on both linear and nonlinear resonant frequencies for the embedded DLGS is quite different from that for a free-standing one. This study is expected to be useful for understanding the nonlinear mechanical behavior of graphenes with their potential applications in nanocomposites.
ANALYTICAL MODEL TO DETERMINE RESPONSE AMPLITUDE OPERATOR OF A FLOATING BODY FOR COUPLED ROLL AND YAW MOTIONS AND FREQUENCY-BASED ANALYSIS
Authors: BAGHFALAKI M. , DAS SAMIR K. , DAS S. N.
Published: December 2012

The paper deals with the mathematical modeling of response amplitude operator (RAO) and frequency-based analysis for coupled roll and yaw motions in regular waves. Prior to obtaining the RAO expressions for linearly coupled conditions, hydrodynamic coefficients are computed by using the strip theory formulation. We consider sinusoidal wave with frequency (ω) varying between 0.3 rad/s and 1.2 rad/s acts on beam to the floating body for zero forward speed. Two limiting cases corresponding to ω → 0 and ω → ∞ are considered and general expressions of RAO for intermediate frequencies are derived. Analytical result shows that the norm of RAO is maximum when ω ≈ ωn≈ 0.74 for coupled roll and yaw motions. The asymptotic convergence of real part, imaginary part and norm of uncoupled yaw transfer functions are noticed with the increase of wave frequency. Using the normalization procedure and frequency based analysis; group based equations are formulated for each case. To understand the relative importance of the hydrodynamic coefficients, analytical solutions are obtained. The sensitivity analysis with respect to the initial conditions is investigated for roll and yaw motions. This study could be useful to model the floating body dynamics and corresponding wave loads in the design stage.
Interactions between hERG and KCNQ1 α-subunits are mediated by their COOH termini and modulated by cAMP
Authors: Organ-Darling Louise E. , Vernon Amanda N. , Giovanniello Jacqueline R. , Lu Yichun , Moshal Karni , Roder Karim , Li Weiyan , Koren Gideon
Published: December 2012

KCNQ1 and hERG encode the voltage-gated potassium channel α-subunits of the cardiac repolarizing currents IKs and IKr, respectively. These currents function in vivo with some redundancy to maintain appropriate action potential durations (APDs), and loss-of-function mutations in these channels manifest clinically as long QT syndrome, characterized by the prolongation of the QT interval, polymorphic ventricular tachycardia, and sudden cardiac death. Previous cellular electrophysiology experiments in transgenic rabbit cardiomyocytes and heterologous cell lines demonstrated functional downregulation of complementary repolarizing currents. Biochemical assays indicated direct, protein-protein interactions between KCNQ1 and hERG may underlie the interplay between IKs and IKr. Our objective was to investigate hERG-KCNQ1 interactions in the intact cellular environment primarily through acceptor photobleach FRET (apFRET) experiments. We quantitatively assessed the extent of interactions based on fluorophore location and the potential regulation of interactions by physiologically relevant signals. apFRET experiments established specific hERG-KCNQ1 associations in both heterologous and primary cardiomyocytes. The largest FRET efficiency ( E f; 12.0 ± 5.2%) was seen between ion channels with GFP variants fused to the COOH termini. Acute treatment with forskolin + IBMX or a membrane-permeable cAMP analog significantly and specifically reduced the extent of hERG-KCNQ1 interactions (by 41 and 38%, respectively). Our results demonstrate direct interactions between KCNQ1 and hERG occur in both intact heterologous cells and primary cardiomyocytes and are mediated by their COOH termini. Furthermore, this interplay between channel proteins is regulated by intracellular cAMP.
Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation
Authors: Wan William , Gleason Rudolph L.
Published: December 2012

Elastin fragmentation is a common characteristic of vascular diseases, such as abdominal aortic aneurysms, peripheral arterial disease, and aortic dissection. Examining growth and remodeling in the presence of dysfunctional elastic fibers provides insight into the adaptive or maladaptive changes that tissues undergo in compensating for structural deficiencies. This study used the maturation of fibulin-5 knockout (KO) and wild-type mice to study the effects of fragmented elastic fibers on the growth and remodeling of carotid arteries. The microstructural content and organization and the biaxial mechanical behavior of common carotid arteries were measured, and parameter estimation performed from KO and WT mice aged 3, 4, 8, and 13 wk. Gross measurements and biaxial tests revealed significant differences in pressure-diameter behavior, in vivo axial stretch, opening angle, compliance, and wall stresses during maturation of wild-type arteries, but little change in these values in KO mice. Multiphoton microscopy used to image collagen fibers across the vessel wall in pressurized and stretched arteries suggests that there is little variation in fiber angles between different ages. Parameter estimation revealed significant differences in material parameters between genotypes and age groups. This study suggests that neonatal formation and cross-linking of functional elastic fibers, followed by increases in artery size due to growth with little remodeling of the elastic fibers, endow arteries with large distensibility and contribute to the evolution of mechanical behavior of arteries during maturation. Dysfunction in neonatal formation of elastic fibers abrogates many of the changes in mechanical response that take place during the maturation.
Mesenchymal stem cells improve cardiac conduction by upregulation of connexin 43 through paracrine signaling
Authors: Mureli Shwetha , Gans Christopher P. , Bare Dan J. , Geenen David L. , Kumar Nalin M. , Banach Kathrin
Published: December 2012

Mesenchymal stem cells (MSCs) were shown to improve cell survival and alleviate cardiac arrhythmias when transplanted into cardiac tissue; however, little is known about the mechanism by which MSCs modify the electrophysiological properties of cardiac tissue. We aimed to distinguish the influence of cell-cell coupling between myocytes and MSCs from that of MSC-derived paracrine factors on the spontaneous activity and conduction velocity (θ) of multicellular cardiomyocyte preparations. HL-1 cells were plated on microelectrode arrays and their spontaneous activity and θ was determined from field potential recordings. In heterocellular cultures of MSCs and HL-1 cells the beating frequency was attenuated ( t0h: 2.26 ± 0.18 Hz; t4h: 1.98 ± 0.26 Hz; P < 0.01) concomitant to the intercellular coupling between MSCs and cardiomyocytes. In HL-1 monolayers supplemented with MSC conditioned media (ConM) or tyrode (ConT) θ significantly increased in a time-dependent manner (ConT: t0h: 2.4 cm/s ± 0.2; t4h: 3.1 ± 0.4 cm/s), whereas the beating frequency remained constant. Connexin (Cx)43 mRNA and protein expression levels also increased after ConM or ConT treatment over the same time period. Enhanced low-density lipoprotein receptor-related protein 6 (LRP6) phosphorylation after ConT treatment implicates the Wnt signaling pathway. Suppression of Wnt secretion from MSCs (IWP-2; 5 μmol/l) reduced the efficacy of ConT to induce phospho-LRP6 and to increase θ. Inhibition of β-catenin (cardamonin; 10 μmol/l) or GSK3-α/β (LiCl; 5 mmol/l) also suppressed changes in θ, further supporting the hypothesis that MSC-mediated Cx43 upregulation occurs in part through secreted Wnt ligands and activation of the canonical Wnt signaling pathway.
Enhanced resistance to permeability transition in interfibrillar cardiac mitochondria in dogs: effects of aging and long-term aldosterone infusion
Authors: Asemu Girma , O'Connell Kelly A. , Cox James W. , Dabkowski Erinne R. , Xu Wenhong , Ribeiro Rogerio F. , Shekar Kadambari C. , Hecker Peter A. , Rastogi Sharad , Sabbah Hani N. , Hoppel Charles L. , Stanley William C.
Published: December 2012

Functional differences between subsarcolemmal and interfibrillar cardiac mitochondria (SSM and IFM) have been observed with aging and pathological conditions in rodents. Results are contradictory, and there is little information from large animal models. We assessed the respiratory function and resistance to mitochondrial permeability transition (MPT) in SSM and IFM from healthy young (1 yr) and old (8 yr) female beagles and in old beagles with hypertension and left ventricular (LV) wall thickening induced by 16 wk of aldosterone infusion. MPT was assessed in SSM and IFM by Ca2+retention and swelling. Healthy young and old beagles had similar mitochondrial structure, respiratory function, and Ca2+-induced MPT within SSM and IFM subpopulations. On the other hand, oxidative capacity and resistance to Ca2+-induced MPT were significantly greater in IFM compared with SSM in all groups. Old beagles treated with aldosterone had greater LV wall thickness and worse diastolic filling but normal LV chamber volume and systolic function. Treatment with aldosterone did not alter mitochondrial respiratory function but accelerated Ca2+-induced MPT in SSM, but not IFM, compared with healthy old and young beagles. In conclusion, in a large animal model, oxidative capacity and resistance to MPT were greater in IFM than in SSM. Furthermore, aldosterone infusion increased susceptibility to MPT in SSM, but not IFM. Together this suggests that SSM are less resilient to acute stress than IFM in the healthy heart and are more susceptible to the development of pathology with chronic stress.
Pressure overload differentially affects respiratory capacity in interfibrillar and subsarcolemmal mitochondria
Authors: Schwarzer Michael , Schrepper Andrea , Amorim Paulo A. , Osterholt Moritz , Doenst Torsten
Published: December 2012

Years ago a debate arose as to whether two functionally different mitochondrial subpopulations, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), exist in heart muscle. Nowadays potential differences are often ignored. Presumably, SSM are providing ATP for basic cell function, whereas IFM provide energy for the contractile apparatus. We speculated that two distinguishable subpopulations exist that are differentially affected by pressure overload. Male Sprague-Dawley rats were subjected to transverse aortic constriction for 20 wk or sham operation. Contractile function was assessed by echocardiography. Heart tissue was analyzed by electron microscopy. Mitochondria were isolated by differential centrifugation, and respiratory capacity was analyzed using a Clark electrode. Pressure overload induced left ventricular hypertrophy with increased posterior wall diameter and impaired contractile function. Mitochondrial state 3 respiration in control was 50% higher in IFM than in SSM. Pressure overload significantly impaired respiratory rates in both IFM and SSM, but in SSM to a lower extent. As a result, there were no differences between SSM and IFM after 20 wk of pressure overload. Pressure overload reduced total citrate synthase activity, suggesting reduced total mitochondrial content. Electron microscopy revealed normal morphology of mitochondria but reduced total mitochondrial volume density. In conclusion, IFM show greater respiratory capacity in the healthy rat heart and a greater depression of respiratory capacity by pressure overload than SSM. The differences in respiratory capacity of cardiac IFM and SSM in healthy hearts are eliminated with pressure overload-induced heart failure. The strong effect of pressure overload on IFM together with the simultaneous appearance of mitochondrial and contractile dysfunction may support the notion of IFM primarily producing ATP for contractile function.
Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease
Authors: Hecker Peter A. , Leopold Jane A. , Gupte Sachin A. , Recchia Fabio A. , Stanley William C.
Published: December 2012

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-determining step in the pentose phosphate pathway and produces NADPH to fuel glutathione recycling. G6PD deficiency is the most common enzyme deficiency in humans and affects over 400 million people worldwide; however, its impact on cardiovascular disease is poorly understood. The glutathione pathway is paramount to antioxidant defense, and G6PD-deficient cells do not cope well with oxidative damage. Limited clinical evidence indicates that G6PD deficiency may be associated with hypertension. However, there are also data to support a protective role of G6PD deficiency in decreasing the risk of heart disease and cardiovascular-associated deaths, perhaps through a decrease in cholesterol synthesis. Studies in G6PD-deficient (G6PDX) mice are mixed and provide evidence for both protective and deleterious effects. G6PD deficiency may provide a protective effect through decreasing cholesterol synthesis, superoxide production, and reductive stress. However, recent studies indicate that G6PDX mice are moderately more susceptible to ventricular dilation in response to myocardial infarction or pressure overload-induced heart failure. Furthermore, G6PDX hearts do not recover as well as nondeficient mice when faced with ischemia-reperfusion injury, and G6PDX mice are susceptible to the development of age-associated cardiac hypertrophy. Overall, the limited available data indicate a complex interplay in which adverse effects of G6PD deficiency may outweigh potential protective effects in the face of cardiac stress. Definitive clinical studies in large populations are needed to determine the effects of G6PD deficiency on the development of cardiovascular disease and subsequent outcomes.
Functional differences between junctional and extrajunctional adrenergic receptor activation in mammalian ventricle
Authors: Ajijola Olujimi A. , Vaseghi Marmar , Zhou Wei , Yamakawa Kentaro , Benharash Peyman , Hadaya Joseph , Lux Robert L. , Mahajan Aman , Shivkumar Kalyanam
Published: December 2012

Increased cardiac sympathetic activation worsens dispersion of repolarization and is proarrhythmic. The functional differences between intrinsic nerve stimulation and adrenergic receptor activation remain incompletely understood. This study was undertaken to determine the functional differences between efferent cardiac sympathetic nerve stimulation and direct adrenergic receptor activation in porcine ventricles. Female Yorkshire pigs ( n = 13) underwent surgical exposure of the heart and stellate ganglia. A 56-electrode sock was placed over the ventricles to record epicardial electrograms. Animals underwent bilateral sympathetic stimulation (BSS) ( n = 8) or norepinephrine (NE) administration ( n = 5). Activation recovery intervals (ARIs) were measured at each electrode before and during BSS or NE. The degree of ARI shortening during BSS or NE administration was used as a measure of functional nerve or adrenergic receptor density. During BSS, ARI shortening was nonuniform across the epicardium (F value 9.62, P = 0.003), with ARI shortening greatest in the mid-basal lateral right ventricle and least in the midposterior left ventricle (LV) (mean normalized values: 0.9 ± 0.08 vs. 0.56 ± 0.08; P = 0.03). NE administration resulted in greater ARI shortening in the LV apex than basal segments [0.91 ± 0.04 vs. 0.63 ± 0.05 (averaged basal segments); P = 0.003]. Dispersion of ARIs increased in 50% and 60% of the subjects undergoing BSS and NE, respectively, but decreased in the others. There is nonuniform response to cardiac sympathetic activation of both porcine ventricles, which is not fully explained by adrenergic receptor density. Different pools of adrenergic receptors may mediate the cardiac electrophysiological effects of efferent sympathetic nerve activity and circulating catecholamines.
Geranylgeranyl transferase regulates CXC chemokine formation in alveolar macrophages and neutrophil recruitment in septic lung injury
Authors: Hasan Zirak , Rahman Milladur , Palani Karzan , Syk Ingvar , Jeppsson Bengt , Thorlacius Henrik
Published: December 2012

Overwhelming accumulation of neutrophils is a significant component in septic lung damage, although the signaling mechanisms behind neutrophil infiltration in the lung remain elusive. In the present study, we hypothesized that geranylgeranylation might regulate the inflammatory response in abdominal sepsis. Male C57BL/6 mice received the geranylgeranyl transferase inhibitor, GGTI-2133, before cecal ligation and puncture (CLP). Bronchoalveolar lavage fluid and lung tissue were harvested for analysis of neutrophil infiltration, as well as edema and CXC chemokine formation. Blood was collected for analysis of Mac-1 on neutrophils and CD40L on platelets. Gene expression of CXC chemokines, tumor necrosis factor-α (TNF-α), and CCL2 chemokine was determined by quantitative RT-PCR in isolated alveolar macrophages. Administration of GGTI-2133 markedly decreased CLP-induced infiltration of neutrophils, edema, and tissue injury in the lung. CLP triggered clear-cut upregulation of Mac-1 on neutrophils. Inhibition of geranylgeranyl transferase reduced CLP-evoked upregulation of Mac-1 on neutrophils in vivo but had no effect on chemokine-induced expression of Mac-1 on isolated neutrophils in vitro. Notably, GGTI-2133 abolished CLP-induced formation of CXC chemokines, TNF-α, and CCL2 in alveolar macrophages in the lung. Geranylgeranyl transferase inhibition had no effect on sepsis-induced platelet shedding of CD40L. In addition, inhibition of geranylgeranyl transferase markedly decreased CXC chemokine-triggered neutrophil chemotaxis in vitro. Taken together, our findings suggest that geranylgeranyl transferase is an important regulator of CXC chemokine production and neutrophil recruitment in the lung. We conclude that inhibition of geranylgeranyl transferase might be a potent way to attenuate acute lung injury in abdominal sepsis.
Ozone exposed epithelial cells modify cocultured natural killer cells
Authors: Müller Loretta , Brighton Luisa E. , Jaspers Ilona
Published: December 2012

Ozone (O3) causes significant adverse health effects worldwide. Nasal epithelial cells (NECs) are among the first sites within the respiratory system to be exposed to inhaled air pollutants. They recruit, activate, and interact with immune cells via soluble mediators and direct cell-cell contacts. Based on our recent observation demonstrating the presence of natural killer (NK) cells in nasal lavages, the goal of this study was to establish a coculture model of NECs and NK cells and examine how exposure to O3modifies this interaction. Flow cytometry analysis was used to assess immunophenotypes of NK cells cocultured with either air- or O3-exposed NECs. Our data show that coculturing NK cells with O3-exposed NECs decreased intracellular interferon-γ (IFN-γ), enhanced, albeit not statistically significant, IL-4, and increased CD16 expression on NK cells compared with air controls. Additionally, the cytotoxicity potential of NK cells was reduced after coculturing with O3-exposed NECs. To determine whether soluble mediators released by O3-exposed NECs caused this shift, apical and basolateral supernatants of air- and O3-exposed NECs were used to stimulate NK cells. While the conditioned media of O3-exposed NECs alone did not reduce intracellular IFN-γ, O3enhanced the expression of NK cell ligands ULBP3 and MICA/B on NECs. Blocking ULBP3 and MICA/B reversed the effects of O3-exposed NECs on IFN-γ production in NK cells. Taken together, these data showed that interactions between NECs and NK cells in the context of O3exposure changes NK cell activity via direct cell-cell interactions and is dependent on ULBP3/MICA/B expressed on NECs.
The Resistive Index Is a Marker of Renal Function, Pathology, Prognosis, and Responsiveness to Steroid Therapy in Chronic Kidney Disease Patients
Authors: Hanamura Kikuno , Tojo Akihiro , Kinugasa Satoshi , Asaba Kensuke , Fujita Toshiro
Published: December 2012

To evaluate the significance of the renal resistive index (RI) as a noninvasive marker of renal histological damage and a prognostic indicator, we examined RI by Doppler ultrasonography in 202 chronic kidney disease (CKD) patients who underwent renal biopsy. RI increased as the CKD stage progressed and correlated with age, systolic blood pressure, estimated glomerular filtration rate (eGFR), and renal histological changes, including glomerulosclerosis, arteriolosclerosis, and tubulointerstitial damage. Prognostic evaluation with a median follow-up period of 38.5 months revealed that patients withRI≥0.7(high RI group,n=39) had significantly poorer renal survival than those withRI<0.65(normal RI group,n=120) and0.65≤RI<0.7(high-normal RI group,n=43). The patients in the high-normal RI group showed good response to steroids. However, in the high RI group, steroid therapy did not significantly improve renal survival. Of the clinical indices studied,RI≥0.7, hypertension, proteinuria, and low eGFR at diagnosis were independent risk factors for worsening renal dysfunction. In conclusion, RI in CKD patients was considered as a marker of renal function, histological damage, and renal prognosis, and a possible determinant of indication for steroids.
Comprehension of Postmetallization Annealed MOCVD-TiO2on(NH4)2STreated III-V Semiconductors
Authors: Lee Ming-Kwei , Yen Chih-Feng
Published: December 2012

The electrical characteristics of TiO2films grown on III-V semiconductors (e.g., p-type InP and GaAs) by metal-organic chemical vapor deposition were studied. With (NH4)2S treatment, the electrical characteristics of MOS capacitors are improved due to the reduction of native oxides. The electrical characteristics can be further improved by the postmetallization annealing, which causes hydrogen atomic ion to passivate defects and the grain boundary of polycrystalline TiO2films. For postmetallization annealed TiO2on (NH4)2S treated InP MOS, the leakage current densities can reach2.7×10−7and2.3×10−7 A/cm2at±1 MV/cm, respectively. The dielectric constant and effective oxide charges are 46 and1.96×1012 C/cm2, respectively. The interface state density is7.13×1011 cm−2eV−1at the energy of 0.67 eV from the edge of valence band. For postmetallization annealed TiO2on (NH4)2S treated GaAs MOS, The leakage current densities can reach9.7×10−8and1.4×10−7at±1 MV/cm, respectively. The dielectric constant and effective oxide charges are 66 and1.86×1012 C/cm2, respectively. The interface state density is5.96×1011 cm−2eV−1at the energy of 0.7 eV from the edge of valence band.
Structural Health Monitoring of Tall Buildings with Numerical Integrator and Convex‐Concave Hull Classification
Authors: Thenozhi Suresh , Yu Wen , López Chau Asdrúbal , Li Xiaoou
Published: December 2012

An important objective of health monitoring systems for tall buildings is to diagnose the state of the building and to evaluate its possible damage. In this paper, we use our prototype to evaluate our data‐mining approach for the fault monitoring. The offset cancellation and high‐pass filtering techniques are combined effectively to solve common problems in numerical integration of acceleration signals in real‐time applications. The integration accuracy is improved compared with other numerical integrators. Then we introduce a novel method for support vector machine (SVM) classification, called convex‐concave hull. We use the Jarvis march method to decide the concave (nonconvex) hull for the inseparable points. Finally the vertices of the convex‐concave hull are applied for SVM training.
1H and13C NMR Assignments of Cytotoxic 3S-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic Acid from the Leaves ofCichorium endivia
Authors: Wang Fu-Xin , Deng An-Jun , Wei Jin-Feng , Qin Hai-Lin , Wang Ai-Ping
Published: December 2012

An amino acid, 3S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, was isolated for the first time from the leaves ofCichorium endivia. The complete assignment of its1H and13C NMR spectroscopic data was carried out also for the first time based on extensive 1D and 2D NMR experiments. Cytotoxicity of this isolated compound against HCT-8 and HepG2 human cancer cell lines was evaluated for the first time, with moderate activities being found.
Rapid Resolution of Acute Fulminant Myocarditis after IVIG and Steroid Treatment
Authors: Barrie Michael , McKnight Lucas , Solanki Pallavi
Published: December 2012

We report a case of a 59-year-old woman who presented with worsening dyspnea which rapidly progressed to severe heart failure. Coronary arteries showed no obstruction. Supportive measures stabilized the patient’s hemodynamics. Initially intravenous solumedrol was given, but when the patient’s condition continued to deteriorate, intravenous immunoglobulin (IVIG) was added to the treatment regimen and her condition improved. Studies show no benefit to using immunosuppressive agents in viral myocarditis, but benefits have been demonstrated in other etiologies. Patients presenting with acute fulminant myocarditis with unknown etiology that continue to deteriorate with aggressive heart failure treatment may benefit from steroids and IVIG.
Efficacy of Eosin B as a New Antimalarial Drug in a Murine Model
Authors: Zamani Zahra , Tafreshi Alireza Sadeghi , Nahrevanian Hossein , Lame-Rad Behzad , Pourfallah Fatemeh , Eslamifar Hossein , Sadeghi Sedigheh , Vahabi Farideh , Iravani Ayda , Arjmand Mohammad
Published: December 2012

The initial success of any adopted anti-infective strategy to malaria is followed by a descent due to the emergence of resistance to it. The search for new drugs and drug targets is a consistent demand in this disease. Eosin B, a common laboratory dye, is reported to have good antiparasitic properties in vitro. It was studied for its antiparasitic effect in vivo on chloroquine-sensitive Plasmodium berghei murine malaria. Eosin B was administered in 2 different doses by either the oral or parenteral route, once or twice daily to mice infected with Plasmodium berghei. Both the doses of eosin B 400 mg/kg and 800 mg/kg gave better results than the controls which were 40 mg/kg chloroquine and 100 mg/kg of arteether with P<0.005 significance. Percentage suppressive activity by Peter’s test of eosin B was better, though at a higher dose than both the controls. Survival rate of mice receiving the higher dose of eosin B was longer than that of the controls. When administered twice daily, the mice were fully cured after 4 days. Eosin B seems to be a promising drug exhibiting good antimalarial effects in the murine model of the disease.
Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes
Authors: Wu Hui , Wu Michael , Chen Yi , Allan Carolyn A. , Phillips David J. , Hedger Mark P.
Published: December 2012

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined.Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein.Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P>0.05) between subjects with normal OGTT (n=39), impaired glucose tolerance and/or fasting glucose (n=17), or T2D (n=36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P<0.001), fasting insulin (P=0.02), glycated hemoglobin (P=0.003), and homeostasis model assessment of insulin resistance (HOMA-IR;P<0.001). Follistatin was positively correlated with HOMA-IR alone (P=0.01).Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.
How to Implement Return Policies in a Two‐Echelon Supply Chain?
Authors: Hu Wei , Li Jianbin
Published: December 2012

We integrate a retailer′s return policy and a supplier′s buyback policy within a modeling framework. In this setting, consumers decide whether to buy and then whether to return the product, the retailer sets the retail price, quantity, and refund price, and the supplier chooses the wholesale price and buyback price. Both the demand uncertainty and consumers′ valuation uncertainty are considered; consumers realize their valuations only after purchase. We discuss four scenarios for each party in the supply chain that may offer or not offer return policy. We characterize each party′s optimal decisions for all scenarios and we show that the supplier′s best choice is to provide buyback policy and the retailer′s optimal response is to set refund price to be the same as supplier′s buyback price.