bluuebunny/crossref_metadata_2025 huggingface dataset:
Computer Simulation of Combustion Process in a Piston Engine With a Porous Medium Regenerator
Authors: Zhou Lei , Xie Maozhao , Jia Ming , Shi Junrui
Published: September 2013

In the regenerative engine, effective heat exchange and recurrence between gas and solid can be achieved by the reciprocating movement of a porous medium regenerator in the cylinder, which considerably promotes the fuel-air mixture formation and a homogeneous and stable combustion. A two-dimensional numerical model for the regenerative engine is presented in this study based on a modified version of the engine computational fluid dynamics (CFD) software KIVA-3V. The engine was fueled with methane and a detailed kinetic mechanism was used to describe its oxidation process. The characteristics of combustion and emission of the engine were computed and analyzed under different equivalence ratios and porosities of the regenerator. Comparisons with the prototype engine without the regenerator were conducted. Results show that the regenerative engine has advantages in both combustion efficiency and pollutant emissions over the prototype engine and that using lower equivalence ratios can reduce emissions significantly, while the effect of the porosity is dependent on the equivalence ratio used.
Analysis of Parallel Microchannels for Flow Control and Hot Spot Cooling
Authors: Solovitz Stephen A.
Published: September 2013

Microchannel heat transfer is commonly applied in the thermal management of high-power electronics. Most designs involve a series of parallel microchannels, which are typically analyzed by assuming a uniform flow distribution. However, many devices have a nonuniform thermal distribution, with hot spots producing much higher heat fluxes and temperatures than the baseline. Although solutions have been developed to improve local heat transfer, these are advanced methods using embedded cooling devices. As an alternative, a passive solution is developed here using analytical methods to optimize the channel geometry for a desired, nonuniform flow distribution. This results in a simple power law for the passage diameter, which may be useful for many microfluidic systems, including electronics cooling devices. Computational simulations are then applied to demonstrate the effectiveness of the power law for laminar conditions. At low Reynolds numbers, the flow distribution can be controlled to good accuracy, matching the desired distribution to within less than 1%. Further simulations consider the control of hot spots in laminar developing flow. Under these circumstances, temperatures can be made uniform to within 2 °C over a range of Reynolds numbers (60 to 300), demonstrating the capability of this power law solution.
Falling-Film Absorption Around Microchannel Tube Banks
Authors: Nagavarapu Ananda Krishna , Garimella Srinivas
Published: September 2013

An experimental investigation of heat and mass transfer in a falling-film absorber with microchannel tube arrays was conducted. Liquid ammonia–water solution flows in a falling-film mode around an array of small diameter coolant tubes, while vapor flows upward through the tube array counter-current to the falling film. This absorber was installed in a test facility consisting of all components of a functional single-effect absorption chiller, including a desorber, rectifier, condenser, evaporator, solution heat exchanger, and refrigerant precooler, to obtain realistic operating conditions at the absorber and to account for the influence of the other components in the system. Unlike studies in the literature on bench-top, single-component, single-pressure test stands, here the experiments were conducted on the absorber at vapor, solution, and coupling fluid conditions representative of space-conditioning systems in the heating and cooling modes. Absorption measurements were taken over a wide range of solution flow rates, concentrations, and coupling fluid temperatures, which simulated operation of thermally activated absorption systems at different cooling capacities and ambient conditions. These measurements are used to interpret the effects of solution and vapor flow rates, concentrations, and coupling fluid conditions on the respective heat and mass transfer coefficients.
A Methodology to Solve 2D and Axisymmetric Radiative Transfer Problems Using a General 3D Solver
Authors: Kumar P. , Eswaran V.
Published: September 2013

A method to solve the radiative transfer equation (RTE) for absorbing-emitting and/or scattering media for 2-D and axisymmetric geometries using a general 3-D solver with a special treatment of the boundary condition in the third direction is presented. It allows a choice of first- or second- order schemes and can be used with non-orthogonal hexahedral grids for complex domains. Two-dimensional or axisymmetric problems are treated as different special cases of a three-dimensional problem. The method is tested on axisymmetric problems with absorbing-emitting and/or scattering media and on a 2D planar problem with a transparent medium and validated by comparisons with benchmark solutions.
Multipoint Design Optimization of a Transonic Compressor Blade by Using an Adjoint Method
Authors: Luo Jiaqi , Zhou Chao , Liu Feng
Published: September 2013

This paper presents the application of a viscous adjoint method to the multipoint design optimization of a rotor blade through blade profiling. The adjoint method requires about twice the computational effort of the flow solution to obtain the complete gradient information at each operating condition, regardless of the number of design parameters. NASA Rotor 67 is redesigned through blade profiling. A single point design optimization is first performed to verify the effectiveness and feasibility of the optimization method. Then in order to improve the performance for a wide range of operating conditions, the blade is redesigned at three operating conditions: near peak efficiency, near stall, and near choke. Entropy production through the blade row combined with the constraints of mass flow rate and total pressure ratio is used as the objective function. The design results are presented in detail and the effects of blade profiling on performance improvement and shock/tip-leakage interaction are examined.
Detailed Measurements of Spike Formation in an Axial Compressor
Authors: Weichert Stephanie , Day Ivor
Published: September 2013

This paper presents new experimental measurements of spike-type stall inception. The measurements were carried out in the single stage Deverson compressor at the Whittle Laboratory. The primary objective was to characterize the flow field in the tip clearance gap during stall inception using sufficient instrumentation to give high spatial and temporal resolution. Measurements were recorded using arrays of unsteady pressure transducers over the rotor tips and hot-wires in the tip gap. Prestall ensemble averaged velocity and pressure maps were obtained as well as pressure contours of the stall event. In order to study the transient inception process in greater detail, vector maps were built up from hundreds of stalling events using a triggering system based on the stalling event itself. The results show an embryonic disturbance starting within the blade passage and leading to the formation of a clear spike. The origins of the spike and its relation to the tip leakage vortex are discussed. It has also been shown that before stall, the flow in the blade passage which is most likely to stall is generally more unsteady, from revolution to revolution, than the other passages in the annulus.
Improving Pin-Fin Heat Transfer Predictions Using Artificial Neural Networks
Authors: Ostanek Jason K.
Published: September 2013

In much of the public literature on pin-fin heat transfer, the Nusselt number is presented as a function of Reynolds number using a power-law correlation. Power-law correlations typically have an accuracy of 20% while the experimental uncertainty of such measurements is typically between 5% and 10%. Additionally, the use of power-law correlations may require many sets of empirical constants to fully characterize heat transfer for different geometrical arrangements. In the present work, artificial neural networks were used to predict heat transfer as a function of streamwise spacing, spanwise spacing, pin-fin height, Reynolds number, and row position. When predicting experimental heat transfer data, the neural network was able to predict 73% of array-averaged heat transfer data to within 10% accuracy while published power-law correlations predicted 48% of the data to within 10% accuracy. Similarly, the neural network predicted 81% of row-averaged data to within 10% accuracy while 52% of the data was predicted to within 10% accuracy using power-law correlations. The present work shows that first-order heat transfer predictions may be simplified by using a single neural network model rather than combining or interpolating between power-law correlations. Furthermore, the neural network may be expanded to include additional pin-fin features of interest such as fillets, duct rotation, pin shape, pin inclination angle, and more making neural networks expandable and adaptable models for predicting pin-fin heat transfer.
Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in patients with a previous myocardial infarction: a randomised controlled trial
Authors: Din Jehangir N , Sarma Jaydeep , Harding Scott A , Lyall Karin , Newby David E , Flapan Andrew D
Published: September 2013

Objective

The mechanisms through which ω-3 fatty acids reduce adverse cardiac events remain uncertain. We aimed to investigate the effect of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in patients with coronary heart disease.

Design

Randomised, double-blind, placebo-controlled, cross-over trial.

Setting

Academic cardiac centre.

Participants

20 male patients with a previous myocardial infarction.

Intervention

ω-3 Fatty acid supplementation (2 g/day for 6 weeks) versus olive oil placebo.

Outcome measures

Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 patients during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion.

Results

All vasodilators caused dose-dependent increases in FBF (p<0.0001). ω-3 Fatty acid supplementation did not affect endothelium-dependent vasodilation with acetylcholine and substance P compared with placebo (p=0.5 and 0.9). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001), which was not affected by ω-3 fatty acid supplementation (p=0.9). ω-3 Fatty acids did not affect platelet–monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40.

Conclusions

We have demonstrated that dietary supplementation with ω-3 fatty acids does not affect endothelial vasomotor function, endothelial t-PA release, or platelet and monocyte activation in patients with coronary heart disease. Cardiac benefits conferred by ω-3 fatty acids in coronary heart disease are unlikely to be mediated through effects on these systems.
Depression and blood pressure in high-risk children and adolescents: an investigation using two longitudinal cohorts
Authors: Hammerton Gemma , Harold Gordon , Thapar Anita , Thapar Ajay
Published: September 2013

Objective

To examine the relationship between blood pressure and depressive disorder in children and adolescents at high risk for depression.

Design

Multisample longitudinal design including a prospective longitudinal three-wave high-risk study of offspring of parents with recurrent depression and an on-going birth cohort for replication.

Setting

Community-based studies.

Participants

High-risk sample includes 281 families where children were aged 9–17 years at baseline and 10–19 years at the final data point. Replication cohort includes 4830 families where children were aged 11–14 years at baseline and 14–17 years at follow-up and a high-risk subsample of 612 offspring with mothers that had reported recurrent depression.

Main outcome measures

The new-onset of Diagnostic and Statistical Manual of Mental Disorder, fourth edition defined depressive disorder in the offspring using established research diagnostic assessments—the Child and Adolescent Psychiatric Assessment in the high-risk sample and the Development and Wellbeing Assessment in the replication sample.

Results

Blood pressure was standardised for age and gender to create SD scores and child's weight was statistically controlled in all analyses. In the high-risk sample, lower systolic blood pressure at wave 1 significantly predicted new-onset depressive disorder in children (OR=0.65, 95% CI 0.44 to 0.96; p=0.029) but diastolic blood pressure did not. Depressive disorder at wave 1 did not predict systolic blood pressure at wave 3. A significant association between lower systolic blood pressure and future depression was also found in the replication cohort in the second subset of high-risk children whose mothers had experienced recurrent depression in the past.

Conclusions

Lower systolic blood pressure predicts new-onset depressive disorder in the offspring of parents with depression. Further studies are needed to investigate how this association arises.
Pregnancy e-health: a multicenter Italian cross-sectional study on internet use and decision-making among pregnant women
Authors: Bert Fabrizio , Gualano Maria Rosaria , Brusaferro Silvio , De Vito Elisabetta , de Waure Chiara , Torre Giuseppe La , Manzoli Lamberto , Messina Gabriele , Todros Tullia , Torregrossa Maria Valeria , Siliquini Roberta
Published: September 2013

Background

Our study aimed to estimate the prevalence of pregnancy e-health seekers in a large Italian sample; to explore the factors influencing the choices of the childbearing women regarding their lifestyles after internet consultation; and finally to investigate potential differences between primiparous and multiparous women in internet use to find information about pregnancy.

Methods

A multicentre survey was carried out in seven Italian cities. Data were collected through a validated questionnaire administered in waiting rooms of outpatient departments by medical doctors. Respondents were questioned about their sociodemographic status, their use of the internet to seek pregnancy information and their consequent choices to modify their lifestyles. Data were analysed using descriptive statistics and logistic regression.

Results

Almost all women were pregnancy e-health seekers (95%), including those who also received information from healthcare professionals. Indeed, the main reason for searching the web was the need of further knowledge on pregnancy-related topic, over and beyond other key advantages of the net such as anonymity, simplicity and rapidity. A higher likelihood of changing lifestyle after pregnancy e-health was observed among the women who searched institutional websites; declared more confidence in the information retrieved; participated into pregnancy-centred forum online; and were residents in Italy.

Conclusions

To reduce the likelihood for women of both finding erroneous information or misinterpreting correct ones, healthcare professionals should commit to fill the information gap and guide pregnant women in the online searches. Also, future studies are strongly needed to analyse the quality and accuracy of health information found on the web.
Accounting for personhood in palliative sedation: the Ring Theory of Personhood
Authors: Radha Krishna Lalit Kumar
Published: September 2013

Application of sedation at the end of life has been fraught with ethical and clinical concerns, primarily focused on its potential to hasten death. However, in the face of clinical data that assuage most of these concerns, a new threat to this treatment of last resort has arisen. Concern now pivots on its effects on the personhood of the patient, underpinned by the manner in which personhood has been conceptualised. For many authors, it is consciousness that is seen to be the seat of personhood, thus its loss is seen to rob a patient of their moral and ethical worth, leaving them in a state that cannot ethically be differentiated from death. Here I proffer a clinically based alternative to this view, the Ring Theory of Personhood, which dispels these concerns about sedation at the end of life. The Ring Theory envisages personhood as a coadunation of three domains of concern: the innate, the individual and the relational elements of personhood. The innate element of personhood is held to be present among all humans by virtue of their links with the Divine and or their human characteristics. The individual elements of personhood pivot on the presence of consciousness-dependent features such as self-awareness, self-determination and personality traits. The relational component of personhood envisages an individual as being ‘socially embedded’ replete with social and familial ties. It is these three equally important inter-related domains that define personhood.
GENDER, PERFORMANCE AND FINANCIAL STRATEGY: A DYNAMIC CAPABILITIES PERSPECTIVE
Authors: COLEMAN SUSAN , KARIV DAFNA
Published: September 2013

This article explores the impact of financial strategy, by gender, on firm performance using data from the Panel Study of Entrepreneurial Dynamics (PSED). Our findings reveal that financial strategies do have an impact on performance and that female and male entrepreneurs use different financial strategies. Our findings also show no significant performance differences in female- versus male-owned firms in the earliest years of the firm, although significant differences did emerge in the later years. Finally, our findings attest to the dynamic and "cumulative" effect of financial strategy.
THE DIASPORA AS A CHANGE AGENT IN ENTREPRENEURSHIP-RELATED INSTITUTIONS IN SUB-SAHARAN AFRICA
Authors: KSHETRI NIR
Published: September 2013

Diaspora networks' role in supporting and stimulating entrepreneurial activities in Sub-Saharan African (SSA) economies need hardly be elaborated. For instance, some SSA countries have established government agencies to encourage diasporas to help local communities and provide policy advice. At the 2003 Extra-Ordinary Summit of the Assembly of Heads of State and Governments, the African Union (AU) amended Article Three of its Constitutive Act to invite and encourage African diaspora's active participation. However, institutional changes associated with diaspora networks are a phenomenon that has been noted but poorly understood. This paper addresses a little examined intersection between the diaspora literature and the institutions literature. We examine the contexts, mechanisms and processes associated with diaspora networks' roles as institutional change agents in the context of entrepreneurial behaviors in SSA economies. Our dependent variables are measures of changes in institutions associated with diaspora network. We have related our analysis mainly to the nature of the diaspora networks compared to other networks, characteristics of the environments in which diaspora networks are embedded in and operate, and some activities, mechanisms and modes that serve to transmit institutions from the host country to the homeland.
Cretaceous Oceanic Anoxic Event 2 in the Arobes section, northern Spain: nannofossil fluctuations and isotope events
Authors: Melinte-Dobrinescu Mihaela C. , Bernárdez Enrique , Kaiho Kunio , Lamolda Marcos A.
Published: September 2013

The Cenomanian–Turonian boundary interval of the Arobes section, northern Spain, represents the maximum depth of a relatively shallow succession. The investigated section extends within the
Rotalipora cushmani
and
Whiteinella archaeocretacea
planktonic foraminiferal zones, and from UC3 up to UC8 nannofloral zones, respectively. The Oceanic Anoxic Event 2 (OAE2) is about 16 m thick and includes a positive δ
13
C excursion, from 3 up to 5.5‰. The first peak of δ
13
C is situated towards the upper part of the
Rotalipora cushmani
planktonic foraminiferal zone, while the second peak of δ
13
C is situated in the lower part of the
Whiteinella archaeocretacea
planktonic foraminiferal zone. The plateau, the youngest phase of OAE2, ends slightly above the first occurrence (FO) of the nannofossil
Quadrum gartneri
. Based on nannofloral fluctuation, an unstable environment is recognized from the last occurrence (LO) of the nannofossil
Axopodorhabdus albianus
up to the FO of the nannofossil
Quadrum gartneri
. Mesotrophic, eutrophic and oligotrophic nannofossils have successive peaks throughout the OAE2. In the lower part of OAE2, especially in the trough phase and second build-up, productivity increased. The calcareous dinoflagellate
Thoracosphaera
spp. peaks up to almost 30% in the lower part of the second build-up phase. The critical nannofloral turnover episode is characterized by impoverished calcareous nannofossil assemblages and temporary disappearances of high-fertility taxa, such as
Biscutum constans
and
Zeugrhabdotus erectus
. This shift in nannofloral assemblages starts in the last stages of OAE2; that is, towards the top of the second build-up phase and also covers the main part of the plateau phase of δ
13
C.
Geochemical evolution of Caledonian volcanism recorded in the sedimentary rocks of the eastern Baltic region
Authors: Kiipli T. , Soesoo A. , Kallaste T.
Published: September 2013

This article describes the occurrence, bulk geochemistry and phenocryst compositions of Caledonian volcanic ash beds (bentonites) in the sedimentary sections of the Palaeozoic Baltic sedimentary basin. Four periods of volcanism are recognized in the eastern Baltic region: (a) Late Sandbian with sources derived from the convergent margin between Avalonia and Baltica; (b) Late Katian with sources from the margin of the Iapetus Ocean (Norwegian Caledonides); (c) Aeronian (with extension into Telychian and Sheinwoodian) with sources in the Central European Caledonides; and (d) Telychian to Early Ludlow with sources derived from the convergent margin between Laurentia and Baltica (Norwegian Caledonides). Trace element compositions in bentonites indicate mostly evolved source magmas of rhyolitic and dacitic composition. The volcanism in the Aeronian is characterized by less evolved basaltic and trachyandesitic compositions. Sanidine compositions indicate the existence of potassium-dominated (over sodium) source magmas in Late Sandbian and from the late Homerian to Early Ludlow. During other periods both potassium- and sodium-dominated source magmas occur. The presence of sodium-rich sanidine in many bentonites combined with the scarcity of biotite suggests that the source magmas were water-undersaturated. Biotite phenocrysts are mostly Mg-rich, but Fe-rich varieties occur in the Late Sandbian and Early Telychian.
A Small-Molecule Blocking Ribonucleotide Reductase Holoenzyme Formation Inhibits Cancer Cell Growth and Overcomes Drug Resistance
Authors: Zhou Bingsen , Su Leila , Hu Shuya , Hu Weidong , Yip M.L. Richard , Wu Jun , Gaur Shikha , Smith D. Lynne , Yuan Yate-Ching , Synold Timothy W. , Horne David , Yen Yun
Published: September 2013

Ribonucleotide reductase (RNR) is an attractive target for anticancer agents given its central function in DNA synthesis, growth, metastasis, and drug resistance of cancer cells. The current clinically established RNR inhibitors have the shortcomings of short half-life, drug resistance, and iron chelation. Here, we report the development of a novel class of effective RNR inhibitors addressing these issues. A novel ligand-binding pocket on the RNR small subunit (RRM2) near the C-terminal tail was proposed by computer modeling and verified by site-directed mutagenesis and nuclear magnetic resonance (NMR) techniques. A compound targeting this pocket was identified by virtual screening of the National Cancer Institute (NCI) diverse small-molecule database. By lead optimization, we developed the novel RNR inhibitor COH29 that acted as a potent inhibitor of both recombinant and cellular human RNR enzymes. COH29 overcame hydroxyurea and gemcitabine resistance in cancer cells. It effectively inhibited proliferation of most cell lines in the NCI 60 human cancer panel, most notably ovarian cancer and leukemia, but exerted little effect on normal fibroblasts or endothelial cells. In mouse xenograft models of human cancer, COH29 treatment reduced tumor growth compared with vehicle. Site-directed mutagenesis, NMR, and surface plasmon resonance biosensor studies confirmed COH29 binding to the proposed ligand-binding pocket and offered evidence for assembly blockade of the RRM1-RRM2 quaternary structure. Our findings offer preclinical validation of COH29 as a promising new class of RNR inhibitors with a new mechanism of inhibition, with broad potential for improved treatment of human cancer. Cancer Res; 73(21); 6484–93. ©2013 AACR.
Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid
Authors: Junco Jacob J. , Mancha Anna , Malik Gunjan , Wei Sung-Jen , Kim Dae Joon , Liang Huiyun , Slaga Thomas J.
Published: September 2013

Ursolic acid, present in apples, rosemary, and other sources, is known to inhibit tumor formation and tumor cell viability in multiple systems, including skin. However, various cancers are resistant to ursolic acid treatment. Herein, skin carcinoma cells (Ca3/7) as compared with skin papilloma cells (MT1/2) displayed more resistance to ursolic acid-induced cytotoxicity. Interestingly, Ca3/7 cells had elevated levels of P-glycoprotein (P-gp), an ATP-dependent efflux pump that mediates resistance to chemotherapy in preclinical and clinical settings, and not only accumulated less but also more rapidly expelled the P-gp substrate rhodamine 123 (Rh123) indicating ursolic acid is transported by P-gp. To determine whether P-gp inhibition can enhance ursolic acid-mediated cytotoxicity, cells were challenged with P-gp inhibitors verapamil or cyclosporin A. Alternatively, cells were pretreated with the natural compound resveratrol, a known chemotherapy sensitizer. Verapamil and resveratrol enhanced the effects of ursolic acid in both cell lines, whereas cyclosporin A only did so in Ca3/7 cells. Similarly, verapamil inhibited Rh123 efflux in both lines, whereas cyclosporin A only inhibited Rh123 efflux in Ca3/7 cells. Resveratrol did not inhibit Rh123 efflux in either line, indicating the synergistic effects of resveratrol and ursolic acid are not manifest by inhibition of P-gp–mediated efflux of ursolic acid. These results indicate that the anti-skin cancer effects of ursolic acid are enhanced with P-gp inhibitors. In addition, resveratrol and ursolic acid interact synergistically, but not through inhibition of P-gp.

Implications: Resveratrol and/or p-glycoprotein inhibitors in combination with ursolic acid are an effective anti-skin cancer regimen. Mol Cancer Res; 11(12); 1521–9. ©2013 AACR.
Combination of Chemopreventive Agents in Nanoparticles for Cancer Prevention
Authors: Yang Chung S. , Wang Hong , Hu Bing
Published: September 2013

Carcinogenesis involves multiple genetic and epigenetic alterations, and a single chemopreventive agent may not be sufficient to prevent these events. Therefore, the use of a combination of agents is an attractive approach for cancer chemoprevention. In this issue of the journal, Prabhu and colleagues examined a combination of aspirin, curcumin, and sulforaphane for the prevention of pancreatic cancer in hamsters (beginning page 1015). The novelty of this work is that when aspirin and curcumin were incorporated in nanoparticles and administered orally, in combination with sulforaphane, the effective dosages were decreased by 10-fold in comparison with the free form mixture. In this commentary, the possible mechanisms of synergistic action among multiple chemopreventive agents and the use of stable nanoparticles for oral delivery are discussed. Also discussed is the importance of measuring tissue levels of the chemopreventive agents to understand the mode of action of these nanoparticles and to avoid toxicity. Cancer Prev Res; 6(10); 1011–4. ©2013 AACR.
Effect of Simvastatin on Hemostasis in Patients with Isolated Hypertriglyceridemia
Authors: Krysiak Robert , Okopien Boguslaw
Published: September 2013

Backgrounds/Aims: Elevated triglyceride levels seem to predispose to the earlier development and accelerated progression of coronary artery disease. In our study, we assessed for the first time whether simvastatin treatment affects coagulation and fibrinolysis in patients with isolated hypertriglyceridemia. Methods: The study included 39 patients with elevated triglyceride levels and peripheral artery sclerosis, treated for 90 days with either simvastatin (40 mg daily) or placebo. Plasma lipids, glucose homeostasis markers and hemostasic variables were assessed at baseline and after treatment. Results: Simvastatin, but not placebo, administered to these patients reduced plasma levels/activity of fibrinogen (from 3.5 ± 0.4 to 2.8 ± 0.3 g/l, p < 0.01), factor VII (from 144.2 ± 16.9 to 112.5 ± 14.0%, p < 0.01) and plasminogen activator inhibitor-1 (from 76.9 ± 13.5 to 50.2 ± 9.2 ng/ml, p < 0.001), without a significant reduction in von Willebrand factor levels, and tended to prolong the prothrombin and partial thromboplastin times. Conclusion: Our results suggest that statin treatment produces a multidirectional effect on coagulation and fibrinolysis in patients with isolated hypertriglyceridemia and that this treatment may bring some benefits to patients with elevated triglyceride levels.
Propagation of Obesity across Generations: The Roles of Differential Realized Fertility and Assortative Mating by Body Mass Index
Authors: Dawson John A. , Dhurandhar Emily J. , Vazquez Ana I. , Peng Bo , Allison David B.
Published: September 2013

Background/Aims: To quantify the extent to which the increase in obesity observed across recent generations of the American population is associated with the individual or combined effects of assortative mating (AM) for body mass index (BMI) and differential realized fertility by BMI. Methods: A Monte Carlo framework is formed and informed using data collected from the National Longitudinal Survey of Youth (NLSY). The model has 2 portions: one that generates childbirth events on an annual basis and another that produces a BMI for each child. Once the model is informed using the data, a reference distribution of offspring BMIs is simulated. We quantify the effects of our factors of interest by removing them from the model and comparing the resulting offspring BMI distributions with that of the baseline scenario. Results: An association between maternal BMI and number of offspring is evidenced in the NLSY data as well as the presence of AM. These 2 factors combined are associated with an increased mean BMI (+0.067, 95% CI: 0.056; 0.078), an increased BMI variance (+0.578, 95% CI: 0.418; 0.736) and an increased prevalence of obesity (RR 1.032, 95% CI: 1.023; 1.041) and BMIs >40 (RR 1.083, 95% CI: 1.053; 1.118) among offspring. Conclusion: Our investigation suggests that both differential realized fertility and AM by BMI appear to play a role in the increasing prevalence of obesity in America.
Genetic Admixture and Obesity: Recent Perspectives and Future Applications
Authors: Fernández José R. , Pearson Keith E. , Kell Kenneth P. , Bohan Brown Michelle M.
Published: September 2013

The process of the colonization of the New World that occurred centuries ago served as a natural experiment, creating unique combinations of genetic material in newly formed admixed populations. Through a genetic admixture approach, the identification and genotyping of ancestry informative markers have allowed for the estimation of proportions of ancestral parental populations among individuals in a sample. These admixture estimates have been used in different ways to understand the genetic contributions to individual variation in obesity and body composition parameters, particularly among diverse admixed groups known to differ in obesity prevalence within the United States. Although progress has been made through the use of genetic admixture approaches, further investigations are needed in order to explore the interaction of environmental factors with the degree of genetic ancestry in individuals. A challenge to confront at this time would be to further stratify and define environments in progressively more granular terms, including nutrients, muscle biology, stress responses at the cellular level, and the social and built environments.
Functional Analysis of Seven Genes Linked to Body Mass Index and Adiposity by Genome-Wide Association Studies: A Review
Authors: Speakman John R.
Published: September 2013

Genome-wide association studies (GWAS) have identified a total of about 40 single nucleotide polymorphisms (SNPs) that show significant linkage to body mass index, a widely utilised surrogate measure of adiposity. However, only 8 of these associations have been confirmed by follow-up GWAS using more sophisticated measures of adiposity (computed tomography). Among these 8, there is a SNP close to the gene FTO which has been the subject of considerable work to diagnose its function. The remaining 7 SNPs are adjacent to, or within, the genes NEGR1, TMEM18, ETV5, FLJ35779, LINGO2, SH2B1 and GIPR, most of which are less well studied than FTO, particularly in the context of obesity. This article reviews the available data on the functions of these genes, including information gleaned from studies in humans and animal models. At present, we have virtually no information on the putative mechanism associating the genes FLJ35779 and LINGO2 to obesity. All of these genes are expressed in the brain, and for 2 of them (SH2B1 and GIPR), a direct link to the appetite regulation system is known. SH2B1 is an enhancer of intracellular signalling in the JAK-STAT pathway, and GIPR is the receptor for an appetite-linked hormone (GIP) produced by the alimentary tract. NEGR1, ETV5 and SH2B1 all have suggested roles in neurite outgrowth, and hence SNPs adjacent to these genes may affect development of the energy balance circuitry. Although the genes have central patterns of gene expression, implying a central neuronal connection to energy balance, for at least 4 of them (NEGR1, TMEM18, SH2B1 and GIPR), there are also significant peripheral functions related to adipose tissue biology. These functions may contribute to their effects on the obese phenotype.
TFAP2B-Dietary Protein and Glycemic Index Interactions and Weight Maintenance after Weight Loss in the DiOGenes Trial
Authors: Stocks Tanja , Ängquist Lars , Hager Jörg , Charon Celine , Holst Claus , Martinez J. Alfredo , Saris Wim H.M. , Astrup Arne , Sørensen Thorkild I.A. , Larsen Lesli H.
Published: September 2013

Background:TFAP2B rs987237 is associated with obesity and has shown interaction with the dietary fat-to-carbohydrate ratio, which has an effect on weight loss. We investigated interactions between rs987237 and protein-to-carbohydrate ratio or glycemic index (GI) in relation to weight maintenance after weight loss. Methods: This study included 742 obese individuals from 8 European countries who participated in the Diet, Obesity, and Genes (DiOGenes) trial, lost ≥8% of their initial body weight during an 8-week low-calorie diet and were randomized to one of 5 ad libitum diets with a fixed energy percentage from fat: either low-protein/low-GI, low-protein/high-GI, high-protein/low-GI, or high-protein/high-GI diets, or a control diet for a 6-month weight maintenance period. Using linear regression analyses and additive genetic models, we investigated main and dietary interaction effects of TFAP2B rs987237 in relation to weight maintenance. Results: In total, 468 completers of the trial were genotyped for rs987237. High-protein diets were beneficial for weight maintenance in the AA genotype group (67% of participants), but in the AG and GG groups no differences were observed for low- or high-protein diets. On the high-protein diet, carriers of the obesity risk allele (G allele) regained 1.84 kg (95% CI: 0.02; 3.67, p = 0.047) more body weight per risk allele than individuals on a low-protein diet. There was no interaction effect between rs987237 and GI on weight maintenance. Conclusion:TFAP2B rs987237 and dietary protein/carbohydrate interacted to modify weight maintenance. Considering the carbohydrate proportion of the diet, the interaction was different from the previously reported rs987237-fat-to-carbohydrate ratio interaction for weight loss. Thus, TFAP2B-macronutrient interactions might diverge depending on the nutritional state.
Cranial Compression Using Distractors in Reverse Fashion as an Alternative Method for Correcting Scaphocephaly in Older Patients
Authors: Oh Tae Suk , Ra Young Shin , Hong Seok Ho , Koh Kyung S. , Kim Yong Oock , Choi Jong-Woo
Published: September 2013

Background: Intraoperative calvarial contraction of conventional calvarial remodeling is more difficult in scaphocephaly patients who are 1 year or older in age. In our current study, gradual cranial compression with a distractor was used to correct scaphocephaly in this older age group and the surgical results were quantitatively analyzed. Methods: Gradual cranial compression was used to treat 7 sagittal craniosynostosis patients. The mean age was 20.9 months (range, 12-32 months) and the mean follow-up period was 65 months (range, 3-81 months). Computed tomography was used to calculate the cephalic index (CI; equal to the maximum width of the head/maximum length of the head ×100), and the ratios of these indices at 3 different time periods (before, immediately after, and at 1 year postoperatively) were evaluated. Results: An average cranial compression of 18 mm was found to be possible with an average CI increase from 67.9 to 73.5. The CI ratio at 1 year after surgery was found to be the highest, showing a 9.8% increase. Conclusion: Sagittal craniosynostosis patients are less easy to treat with conventional calvarial remodeling surgery if they are older than 1 year. Gradual cranial vault compression with distractors can be another option in these cases.
Racial Differences in Attitudes toward Personalized Medicine
Authors: Diaz V.A. , Mainous III A.G. , Gavin J.K. , Wilson D.
Published: September 2013

Background/Aims: Patient concerns regarding personalized medicine may limit its use. This study assesses racial differences in attitudes toward personalized medicine, evaluating variables that may influence these attitudes. Methods: A convenience sample of 190 adults (≥18 years) from an academic primary care practice was surveyed regarding awareness and acceptance of personalized medicine, plus concerns and benefits regarding its use. Logistic regressions predicting awareness, acceptance and concerns were performed, controlling for race, gender, marital status, education, children, internet use, and self-reported discrimination. Results: The sample was 35% non-Hispanic white (NHW) and 34.7% male. More NHW participants expressed acceptance of personalized medicine than non-Hispanic black (NHB) participants (94.4 vs. 81.9%, p = 0.0190). More NHBs were concerned about the use of genes without consent (57.3 vs. 20.6%, p < 0.0001), sharing genetic information without consent (65.0 vs. 35.6%, p < 0.0001), discrimination based on genes (62.4 vs. 34.3%, p = 0.0002), and lack of access due to cost (75.0 vs. 48.0%, p = 0.0002). In logistic regressions, NHBs (OR = 7.46, 95% CI = 3.04-18.32) and those self-reporting discrimination (OR = 2.87, 95% CI = 1.22-6.78) had more concerns about the misuse of genes and costs associated with personalized medicine. Conclusion: Racial differences exist in attitudes toward personalized medicine and may be influenced by self-reported discrimination. Further study to understand factors influencing the acceptance of personalized medicine could help encourage its use.
Chromosome Painting Reveals Multiple Rearrangements between Gymnotus capanema and Gymnotus carapo (Gymnotidae, Gymnotiformes)
Authors: Nagamachi C.Y. , Pieczarka J.C. , Milhomem S.S.R. , Batista J.A. , O'Brien P.C.M. , Ferguson-Smith M.A.
Published: September 2013

The genus Gymnotus (Gymnotiformes) is a group of fishes with karyotypic plasticity, demonstrated by cytogenetic studies using whole chromosome probes of G. carapo (GCA, 2n = 42) that were obtained by flow-sorting from fibroblast cultures. In the present work we undertook comparative mapping of the karyotype of G. capanema (GCP, 2n = 34) with GCA, 2n = 42 painting probes. The results demonstrate that the karyotype of G. capanema is extensively rearranged when compared to G. carapo. From the 12 chromosome pairs of G. carapo that can be individually differentiated (GCA1-3, 6, 7, 9, 14, 16 and 18-21), only 4 pairs (GCA6, 7, 19, and 20) maintained conserved synteny in G. capanema. From these 4, GCA6 and GCA20 correspond to individual chromosomes (GCP8 and GCP15), while the other 2 share homology with parts of GCP1 and GCP2, respectively. The remaining GCP chromosomes showed more complex hybridization patterns with homologies to other GCA pairs. These results demonstrate that the level of reorganization in the genome of G. capanema is much greater than in GCA, 2n = 42 and in karyomorph GCA, 2n = 40 which was previously analyzed by chromosome painting.
Bortezomib Administered Subcutaneously Is Well Tolerated in Bortezomib-Based Combination Regimens Used in Patients with Multiple Myeloma
Authors: Lamm W. , Drach-Schauer B. , Eder S. , Drach J.
Published: September 2013

Objective: Bortezomib (Btz) has emerged as a standard of care in the treatment of patients with multiple myeloma (MM), but Btz-induced peripheral neuropathy (PNP) has a particularly negative impact on patients' quality of life. According to a recent study, PNP was significantly less frequent with subcutaneous administration of Btz. Here, we report our experience regarding the efficacy and tolerability of standard combination regimens in MM with subcutaneous Btz. Methods: 14 consecutive patients with newly diagnosed MM were included in this analysis. Btz was used in different combination regimens (Btz with dexamethasone with/without thalidomide or Btz combined with melphalan and prednisone). Standard criteria were applied to evaluate response and toxicity. Results: Hematological toxicities occurred only at grades 1-2 and included anemia (71%) and thrombocytopenia (21%). Nonhematologic side effects at grades 1-2 were local skin reactions at the subcutaneous injection site, which were self-limited. No notable gastrointestinal toxicity was observed with subcutaneous Btz, and therefore routine use of intravenous hydration and antiemetics was abandoned. Overall response rate for transplant-eligible patients was 86%. Conclusions: Our results confirm the improved toxicity profile of the subcutaneous administration of Btz in various standard Btz-based combination regimens. In addition, patient management with subcutaneous administration has been markedly ameliorated at our center.
Hypoxia Induces Metalloproteinase-9 Activation and Human Vascular Smooth Muscle Cell Migration Through Low-Density Lipoprotein Receptor–Related Protein 1–Mediated Pyk2 Phosphorylation
Authors: Revuelta-López Elena , Castellano José , Roura Santiago , Gálvez-Montón Carolina , Nasarre Laura , Benitez Sonia , Bayes-Genis Antoni , Badimon Lina , Llorente-Cortés Vicenta
Published: September 2013

Objective—

Hypoxia disturbs vascular function by promoting extracellular matrix remodeling. Extracellular matrix integrity and composition are modulated by metalloproteinases (MMPs). Our aim was to investigate the role of low-density lipoprotein receptor–related protein 1 (LRP1) in regulating MMP-9/MMP-2 activation and vascular smooth muscle cells (VSMCs) migration in response to hypoxia, and to elucidate the LRP1-signaling pathways involved in this process.

Approach and Results—

Western blot analysis showed that hypoxia induced a sustained phosphorylation of proline-rich tyrosine kinase 2 concomitantly with LRP1 overexpression in human VSMCs (hVSMCs). Deletion of LRP1 using small-interfering RNA technology or treatment of hVSMCs with the Src family kinase inhibitor PP2 impaired hypoxia-induced phosphorylation of proline-rich tyrosine kinase 2 levels. Coimmunoprecipitation experiments showed that the higher amounts of phosphorylation of proline-rich tyrosine kinase 2/LRP1β immunoprecipitates in hypoxic hVSMCs were abolished in PP2-treated hVSMCs. Both LRP1 silencing and PP2 treatment were highly effective in the prevention of hypoxia-induced MMP-9 activation and hVSMC migration. Cellular subfractionation experiments revealed that PP2 effects may be caused by impairment of hypoxia-induced nuclear factor-κβ translocation to the nucleus. ELISA measurements showed that LRP1 silencing but not PP2 treatment increased interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 secretion by hypoxic hVSMCs.

Conclusions—

Our findings determine a crucial role of LRP1-mediated Pyk2 phosphorylation on hypoxia-induced MMP-9 activation and hVSMC migration and therefore in hypoxia-induced vascular remodeling. Both LRP1 silencing and PP2 treatments also influence hypoxia-induced proinflammatory effects in hVSMCs. Therefore, further studies are required to establish therapeutical strategies that efficiently modulate vascular remodeling and inflammation associated with hypoxia-vascular diseases.
Compound and Digenic Heterozygosity Predicts Lifetime Arrhythmic Outcome and Sudden Cardiac Death in Desmosomal Gene–Related Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Rigato Ilaria , Bauce Barbara , Rampazzo Alessandra , Zorzi Alessandro , Pilichou Kalliopi , Mazzotti Elisa , Migliore Federico , Marra Martina Perazzolo , Lorenzon Alessandra , De Bortoli Marzia , Calore Martina , Nava Andrea , Daliento Luciano , Gregori Dario , Iliceto Sabino , Thiene Gaetano , Basso Cristina , Corrado Domenico
Published: September 2013

Background—

Mutations in genes encoding for desmosomal proteins are the most common cause of arrhythmogenic right ventricular cardiomyopathy (ARVC). We assessed the value of genotype for prediction of lifetime major arrhythmic events and sudden cardiac death (SCD) in desmosomal gene–related ARVC.

Methods and Results—

The overall study population included 134 desmosomal gene mutation carriers (68 men; median age 36 years [22–52]) from 44 consecutive ARVC families undergoing comprehensive genetic screening. The probability of experiencing a first major arrhythmic event or SCD during a lifetime was determined by using date of birth as start point for the time-to-event analysis, and was stratified by sex, desmosomal genes, mutation types, and genotype complexity (single versus multiple mutations). One hundred thirteen patients (84%) carried a single desmosomal gene mutation in desmoplakin (n=44; 39%), plakophilin-2 (n=38; 34%), desmoglein-2 (n=30; 26%), and desmocollin-2 (n=1; 1%), whereas 21 patients (16%) had a complex genotype with compound heterozygosity in 7 and digenic heterozygosity in 14. Over a median observation period of 39 (22–52) years, 22 patients (16%) from 20 different families had arrhythmic events, such as SCD (n=1), aborted SCD because of ventricular fibrillation (n=6), sustained ventricular tachycardia (n=14), and appropriate defibrillator intervention (n=1). Multiple desmosomal gene mutations and male sex were independent predictors of lifetime arrhythmic events with a hazard ratio of 3.71 (95% confidence interval, 1.54–8.92;
P
=0.003) and 2.76 (95% confidence interval, 1.19–6.41;
P
=0.02), respectively.

Conclusions—

Compound/digenic heterozygosity was identified in 16% of ARVC-causing desmosomal gene mutation carriers and was a powerful risk factor for lifetime major arrhythmic events and SCD. These results support the use of comprehensive genetic screening of desmosomal genes for arrhythmic risk stratification in ARVC.