bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect ofVetiveria zizanioidesEssential Oil on Melanogenesis in Melanoma Cells: Downregulation of Tyrosinase Expression and Suppression of Oxidative Stress
Authors: Peng Hsin-Yi , Lai Chin-Chun , Lin Chih-Chien , Chou Su-Tze
Published: March 2014

The major objective of this study was to estimate the hypopigmentation function of the essential oil fromVetiveria zizanioides(VZ-EO). Our results indicated that VZ-EO exhibits potent lipid peroxidation inhibitory activity to moderate the bleaching ofβ-carotene and to maintain the cellular glutathione (GSH) levels. VZ-EO can markedly decrease melanin production and tyrosinase activity inα-melanin-stimulating-hormone- (α-MSH-) stimulated B16 cells. The effect of VZ-EO on melanogenesis is achieved by the suppression of cellular tyrosinase expression. The results demonstrated that the activity of VZ-EO on melanogenesis might be the result of its potent antioxidative ability, which was reflected in the decreased cellular oxidant and malondialdehyde (MDA) levels and the recovered activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) inα-MSH-stimulated B16 cells. The most abundant compound in VZ-EO is cedr-8-en-13-ol (12.4%), which has a strong capability to inhibit lipid peroxidation. Therefore, VZ-EO has the potential to become an ingredient in future hypopigmentation drugs, foods, and cosmetics.
Common Bile Duct Dilatations in Asymptomatic Neonates: Incidence and Prognosis
Authors: Lin Shun-Feng , Lee Hung-Chang , Yeung Chun-Yan , Jiang Chuen-Bin , Chan Wai-Tao
Published: March 2014

Background. This retrospective study reviewed 213 asymptomatic neonates with common bile duct (CBD) dilatations diagnosed via ultrasound to evaluate their incidence and outcomes.Materials and Methods. From August 2001 to July 2010, 18,230 abdominal ultrasound scans were performed as newborn screening. There were 213 (1.17%) cases of CBD dilatation. Dilatation of neonatal CBD was defined when its diameter was ≥2 mm. The neonates’ birth history, CBD size, and follow-up results were analyzed.Results. In the 213 infants, four cystic dilatations (1.88%, 4/213) that were eventually diagnosed as choledochal cysts (CC). Among 209 neonates with fusiform dilatations (size 2.0–6.7 mm), 77 had ultrasound follow-up and 87% of them resolved spontaneously which were diagnosed as transient CBD dilatation (TCBDD). Eighty percent of TCBDDs resolved within 6 months. Patients with initial CBD size ≥3 mm had significantly lower resolution rate and neonates whose mothers are older than 35 years took longer time to resolve.Conclusion. The incidence of CBD dilatation in asymptomatic neonates was 1.17%. Eighty percent of TCBDDs resolved within 6 months. Regular ultrasound follow-up every 6 months may be appropriate for asymptomatic neonates with fusiform CBD dilatations to ensure resolution or progression.
Comparison of Exact Solutions for Heat Transfer in Extended Surfaces of Different Geometries
Authors: Moleofane K. J. , Moitsheki R. J.
Published: March 2014

We consider a steady state problem for heat transfer in fins of various geometries, namely, rectangular, radial, and spherical. The nonlinear steady state problem is linearizable provided that the thermal conductivity is the differential consequence of the term involving the heat transfer coefficient. As such, one is able to construct exact solutions. On the other hand, we employ the Lie point symmetry methods when the problem is not linearizable. Some interesting results are obtained and analyzed. The effects of the parameters such as thermogeometric fin parameter and the exponent on temperature are studied. Furthermore, fin efficiency and heat flux along the fin length of a spherical geometry are also studied.
Validation of the SF-6D Health State Utilities Measure in Lower Extremity Sarcoma
Authors: Gundle Kenneth R. , Cizik Amy M. , Punt Stephanie E. W. , Conrad Ernest U. , Davidson Darin J.
Published: March 2014

Aim. Health state utilities measures are preference-weighted patient-reported outcome (PRO) instruments that facilitate comparative effectiveness research. One such measure, the SF-6D, is generated from the Short Form 36 (SF-36). This report describes a psychometric evaluation of the SF-6D in a cross-sectional population of lower extremity sarcoma patients.Methods. Patients with lower extremity sarcoma from a prospective database who had completed the SF-36 and Toronto Extremity Salvage Score (TESS) were eligible for inclusion. Computed SF-6D health states were given preference weights based on a prior valuation. The primary outcome was correlation between the SF-6D and TESS.Results. In 63 pairs of surveys in a lower extremity sarcoma population, the mean preference-weighted SF-6D score was 0.59 (95% CI 0.4–0.81). The distribution of SF-6D scores approximated a normal curve (skewness = 0.11). There was a positive correlation between the SF-6D and TESS (r=0.75,P<0.01). Respondents who reported walking aid use had lower SF-6D scores (0.53 versus 0.61,P=0.03). Five respondents underwent amputation, with lower SF-6D scores that approached significance (0.48 versus 0.6,P=0.06).Conclusions. The SF-6D health state utilities measure demonstrated convergent validity without evidence of ceiling or floor effects. The SF-6D is a health state utilities measure suitable for further research in sarcoma patients.
Extended Linear Embedding via Green's Operators for Analyzing Wave Scattering from Anisotropic Bodies
Authors: Lancellotti V. , Tijhuis A. G.
Published: March 2014

Linear embedding via Green’s operators (LEGO) is a domain decomposition method particularly well suited for the solution of scattering and radiation problems comprised of many objects. The latter are enclosed in simple-shaped subdomains (electromagnetic bricks) which are in turn described by means of scattering operators. In this paper we outline the extension of the LEGO approach to the case of penetrable objects with dyadic permittivity or permeability. Since a volume integral equation is only required to solve the scattering problem inside a brick and the scattering operators are inherently surface operators, the LEGO procedureper secan afford a reduction of the number of unknowns in the numerical solution with the Method of Moments and subsectional basis functions. Further substantial reduction is achieved with the eigencurrents expansion method (EEM) which employs the eigenvectors of the scattering operator as local entire-domain basis functions over a brick’s surface. Through a few selected numerical examples we discuss the validation and the efficiency of the LEGO-EEM technique applied to clusters of anisotropic bodies.
Two-Level Brezzi-Pitkäranta Discretization Method Based on Newton Iteration for Navier-Stokes Equations with Friction Boundary Conditions
Authors: An Rong , Wang Xian
Published: March 2014

We present a new stabilized finite element method for Navier-Stokes equations with friction slip boundary conditions based on Brezzi-Pitkäranta stabilized method. The stability and error estimates of numerical solutions in some norms are derived for standard one-level method. Combining the techniques of two-level discretization method, we propose two-level Newton iteration method and show the stability and error estimate. Finally, the numerical experiments are given to support the theoretical results and to check the efficiency of this two-level iteration method.
Fast Readout Architectures for Large Arrays of Digital Pixels: Examples and Applications
Authors: Gabrielli A.
Published: March 2014

Modern pixel detectors, particularly those designed and constructed for applications and experiments for high-energy physics, are commonly built implementing general readout architectures, not specifically optimized in terms of speed. High-energy physics experiments use bidimensional matrices of sensitive elements located on a silicon die. Sensors are read out via other integrated circuits bump bonded over the sensor dies. The speed of the readout electronics can significantly increase the overall performance of the system, and so here novel forms of readout architectures are studied and described. These circuits have been investigated in terms of speed and are particularly suited for large monolithic, low-pitch pixel detectors. The idea is to have a small simple structure that may be expanded to fit large matrices without affecting the layout complexity of the chip, while maintaining a reasonably high readout speed. The solutions might be applied to devices for applications not only in physics but also to general-purpose pixel detectors whenever online fast data sparsification is required. The paper presents also simulations on the efficiencies of the systems as proof of concept for the proposed ideas.
A Modification of the Moving Least-Squares Approximation in the Element-Free Galerkin Method
Authors: Cao Yang , Dong Jun-Liang , Yao Lin-Quan
Published: March 2014

The element-free Galerkin (EFG) method is one of the widely used meshfree methods for solving partial differential equations. In the EFG method, shape functions are derived from a moving least-squares (MLS) approximation, which involves the inversion of a small matrix for every point of interest. To avoid the calculation of matrix inversion in the formulation of the shape functions, an improved MLS approximation is presented, where an orthogonal function system with a weight function is used. However, it can also lead to ill-conditioned or even singular system of equations. In this paper, aspects of the IMLS approximation are analyzed in detail. The reason why singularity problem occurs is studied. A novel technique based on matrix triangular process is proposed to solve this problem. It is shown that the EFG method with present technique is very effective in constructing shape functions. Numerical examples are illustrated to show the efficiency and accuracy of the proposed method. Although our study relies on monomial basis functions, it is more general than existing methods and can be extended to any basis functions.
Users Behavior in Location-Aware Services: Digital Natives versus Digital Immigrants
Authors: Furini Marco
Published: March 2014

Location-aware services may expose users to privacy risks as they usually attach user’s location to the generated contents. Different studies have focused on privacy in location-aware services, but the results are often conflicting. Our hypothesis is that users are not fully aware of the features of the location-aware scenario and this lack of knowledge affects the results. Hence, in this paper we present a different approach: the analysis is conducted on two different groups of users (digital natives and digital immigrants) and is divided into two steps: (i) understanding users’ knowledge of a location-aware scenario and (ii) investigating users’ opinion toward location-aware services after showing them an example of an effective location-aware service able to extract personal and sensitive information from contents publicly available in social media platforms. The analysis reveals that there is relation between users’ knowledge and users’ concerns toward privacy in location-aware services and also reveals that digital natives are more interested in the location-aware scenario than digital immigrants. The analysis also discloses that users’ concerns toward these services may be ameliorated if these services ask for users’ authorization and provide benefits to users. Other interesting findings allow us to draw guidelines that might be helpful in developing effective location-aware services.
New Types of Doubly Periodic Standing Wave Solutions for the Coupled Higgs Field Equation
Authors: Xu Gui-qiong
Published: March 2014

Based on the Hirota bilinear method and theta function identities, we obtain a new type of doubly periodic standing wave solutions for a coupled Higgs field equation. The Jacobi elliptic function expression and long wave limits of the periodic solutions are also presented. By selecting appropriate parameter values, we analyze the interaction properties of periodic-periodic waves and periodic-solitary waves by some figures.
Inflation and Topological Phase Transition Driven by Exotic Smoothness
Authors: Asselmeyer-Maluga Torsten , Król Jerzy
Published: March 2014

We will discuss a model which describes the cause of inflation by a topological transition. The guiding principle is the choice of an exotic smoothness structure for the space-time. Here we consider a space-time with topologyS3×ℝ. In case of an exoticS3×ℝ, there is a change in the spatial topology from a 3-sphere to a homology 3-sphere which can carry a hyperbolic structure. From the physical point of view, we will discuss the path integral for the Einstein-Hilbert action with respect to a decomposition of the space-time. The inclusion of the boundary terms produces fermionic contributions to the partition function. The expectation value of an area (with respect to some surface) shows an exponential increase; that is, we obtain inflationary behavior. We will calculate the amount of this increase to be a topological invariant. Then we will describe this transition by an effective model, the Starobinski orR2model which is consistent with the current measurement of the Planck satellite. The spectral index and other observables are also calculated.
Dynamic Properties of the Solow Model with Bounded Technological Progress and Time-to-Build Technology
Authors: Guerrini Luca , Sodini Mauro
Published: March 2014

We introduce a time-to-build technology in a Solow model with bounded technological progress. Our analysis shows that the system may be asymptotically stable, or it can produce stability switches and Hopf bifurcations when time delay varies. The direction and the stability criteria of the bifurcating periodic solutions are obtained by the normal form theory and the center manifold theorem. Numerical simulations confirms the theoretical results.
Global Solutions for a Simplified Shallow Elastic Fluids Model
Authors: Lu Yun-guang , Klingenberg Christian , Rendon Leonardo , Zheng De-Yin
Published: March 2014

The Cauchy problem for a simplified shallow elastic fluids model, one3×3system of Temple’s type, is studied and a global weak solution is obtained by using the compensated compactness theorem coupled with the total variation estimates on the first and third Riemann invariants, where the second Riemann invariant is singular near the zero layer depthρ=0. This work extends in some sense the previous works, (Serre, 1987) and (Leveque and Temple, 1985), which provided the global existence of weak solutions for2×2strictly hyperbolic system and (Heibig, 1994) forn×nstrictly hyperbolic system with smooth Riemann invariants.
On the Steady-State System Size Distribution for a Discrete-Time Geo/G/1 Repairable Queue
Authors: Liu Renbin , Deng Zhaohui
Published: March 2014

This paper studies a discrete-time N-policy Geo/G/1 queueing system with feedback and repairable server. With a probabilistic analysis method and renewal process theory, the steady-state system size distribution is derived. Further, the steady-state system size distribution derived in this work is extremely suitable for numerical calculations. Numerical example illustrates the important application of steady-state system size distribution in system capacity design for a network access proxy system.
Geometric Analysis of an Integrated Pest Management Model Including Two State Impulses
Authors: Zhao Wencai , Liu Yulin , Zhang Tongqian , Meng Xinzhu
Published: March 2014

According to integrated pest management strategies, we construct and investigate the dynamics of a Holling-Tanner predator-prey system with state dependent impulsive effects by releasing natural enemies and spraying pesticide at different thresholds. Applying the Dulacs criterion, the global stability of the positive equilibrium in the system without impulsive effect is discussed. By using impulsive differential equation geometry theory and the method of successor functions, we prove the existence of periodic solution of the system with state dependent impulsive effects. Furthermore, the stability conditions of periodic solutions are obtained. Some simulations are exerted to illustrate the feasibility of our main results.
Variants Associated with Susceptibility to Pancreatic Cancer and Melanoma Do Not Reciprocally Affect Risk
Authors: Wu Lang , Goldstein Alisa M. , Yu Kai , Yang Xiaohong Rose , Rabe Kari G. , Arslan Alan A. , Canzian Federico , Wolpin Brian M. , Stolzenberg-Solomon Rachael , Amundadottir Laufey T. , Petersen Gloria M.
Published: March 2014

Background: Melanoma cases may exist in pancreatic cancer kindreds, whereas there is increased risk of pancreatic cancer in familial melanoma. The two cancers may share genetic susceptibility variants in common.

Methods: Three dbGaP (datasets in Genotypes and Phenotypes)-deposited GWAS (genome-wide association study) datasets (MD Anderson melanoma, PanScan 1, and PanScan 2 for pancreatic cancer) were used. Thirty-seven melanoma susceptibility variants in 22 genomic regions from published GWAS, plus melanoma-related genes and pathways were examined for pancreatic cancer risk in the PanScan datasets. Conversely, nine known pancreatic cancer susceptibility variants were examined for melanoma risk in the MD Anderson dataset.

Results: In the PanScan data, initial associations were found with melanoma susceptibility variants in NCOA6 [rs4911442; OR, 1.32; 95% confidence interval (CI), 1.03–1.70; P = 0.03], YWHAZP5 (rs17119461; OR, 2.62; 95% CI, 1.08–6.35; P = 0.03), and YWHAZP5 (rs17119490; OR, 2.62; 95% CI, 1.08–6.34; P = 0.03), TYRP1 (P = 0.04), and IFNA13 (P = 0.04). In the melanoma dataset, two pancreatic cancer susceptibility variants were associated: NR5A2 (rs12029406; OR, 1.39; 95% CI, 1.01–1.92; P = 0.04) and CLPTM1L-TERT (rs401681; OR, 1.16; 95% CI, 1.01–1.34; P = 0.04). None of these associations remained significant after correcting for multiple comparisons.

Conclusion: Reported variants of melanoma genes and pathways do not play a role in pancreatic cancer predisposition. Reciprocally, pancreatic cancer susceptibility variants are not associated with melanoma risk.

Impact: Known melanoma-related genes and pathways, as well as GWAS-derived susceptibility variants of melanoma and pancreatic cancer, do not explain the shared genetic etiology of these two cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1121–4. ©2014 AACR.
Classifying Patients for Breast Cancer by Detection of Autoantibodies against a Panel of Conformation-Carrying Antigens
Authors: Evans Rick L. , Pottala James V. , Egland Kristi A.
Published: March 2014

Patients with breast cancer elicit an autoantibody response against cancer proteins, which reflects and amplifies the cellular changes associated with tumorigenesis. Detection of autoantibodies in plasma may provide a minimally invasive mechanism for early detection of breast cancer. To identify cancer proteins that elicit a humoral response, we generated a cDNA library enriched for breast cancer genes that encode membrane and secreted proteins, which are more likely to induce an antibody response compared with intracellular proteins. To generate conformation-carrying antigens that are efficiently recognized by patients' antibodies, a eukaryotic expression strategy was established. Plasma from 200 patients with breast cancer and 200 age-matched healthy controls were measured for autoantibody activity against 20 different antigens designed to have conformational epitopes using ELISA. A conditional logistic regression model was used to select a combination of autoantibody responses against the 20 different antigens to classify patients with breast cancer from healthy controls. The best combination included ANGPTL4, DKK1, GAL1, MUC1, GFRA1, GRN, and LRRC15; however, autoantibody responses against GFRA1, GRN, and LRRC15 were inversely correlated with breast cancer. When the autoantibody responses against the 7 antigens were added to the base model, including age, BMI, race and current smoking status, the assay had the following diagnostic capabilities: c-stat (95% CI), 0.82 (0.78–0.86); sensitivity, 73%; specificity, 76%; and positive likelihood ratio (95% CI), 3.04 (2.34–3.94). The model was calibrated across risk deciles (Hosmer–Lemeshow, P = 0.13) and performed well in specific subtypes of breast cancer including estrogen receptor positive, HER-2 positive, invasive, in situ and tumor sizes >1 cm. Cancer Prev Res; 7(5); 545–55. ©2014 AACR.
Clinical Presentations of Coenzyme Q10 Deficiency Syndrome
Authors: Quinzii Catarina M. , Emmanuele Valentina , Hirano Michio
Published: March 2014

Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous syndrome which has been associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ10 deficiency predominantly presents in childhood. To date, causative mutations have been identified in a small proportion of patients, making it difficult to identify a phenotype-genotype correlation. Identification of CoQ10 deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ10 supplementation.
Mycophenolate Mofetil-Induced Segmental Colitis Mimicking Ischemic Colitis
Authors: Johal Kevin , Ratuapli Shiva K. , Lam-Himlin Dora M. , Gurudu Suryakanth R.
Published: March 2014

Mycophenolate mofetil (MMF) is a commonly used drug in the prevention of allograft rejection in patients with solid organ transplants. Although diffuse colitis has been described in MMF-related colitis, segmental colitis has not been reported. We report the case of a 64-year-old male on MMF therapy who presented for evaluation of afebrile diarrhea and abdominal pain. Flexible sigmoidoscopy revealed a segmental erythematous mucosa with ulceration in the sigmoid colon, descending colon, splenic flexure and proximal transverse colon. Biopsies of these areas showed dilated damaged crypts, eosinophilic epithelial changes and crypt abscesses with apoptotic bodies consistent with MMF-induced injury. MMF was discontinued, leading to a significant improvement of his symptoms.
Incomplete Stent Apposition Causes High Shear Flow Disturbances and Delay in Neointimal Coverage as a Function of Strut to Wall Detachment Distance
Authors: Foin Nicolas , Gutiérrez-Chico Juan Luis , Nakatani Shimpei , Torii Ryo , Bourantas Christos V. , Sen Sayan , Nijjer Sukhjinder , Petraco Ricardo , Kousera Chrysa , Ghione Matteo , Onuma Yoshinobu , Garcia-Garcia Hector M. , Francis Darrel P. , Wong Philip , Di Mario Carlo , Davies Justin E. , Serruys Patrick W.
Published: March 2014

Background—

Lack of re-endothelialization and neointimal coverage on stent struts has been put forward as the main underlying mechanism leading to late stent thrombosis. Incomplete stent apposition (ISA) has been observed frequently in patients with very late stent thrombosis after drug eluting stent implantation, suggesting a role of ISA in the pathogenesis of this adverse event. The aim of this study was to evaluate the impact of different degrees of ISA severity on abnormal shear rate and healing response with coverage, because of its potential implications for stent optimization in clinical practice.

Methods and Results—

We characterized flow profile and shear distribution in different cases of ISA with increasing strut-wall detachment distance (ranging from 100 to 500 μm). Protruding strut and strut malapposed with moderate detachment (ISA detachment distance <100 μm) have minimal disturbance to blood flow as compared with floating strut that has more significant ISA distance. In vivo impact on strut coverage was assessed retrospectively using optical coherence tomography evaluation on 72 stents (48 patients) sequentially at baseline and after 6-month follow-up. Analysis of coverage revealed an important impact of baseline strut-wall ISA distance on the risk of incomplete strut coverage at follow-up. Malapposed segments with an ISA detachment <100 μm at baseline showed complete strut coverage at follow-up, whereas segments with a maximal ISA detachment distance of 100 to 300 μm and >300 μm had 6.1% and 15.7% of their struts still uncovered at follow-up, respectively (
P
<0.001).

Conclusions—

Flow disturbances and risk of delayed strut coverage both increase with ISA detachment distance. Insights from this study are important for understanding malapposition as a quantitative, rather than binary phenomenon (present or absent) and to define the threshold of ISA detachment that might benefit from optimization during stent implantation.
Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?
Authors: Curzen Nick , Rana Omar , Nicholas Zoe , Golledge Peter , Zaman Azfar , Oldroyd Keith , Hanratty Colm , Banning Adrian , Wheatcroft Stephen , Hobson Alex , Chitkara Kam , Hildick-Smith David , McKenzie Dan , Calver Alison , Dimitrov Borislav D. , Corbett Simon
Published: March 2014

Background—

The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws. The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined.

Methods and Results—

Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (≥2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA.

Conclusions—

Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice.

Clinical Trial Registration—

URL:
http://www.clinicaltrial.gov
. Unique identifier: NCT01070771.
β-Adrenergic Signaling Inhibits G
q
-Dependent Protein Kinase D Activation by Preventing Protein Kinase D Translocation
Authors: Nichols C. Blake , Chang Chia-Wei , Ferrero Maura , Wood Brent M. , Stein Matthew L. , Ferguson Amanda J. , Ha Derrick , Rigor Robert R. , Bossuyt Sven , Bossuyt Julie
Published: March 2014

Rationale:

Both β-adrenergic receptor (β-AR) and G
q
-coupled receptor (G
q
R) agonist–driven signaling play key roles in the events, leading up to and during cardiac dysfunction. How these stimuli interact at the level of protein kinase D (PKD), a nodal point in cardiac hypertrophic signaling, remains unclear.

Objective:

To assess the spatiotemporal dynamics of PKD activation in response to β-AR signaling alone and on coactivation with G
q
R-agonists. This will test our hypothesis that compartmentalized PKD signaling reconciles disparate findings of PKA facilitation and inhibition of PKD activation.

Methods and Results:

We report on the spatial and temporal profiles of PKD activation using green fluorescent protein-tagged PKD (wildtype or mutant S427E) and targeted fluorescence resonance energy transfer–based biosensors (D-kinase activity reporters) in adult cardiomyocytes. We find that β-AR/PKA signaling drives local nuclear activation of PKD, without preceding sarcolemmal translocation. We also discover pronounced interference of β-AR/cAMP/PKA signaling on G
q
R-induced translocation and activation of PKD throughout the cardiomyocyte. We attribute these effects to direct, PKA-dependent phosphorylation of PKD-S427. We also show that phosphomimetic substitution of S427 likewise impedes G
q
R-induced PKD translocation and activation. In neonatal myocytes, S427E inhibits G
q
R-evoked cell growth and expression of hypertrophic markers. Finally, we show altered S427 phosphorylation in transverse aortic constriction–induced hypertrophy.

Conclusions:

β-AR signaling triggers local nuclear signaling and inhibits G
q
R-mediated PKD activation by preventing its intracellular translocation. PKA-dependent phosphorylation of PKD-S427 fine-tunes the PKD responsiveness to G
q
R-agonists, serving as a key integration point for β-adrenergic and G
q
-coupled stimuli.
Translational Neurorehabilitation Research in the Third World
Authors: Anjos Sarah M. , Cohen Leonardo G. , Sterr Annette , de Andrade Karina N.F. , Conforto Adriana B.
Published: March 2014

Background and Purpose—

Most stroke rehabilitation studies have been performed in high-income countries. The aim of this study was to identify the main barriers for patient inclusion in a research protocol performed in Brazil.

Methods
—

We evaluated reasons for exclusion of patients in a pilot, randomized, double-blinded clinical trial of stroke rehabilitation. Descriptive statistical analysis was performed.

Results
—

Only 5.6% of 571 screened patients were included. Recurrent stroke was responsible for exclusion of 45.4% of potentially eligible patients.

Conclusions
—

Recurrent stroke represented a big barrier to enroll patients in the protocol. External validity of rehabilitation trials will benefit from definition of study criteria according to regional characteristics of patients, including rates of recurrent stroke.

Clinical Trial Registration
—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01333579.
Accuracy of Emergency Medical Services–Reported Last Known Normal Times in Patients Suspected With Acute Stroke
Authors: Curfman David , Connor Lisa Tabor , Moy Hawnwan Philip , Heitsch Laura , Panagos Peter , Lee Jin-Moo , Tan David K. , Ford Andria L.
Published: March 2014

Background and Purpose—

The last known normal (LKN) time is a critical determinant of IV tissue-type plasminogen activator (IV tPA) eligibility; however, the accuracy of emergency medical services (EMS)-reported LKN times is unknown. We determined the congruence between neurologist-determined and EMS-reported LKN times and identified predictors of incongruent LKN times.

Methods—

We prospectively collected EMS-reported LKN times for patients brought into the emergency department with suspected acute stroke and calculated the absolute difference between the neurologist-determined and EMS-reported LKN times (|ΔLKN|). We determined the rate of inappropriate IV tPA use if EMS-reported times had been used in place of neurologist-determined times. Univariate and multivariable linear regression assessed for any predictors of prolonged |ΔLKN|.

Results—

Of 251 patients, mean and median |ΔLKN| were 28 and 0 minutes, respectively. |ΔLKN| was <15 minutes in 91% of the entire cohort and <15 minutes in 80% of patients with a diagnosis of stroke (n=86). Of patients who received IV tPA, none would have been incorrectly excluded from IV tPA if the EMS LKN time had been used. Conversely, of patients who did not receive IV tPA, 6% would have been incorrectly included for IV tPA consideration had the EMS time been used. In patients with wake-up stroke symptoms, EMS underestimated LKN times: mean neurologist LKN time−EMS LKN time =208 minutes. The presence of wake-up stroke symptoms (
P
<0.0001) and older age (
P
=0.019) were independent predictors of prolonged |ΔLKN|.

Conclusions—

EMS-reported LKN times were largely congruent with neurologist-determined times. Focused EMS training regarding wake-up stroke symptoms may further improve accuracy.
Excitotoxicity and Metabolic Changes in Association With Infarct Progression
Authors: Woitzik Johannes , Pinczolits Alexandra , Hecht Nils , Sandow Nora , Scheel Michael , Drenckhahn Christoph , Dreier Jens P. , Vajkoczy Peter
Published: March 2014

Background and Purpose—

We investigated to what extent excitotoxicity and metabolic changes in the peri-infarct region of patients with malignant hemispheric stroke are associated with delayed infarct progression.

Methods—

In 18 patients with malignant hemispheric stroke, 2 microdialysis probes were implanted within the peri-infarct tissue at a distance of 5 and 15 mm to the infarct. Precise probe placement was achieved by intraoperative laser speckle imaging. Glutamate, glucose, pyruvate, and lactate levels were monitored for 5 days after surgery. Delayed infarct progression was determined from serial MRI on the day after surgery and after the monitoring period.

Results—

Initial stroke volume ranged from 122 to 479 cm
3
with a median of 295 cm
3
. Nine of 18 patients (50%) had delayed infarct progression (median, 44 cm
3
; range, 19–93 cm
3
). In these patients, glucose and individual pyruvate levels were significantly lower when compared with patients without infarct progression, whereas glutamate and the lactate–pyruvate ratio were significantly elevated in patients with infarct progression early after surgery (12–36 hours) at the 15-mm microdialysis probe location. Lactate was elevated but without difference between groups.

Conclusions—

Excitotoxic or metabolic impairment was associated with delayed infarct progression and could serve as a treatment target.
Cerebral Cavernous Malformations Arise Independent of the Heart of Glass Receptor
Authors: Zheng Xiangjian , Riant Florence , Bergametti Françoise , Myers Cynthia D. , Tang Alan T. , Kleaveland Benjamin , Pan Wei , Yang Jisheng , Tournier-Lasserve Elisabeth , Kahn Mark L.
Published: March 2014

Background and Purpose—

The Heart of Glass (HEG) receptor binds KRIT1 and functions with KRIT1, CCM2, and PDCD10 in a common signaling pathway required for heart and vascular development. Mutations in
KRIT1, CCM2
, and
PDCD10
also underlie human cerebral cavernous malformation (CCM) and postnatal loss of these genes in the mouse endothelium results in rapid CCM formation. Here, we test the role of HEG in CCM formation in mice and in humans.

Methods—

We constitutively or conditionally deleted
Heg
and
Ccm2
genes in genetically modified mice. Mouse embryos, brain, and retina tissues were analyzed to assess CCM lesion formation.

Results—

In postnatal mice, CCMs form with
Ccm2
−/−
but not with
Heg
−/−
or
Heg
−/−
;
Ccm2
+/-
endothelial cells. Consistent with these findings, human patients with CCM who lack exonic mutations in
KRIT1, CCM2
, or
PDCD10
do not have mutations in
HEG
.

Conclusions—

These findings suggest that the HEG-CCM signaling functions during cardiovascular development and growth, whereas CCMs arise because of loss of HEG-independent CCM signaling in the endothelium of the central nervous system after birth.
Incident Stroke Is Associated With Common Carotid Artery Diameter and Not Common Carotid Artery Intima-Media Thickness
Authors: Polak Joseph F. , Sacco Ralph L. , Post Wendy S. , Vaidya Dhananjay , Arnan Martinson Kweku , O’Leary Daniel H.
Published: March 2014

Background and Purpose—

The common carotid artery interadventitial diameter is measured on ultrasound images as the distance between the media-adventitia interfaces of the near and far walls. It is associated with common carotid intima-media thickness (IMT) and left ventricular mass and might therefore also have an association with incident stroke.

Methods—

We studied 6255 individuals free of coronary heart disease and stroke at baseline with mean age of 62.2 years (47.3% men), members of a multiethnic community–based cohort of whites, blacks, Hispanics, and Chinese. Ischemic stroke events were centrally adjudicated. Common carotid artery interadventitial diameter and IMT were measured. Cases with incident atrial fibrillation (n=385) were excluded. Multivariable Cox proportional hazards models were generated with time to ischemic event as outcome, adjusting for risk factors.

Results—

There were 115 first-time ischemic strokes at 7.8 years of follow-up. Common carotid artery interadventitial diameter was a significant predictor of ischemic stroke (hazard ratio, 1.86; 95% confidence interval, 1.59–2.17 per millimeter) and remained so after adjustment for risk factors and common carotid IMT with a hazard ratio of 1.52/mm (95% confidence interval, 1.22–1.88). Common carotid IMT was not an independent predictor after adjustment (hazard ratio, 0.14; 95% confidence interval, 0.14–1.19).

Conclusions—

Although common carotid IMT is not associated with stroke, interadventitial diameter of the common carotid artery is independently associated with first-time incident ischemic stroke even after adjusting for IMT. Our hypothesis that this is in part attributable to the effects of exposure to blood pressure needs confirmation by other studies.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00063440.
Influence of photoperiod on cold-adapted thermogenesis and endocrine aspects in the tree shrew (Tupaia belangeri)
Authors: Zhang Lin , Zhu Wanlong , Yang Fang , Wang Zhengkun
Published: March 2014

Environmental factors play an important role in the regulation of a mammal’s physiology and behavior. Consequently, particular species may provide valuable models for understanding the regulation of energy balance. In the present study, tree shrews (Tupaia belangeri) were transferred from a short to a long day photoperiod in cold conditions, in order to test our prediction that short photoperiod may stimulate an increase in thermogenic capacity and energy intake in tree shrews. During the first four weeks of acclimation to short days, T. belangeri increased body mass, whereas during the second four weeks of acclimation to long days, the body mass of tree shrews decreased compared with the short day group. The increase in body mass reflected a significant increase in absolute amounts of body components, such as carcass mass. During long photoperiod associated with cold exposure, livers, kidney, and small intestine mass decreased. T. belangeri decreased resting metabolic rate and energy intake after exposure to long days while during the exposure to short days the shrews started to maintain a stable level after 28 days. Serum leptin levels were positively correlated with body mass, as well as resting metabolic rate and energy intake. The results show that T. belangeri may provide an attractive novel model system for investigation of the regulation of body mass and energy balance at individual levels. Leptin is potentially stimulated by the photoperiod and cold exposure and is responsible for body mass regulation and thermogenesis in T. belangeri.
Effect of a brief stress on progesterone plasma levels in pregnant and non-pregnant guinea pigs
Authors: Michel Catherine L. , Bonnet Xavier
Published: March 2014

Steroid hormones are essential for vertebrate reproduction. They are involved in the regulation of major female reproductive events like ovulation, embryo implantation, or gestation. For instance, progesterone promotes foeto-maternal exchanges whereas glucocorticoids stimulate the mobilization of the required energy resources. However, glucocorticoids are key effectors of the stress response; chronic elevations of these hormones can exert negative effects on reproduction. Yet, little is known about the effects of a brief exposure to a stressor on the respective plasma concentrations of sex steroids and glucocorticoids, notably during pregnancy. We examined the impact of a brief stress (handling + 1.5 hours in a bag) on progesterone and cortisol plasma concentrations in pregnant and non-pregnant female guinea pigs. Analyses revealed that: 1) pregnant females exhibited higher baseline progesterone and cortisol concentrations compared to non-pregnant females, as expected; 2) cortisol concentrations increased rapidly following manipulation, revealing a typical hormonal stress response; and, 3) progesterone concentrations decreased on average by 50.9% following the brief stress period, both in pregnant and non-pregnant individuals. These experimental results show for the first time a drastic and rapid impact on progesterone concentration caused by a brief stress.
A tradeoff between mate-quality recognition and species recognition in male Bufo gargarizans that co-occur with Rana catesbeiana
Authors: Yu Tong Lei , Busam Michael , Pike David A.
Published: March 2014

Typically, anuran amphibians favor larger females as mates because larger females lay more eggs; thus, males in amplexus can increase the number of eggs fertilized, and fitness. However, males may also prefer those females that were closest to the norm for their population in overlapping populations, and these individuals do not receive the benefits of enhanced fertilization success. In this study, we test how male Bufo gargarizans choose mates in the presence and absence of an invasive species, bullfrogs (Rana catesbeiana). When given a simultaneous choice between a small male and a large female toad, males discriminated between the sexes and attempted to clasp a large female. However, when one male toad was presented with a large female bullfrog and a small female toad, the males chose both with equal frequency. Therefore, male B. gargarizans appears to trade-off between species and mate-quality recognition, such that those toads co-occurring with heterospecifics do not blindly prefer mate-quality to ensure conspecific matings.
Pattern of sexual size dimorphism supports the inverse of Rensch’s rule in two frog species
Authors: Lu Di , Zhou Cai Quan , Zhao Lian Jun , Liao Wen Bo
Published: March 2014

Rensch’s rule describes that sexual size dimorphism (SSD) increases with body size (hyperallometry) when males are larger, and decreases with body size (hypoallometry) when males are smaller. In this paper, on the basis of mean adult body size resulting from 18 populations of the common frogRana temporariaand 24 populations of the Tibetan frogNanorana parkeri, we tested the consistency of allometric relationships between males and females with Rensch’s rule. Our results show that the variation in degree of female-biased SSD increased with increasing mean size at intraspecific levels in two species, which is consistent with the inverse of Rensch’s rule. Furthermore, we tested the hypothesis that the degree of SSD decreased with increasing altitudes. Inconsistent with the predications of our hypothesis, we found no relationships between the degree of SSD and altitude for the two species investigated. These findings suggest that females living in adverse climates in high altitudes cannot adjust their body size as plastically as males.
A field study on using artificial substrate for nesting of introduced pumpkinseed sunfish, Lepomis gibbosus (Linnaeus, 1758)
Authors: Petrova Uzunova Eliza , Studenkov Slavi , Simeonovska-Nikolova Danilela
Published: March 2014

We experimentally tested the potential use of artificial substrate – plastic bottles for egg deposition of non-native pumpkinseed sunfish,Lepomis gibbosusL. in a former sand-pit lake in western Bulgaria. The lake is situated close to an urban area, and is characterised by high pumpkinseed abundance. The study was carried out for a period of 105 days during the active pumpkinseed breeding season (from May to August). Five sites along the littoral area of the lake, with different habitat characteristics were selected. Each site was divided into two sections – an experimental and a control section. The plastic bottles (cut into two) were fixed to the lake bottom in the area of the experimental sections. Pumpkinseeds actively used the artificial substrate for nesting and the average use of each bottle was 2.3 times. Simultaneously, on the natural substrate of the experimental sections a total of 372 nests were built. The results showed that the choice of artificial substrate was neither associated with the type of bottom substrate, nor the remaining environmental traits that were studied. However, the use of artificial substrate has made a significant contribution to the total number of nests only on sites with “unsuitable” habitat parameters. These results show that waste products can seriously facilitate pumpkinseed’s abundance.
Selfing and brooding in Alinda biplicata (Gastropoda: Pulmonata: Clausiliidae) – life history traits of a good coloniser
Authors: Maltz Tomasz K. , Sulikowska-Drozd Anna
Published: March 2014

Alinda biplicatais capable of uniparental reproduction (selfing). The snails need 18 to 24 weeks to reach their ultimate size, and the first reproduction takes place 26 to 39 weeks after shell growth completion. Besides giving birth to juveniles, which is typical ofA. biplicata(39% of litters), the uniparentally reproducing individuals laid egg batches (38%) as well as mixed batches (eggs and juveniles; 23%). Within a few days the eggs decomposed, and in mixed batches they were often consumed by the accompanying neonates. In the next season, 70% of the remaining 20 snails reproduced (all of which had reproduced in the previous season). In the first season the neonate:egg proportion was 54:46, in the second 74:26. The egg-laying should be regarded as an anomaly – getting rid of eggs which were not fertilised or in which embryos died at early cleavage stages. The combination of selfing and brooding may explain the wide distribution and wide range of habitats occupied byA. biplicata.
Legitimate Representation: Civil Society Actors in Peace Negotiations Revisited
Authors: Zanker Franzisca
Published: March 2014

Abstract

Current research suggests that negotiations which are more inclusive are more likely to achieve durable peace since they speak to the entire population. One way to ensure public support is through the inclusion of civil society groups, either directly at the negotiation table or indirectly in supportive roles. It is argued that through their inclusion there is a positive effect on the legitimacy of negotiations which in turn leads to more durable peace. Nonetheless, the reasons why and how involving civil society groups improves the legitimacy of negotiations remains little understood. This article considers the gap in research by using original empirical data to look at the peace negotiations held in Liberia in 2003 and Kenya in early 2008. A theoretical model of legitimate negotiations will be used to show in what ways the involvement of civil society groups can in fact make the conduct of negotiations and the outcome of an agreement more legitimate for the aggrieved population.
On Success and Failure: Readiness Theory and the Aceh and Sri Lanka Peace Processes
Authors: Schiff Amira
Published: March 2014

Abstract

This study presents a comparative analysis of two case studies in which attempts were made to resolve intractable ethno-national conflicts: the peace process undertaken in Aceh between the Government of Indonesia and the Free Aceh Movement, which led to the signing of the Helsinki Memorandum of Understanding (mou) ending the conflict in Aceh; and the process conducted in the Sri Lanka conflict from 2001 through 2004 between the Government of Sri Lanka and the Tamil Tigers, which failed to yield an agreement. The two peace processes will be examined using readiness theory, which focuses on the factors influencing the decision to enter into negotiations. This article also attempts to extend the hypotheses of readiness theory to explore the process of concession-making during the negotiations that took place in the two case studies. The findings indicate that the theory does contribute to understanding the dynamics of the pre-negotiation in both case studies and that applying its hypotheses may contribute to the understanding of the dynamics of the process of reaching an agreement in the Aceh process and of the factors leading to the failure of the negotiations in the Sri Lanka conflict. The analysis also gives rise to some questions that challenge readiness theory and its hypotheses – empirically and methodologically.