bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the Platysma Muscle and the Superficial Musculoaponeurotic System (Human Specimens at 8–17 Weeks of Development)
Authors: De la Cuadra-Blanco C. , Peces-Peña M. D. , Carvallo-de Moraes L. O. , Herrera-Lara M. E. , Mérida-Velasco J. R.
Published: December 2013

There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8–17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region.
Synchronization and Stabilization of Chaotic Dynamics in a Quasi-1D Bose-Einstein Condensate
Authors: Idowu B. A. , Vincent U. E.
Published: December 2013

A nonlinear control is proposed for the exponential stabilization and synchronization of chaotic behaviour in a model of Bose-Einstein condensate (BEC). The active control technique is designed based on Lyapunov stability theory and Routh-Hurwitz criteria. The control design approach in both cases guarantees the stability of the controlled states. Whereas the synchronization of two identical BEC in their chaotic states can be realized using the scheme; a suitable controller is also capable of driving the otherwise chaotic oscillation to a stable state which could be expected in practice. The effectiveness of this technique is theoretically and numerically demonstrated.
smoothHR: An R Package for Pointwise Nonparametric Estimation of Hazard Ratio Curves of Continuous Predictors
Authors: Meira-Machado Luís , Cadarso-Suárez Carmen , Gude Francisco , Araújo Artur
Published: December 2013

The Cox proportional hazards regression model has become the traditional choice for modeling survival data in medical studies. To introduce flexibility into the Cox model, several smoothing methods may be applied, and approaches based on splines are the most frequently considered in this context. To better understand the effects that each continuous covariate has on the outcome, results can be expressed in terms of splines-based hazard ratio (HR) curves, taking a specific covariate value as reference. Despite the potential advantages of using spline smoothing methods in survival analysis, there is currently no analytical method in theRsoftware to choose the optimal degrees of freedom in multivariable Cox models (with two or more nonlinear covariate effects). This paper describes anRpackage, calledsmoothHR, that allows the computation of pointwise estimates of the HRs—and their corresponding confidence limits—of continuous predictors introduced nonlinearly. In addition the package provides functions for choosing automatically the degrees of freedom in multivariable Cox models. The package is available from theRhomepage. We illustrate the use of the key functions of thesmoothHRpackage using data from a study on breast cancer and data on acute coronary syndrome, from Galicia, Spain.
Identification of Biomarkers for Esophageal Squamous Cell Carcinoma Using Feature Selection and Decision Tree Methods
Authors: Tung Chun-Wei , Wu Ming-Tsang , Chen Yu-Kuei , Wu Chun-Chieh , Chen Wei-Chung , Li Hsien-Pin , Chou Shah-Hwa , Wu Deng-Chyang , Wu I-Chen
Published: December 2013

Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.
Recombinant Protein Production of Earthworm Lumbrokinase for Potential Antithrombotic Application
Authors: Wang Kevin Yueju , Tull Lauren , Cooper Edwin , Wang Nan , Liu Dehu
Published: December 2013

Earthworms have been used as a traditional medicine in China, Japan, and other Far East countries for thousands of years. Oral administration of dry earthworm powder is considered as a potent and effective supplement for supporting healthy blood circulation. Lumbrokinases are a group of enzymes that were isolated and purified from different species of earthworms. These enzymes are recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. Many lumbrokinase (LK) genes have been cloned and characterized. Advances in genetic technology have provided the ability to produce recombinant LK and have made it feasible to purify a single lumbrokinase enzyme for potential antithrombotic application. In this review, we focus on expression systems that can be used for lumbrokinase production. In particular, the advantages of using a transgenic plant system to produce edible lumbrokinase are described.
Key Factors Influencing Sustainable Development of a Green Energy Industry in Taiwan
Authors: Huang Wen-Chih , Jhong Chiu-Hua , Ding Ji-Feng
Published: December 2013

The main purpose of this paper was to apply the fuzzy analytic hierarchy process (FAHP) approach to explore key factors influencing the sustainable development of a green energy industry in Taiwan. Based on the literature and experts' opinions, a hierarchical structure with five assessment aspects and fifteen development factors was first constructed, and a FAHP algorithm model was then proposed. Finally, based on the AHP experts' questionnaires, we used the FAHP approach to evaluate the key factors. The results showed the following. (1) “Technology” is the most important aspect influencing sustainable development of green energy industry in Taiwan. (2) In order of relative importance, the top six key factors influencing sustainable development of green energy industry in Taiwan are “establishment of key technological capabilities,” “degree of integration of relevant laws and regulations,” “establishment of an industry chain,” “key raw materials and production equipment,” “protection of intellectual property,” and “preferential purchase price rates and various subsidies,” respectively.
Study of Evolution Model of China Education and Research Network
Authors: Mao Guoyong , Zhang Ning
Published: December 2013

By searching the hyperlinks with domain name “.edu.cn” which constitutes the China Education and Research Network, we build a complex directed network containing 366,422 web pages containing 540,755 URLs. These URLs constitute a complex directed network through self-organization. By analyzing the topology of China Education and Research Network, we found that it is different from the common Internet in several aspects. Most of the vertices have incoming links, a few vertices have outgoing links, and very few vertices have both incoming and outgoing links. The vertex distribution has a power-law tail. A large proportion of newly added edges always connect with those pages selected from one subnetwork that they belong to, instead of connecting with the pages selected from the whole network. According to these features, we presented the evolution model of this complex directed network. The results indicate that this model reflects some main characteristics of China Education and Research Network.
Androgen Receptor Gene CAG Repeat Polymorphism Regulates the Metabolic Effects of Testosterone Replacement Therapy in Male Postsurgical Hypogonadotropic Hypogonadism
Authors: Tirabassi Giacomo , delli Muti Nicola , Corona Giovanni , Maggi Mario , Balercia Giancarlo
Published: December 2013

Aim. To evaluate the independent role of androgen receptor (AR) gene CAG repeat polymorphism on metabolic effects of testosterone replacement therapy (TRT) in male postsurgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the TRT-related metabolic effects are combined with those deriving from concomitant administration of metabolically active pituitary-function replacement therapies.Methods. 15 men affected by postsurgical hypogonadotropic hypogonadism were evaluated before and after TRT. Cardiovascular risk factors (CVRFs), pituitary-dependent hormones, and AR gene CAG repeat polymorphism were considered.Results. Testosterone, insulin-like growth factor 1 (IGF-1), and estradiol were the only hormones, which varied significantly between the two phases. All CVRFs significantly improved after TRT. The number of CAG triplets was positively and significantly correlated with all the variations (Δ-) of CVRFs (except for a significant negative correlation with Δ-high-density lipoprotein); the opposite occurred between the latter and Δ-testosterone. No correlation between Δ-IGF-1 or estradiol and Δ-CVRFs was found. At multiple linear regression, after correction for Δ-testosterone, nearly all the associations between the number of CAG triplets and Δ-CVRFs were confirmed.Conclusions. In male postsurgical hypogonadotropic hypogonadism, shorter AR gene CAG tract length seems to yield greater metabolic improvement after TRT, independently of the effects of concomitant pituitary-function replacement therapies.
Design and Implementation of an Emergency Vehicle Signal Preemption System Based on Cooperative Vehicle-Infrastructure Technology
Authors: Wang Yinsong , Wu Zhizhou , Yang Xiaoguang , Huang Luoyi
Published: December 2013

Emergency vehicle is an important part of traffic flow. The efficiency, reliability, and safety of emergency vehicle operations dropped due to increasing traffic congestion. With the advancement of the wireless communication technologies and the development of the vehicle-to-vehicle (v2v) and vehicle-to-infrastructure (v2i) systems, called Cooperative Vehicle-Infrastructure System (CVIS), there is an opportunity to provide appropriate traffic signal preemption for emergency vehicle based on real-ime emergency vehicle data, traffic volume data, and traffic signal timings. This paper describes the design and implementation of an Emergency Vehicle Signal Preemption System (TJ-EVSP) in CVIS environment. The system function, system architecture, and operation strategies were presented. Then, the system was deployed and validated at two adjacent intersections in Taicang City, Jiangsu Province, China. Results show that the proposed system can improve the efficiency of emergency vehicle operations with less waste of traffic resources.
Chebyshev Wavelet Finite Difference Method: A New Approach for Solving Initial and Boundary Value Problems of Fractional Order
Authors: Kazemi Nasab A. , Kılıçman A. , Pashazadeh Atabakan Z. , Abbasbandy S.
Published: December 2013

A new method based on a hybrid of Chebyshev wavelets and finite difference methods is introduced for solving linear and nonlinear fractional differential equations. The useful properties of the Chebyshev wavelets and finite difference method are utilized to reduce the computation of the problem to a set of linear or nonlinear algebraic equations. This method can be considered as a nonuniform finite difference method. Some examples are given to verify and illustrate the efficiency and simplicity of the proposed method.
Analysis of DNS Cache Effects on Query Distribution
Authors: Wang Zheng
Published: December 2013

This paper studies the DNS cache effects that occur on query distribution at the CN top‐level domain (TLD) server. We first filter out the malformed DNS queries to purify the log data pollution according to six categories. A model for DNS resolution, more specifically DNS caching, is presented. We demonstrate the presence and magnitude of DNS cache effects and the cache sharing effects on the request distribution through analytic model and simulation. CN TLD log data results are provided and analyzed based on the cache model. The approximate TTL distribution for domain name is inferred quantificationally.
State of Charge Estimation Based on Microscopic Driving Parameters for Electric Vehicle's Battery
Authors: Yao Enjian , Wang Meiying , Song Yuanyuan , Yang Yang
Published: December 2013

Recently, battery-powered electric vehicle (EV) has received wide attention due to less pollution during use, low noise, and high energy efficiency and is highly expected to improve urban air quality and then mitigate energy and environmental pressure. However, the widespread use of EV is still hindered by limited battery capacity and relatively short cruising range. This paper aims to propose a state of charge (SOC) estimation method for EV’s battery necessary for route planning and dynamic route guidance, which can help EV drivers to search for the optimal energy-efficient routes and to reduce the risk of running out of electricity before arriving at the destination or charging station. Firstly, by analyzing the variation characteristics of power consumption rate with initial SOC and microscopic driving parameters (instantaneous speed and acceleration), a set of energy consumption rate models are established according to different operation modes. Then, the SOC estimation model is proposed based on the presented EV power consumption model. Finally, by comparing the estimated SOC with the measured SOC, the proposed SOC estimation method is proved to be highly accurate and effective, which can be well used in EV route planning and navigation systems.
Adaptive Two-Stage Extended Kalman Filter Theory in Application of Sensorless Control for Permanent Magnet Synchronous Motor
Authors: Yi Boyu , Kang Longyun , Tao Sinian , Zhao Xianxian , Jing Zhaoxia
Published: December 2013

Extended Kalman filters (EKF) have been widely used for sensorless field oriented control (FOC) in permanent magnet synchronous motor (PMSM). The first key problem associated with EKF is that the estimator requires all the plant dynamics and noise processes are exactly known. To compensate inaccurate model information and improve tracking ability, adaptive fading extended Kalman filtering algorithms have been proposed for the nonlinear system. The second key problem is that the EKF suffers from computational burden and numerical problems when state dimension is large. The two-stage extended Kalman filter (TSEKF) with respect to this problem has been extensively studied in the past. Combining the advantages of both AFEKF and TSEKF, this paper presents an adaptive two-stage extended Kalman filter (ATEKF) for closed-loop position and speed estimation of a PMSM to achieve sensorless operation. Experimental results demonstrate that the proposed ATEKF algorithm for PMSMs has strong robustness against model uncertainties and very good real-time state tracking ability.
Cancer Mortality among Asians and Pacific Islanders in New York City, 2001–2010
Authors: Huang Vivian , Li Wenhui , Tsai Josephine , Begier Elizabeth
Published: December 2013

Asians and Pacific Islanders’ (APIs) leading cause of death is cancer. We compared APIs’ age-adjusted cancer mortality rates to other racial/ethnic groups and by API subgroup (i.e., Chinese, Koreans, Asian Indians, and Filipinos) using New York City (NYC) Mortality data and Census Bureau population estimates for 2001–2010. While other racial/ethnic groups’ overall cancer mortality rates declined in NYC during the last decade, APIs remained stable. APIs overall had the lowest mortality rates for more common cancer types (i.e., lung, colorectal, breast, and prostate), but the highest mortality rates for certain less common cancers (i.e., nasopharyngeal, stomach, and liver). Chinese New Yorkers’ lung cancer death rates were very high compared to other APIs and comparable to non-Hispanic whites (47.1/100,000 versus 49.5/100,000, resp.). Chinese men had much higher nasopharyngeal cancer mortality rates (4.5/100,000 versus 0.3/100,000 for non-Hispanic whites). Korean men had the highest liver and stomach cancer mortality rates (25.3/100,000 and 27.7/100,000, resp., versus 7.9/100,000 and 6.0/100,000 for non-Hispanic whites). Analysis of cancer rates by API subgroup provides the detailed information needed to plan cancer prevention efforts. These findings warrant consideration of targeted cancer mortality prevention efforts for affected subgroups, including hepatitis vaccination, screening, and treatment; smoking cessation; and cancer screening.
Beckwith-Wiedemann Syndrome: Growth Pattern and Tumor Risk according to Molecular Mechanism, and Guidelines for Tumor Surveillance
Authors: Brioude F. , Lacoste A. , Netchine I. , Vazquez M.-P. , Auber F. , Audry G. , Gauthier-Villars M. , Brugieres L. , Gicquel C. , Le Bouc Y. , Rossignol S.
Published: December 2013

Background: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with an increased risk of pediatric tumors. The underlying molecular abnormalities may be genetic (CDKN1C mutations or 11p15 paternal uniparental isodisomy, pUPD) or epigenetic (imprinting center region 1, ICR1, gain of methylation, ICR1 GOM, or ICR2 loss of methylation, ICR2 LOM). Aim: We aimed to describe a cohort of 407 BWS patients with molecular defects of the 11p15 domain followed prospectively after molecular diagnosis. Results: Birth weight and length were significantly higher in patients with ICR1 GOM than in the other groups. ICR2 LOM and CDKN1C mutations were associated with a higher prevalence of exomphalos. Mean adult height (regardless of molecular subtype, n = 35) was 1.8 ± 1.2 SDS, with 18 patients having a final height above +2 SDS. The prevalence of tumors was 8.6% in the whole population; 28.6 and 17.3% of the patients with ICR1 GOM (all Wilms tumors) and 11p15 pUPD, respectively, developed a tumor during infancy. Conversely, the prevalence of tumors in patients with ICR2 LOM and CDKN1C mutations were 3.1 and 8.8%, respectively, with no Wilms tumors. Conclusion: Based on these results for a large cohort, we formulated guidelines for the follow-up of these patients according to the molecular subtype of BWS.
Obesity Does Not Influence Hepcidin and Hemojuvelin Levels in Hemodialysis Patients
Authors: Sarafidis Pantelis A. , Rumjon Adam , Ackland Daniel , MacLaughlin Helen L. , Bansal Sukhvinder S. , Brasse-Lagnel Carole , Macdougall Iain C.
Published: December 2013

Background/Aims: Clinical studies have shown increased levels of hepcidin causing functional iron deficiency in obese individuals. This study examined whether obesity contributes to increased hepcidin and hemojuvelin levels in adult hemodialysis patients. Methods: In a case-control design, 37 obese [body mass index (BMI) >30 kg/m2] stable hemodialysis patients and 37 patients with normal BMI (20-25 kg/m2), matched for age, gender and race, who fulfilled a strict set of inclusion and exclusion criteria were included in the study. Serum hepcidin and hemojuvelin, markers of iron status and inflammation, and routine hematological and biochemical variables were measured on samples obtained prior to the midweek hemodialysis session. Results: Obese and nonobese patients (BMI 35.1 ± 3.4 vs. 22.8 ± 1.4 kg/m2; p < 0.001) were similar with regard to basic comorbidities and use of erythropoietin and iron. Levels of hemoglobin, hypochromic red cells and reticulocytes were similar in the two groups. Serum iron and transferrin saturation levels were on the low side and not different between obese and lean individuals; total iron-binding capacity showed a trend towards higher levels in obese patients (48.4 ± 8.3 vs. 44.9 ± 7.4 μmol/l; p = 0.065). Levels of serum ferritin (651 ± 302 vs. 705 ± 327 μg/l; p = 0.46), hepcidin (118.3 ± 67.7 vs. 119.3 ± 78.0 ng/ml; p = 0.95) and hemojuvelin (1.90 ± 1.11 vs. 1.94 ± 1.24 mg/l; p = 0.90) were high but similar between the two groups. Serum hepcidin showed a significant correlation only with ferritin (r = 0.287, p = 0.013). Conclusions: Hepcidin and hemojuvelin levels are already considerably elevated in dialysis patients, but obesity does not have an additional impact. Further studies should examine whether increased weight contributes towards hepcidin elevation in predialysis individuals, in whom there is a lesser burden of systemic inflammation.
Measuring Life Space in Older Adults with Mild-to-Moderate Alzheimer's Disease Using Mobile Phone GPS
Authors: Tung James Yungjen , Rose Rhiannon Victoria , Gammada Emnet , Lam Isabel , Roy Eric Alexander , Black Sandra E. , Poupart Pascal
Published: December 2013

Background: As an indicator of physical and cognitive functioning in community-dwelling older adults, there is increasing interest in measuring life space, defined as the geographical area a person covers in daily life. Typically measured through questionnaires, life space can be challenging to assess in amnestic dementia associated with Alzheimer's disease (AD). While global positioning system (GPS) technology has been suggested as a potential solution, there remains a lack of data validating GPS-based methods to measure life space in cognitively impaired populations. Objective: The purpose of the study was to evaluate the construct validity of a GPS system to provide quantitative measurements of global movement for individuals with mild-to-moderate AD. Methods: Nineteen community-dwelling older adults with mild-to-moderate AD (Mini-Mental State Examination score 14-28, age 70.7 ± 2.2 years) and 33 controls (CTL; age 74.0 ± 1.2 years) wore a GPS-enabled mobile phone during the day for 3 days. Measures of geographical territory (area, perimeter, mean distance from home, and time away from home) were calculated from the GPS log. Following a log-transformation to produce symmetrical distributions, group differences were tested using two-sample t tests. Construct validity of the GPS measures was tested by examining the correlation between the GPS measures and indicators of physical function [steps/day, gait velocity, and Disability Assessment for Dementia (DAD)] and affective state (Apathy Evaluation Scale and Geriatric Depression Scale). Multivariate regression was performed to evaluate the relative strength of significantly correlated factors. Results: GPS-derived area (p < 0.01), perimeter (p < 0.01), and mean distance from home (p < 0.05) were smaller in the AD group compared to CTL. The correlation analysis found significant associations of the GPS measures area and perimeter with all measures of physical function (steps/day, DAD, and gait velocity; p < 0.01), symptoms of apathy (p < 0.01), and depression (p < 0.05). Multivariate regression analysis indicated that gait velocity and dependence were the strongest variables associated with GPS measures. Conclusion: This study demonstrated that GPS-derived area and perimeter: (1) distinguished mild-to-moderate AD patients from CTL and (2) were strongly correlated with physical function and affective state. These findings confirm the ability of GPS technology to assess life space behaviour and may be particularly valuable to continuously monitor functional decline associated with neurodegenerative disease, such as AD.
Homology versus Convergence in Resolving Transphyletic Correspondences of Brain Organization
Authors: Strausfeld Nicholas J. , Hirth Frank
Published: December 2013

Due to the largely absent fossil record, phylogenetic comparisons of brain structures rely on the analysis of nervous systems in extant taxa, many of which appear to have distinctive and dissimilar neural arrangements. The use of a multitude of comparative criteria, including developmental genetics, phylogenomics and neural circuit architecture, has recently resolved a highly conserved structural and functional ground pattern organization in the arthropod central complex and vertebrate basal ganglia. The minuteness of resemblance is exemplified by orthologous action selection circuits that are formed by homologous gene networks and which can lead to similar pathologies and behavioral disorders. It has been argued, however, that these similarities of brain centers can only be due to convergent evolution. What is still missing is a plausible scenario to explain how convergence could result in such a multitude of similarities and minuteness of resemblances, including gene expression, functional attributes and pathologies. In contrast, homology by common descent is the more parsimonious explanation. Moreover, the divergent elaboration of arthropod central complex and vertebrate basal ganglia does not obscure their shared ground pattern organization and thus genealogical correspondence.
Human-Derived Alternatives to Fetal Bovine Serum in Cell Culture
Authors: Witzeneder Karin , Lindenmair Andrea , Gabriel Christian , Höller Katharina , Theiß Denise , Redl Heinz , Hennerbichler Simone
Published: December 2013

SummaryObjective: The need for an alternative to fetal bovine serum (FBS) is known to scientists and users involved in cell therapy or advanced therapy medicinal products. Human serum (huS) and platelet lysate (hPL) can be used as alternatives resulting in similar or even superior results concerning cell expansion. Methods: We developed protocols for the production of huS and two types of hPL and tested them in the expansion of human fibroblasts and adipose tissue-derived stem cells (ASC). Quality control included cell counts (platelets, red and white blood cells), sterility testing, pH levels, total protein concentrations and growth factor levels. ASC and fibroblasts were expanded for three passages in media supplemented with FBS, huS or hPL and evaluated microscopically. Proliferation in terms of population doubling times (PDT) was determined. In case of ASC, differentiation was performed as well. Results: All three alternatives demonstrated shorter PDT for fibroblasts and ASC compared to FBS. Furthermore, ASC maintained their differentiation potential. Conclusion: We conclude that hPL and huS can be used as alternatives to FBS for the cultivation and expansion of cells intended for human use.
Acute Stroke Thrombolysis in End-Stage Renal Disease: A National Survey of Nephrologist Opinion
Authors: Power Albert , Fogarty Damian , Wheeler David C.
Published: December 2013

Background/Aims: Systemic thrombolysis for acute ischaemic stroke is the standard of care in the UK. In the absence of trial data on the safety and efficacy of this treatment in patients with end-stage renal disease, we captured the views of UK nephrologists to highlight health care policy and research objectives. Methods: Consultant nephrologists participated in an internet-based questionnaire. Respondents were asked about their involvement in thrombolysis decisions, safety concerns in dialysis patients, views on stroke rehabilitation and opinions on antiplatelet and warfarin use for stroke prevention. Results: 122/433 (28%) clinicians responded. 75% wanted involvement in thrombolysis decisions although just 10% gave input in practice. 64% expressed a high degree of concern (≥7/10) regarding intracranial bleeding risk in haemodialysis (HD). Overall risks of intra- and extracranial bleeding were rated lower in peritoneal dialysis (PD; p < 0.001). 85% felt the HD schedule impacted negatively on rehabilitation, whereas 63% felt this was the case in the context of PD (p = 0.001). More clinicians favoured warfarin for stroke prevention in PD patients with atrial fibrillation in comparison with HD patients (79 vs. 66%, p = 0.04). Conclusion: The majority of nephrologists want involvement in thrombolysis decisions relevant to their patients. Concerns about bleeding risks with thrombolysis are high and we identify a vital need to improve access to stroke rehabilitation in the UK, especially in HD patients.
Genetically Modified T Cells for the Treatment of Malignant Disease
Authors: Wieczorek Agnieszka , Uharek Lutz
Published: December 2013

SummaryThe broaden application of adoptive T-cell transfer has been constrained by the technical abilities to isolate and expand antigen-specific T cells potent to selectively kill tumor cells. With the recent progress in the design and manufacturing of cellular products, T cells used in the treatment of malignant diseases may be regarded as anticancer biopharmaceuticals. Genetical manipulation of T cells has given T cells desired specificity but also enable to tailor their activation and proliferation potential. Here, we summarize the recent developments in genetic engineering of T-cell-based biopharmaceuticals, covering criteria for their clinical application in regard to safety and efficacy.
Low-Dose Bevacizumab Is Effective in Radiation-Induced Necrosis
Authors: Alessandretti Matheus , Buzaid Antonio Carlos , Moreira Raphael , Alessandretti Erika
Published: December 2013

Background: Radiation-induced necrosis is a complication of brain irradiation. Treatment options are limited. Methods: The response to treatment with low-dose bevacizumab in 2 patients with radiation-induced necrosis was reported. Results: Both patients with metastatic melanoma, aged 48 and 51 years, had significant symptomatic and radiological improvement with low-dose bevacizumab treatment. Doses as low as 5 mg/kg every 6 weeks and 7.5 mg/kg i.v. every 4 weeks were used and were highly effective. Conclusions: Low-dose bevacizumab is a solid option in the management of edema associated with radiation necrosis.
Evaluation of patients’ attitudes towards stroke prevention and bleeding risk in atrial fibrillation
Authors: Regpala Steffi , Lacombe Shawn , Sharma Mukul , Gibbens Sabra , Ball David , Francis Kori , LaHaye Stephen
Published: December 2013

Patient’s values and preferences regarding the relative importance of preventing strokes and avoiding bleeding are now recognised to be of great importance in deciding on therapy for the prevention of stroke due to atrial fibrillation (SPAF). We used an iPad questionnaire to determine the minimal clinically important difference (Treatment Threshold) and the maximum number of major bleeding events that a patient would be willing to endure in order to prevent one stroke (Bleeding Ratio) for the initiation of antithrombotic therapy in 172 hospital in-patients with documented non-valvular atrial fibrillation in whom anticoagulant therapy was being considered. Patients expressed strong opinions regarding SPAF. We found that 12% of patients were “medication averse” and were not willing to consider antithrombotic therapy; even if it was 100% effective in preventing strokes. Of those patients who were willing to consider antithrombotic therapy, 42% were identified as “risk averse” and 15% were “risk tolerant”. Patients required at least a 0.8% (NNT=125) annual absolute risk reduction and 15% relative risk reduction in the risk of stroke in order to agree to initiate antithrombotic therapy, and patients were willing to endure 4.4 major bleeds in order to prevent one stroke. In conclusion, there was a substantial amount of inter-patient variability, and often extreme differences in opinion regarding tolerance of bleeding risk in the context of stroke prevention in atrial fibrillation. These findings highlight the importance of considering patient preferences when deciding on SPAF therapy.
Tissue factor/factor VIIa induces cell survival and gene transcription by transactivation of the insulin-like growth factor 1 receptor
Authors: Åberg Mikael , Eriksson Oskar , Mokhtari Dariush , Siegbahn Agneta
Published: December 2013

The insulin-like growth factor 1 receptor (IGF-1R) is known to promote survival and has also been implicated in the pathogenesis of several disease states, including cardiovascular disorders and cancer. Recently, we showed that binding of coagulation factor VIIa (FVIIa) to its receptor tissue factor (TF) protects cancer cells from TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Here we present evidence that this biological function of TF/FVIIa is dependent on the IGF-1R. IGF-1R inhibitors AG1024 and PPP as well as siRNA-mediated downregulation of IGF-1R, abolished the TF/FVIIa-mediated protection against TRAIL-induced apoptosis. Moreover, FVIIa rapidly induced a time- and concentration-dependent tyrosine phosphorylation of the IGF-1R in MDA-MB-231 breast cancer cells and in primary human monocytes, an event that was accompanied by IGF-1R chromatin binding and gene transcription. We hereby present novel evidence of a cross-talk between the coagulation and IGF-1R signalling systems, and propose that the IGF-1R is a key player in mediating TF/FVIIa-induced cell survival.
Fractalkine promotes platelet activation and vascular dysfunction in congestive heart failure
Authors: Hildemann Steven K. , Schulz Christian , Fraccarollo Daniela , Schöpp Corinna , Flierl Ulrike , Wissel Kerstin , Pelisek Jaroslav , Massberg Steffen , Bauersachs Johann , Schäfer Andreas
Published: December 2013

Endothelial dysfunction and enhanced platelet reactivity in congestive heart failure (CHF) contribute to poor prognosis. CHF patients display an impaired responsiveness to clopidogrel. Fractalkine activates platelets and elevated plasma levels of this chemokine are a feature of CHF. We here addressed the interrelation of fractalkine, platelet reactivity and clopidogrel efficacy in humans and rats with CHF. Fractalkine serum levels determined by ELISA were increased in CHF patients (CHF: 1548 ± 650 pg/ml; Control: 968 ± 575 pg/ml, p<0.01) and following CHF induction in rats (CHF: 1509 ± 753 pg/ ml; Sham: 1181 ± 275 pg/ml, p<0.05). Expression of fractalkine and its receptor CX3CR1 was enhanced in aortas of CHF rats as determined by immunofluorescence microscopy and molecular analysis. Fractalkine significantly aggravated endothelial dysfunction and augmented P-selectin expression on platelets from CHF rats. Platelet surface expression of CX3CR1 was increased in CHF rats, who displayed an impaired response to clopidogrel (platelet reactivity to ADP: CHF 30 ± 22%; Sham: 8 ± 5%, p<0.05). Similarly in humans with CHF, elevated fractalkine levels were accompanied by reduced clopidogrel responsiveness. Patients with high on-clopidogrel treatment platelet P2Y12 reactivity displayed higher fractalkine levels (1525 ± 487 pg/ml) than those with sufficient clopidogrel response (684 ± 315 pg/ml, p<0.01). In conclusion, in CHF fractalkine was increased on the endothelium and in blood serum, and platelet surface- expression of CX3CR1 was enhanced. Fractalkine diminished endothelial function beyond the impairment already observed in CHF and was associated with a reduced responsiveness to the platelet inhibitor clopidogrel. These findings may indicate a novel pathophysiological mechanism contributing to impaired clopidogrel responsiveness in CHF.
Thrombin-induced platelet-fibrin clot strength: Relation to high on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes
Authors: Jeong Young-Hoon , Bliden Kevin P. , Shuldiner Alan R. , Tantry Udaya S. , Gurbel Paul A.
Published: December 2013

The relationship between thrombin-induced platelet-fibrin clot strength (MATHROMBIN), genotype and high on-treatment platelet reactivity (HPR) is unknown. The aim of this study is to assess the influence of MATHROMBIN measured by thrombelastography on HPR and long-term major adverse cardiovascular events (MACE) in percutaneous coronary intervention (PCI)-treated patients during aspirin and clopidogrel therapy. MATHROMBIN, platelet aggregation, genotype, and two-year MACE were assessed in 197 PCI-treated patients. HPR was defined as 5 µM ADP-induced PR46% measured by conventional aggregometry. Both high MATHROMBIN ( 68 mm) and CYP2C19*2 allele carriage were independently associated with ADP-induced platelet aggregation ([uni03B2] coefficient: 8.3% and 12.0%, respectively). The combination of CYP2C19*2 allele carriage and high MATHROMBIN increased the predictive value for the risk of HPR (odds ratio: 13.89; 95% confidence interval: 3.41 to 55.56; p < 0.001). MACE occurred in 25 patients (12.7%). HPR and high MATHROMBIN were both associated with MACE (hazard ratio: 3.09 and 2.24, respectively), and patients with both HPR and high MATHROMBIN showed an increased risk for MACE (adjusted hazard ratio: 5.56; 95% confidence interval: 1.85 to 16.67; p = 0.002). In conclusion, this is the first study to demonstrate that high platelet-fibrin clot strength is an independent determinant of HPR in PCI-treated patients. Combining the measurements of platelet aggregation and platelet-fibrin clot strength may enhance post-PCI risk stratification and deserves further study.
Factor XIIa inhibition by Infestin-4: in vitro mode of action and in vivo antithrombotic benefit
Authors: Xu Yiming , Cai Tian-Quan , Castriota Gino , Zhou Yuchen , Hoos Lizbeth , Jochnowitz Nina , Loewrigkeit Christopher , Cook John A. , Wickham Alexandra , Metzger Joseph M. , Ogletree Martin L. , Seiffert Dietmar A. , Chen Zhu
Published: December 2013

Coagulation factor XII (FXII) plays a central role in initiating the intrinsic cascade of blood coagulation. Purified recombinant Human Albumin- tagged Infestin-4 (rHA-Infestin-4) is a recently described FXIIa inhibitor that displayed strong anticoagulant activity without compromising haemostasis in several animal models. We pursued detailed in vitro characterisation of rHA-Infestin-4 and demonstrated that it is a competitive inhibitor of FXIIa with slow on and off rate constants for binding (kon
=5x105 M-1s-1, koff
=6x10–4 s-1), it can block FXIIa activation of its physiological substrates (plasma prekallikrein and FXI), and it can inhibit ellagic acid-triggered thrombin generation in plasma. Potency and selectivity profiling in enzyme assays suggest that rHAInfestin- 4 is indeed highly potent on FXIIa (IC50=0.3 ± 0.06, 1.5 ± 0.06, 1.2 ± 0.09 nM, for human, rat, and rabbit FXIIa, respectively) with at least >100-fold selectivity against factors IIa, Xa, IXa, XIa, VIIa, and plasma kallikrein in all three species. rHA-Infestin-4 dose-dependently and markedly reduced clot weight in the arteriovenous shunt thrombosis model in rats and rabbits, accompanied with minimal increase in cuticle bleeding times in either species. rHA-Infestin-4 treatment at 5 mg/kg in rabbit resulted in a 13% reduction in ex vivo FXa activity, demonstrating a modest off-target effect. In summary, our findings confirmed and extended previous reports that inhibition of FXIIa by rHA-Infestin-4 can produce strong antithrombotic efficacy while preserving haemostasis. Our comprehensive selectivity profiling, mode of action, and kinetic studies of rHA-Infestin-4 reveal limitations of this molecule and offer new perspectives on any potential effort of discovering novel FXIIa inhibitors.
Estructuras focalizadoras em español y portugués
Authors: Sedano Mercedes
Published: December 2013

El presente trabajo, que se basa em la metodología y resultados de Sedano (1994), está destinado a analizar la variación en las cláusulas seudohendidas (SH) y las clásulas com verbo ser focalizador (SF) encontradas en obras literarias del español y del portugués con el fin de observar el comportamiento de las mencionadas estructuras en ambas lenguas. Los resultados indican que, mientras en el español escrito sólo aparecen cláusulas SH, en el portugués escrito se registran tanto SH como SF; el análisis de esta lengua indica que las SH se emplean mayoritariamente para focalizar frases nominales en tanto que las SF se usan sobre todo para focalizar preposicionales. El que los resultados del portugués coincidan com los obtenidos por Sedano (1994) en un corpus del español hablado de Caracas confirma la existencia de razones comunicativo-funcionales que condicionan la selección de cada estructura dependiendo de la categoría gramatical que se desea focalizar.
From Rhetoric to Reality: A Pragmatic Analysis of the Integration of Women into UN Peacekeeping Operations
Authors: Bleckner Julia
Published: December 2013

This paper aims to provide a critical analysis of the integration of women into United Nations (UN) peacekeeping – particularly in the form of all-female units – as a means of deterring sexual exploitation and abuse (SEA) in conflict environments. Results from this study indicate that compared to both male peacekeepers and female peacekeepers from co-ed units, women from all-female units have a greater awareness of gender issues and SEA in a UN mission, sense of responsibility to address such issues, and experience doing so during deployment. The distinct gap in these measures between women from all-female units and co-ed units challenges the widespread assumption that women will inherently address SEA in a UN mission. Analyzing the variables that may contribute to the success of the all-female unit, the article concludes that these same factors may be applied to a wider distribution of women throughout peacekeeping operations. Recommendations presented in the article must be implemented as a component of a broad, long-term gender mainstreaming strategy to address the interrelated nature of gender inequality and sexual violence in conflict. Results of the study are analyzed with a focus on the role of UN peacekeeping in mitigating SEA in the Democratic Republic of Congo (DRC).
Knufia aspidiotus sp. nov., a new black yeast from scale insects
Authors: He Fan , Lin Bin , Sun Jingzu , Liu Xingzhong
Published: December 2013

Three ascomycetes, isolated from the body cavity of the scale insect, Aspidiotus sp., collected in Song Mountain, Yanqing, Beijing, China, were identified to be a new species of Knufia. Knufia aspidiotus sp. nov. is introduced in this paper. The species is characterized by slow-growing, dematiaceous and blastic, endogenous conidia in undifferentiated hyphae, as well as darkly pigmented, enlarged multicellular bodies, and is similar to other Knufia species in morphology. Phylogenetic analyses, based on the small ribosomal subunit (SSU) gene and internal transcribed spacer (ITS) region, indicated that Knufia aspidiotus was related to, but clearly distant from other sequenced species in Knufia.
Investigating Hector Convective Development and Microphysical Structure Using High-Resolution Model Simulations, Ground-Based Radar Data, and TRMM Satellite Data
Authors: Gentile Sabrina , Ferretti Rossella , Marzano Frank Silvio
Published: December 2013

One event of a tropical thunderstorm typically observed in northern Australia, known as Hector, is investigated using high-resolution model output from the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) observations from a ground-based weather radar located in Berrimah (Australia) and data from the Tropical Rainfall Measuring Mission (TRMM) satellite. The analysis is carried out by tracking the full life cycle of Hector from prestorm stage to the decaying stage. In both the prestorm stage, characterized by nonprecipitating cells, and the triggering stage, when the Hector storm is effectively initiated, an analysis is performed with the aid of high-spatial-and-temporal-resolution MM5 output and the Berrimah ground-based radar imagery. During the mature (“old”) stage of Hector, considering the conceptual model for tropical convection suggested by R. Houze, TRMM Microwave Imager satellite-based data were added to ground-based radar data to analyze the storm vertical structure (dynamics, thermodynamics, and hydrometeor contents). Model evaluation with respect to observations (radar reflectivity and TRMM data) suggests that MM5 performed fairly well in reproducing the dynamics of Hector, providing support to the assertion that the strength of convection, in terms of vertical velocity, largely contributes to the vertical distribution of hydrometeors. Moreover, the stages of the storm and its vertical structure display good agreement with Houze’s aforementioned conceptual model. Finally, it was found that the most important triggering mechanisms for this Hector event are topography, the sea breeze, and a gust front produced by previous convection.
An Intensity Index for the East Asian Winter Monsoon
Authors: Wang Lin , Chen Wen
Published: December 2013

The thermal contrast between the Asian continent and the adjacent oceans is the primary aspect of the East Asian winter monsoon (EAWM) that can be well represented in the sea level pressure (SLP) field. Based on this consideration, a new SLP-based index measuring the intensity of the EAWM is proposed by explicitly taking into account both the east–west and the north–south pressure gradients around East Asia. The new index can delineate the EAWM-related circulation anomalies well, including the deepened (shallow) midtropospheric East Asian trough, sharpened and accelerated (widened and decelerated) upper-tropospheric East Asian jet stream, and enhanced (weakened) lower-tropospheric northerly winds in strong (weak) EAWM winters. Compared with previous indices, the new index has a very good performance describing the winter-mean surface air temperature variations over East Asia, especially for the extreme warm or cold winters. The index is strongly correlated with several atmospheric teleconnections including the Arctic Oscillation, the Eurasian pattern, and the North Pacific Oscillation/western Pacific pattern, implying the possible internal dynamics of the EAWM variability. Meanwhile, the index is significantly linked to El Niño–Southern Oscillation (ENSO) and the sea surface temperature (SST) over the tropical Indian Ocean. Moreover, the SST anomalies over the tropical Indian Ocean are more closely related to the index than ENSO as an independent predictor. This adds further knowledge to the prediction potentials of the EAWM apart from ENSO. The predictability of the index is high in the hindcasts of the Centre National de Recherches Météorologiques (CNRM) model from Development of a European Multimodel Ensemble System for Seasonal-to-Interannual Prediction (DEMETER). Hence, it would be a good choice to use this index for the monitoring, prediction, and research of the EAWM.
Coconut fiber reinforced chemically functionalized high-density polyethylene (CNF/CF-HDPE) composites by Palsule process
Authors: Singh Anshu Anjali , Palsule Sanjay
Published: December 2013

Coconut fiber reinforced chemically functionalized high-density polyethylene (CF-HDPE) composites (CNF/CF-HDPE) with in situ fiber/matrix interfacial adhesion have been processed by Palsule process. Chemically functionalized maleic anhydride grafted polyethylene without compatibilizers has been used as matrix (in place of polyethylene with compatibilizer), and no fiber treatment has been performed. In situ fiber/matrix interfacial adhesion has been established by field emission scanning electron microscope and Fourier transform infra red spectroscopy. Mechanical properties of the CNF/CF-HDPE composites have been found to be higher than those of the CF-HDPE matrix and increase with increasing amounts of fibers in composites. Measured tensile modulus of CNF/CF-HDPE composites compares well with values predicted by Rule of Mixtures, Hrisch Model, Halpin-Tsai equations, Nielsen equation and Palsule equation.