bluuebunny/crossref_metadata_2025 huggingface dataset:
Hurricane Sea Surface Inflow Angle and an Observation-Based Parametric Model
Authors: Zhang Jun A. , Uhlhorn Eric W.
Published: May 2012

This study presents an analysis of near-surface (10 m) inflow angles using wind vector data from over 1600 quality-controlled global positioning system dropwindsondes deployed by aircraft on 187 flights into 18 hurricanes. The mean inflow angle in hurricanes is found to be −22.6° ± 2.2° (95% confidence). Composite analysis results indicate little dependence of storm-relative axisymmetric inflow angle on local surface wind speed, and a weak but statistically significant dependence on the radial distance from the storm center. A small, but statistically significant dependence of the axisymmetric inflow angle on storm intensity is also found, especially well outside the eyewall. By compositing observations according to radial and azimuthal location relative to storm motion direction, significant inflow angle asymmetries are found to depend on storm motion speed, although a large amount of unexplained variability remains. Generally, the largest storm-relative inflow angles (<−50°) are found in the fastest-moving storms (>8 m s−1) at large radii (>8 times the radius of maximum wind) in the right-front storm quadrant, while the smallest inflow angles (>−10°) are found in the fastest-moving storms in the left-rear quadrant. Based on these observations, a parametric model of low-wavenumber inflow angle variability as a function of radius, azimuth, storm intensity, and motion speed is developed. This model can be applied for purposes of ocean surface remote sensing studies when wind direction is either unknown or ambiguous, for forcing storm surge, surface wave, and ocean circulation models that require a parametric surface wind vector field, and evaluating surface wind field structure in numerical models of tropical cyclones.
A Case Study of High-Impact Wet Snowfall in Northwest Germany (25–27 November 2005): Observations, Dynamics, and Forecast Performance
Authors: Frick Claudia , Wernli Heini
Published: May 2012

Accurate numerical weather prediction of intense snowfall events requires the correct representation of dynamical and physical processes on various scales. In this study, a specific event of high-impact wet snowfall is examined that occurred in the northwestern part of Germany in November 2005. First, the synoptic evolution is presented, together with observations of precipitation type and vertical temperature profiles, which reveal the existence of a so-called potential melting layer during the early period of wet snowfall. During the main part, the performance of the operational forecasts from the European Centre for Medium-Range Weather Forecasts (ECMWF) is investigated. It is shown that only the short-term predictions captured the snowfall event, whereas earlier forecasts were in error concerning the phase and/or amount of precipitation. However, even the short-term forecasts produced the onset of surface snowfall too late (i.e., during the dry snowfall period). Reasons for the misforecasts are errors on various scales. For the early forecasts, they include an inaccurate representation of the upper-level trough and a misplacement of the surface cyclone. For the later forecasts, a slight overestimation of the depth of the potential melting layer and a potentially too fast snow melting process in the model lead to the erroneous prediction of surface rainfall during the wet snowfall period. Hindcast experiments with the high-resolution Consortium for Small-Scale Modeling (COSMO) model also point to the necessity of improving its snow melting parameterization in order to provide useful predictions of potentially high-impact wet snowfall events.
About the Reliability of Manual Model PV Corrections to Improve Forecasts
Authors: Arbogast Philippe , Maynard Karine , Piriou Catherine
Published: May 2012

The National Weather Forecast Centre of Météo-France has developed a tool that corrects the state of the atmosphere within the Action de Recherche Petite Echelle Grande Echelle (ARPEGE) operational global model by adjusting the potential vorticity when the initial conditions and available observations disagree. Among observational datasets, geostationary satellite data are the primary source of information. Here, the representation of the coherent structures of the tropopause in the model is assessed with Meteosat ozone and water vapor images. Modifications to the initial conditions of the potential vorticity (PV) in areas where the model fails can be applied using a potential vorticity inversion, thus providing a new balanced distribution of the wind and temperature that will then be used as a new initial state. The purpose of the paper is to investigate the degrees of weakness of the present qualitative approach. To this end, PV modifications to the initial conditions are applied by different experts on the eve of the windstorm Klaus (24 January 2009) that hit southwestern France. The different initial PV fields and the subsequent forecasts show significant differences in terms of wind and mean sea level pressure, while sharing some common features. The human modification process is therefore partially reproducible and skillful since the forecast is improved most of the time.
An Objective High-Resolution Hail Climatology of the Contiguous United States
Authors: Cintineo John L. , Smith Travis M. , Lakshmanan Valliappa , Brooks Harold E. , Ortega Kiel L.
Published: May 2012

The threat of damaging hail from severe thunderstorms affects many communities and industries on a yearly basis, with annual economic losses in excess of $1 billion (U.S. dollars). Past hail climatology has typically relied on the National Oceanic and Atmospheric Administration/National Climatic Data Center’s (NOAA/NCDC) Storm Data publication, which has numerous reporting biases and nonmeteorological artifacts. This research seeks to quantify the spatial and temporal characteristics of contiguous United States (CONUS) hail fall, derived from multiradar multisensor (MRMS) algorithms for several years during the Next-Generation Weather Radar (NEXRAD) era, leveraging the Multiyear Reanalysis of Remotely Sensed Storms (MYRORSS) dataset at NOAA’s National Severe Storms Laboratory (NSSL). The primary MRMS product used in this study is the maximum expected size of hail (MESH). The preliminary climatology includes 42 months of quality controlled and reprocessed MESH grids, which spans the warm seasons for four years (2007–10), covering 98% of all Storm Data hail reports during that time. The dataset has 0.01° latitude × 0.01° longitude × 31 vertical levels spatial resolution, and 5-min temporal resolution. Radar-based and reports-based methods of hail climatology are compared. MRMS MESH demonstrates superior coverage and resolution over Storm Data hail reports, and is largely unbiased. The results reveal a broad maximum of annual hail fall in the Great Plains and a diminished secondary maximum in the Southeast United States. Potential explanations for the differences in the two methods of hail climatology are also discussed.
Fatigue resistance of basalt fibers-reinforced laminates
Authors: Dorigato A , Pegoretti A
Published: May 2012

Fabrics of basalt (BFs), E-glass (GFs), and carbon (CFs) fibers with the same areal density were used to prepare epoxy-based laminates. The BF laminates presented elastic moduli and strength values higher than those of the corresponding GF laminates, with tensile strength values near to that of CF laminates. Investigation of the behavior under fatigue conditions indicated superior performances of BF laminates with respect to the corresponding GF composites, with an improved capability of sustaining progressive damaging and slightly higher damping properties. As far as the fatigue behavior is concerned, BFs may therefore represent a valid substitute of GFs in structural composites.
A model for estimating nonlinear deformation and damage in ceramic matrix composites
Authors: Santhosh Unni , Ahmad Jalees
Published: May 2012

The present paper addresses the estimation of global deformation of a continuous-fiber brittle matrix composite over a length much larger than the largest microstructural dimension of the composite, such as the fiber diameter and the fiber spacing. Initial microcracks and progressive microcracking of the matrix and interfaces under time-dependent load and temperature are considered. The model also includes consideration of inelastic deformation of one of the constituents. In this paper, the equations of the model are developed and applied to model the stress–strain behavior of several silicon carbide/silicon carbide ceramic matrix composites and the creep behavior of an oxide/oxide ceramic matrix composite. Comparison with test data shows that the model is able to capture the wide range of deformation behavior seen in these ceramic matrix composites.
Dispute Settlement Mechanisms in Preferential Trade Agreements
Authors: Jo Hyeran , Namgung Hyun
Published: May 2012

Preferential trade agreements (PTAs) have increased dramatically in the past several decades and play an important role in the global economy. Dispute settlement mechanisms (DSMs) in these international agreements significantly influence their functioning. In this article, the authors seek to understand what factors determine the legal arrangements of these mechanisms. The authors argue that the confluence of domestic political regime type, emulation incentives, and the development of the multilateral trade regime determines their legal dimension. Using a data set of PTAs between 1957 and 2008, the authors show that (1) democracies are more likely than autocracies to prefer moderately strict DSMs, (2) trading partners increasingly emulate each other by adopting similar legal templates, and (3) the recent trend against legalistic mechanisms is largely driven by the development of the multilateral trade regime. Their findings have important implications for the design of international institutions by highlighting the importance of member-specific as well as macro-level factors.
Most relevant parameters of woven fabric structure controlling atmospheric air-plasma treatments
Authors: Jelil Radhia Abd , Zeng Xianyi , Koehl Ludovic , Perwuelz Anne
Published: May 2012

In this work, different woven fabrics with varying raw materials, fiber types and weave constructions were used for studying plasma treatment under different atmospheric conditions. Surface modification was characterized using wetting and capillarity surface analysis methods. Moreover, a fuzzy sensitivity variation criterion was used to select the most relevant parameters for woven fabrics from experimental data measured on the fabrics and during the plasma process. In fact, the results obtained using this learning data-based fuzzy sensitivity variation criterion could effectively validate those obtained from the physical and chemical knowledge on plasma treatment. According to the results, air permeability, fiber count, weave construction and summit density were identified as the most relevant parameters, in addition to electrical power, treatment speed and fiber nature. This finding indicated that these parameters had an influence on the plasma treatment results.
Education For Democracy by Young People in Community-Based Organizations
Authors: Checkoway Barry
Published: May 2012

At a time when many young Americans have reduced their civic engagement, and public schools have de-emphasized their civic mission, some youth are taking initiative at the community level, and some community-based organizations are establishing educational programs to promote their participation. These programs originate in economically disinvested and racially segregated areas whose young people require and receive “education for democracy” appropriate for their situation. This article provides perspectives on these programs, including their social purpose, curricular content, pedagogical methods, and implications for a new civics that contrasts with traditionalapproaches. It draws on analysis of educational efforts by organizations affiliated with a national project designed to increase youth participation in the South Bronx, Mississippi Delta, Albuquerque, East Oakland, and other areas.
School Variables as Mediators of Personal and Family Factors on School Violence in Taiwanese Junior High Schools
Authors: Chen Ji-Kang , Astor Ron Avi
Published: May 2012

Using a nationally representative sample of 3,058 junior high school students in Taiwan, this study examines a model of how personal traits, family factors, and school dynamics influence school violence committed by students against students and teachers. This model proposed that school violence is directly influenced by personal traits, victimization, and parental monitoring as well as indirectly influenced by personal traits, victimization, and parental monitoring mediated through school engagement, risky peers, and student–teacher relationship. Structural equation modeling was used to examine the theoretical model. The model showed a good fit for the sample as a whole. Similar findings were also found between male and female students. Overall findings suggested that negative personal traits, victimization, and parental monitoring have direct influence on school violence as well as indirect influence mediated through school variables. Implications for theory, policy and practice, and recommendation for future research are discussed.
Dialectics, Complexity,and the Systemic Approach
Authors: Wan Poe Yu-ze
Published: May 2012

This article attempts to assess Mario Bunge’s important but widely neglected criticisms of dialectics. It begins by providing a contextualized interpretation of Friedrich Engels’s metaphysics of the dialectics of nature before embarking on a detailed discussion of Leon Trotsky’s and contemporary “dialectical” scientists’ views on materialist dialectics. It argues that while some of Bunge’s criticisms are eminently sensible, the principles underlying the works of dialectical scientists are compatible with Bunge’s emergentist and systemic approach and can shed light on such issues as the levels of organization, the diachronic and synchronic aspects of emergence, and the individualism-holism-systemism trilemma. This article also submits that dialectics is best interpreted as a guideline for a philosophy of change instead of a magical wand that liberates the investigator from study of facts. Understood as something that serves heuristic purposes, dialectics can be sensibly utilized by scientists to shore up or refine their methodological principles and thereby to facilitate empirical research.
The Freeman-Mead Controversy Revisited
Authors: Jarvie Ian
Published: May 2012

Shankman holds that Derek Freeman “trashed” Margaret Mead’s reputation as a public intellectual by portraying her as a naïve and gullible anthropologist who perpetrated a serious error about adolescence in American Samoa. Shankman concedes that Mead’s Coming of Age in Samoa was factually in error but argues that her reputation in anthropology did not rest on it but rather on her extensive works on other societies. Ostensibly about Samoa, her book was rather a critique of American society and should be judged as such. It is unjust that its factual errors undermine her status as a public intellectual. Fieldwork method and the lingering influence of inductivism are shown to underlie the controversy.
Universal Credit: Will it work?
Authors: Lakhani Beth
Published: May 2012

The objectives of current UK policy for welfare reform are in conflict: on the one hand, the Government’s determination to drive down the deficit with major cuts to public expenditure; and on the other, the introduction of a new system of welfare intended to protect claimants from poverty, provide clear work incentives and make work pay. The programme of across the board cuts to public services nevertheless shows the axe falling disproportionately on social welfare provision and Universal Credit is not exempt. Against this background and with high unemployment Universal Credit is destined not to work.
A Study of Thrombophilia Testing and Counseling Practices of Family Physicians Using the Script Concordance Method in Calgary, Canada
Authors: Schneider-MacRae N. , Jackson S. C. , Valentine K. A. , Lockyer J. , Poon M-C.
Published: May 2012

Background: Thrombophilia testing helps to identify populations at risk of venous thromboembolism, but motivations for testing individuals are frequently unclear. Objectives: Our goals were to assess the motivations for thrombophilia testing among family physicians (FPs) to determine whether testing was congruent with expert opinion, and to study counseling practices. Methods: The FPs and experts completed a survey involving hypothetical thrombophilia patients. Responses between groups were compared using the script concordance method. Results: The FPs referred 35.9% of cases. Of the five scenarios, two resulted in disagreement regarding appropriateness of testing ( P ≤ .037). The FPs were more likely to test male, obese, or pediatric patients, patients with a family history of myocardial infarction or infertility, and patients with a recent event ( P ≤ .043). The FPs were more likely to counsel patients after testing ( P ≤ .016). Conclusion: Disagreement exists between physician groups about the utility of thrombophilia testing. Self-reported lack of pretest counseling among FPs warrants further study.
Code-switching to first language in repair – A resource for students’ problem solving in a foreign language classroom
Authors: Lehti-Eklund Hanna
Published: May 2012

In foreign language classrooms, students and teachers together create practices for language use; they talk the institutional context and institutional identities into being. According to Lave and Wenger, learning can be seen as a deepening process of participation in a community of practice. Learning a language in a classroom can be regarded as gradual changes in language use that are accomplished through participation in collaborative work. In that case, the study of variation in language alternation, code-switching and the activities the students and the teachers are engaged in can contribute to understand language learning in a foreign language classroom context. The purpose of this article is to describe and analyse how code-switching as a local practice is used in teaching and learning Swedish as a foreign language. The context of the study is classes in Swedish as a foreign language in upper secondary schools in Finland. The material consists of video recordings of one lesson in second grade where the students have been studying Swedish for 5 years. The article focuses especially on the practices of language choice in repair. Students tend to keep up a division of labour between FL used for institutional work and L1 as the language reserved for interaction. The article discusses the conditions of learning repair practices in an FL classroom.
Why Semantic Differentials in Web-Based Research Should Be Made from Visual Analogue Scales and Not from 5-Point Scales
Authors: Funke Frederik , Reips Ulf-Dietrich
Published: May 2012

In a web experiment, participants were randomly assigned to two semantic differentials either made from discrete 5-point ordinal rating scales or from continuous visual analogue scales (VASs) with 250 gradations. Respondents adjusted their ratings with VASs more often to maximize the precision of answers, which had a beneficial effect on data quality. No side effects like differences in means, higher dropout, more nonresponse, or higher response times were observed. Overall, the combination of semantic differentials and VASs results in a number of advantages. Potential for further research is discussed.
Reduction of Skin Closure Time Without Loss of Healing Quality
Authors: Duteille Franck , Rouif Michel , Alfandari Bruno , Andreoletti Jean-Baptiste , Sinna Raphael , Laurent Bruno , Perrot Pierre
Published: May 2012

The authors report the results of a multicenter prospective study evaluating a novel technology: dermal suture using absorbable staples composed of polylactic and polyglycolic acids. From January to June 2009, 59 dermal sutures were performed with Insorb absorbable staples and 41 with absorbable thread. All patients in the study underwent abdominal dermolipectomy (N = 65) or surgery for breast hypertrophy (N = 35). The purpose of the study was to compare the closure time and healing quality obtained with the 2 methods. Ninety-five patients were reexamined by the surgeon after 1 year of follow-up to assess scar width, suppleness, inflammation, and hypertrophy. The overall results were good and quite similar for the 2 groups. Thus, the use of Insorb staples reduced closure time while ensuring good healing quality.
The Use of Multimedia Consent Programs for Surgical Procedures
Authors: Nehme Jean , El-Khani Ussamah , Chow Andre , Hakky Sherif , Ahmed Ahmed R. , Purkayastha Sanjay
Published: May 2012

Objective. To compare multimedia and standard consent, in respect to patient comprehension, anxiety, and satisfaction, for various surgical/interventional procedures. Data sources. Electronic searches of PubMed, MEDLINE, Ovid, Embase, and Google Scholar were performed. Relevant articles were assessed by 2 independent reviewers. Study selection. Comparative (randomized and nonrandomized control trials) studies of multimedia and standard consent for a variety of surgical/interventional procedures were included. Studies had to report on at least one of the outcome measures. Data extraction. Studies were reviewed by 2 independent investigators. The first investigator extracted all relevant data, and consensus of each extraction was performed by a second investigator to verify the data. Conclusion. Overall, this review suggests that the use of multimedia as an adjunct to conventional consent appears to improve patient comprehension. Multimedia leads to high patient satisfaction in terms of feasibility, ease of use, and availability of information. There is no conclusive evidence demonstrating a significant reduction in preoperative anxiety.
Wholesome Foods and Wholesome Morals?
Authors: Eskine Kendall J.
Published: May 2012

Recent research has revealed that specific tastes can influence moral processing, with sweet tastes inducing prosocial behavior and disgusting tastes harshening moral judgments. Do similar effects apply to different food types (comfort foods, organic foods, etc.)? Although organic foods are often marketed with moral terms (e.g., Honest Tea, Purity Life, and Smart Balance), no research to date has investigated the extent to which exposure to organic foods influences moral judgments or behavior. After viewing a few organic foods, comfort foods, or control foods, participants who were exposed to organic foods volunteered significantly less time to help a needy stranger, and they judged moral transgressions significantly harsher than those who viewed nonorganic foods. These results suggest that exposure to organic foods may lead people to affirm their moral identities, which attenuates their desire to be altruistic.
Incidence of health insurance claims for thyroid neoplasm and pancreatic malignancy in association with exenatide: signal refinement using active safety surveillance
Authors: Dore David D. , Seeger John D. , Chan K. Arnold
Published: May 2012

Objectives:

As part of a regulatory postmarketing commitment, we assessed the risk of claims for thyroid and pancreatic cancer among users of exenatide using an active drug safety surveillance system.

Methods:

This active surveillance assessment used cohort methodology and commercial health insurance claims data to identify initiators of exenatide and propensity score-matched initiators of metformin or glyburide between June 2005 and September 2009, with up to 1 year of follow up through December 2009. The primary analysis estimated absolute and relative risk (RR) of inpatient or outpatient claims with diagnosis codes for thyroid neoplasm (benign or malignant) or pancreatic malignancies after exclusion of patients with a history of the same diagnosis at baseline.

Results:

Among the matched comparison cohorts ( N ≈ 32,800 each), there were 37 claims-suggested thyroid malignancies among exenatide initiators and 26 among metformin or glyburide initiators [RR 1.4; 95% confidence interval (CI) 0.8−2.4]. This association was attenuated when limited to inpatient thyroid cancer claims (RR 0.9; CI 0.3–2.6). Exenatide use was not associated with an increased risk of benign thyroid neoplasm (RR 0.7; CI 0.3−1.7), or pancreatic cancer (RR 0.8; CI 0.5−1.6).

Conclusions:

Use of exenatide was associated with a modestly higher incidence of inpatient and outpatient claims, but not inpatient claims for thyroid malignancies. Exenatide was not associated with higher risk of benign thyroid neoplasm or pancreatic cancer. Misclassification of outcomes and exposure, and residual confounding remain limitations of this analysis to be considered when interpreting the results. We have initiated a formal epidemiologic investigation to explore these relationships.
Predictors of Success of a Lifestyle Intervention in Relation to Weight Loss and Improvement in Glucose Tolerance Among Individuals at High Risk for Type 2 Diabetes
Authors: Rautio Nina , Jokelainen Jari , Saaristo Timo , Oksa Heikki , Keinänen-Kiukaanniemi Sirkka ,   the FIN-D2D Writing Group
Published: May 2012

Aim: The authors assessed the predictors of success of a lifestyle intervention (weight loss ≥ 5% and improved glucose tolerance) in individuals at high risk for type 2 diabetes in a 1-year follow-up in a primary health care setting. Methods: High-risk individuals for type 2 diabetes were identified by opportunistic screening in the implementation of the Finnish National Diabetes Prevention Program (FIN-D2D). All together, 3880 individuals participated in the 1-year follow-up. Sociodemographic characteristics, health status and behavior, family history of diabetes, clinical factors, and health care provider were considered possible predictors of lifestyle intervention success. Results: In sum, 19.3% of individuals lost at least 5% of weight, and 32.6% with abnormal glucose tolerance at baseline showed improvement in glucose tolerance. Abnormal glucose tolerance was the strongest predictor of weight loss and improvement in glucose tolerance. High attendance at lifestyle intervention visits, being outside of labor force, and high body mass index at baseline were also related to weight loss, and high education was related to improvement in glucose tolerance. Conclusions: In “real-life settings,” glucose tolerance status, number of intervention visits, employment status, education, and body mass index explained the success of lifestyle intervention. These factors may help in targeting interventions, although they may not be generalized to other cultural settings.
Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study
Authors: Taher Ali T. , Porter John , Viprakasit Vip , Kattamis Antonis , Chuncharunee Suporn , Sutcharitchan Pranee , Siritanaratkul Noppadol , Galanello Renzo , Karakas Zeynep , Lawniczek Tomasz , Ros Jacqueline , Zhang Yiyun , Habr Dany , Cappellini Maria Domenica
Published: May 2012

Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, −2.33 ± 0.7 mg Fe/g dry weight [dw], P = .001, and −4.18 ± 0.69 mg Fe/g dw, P < .001) for the 5 and 10 mg/kg/d deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM −235 and −337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P < .001). In the placebo patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and 115 ng/mL (LSM), respectively. The most common drug-related adverse events were nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is the first randomized study showing that iron chelation with deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo.
Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition
Authors: Gorges Tobias M , Tinhofer Ingeborg , Drosch Michael , Röse Lars , Zollner Thomas M , Krahn Thomas , von Ahsen Oliver
Published: May 2012

Background

Circulating tumour cells (CTCs) have shown prognostic relevance in metastatic breast, prostate, colon and pancreatic cancer. For further development of CTCs as a biomarker, we compared the performance of different protocols for CTC detection in murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468 and KPL-4). Blood samples were taken from tumour bearing animals (20 to 200 mm2) and analysed for CTCs using 1. an epithelial marker based enrichment method (AdnaTest), 2. an antibody independent technique, targeting human gene transcripts (qualitative PCR), and 3. an antibody-independent approach, targeting human DNA-sequences (quantitative PCR). Further, gene expression changes associated with epithelial-to-mesenchymal transition (EMT) were determined with an EMT-specific PCR assay.

Methods

We used the commercially available Adna Test, RT-PCR on human housekeeping genes and a PCR on AluJ sequences to detect CTCs in xenografts models. Phenotypic changes in CTCs were tested with the commercially available “Human Epithelial to Mesenchymal Transition RT-Profiler PCR Array”.

Results

Although the AdnaTest detects as few as 1 tumour cell in 1 ml of mouse blood spiking experiments, no CTCs were detectable with this approach in vivo despite visible metastasis formation. The presence of CTCs could, however, be demonstrated by PCR targeting human transcripts or DNA-sequences - without epithelial pre-enrichment. The failure of CTC detection by the AdnaTest resulted from downregulation of EpCAM, whereas mesenchymal markers like Twist and EGFR were upregulated on CTCs. Such a change in the expression profile during metastatic spread of tumour cells has already been reported and was linked to a biological program termed epithelial-mesenchymal transition (EMT).

Conclusions

The use of EpCAM-based enrichment techniques leads to the failure to detect CTC populations that have undergone EMT. Our findings may explain clinical results where low CTC numbers have been reported even in patients with late metastatic cancers. These results are a starting point for the identification of new markers for detection or capture of CTCs, including the mesenchymal-like subpopulations.
Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells
Authors: Gui Anping , Kobayashi Akira , Motoyama Hiroaki , Kitazawa Masato , Takeoka Michiko , Miyagawa Shinichi
Published: May 2012

Background

Since cholangiocarcinoma has a poor prognosis, several epidermal growth factor receptor (EGFR)-targeted therapies with antibody or small molecule inhibitor treatment have been proposed. However, their effect remains limited. The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR, with emphasis on its degradation and recycling.

Methods

We evaluated EGFR expression and colocalization by immunoblotting and immunofluorescence, cell surface EGFR expression by fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein binding by immunoprecipitation in the human cholangiocarcinoma RBE and immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a depletion by siRNA were adopted for inhibition of EGFR recycling.

Results

Upon stimulation with EGF, ligand-induced EGFR degradation was impaired and the expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting for lysosomal degradation was blocked at the early endosome stage, and non-degradated EGFR was recycled to the cell surface. A disrupted association between EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR at tyrosine 1045 (Tyr1045), were also observed in RBE cells.

Conclusion

In RBE cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful molecular alteration in EGFR-targeted therapy. The combination of molecular-targeted therapy determined by the characteristics of individual EGFR phosphorylation events and EGFR recycling inhibition show promise in future treatments of cholangiocarcinoma.
Static balance and function in children with cerebral palsy submitted to neuromuscular block and neuromuscular electrical stimulation: Study protocol for prospective, randomized, controlled trial
Authors: Kazon Soráia , Grecco Luanda A C , Pasini Hugo , Corrêa João C F , Christovão Thaluanna C L , de Carvalho Paulo de TarsoCamillo , Giannasi Lilian Chrystiane , Lucareli Paulo R G , de Oliveira Luis Vicente Franco , Salgado Afonso Shiguemi Inoue , Sampaio Luciana M M , Oliveira Claudia S
Published: May 2012

Background

The use of botulinum toxin A (BT-A) for the treatment of lower limb spasticity is common in children with cerebral palsy (CP). Following the administration of BT-A, physical therapy plays a fundamental role in potentiating the functionality of the child. The balance deficit found in children with CP is mainly caused by muscle imbalance (spastic agonist and weak antagonist). Neuromuscular electrical stimulation (NMES) is a promising therapeutic modality for muscle strengthening in this population. The aim of the present study is to describe a protocol for a study aimed at analyzing the effects of NMES on dorsiflexors combined with physical therapy on static and functional balance in children with CP submitted to BT- A.

Methods/Design

Protocol for a prospective, randomized, controlled trial with a blinded evaluator. Eligible participants will be children with cerebral palsy (Levels I, II and III of the Gross Motor Function Classification System) between five and 12 years of age, with independent gait with or without a gait-assistance device. All participants will receive BT-A in the lower limbs (triceps surae). The children will then be randomly allocated for either treatment with motor physical therapy combined with NMES on the tibialis anterior or motor physical therapy alone. The participants will be evaluated on three occasions: 1) one week prior to the administration of BT-A; 2) one week after the administration of BT-A; and 3) four months after the administration of BT-A (end of intervention). Spasticity will be assessed by the Modified Ashworth Scale and Modified Tardieu Scale. Static balance will be assessed using the Medicapteurs Fusyo pressure platform and functional balance will be assessed using the Berg Balance Scale.

Discussion

The aim of this protocol study is to describe the methodology of a randomized, controlled, clinical trial comparing the effect of motor physical therapy combined with NMES on the tibialis anterior muscle or motor physical therapy alone on static and functional balance in children with CP submitted to BT-A in the lower limbs. This study describes the background, hypotheses, methodology of the procedures and measurement of the results.

Trial registration

RBR5qzs8h
Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan® in two cases
Authors: Cossetti Rachel Jorge D , Bezerra Regis Otaviano França , Gumz Brenda , Telles Adriana , Costa Frederico P
Published: May 2012

Neuroendocrine tumor (NET) patients must be adequately staged in order to improve a multidisciplinary approach and optimal management for metastatic disease. Currently available imaging studies include somatostatin receptor scintigraphy, like OctreoScan®, computed tomography (CT), scans and magnetic resonance imaging (MRI), which analyze vascular concentration and intravenous contrast enhancement for anatomic tumor localization. However, these techniques require high degree of expertise for interpretation and are limited by their availability, cost, reproducibility, and follow-up imaging comparisons. NETs significantly reduce water diffusion as compared to normal tissue. Diffusion-weighted imaging (DWI) in MRI has an advantageous contrast difference: the tumor is represented with high signal over a black normal surrounding background. The whole-body diffusion (WBD) technique has been suggested to be a useful test for detecting metastasis from various anatomic sites. In this article we report the use of DWI in MRI and WBD in two cases of metastatic pulmonary NET staging in comparison with OctreoScan® in order to illustrate the potential advantage of DWI and WBD in staging NETs.
Nonerosive gastroesophageal reflux disease and mild degree of esophagitis: Comparison of symptoms endoscopic, manometric and pH-metric patterns
Authors: Grande Michele , Sileri Pierpaolo , Attinà Grazia Maria , De Luca Elisabetta , Ciano Paolo , Ciangola Carolina Ilaria , Cadeddu Federica
Published: May 2012

Background

Our aim in the present study was to compare patients presenting with gastroesophageal reflux disease in the presence or absence of mild-grade esophagitis (grade I or II according to the Savary-Miller classification).

Methods

Between 2005 and 2007, 215 patients with gastroesophageal reflux disease (67 with reflux associated with grade I or II esophagitis and 148 without esophagitis) were evaluated at the Department of Surgery, University Hospital Tor Vergata, Rome, and were included in the present study. The evaluations consisted of clinical interviews, endoscopy of the high digestive tract, esophageal manometry and pH monitoring.

Results

There was no significant difference between the two groups with regard to age, sex or symptoms. The incidence of heartburn associated with noncardiac chest pain was greater in the esophagitis group than in the dysphagia group. The incidence of hiatal hernia was similar in both groups. Although the motor pattern was similar in both groups, the length of the abdominal esophagus was greater in patients without esophagitis (1.6 cm vs 1.1 cm; P < 0.05). The reflux pattern was nearly identical in both groups.

Conclusions

Gastroesophageal reflux without esophagitis must be regarded not as a milder form of the disease but as part of a single disease. Furthermore, these patients often demonstrate lower rates of symptom improvement after antireflux treatment in comparison with patients with erosive esophagitis. Therefore, further trials to assess the treatment algorithm for these patients are warranted.
Expression of heat shock protein 70 in nasopharyngeal carcinomas: different expression patterns correlate with distinct clinical prognosis
Authors: Cai Man-Bo , Wang Xiao-Pai , Zhang Jia-Xing , Han Hui-Qiong , Liu Chao-Chun , Bei Jin-Xin , Peng Ruo-Jun , Liang Yi , Feng Qi-Sheng , Wang Hai-Yun , Chen Li-Zhen , Fu Sha , Kang Tiebang , Shao Jian-Yong , Zeng Yi-Xin
Published: May 2012

Background

Heat shock protein 70, a stress protein, has been implicated in tumor progression. However, its role in nasopharyngeal carcinoma (NPC) progression has not yet been clearly investigated.

Methods

Immunohistochemistry (IHC) was employed to examine the expression patterns of Hsp70, human leukocyte antigen –A (HLA-A) in NPC tissue samples.

Results

The expression of Hsp70 exhibited different spatial patterns among nuclear, membrane and cytoplasm in 507 NPC tumor tissues. Kaplan-Meier survival analysis demonstrated that different Hsp70 expression patterns are correlated with different patient outcomes. High membranal and cytoplasmic levels of Hsp70 predicted good survival of patients. In contrast, high nuclear abundance of Hsp70 correlated with poor survival. Moreover, the membranal and cytoplasmic levels of Hsp70 were positively correlated with levels of the MHC I molecule HLA-A.

Conclusions

Different Hsp70 expression patterns had distinct predictive values. The different spatial abundance of Hsp70 may imply its important role in NPC development and provide insight for the development of novel therapeutic strategies involving immunotherapy for NPC.
The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a possible therapeutic target in gastric cancer
Authors: Natsume Hiroko , Shinmura Kazuya , Tao Hong , Igarashi Hisaki , Suzuki Masaya , Nagura Kiyoko , Goto Masanori , Yamada Hidetaka , Maeda Matsuyoshi , Konno Hiroyuki , Nakamura Satoki , Sugimura Haruhiko
Published: May 2012

Background

Genomic DNA amplification is a genetic factor involved in cancer, and some oncogenes, such as ERBB2, are highly amplified in gastric cancer. We searched for the possible amplification of other genes in gastric cancer.

Methods and Results

A genome-wide single nucleotide polymorphism microarray analysis was performed using three cell lines of differentiated gastric cancers, and 22 genes (including ERBB2) in five highly amplified chromosome regions (with a copy number of more than 6) were identified. Particular attention was paid to the CRKL gene, the product of which is an adaptor protein containing Src homology 2 and 3 (SH2/SH3) domains. An extremely high CRKL copy number was confirmed in the MKN74 gastric cancer cell line using fluorescence in situ hybridization (FISH), and a high level of CRKL expression was also observed in the cells. The RNA-interference-mediated knockdown of CRKL in MKN74 disclosed the ability of CRKL to upregulate gastric cell proliferation. An immunohistochemical analysis revealed that CRKL protein was overexpressed in 24.4% (88/360) of the primary gastric cancers that were analyzed. The CRKL copy number was also examined in 360 primary gastric cancers using a FISH analysis, and CRKL amplification was found to be associated with CRKL overexpression. Finally, we showed that MKN74 cells with CRKL amplification were responsive to the dual Src/BCR-ABL kinase inhibitor BMS354825, likely via the inhibition of CRKL phosphorylation, and that the proliferation of MKN74 cells was suppressed by treatment with a CRKL-targeting peptide.

Conclusion

These results suggested that CRKL protein is overexpressed in a subset of gastric cancers and is associated with CRKL amplification in gastric cancer. Furthermore, our results suggested that CRKL protein has the ability to regulate gastric cell proliferation and has the potential to serve as a molecular therapy target for gastric cancer.
Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder
Authors: Park Subin , Kim Jae-Won , Yang Young-Hui , Hong Soon-Beom , Park Min-Hyeon , Kim Boong-Nyun , Shin Min-Sup , Yoo Hee-Jeong , Cho Soo-Churl
Published: May 2012

Background

Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD.

Methods

Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2.

Results

There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes.

Conclusions

Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.
Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics
Authors: Li Pinghua , Bai Xingwen , Sun Pu , Li Dong , Lu Zengjun , Cao Yimei , Fu Yuanfang , Bao Huifang , Chen Yingli , Xie Baoxia , Liu Zaixin
Published: May 2012

Background

Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance.

Results

The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes.

Conclusions

Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China.