bluuebunny/crossref_metadata_2025 huggingface dataset:
Bicycle-related genitourinary injuries in the USA from 2002–2010
Authors: Tasian Gregory E , Appa Ayesha A , Bagga Herman S , Blaschko Sarah , McCulloch Charles E , McAninch Jack W , Breyer Benjamin N
Published: March 2014

Among children, the incidence of bicycle-related genitourinary (GU) injuries was 448 per 100 000 (95% CI 383 to 514) and, among adults, was 53 per 100 000 (95% CI 36 to 71). Although children sustained more injuries, adults were more likely to being admitted to the hospital for the GU injury (OR 1.95, 95% CI 1.13 to 3.37). Children sustain nearly 10 times more GU injuries due to bicycles than adults, but adults have higher odds of sustaining injuries requiring admission.
Income-related inequality in health and health-related behaviour: exploring the equalisation hypothesis
Authors: Vallejo-Torres Laura , Hale Daniel , Morris Stephen , Viner Russell M
Published: March 2014

Background

Previous studies have found the socioeconomic gradient in health among adolescents to be lower than that observed during childhood and adulthood. The aim of this study was to examine income-related inequalities in health and health-related behaviour across the lifespan in England to explore ‘equalisation’ in adolescence.

Methods

We used five years of data (2006–2010) from the Health Survey for England to explore inequalities in six indicators: self-assessed general health, longstanding illness, limiting longstanding illness, psychosocial wellbeing, obesity and smoking status. We ran separate analyses by age/gender groups. Inequality was measured using concentration indices.

Results

Our findings for longstanding illnesses, psychosocial wellbeing and obesity were consistent with the equalisation hypothesis. For these indicators, the extent of income-related inequality was lower among late adolescents (16–19 years) and young adults (20–24 years) compared to children and young adolescents (under 15 years), mid- and late-adults (25–44 and 45–64 years) and the elderly (65+ years). The remaining indicators showed lower inequality among adolescents compared to adults, but higher inequality when compared with children.

Conclusions

Our work shows that inequalities occur across the life-course but that for some health issues there may be a period of equalisation in late adolescence and early adulthood.
Validation of a population coronary disease predictive system: the CASSANDRA model
Authors: Grau Maria , Subirana Isaac , Vila Joan , Elosua Roberto , Ramos Rafel , Sala Joan , Dégano Irene R , Tresserras Ricard , Bielsa Oscar , Marrugat Jaume
Published: March 2014

Background

The use of validated multivariate cardiovascular predictive models in a population setting is of interest for public health policy makers. We aimed to validate the estimations of the CASSANDRA model (coronary heart disease (CHD) incidence and CHD risk distribution), considering the population changes in age, sex and CHD risk factors prevalence in a 10-year period.

Methods

We compared the projected CHD incidence estimated with CASSANDRA with that observed in the Girona Heart Registry (REGICOR) for 1995–2004 and 2000–2009 in the population of Girona (Spain) aged 35–74 years. We used official age and sex distributions for this population. Baseline cardiovascular risk factors prevalence and the distribution of cardiovascular risk were obtained from three cross-sectional studies performed in 1995, 2000 and 2005. To validate the future distribution of cardiovascular risk, we tested the yearly CHD risk variance over the study period.

Results

No significant differences between the estimated and observed annual CHD incidence per 100 000 men were found in 1995–2004 (CASSANDRA=457.8 and REGICOR=420.3, incidence rate ratio (IRR) (95% CI)=0.92 (0.89 to 0.96)) and in 2000–2009 (441.4 and 409.6, respectively, IRR=0.93 (0.90 to 0.96)). However, overpredictions of 18% and 22%, respectively, were observed in women (198.8 and 160.4, IRR=0.82 (0.77 to 0.86), and 197.1 and 152.8, IRR=0.78 (0.74 to 0.83), respectively). No significant differences were found in the CHD risk variance in the three different cross-sectional studies.

Conclusions

The CASSANDRA model produces valid estimates, particularly in men, of the future burden of disease and in the distribution of cardiovascular risk in individuals aged 35–74 years.
Analysis of train movement dynamics under various temporal–spatial constraints in fixed-block railway network using extended cellular automaton model
Authors: Zhou Yonghua , Zhang Zhenlin , Liu Deng
Published: March 2014

In the fixed-block railway traffic, the trains adjust their speeds in view of their preceding allowable spaces caused by their respective front adjacent trains or specified by scheduling commands. The railway lines have the line-type speed limits within some block sections and the point-type ones at the terminals of block sections. Those speed limits originate from line conditions, scheduling commands and indications of signal equipment. This paper attempts to in detail reveal the train movement mechanism synthetically considering those temporal–spatial constraints. The proposed train movement model defines four kinds of target points and utilizes them to successively engender the instantaneous target points with their corresponding target speeds. It adopts the rule-based description mechanism in cellular automata (CA) but with continuous spaces to replicate restrictive, autonomous and synergistic behaviors of and among trains. The selections of accelerations and decelerations are based upon the data models of practical acceleration and deceleration processes; thereupon, the model is data-driven. The analysis of train movement dynamics through case studies demonstrates that the extended CA model can reproduce the train movement mechanism of grading speed control to satisfy the aforementioned temporal–spatial constraints. The model is applicable to represent the as-is or should-be states of train movements when adjustable parameters are properly configured.
SPARSE REPRESENTATION-BASED APPROACH FOR UNSUPERVISED FEATURE SELECTION
Authors: SU YA-RU , LI CHUAN-XI , WANG RU-JING , CHEN PENG
Published: March 2014

Dimension reduction methods including feature selection and feature extraction have played an important role in data mining and pattern recognition. In this study, we propose a novel unsupervised feature selection approach based on sparse representation theory, namely Sparsity Score (SS). Due to the sparse representation procedure, SS not only owns the global property of Variance Score (VS) and the local property of Laplacian Score (LS), but also possesses the discriminating nature. Experimental results, based on three well-known face datasets (Yale, ORL and CMU PIE), reveal that SS performs well in the evaluation of the feature significance, and it significantly outperforms VS and LS.
An optimal control problem in photoacoustic tomography
Authors: Bergounioux Maïtine , Bonnefond Xavier , Haberkorn Thomas , Privat Yannick
Published: March 2014

This paper is devoted to the introduction and study of a photoacoustic tomography model, an imaging technique based on the reconstruction of an internal photoacoustic source distribution from measurements acquired by scanning ultrasound detectors over a surface that encloses the body containing the source under study. In a nutshell, the inverse problem consists in determining absorption and diffusion coefficients in a system coupling a hyperbolic equation (acoustic pressure wave) with a parabolic equation (diffusion of the fluence rate), from boundary measurements of the photoacoustic pressure. Since such kinds of inverse problems are known to be generically ill-posed, we propose here an optimal control approach, introducing a penalized functional with a regularizing term in order to deal with such difficulties. The coefficients we want to recover stand for the control variable. We provide a mathematical analysis of this problem, showing that this approach makes sense. We finally write necessary first-order optimality conditions and give preliminary numerical results.
Two-fold branched covers
Authors: Auckly David
Published: March 2014

Many three-dimensional manifolds are two-fold branched covers of the three-dimensional sphere. However, there are some that are not. This paper includes exposition about two-fold branched covers and includes many examples. It shows that there are three-dimensional homology spheres that do not two-fold branched cover any manifold, ones that only two-fold branched cover the three-dimensional sphere, ones that just two-fold branched cover a non-trivial manifold, and ones that two-fold branched cover both the sphere and non-trivial manifolds. When a manifold is surgery on a knot, the possible quotients via involutions generically correspond to quotients of the knot. There can, however, be a finite number of surgeries for which there are exceptional additional symmetries. The included proof of this result follows the proof of Thurston's Dehn surgery theorem. The paper also includes examples of such exceptional symmetries. Since the quotients follow the behavior of knots, a census of the behavior for knots with less than 11 crossings is included.
Local moves and restrictions on the Jones polynomial
Authors: Ganzell Sandy
Published: March 2014

We analyze various local moves on knot diagrams to show that Jones polynomials must have certain algebraic properties. In particular, we show that the Jones polynomial of a knot cannot be a nontrivial monomial.
ℓ1-Norm support vector machine for ranking with exponentially strongly mixing sequence
Authors: Chen Di-Rong , Huang Shou-You
Published: March 2014

The problem of ranking/ordering instances, instead of simply classifying them, has recently gained much attention in machine learning. Ranking from binary comparisons is a ubiquitous problem in modern machine learning applications. In this paper, we consider ℓ1-norm SVM for ranking. As well known, learning with ℓ1-norm restrictions usually leads to sparsity. Moreover, instead of independently draw sample sequence, we are given sample of exponentially strongly mixing sequence. Under some mild conditions, a learning rate is established.
Best restriction L1-approximation of periodic convolution class by generalized splines
Authors: Huang Rong , Liu Yongping
Published: March 2014

We consider the estimate of the best L1-approximation of convolution classes [Formula: see text], defined by a self-adjoint polynomial differential operator Pr(D), in the term of some kinds of generalized splines and get some exact constants.
Adaptive Fourier decompositions and rational approximations, part I: Theory
Authors: Qian Tao
Published: March 2014

In this paper, we will give a survey on adaptive Fourier decompositions (AFDs) in one- and multi-dimensions. Theoretical formulations of three different types of AFDs in one-dimension, viz., Core AFD, Cyclic AFD in conjunction with best rational approximation and Unwending AFD are provided.
Approximation of functions on the sphere on a Sobolev space with a Gaussian measure in the probabilistic case setting
Authors: Wang Heping , Zhai Xuebo
Published: March 2014

In this paper, we discuss the best approximation of functions on the sphere by spherical polynomials and the approximation by the Fourier partial summation operators and the Vallée-Poussin operators, on a Sobolev space with a Gaussian measure in the probabilistic case setting, and get the probabilistic error estimation. We show that in the probabilistic case setting, the Fourier partial summation operators and the Vallée-Poussin operators are the order optimal linear operators in the Lq space for 1 ≤ q ≤ ∞, but the spherical polynomial spaces are not order optimal in the Lq space for 2 < q ≤ ∞. This is completely different from the situation in the average case setting, which the spherical polynomial spaces are order optimal in the Lq space for 1 ≤ q < ∞. Also, in the Lq space for 1 ≤ q ≤ ∞, worst-case order optimal subspaces are also order optimal in the probabilistic case setting.
Realization on indoor positioning in basis of reference tag
Authors: Yu Chunwu , Zhang Jian , Dong Yansong , Pan Jian
Published: March 2014

In this paper, we analyze and explore the layout of reference tags and interpolation method in the reference tag based RFID scene analysis of indoor localization method, and propose triangular layout mode, as well as adopt Newtons interpolation polynomial to calculate virtual reference tags RSSI values instead of linear interpolation. Simulation experiment result shows that when given a error value, distribution probability accumulated by the triangular layout mode is larger than rectangular layout mode, with triangular accounting for a larger proportion and having better localization accuracy. Using of Newtons interpolation polynomial makes an improvement in localization accuracy over linear interpolation, but in terms of computational complexity, Newtons interpolation polynomial pay the price.
Isochronous cosmologies
Authors: Briscese Fabio , Calogero Francesco
Published: March 2014

The possibility has been recently demonstrated to manufacture (nonrelativistic, Hamiltonian) many-body problems which feature an isochronous time evolution with an arbitrarily assigned period T yet mimic with good approximation, or even exactly, any given many-body problem (within a large, physically relevant, class) over times [Formula: see text] which may also be arbitrarily large (but of course such that [Formula: see text]). Purpose and scope of this paper is to explore the possibility to extend this finding to a general relativity context. For simplicity we restrict our consideration to the case of homogeneous and isotropic metrics and show that, via an approach analogous to that used for the nonrelativistic many-body problem, a class of homogeneous and isotropic cyclic solutions of Einstein's equations may be obtained. For these solutions the duration of the cycles does not depend on the initial conditions, so we call these models isochronous cosmologies. We give a physical interpretation of such metrics and in particular we show that they may behave arbitrarily closely, or even identically, to the Friedman–Robertson–Walker solutions of Einstein's equations for an arbitrarily long time (of course shorter than their period, which can also be assigned arbitrarily), so that they may reproduce all the satisfactory phenomenological features of the standard cosmological Λ-CDM model in a portion of their cycle; while these isochronous cosmologies may be geodesically complete and therefore singularity-free.
Synthesis of porphyrin-bis(polyazamacrocycle) triads via Suzuki coupling reaction
Authors: Michalak Julien , Birin Kiril P. , Muniappan Sankar , Ranyuk Elena , Enakieva Yulia Yu. , Gorbunova Yulia G. , Stern Christine , Bessmertnykh-Lemeune Alla , Guilard Roger
Published: March 2014

Suzuki–Miyaura cross-coupling reaction has been used for the synthesis of tricyclic architectures based on trans-A2B2-porphyrins and bisaminal-protected polyazamacrocycles which are linked directly or by a p-phenylene spacer. This modular approach allowed the synthesis of ligands with various substituted porphyrin macrocycles and bisaminal-protected tetraazamacrocycles possessing different cavity sizes. These molecules can be assembled into dimers using a DABCO linker. Deprotection of these compounds afforded porphyrin-bis(polyazamacrocycle) triads.
Survey on Railway Operator Actions and Preparedness in Transportation Against 2010 Chile Earthquake Tsunami and 2011 Tohoku Earthquake Tsunami
Authors: Fujisaki Koichi , Morita Yasutomo , Kajitani Toshio , Yokota Shigeru , Okuyama Tadahiro , Muroi Toshiaki , Hori Muneo
Published: March 2014

The preparedness and the emergency management against tsunami are an increasingly important issue for public transportation operators. The current state of these two is studied by conducting the hearing and questionnaire survey for domestic operators, in addition to the hearing by the national and local governments, focusing on actual actions taken against the 2010 Chile Earthquake Tsunami and the 2011 Tohoku Earthquake Tsunami. Critical issues are discussed in order to promote the preparedness against Tokai–Tonankai–Nankai Earthquake Tsunami which is likely to occur in the near future.
Multiscale microstructures and improved thermoelectric performance of Mg2(Si0.4Sn0.6)Sbx solid solutions
Authors: Zhang Xin , Liu Hongliang , Li Songhao , Zhang Feipeng , Lu Qingmei , Li Jingfeng
Published: March 2014

A series of Sb -doped Mg 2( Si 0.4 Sn 0.6) Sb x (0 ≤ x ≤ 0.025) solid solutions were prepared by an induction melting, Melt Spinning (MS) and Spark Plasma Sintering (SPS) method, namely the non-equilibrium technique MS–SPS, using bulks of Magnesium, Silicon, Tin, and Antimony as raw materials. The non-equilibrium technique generates the unique multiscale microstructures of samples containing micronscale grains and nanoscale precipitates, the multiscale microstructures remarkably make the lattice thermal conductivities decreased, particularly for samples with the nanoscale precipitates having the size of 10–20 nm. Meanwhile, Sb -doping greatly increased the electrical performance of samples. Consequently, the Sb -doping combined with the multiscale microstructures strategy remarkably improves the overall thermoelectric (TE) performance of Sb doped samples, and a high dimensionless figure of merit (ZT) value of up to 1.25 at 723 K is obtained with Mg 2( Si 0.4 Sn 0.6) Sb 0.02 sample in a relatively wide temperature range.
Preparation and tunable luminescence of CaCO3:Eu3+,Dy3+ phosphors
Authors: Dong Yanwei , Kang Ming , Zhang Ping , Cheng Qijun , Wang Jie
Published: March 2014

Phosphors based on calcium carbonate, co-doped with various Eu 3+ and Dy 3+ concentrations were prepared by microwave co-precipitation method. The prepared phosphors were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), thermogravimetry and differential scanning calorimetry (TG-DSC) and photoluminescence and photoluminescence excitation (PL-PLE) spectroscopy. Results showed that Dy 3+ and Eu 3+ ions were uniformly introduced into the host lattice of CaCO 3 taking the place of Ca 2+ ions. Under the excitation at 382 nm, the emission peak wavelengths were at 487 nm (4 F 9/2 → 6 H 15/2 of Dy 3+), 576 nm (4 F 9/2 → 6 H 13/2 of Dy 3+), and 614 nm (5 D 0 → 7 F 2 of Eu 3+). The luminescent intensities and emitting colors of Eu 3+- Dy 3+ co-doped CaCO 3 phosphors could be controlled by UV–violet excitations wavelengths or the rare-earth ions concentrations of Eu 3+ and Dy 3+ in phosphors. The chromaticity coordinates and photographs of samples under UV light showed the changes of the luminescence color intuitively through the varing UV–violet excitations wavelengths or the rare-earth ions concentrations of Eu 3+ and Dy 3+.
COLLOIDAL PREPARATION OF MONODISPERSE NANOCRYSTALS
Authors: ZHANG SHUANG-YUAN , REGULACIO MICHELLE D. , SHAH KWOK WEI , SREETHAWONG THAMMANOON , ZHENG YUANGANG , HAN MING-YONG
Published: March 2014

In the field of nanoscience, the ability to prepare high-quality nanocrystals is crucial for fundamental research and technology development. Herein, we review a general route for the colloidal preparation of monodisperse nanocrystals, which is divided into five different stages, namely (i) nucleation, (ii) growth, (iii) Ostwald ripening, (iv) surfactant capping and (v) precipitation. Each of the five stages is discussed in detail to provide a comprehensive understanding of the mechanism behind nanocrystal formation and the subsequent processing steps. We put emphasis on the classical theories and experimental techniques that are most frequently practiced. These are useful for the successful design and fabrication of nanocrystals with properties that are beneficial for use in a plethora of technological applications.
MICRO-OPTOMECHANICAL MOVEMENTS (MOMs) WITH SOFT OXOMETALATES (SOMs): CONTROLLED MOTION OF SINGLE SOFT OXOMETALATE PEAPODS USING EXOTIC OPTICAL POTENTIALS
Authors: ROY BASUDEV , GHOSH NIRMALYA , PANIGRAHI PRASANTA K. , BANERJEE AYAN , SAHASRABUDHE ATHARVA , PARASAR BIBUDHA , ROY SOUMYAJIT
Published: March 2014

An important challenge in the field of materials design and synthesis is to deliberately design mesoscopic objects starting from well-defined precursors and inducing directed movements in them to emulate biological processes. Recently, mesoscopic metal-oxide-based soft oxometalates (SOMs) have been synthesized from well-defined molecular precursors transcending the regime of translational periodicity. Here, we show that it is actually possible to controllably move such an asymmetric SOM, with the shape of a "peapod" along complex paths using tailor-made sophisticated optical potentials created by spin–orbit interaction of light due to a tightly focused linearly polarized Gaussian beam propagating through a stratified medium in an optical trap. We demonstrate motion of individual trapped SOMs along circular paths of more than 15 μm in a perfectly controlled manner by simply varying the input polarization of the trapping laser. Such controlled motion can have a wide range of applications starting from catalysis to the construction of dynamic mesoscopic architectures.
Extended two-phase flow model with mechanical capability to simulate gas migration in bentonite
Authors: Tawara Y. , Hazart A. , Mori K. , Tada K. , Shimura T. , Sato S. , Yamamoto S. , Asano H. , Namiki K.
Published: March 2014

Long-term gas migration through clays cannot be simulated by conventional two-phase flow models alone owing to the presence of material deformation. In this article, an extended two-phase flow model that incorporates mechanical effects is proposed. The model allows the formation of preferential pathway and considers the relation between pore moisture and pore deformation. It was carried out with the intention of avoiding the complexity of a fully coupled thermal, hydraulic and mechanical modelling. In the new model, porosity, permeability, swelling pressure and pathways formation threshold depend on the water saturation. The model is validated on different gas injection experiments with controlled flow rate and controlled pressure. Some experiments are well known in the literature; some are new. In each case, an inverse approach is used to identify the model parameters. The results confirm that, depending on the type of bentonite (MX80, Avonlea, KunigelV1), modelling the gas migration could require the existence of a pressure-induced saturation-depending preferential pathway. In laboratory-scale experiments, the model leads to an accurate evaluation of the long-term gas migration trends, including not just the gas migration stage but also the water re-saturation level. In a field-scale experiment, the behaviour of the model in a realistic context is revealed.
A downscaling approach for geological characterization of the Raditladi basin of Mercury
Authors: Mancinelli Paolo , Minelli Francesco , Mondini Alessandro , Pauselli Cristina , Federico Costanzo
Published: March 2014

In this work, we combined multi-scale geological maps of Mercury to produce a new global map where geological units are classified based on albedo, crater density and morphological relationships with other units. To create this map, we used the 250 m/pixel mosaic of images acquired by the narrow- and wide-angle cameras onboard the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft during its orbital phase. The geological mapping is supported by digital terrain model data and surface mineralogical variation from the global mosaic of MESSENGER Mercury Atmospheric and Surface Composition Spectrometer observations. This map comprises the global-scale intercrater plains, smooth plains and Odin-type units as reported in previous studies, as well as units we term bright intercrater plains, Caloris rough ejecta and dark material deposits. We mapped a portion of the Raditladi quadrangle (19–35°N, 106–133°E) at a regional scale at a resolution of 166 m/pixel. We characterized the geological context of the area and evaluated the stratigraphic relationships between the units. To obtain a representative geological section, we analysed and corrected available topographical data. The geological cross-section derived from our regional mapping suggests that volcanic emplacement of Raditladi's inner plains followed the topography of the basin after the deposition of impact-related units (i.e. melts, breccias and rim collapse) and was driven by low-viscosity flows. Hollows that appear on Raditladi's peak ring were possibly formed from low-reflectance intercrater plains materials exposed through the peak ring unit.

Supplementary material:

Cleaner, larger version of the global-scale geological map and a local-scale map for comparison are available at
http://www.geolsoc.org.uk/SUP18741
.
Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction
Authors: Gatford Kathryn L. , Kaur Gunveen , Falcão-Tebas Filippe , Wadley Glenn D. , Wlodek Mary E. , Laker Rhianna C. , Ebeling Peter R , McConell Glenn K.
Published: March 2014

Individuals born after intrauterine growth restriction (IUGR) are at an increased risk of developing diabetes in their adult life. IUGR impairs β-cell function and reduces β-cell mass, thereby diminishing insulin secretion. IUGR also induces insulin resistance, with impaired insulin signaling in muscle in adult humans who were small for gestational age (SGA) and in rodent models of IUGR. There is epidemiological evidence in humans that exercise in adults can reduce the risk of metabolic disease following IUGR. However, it is not clear whether adult IUGR individuals benefit to the same extent from exercise as do normal-birth-weight individuals, as our rat studies suggest less of a benefit in those born IUGR. Importantly, however, there is some evidence from studies in rats that exercise in early life might be able to reverse or reprogram the long-term metabolic effects of IUGR. Studies are needed to address gaps in current knowledge, including determining the mechanisms involved in the reprogramming effects of early exercise in rats, whether exercise early in life or in adulthood has similar beneficial metabolic effects in larger animal models in which insulin resistance develops after IUGR. Human studies are also needed to determine whether exercise training improves insulin secretion and insulin sensitivity to the same extent in IUGR adults as in control populations. Such investigations will have implications for customizing the recommended level and timing of exercise to improve metabolic health after IUGR.
PPARγ activation attenuates glucose intolerance induced by mTOR inhibition with rapamycin in rats
Authors: Festuccia William T. , Blanchard Pierre-Gilles , Belchior Thiago , Chimin Patricia , Paschoal Vivian A. , Magdalon Juliana , Hirabara Sandro M. , Simões Daniel , St-Pierre Philippe , Carpinelli Angelo , Marette André , Deshaies Yves
Published: March 2014

mTOR inhibition with rapamycin induces a diabetes-like syndrome characterized by severe glucose intolerance, hyperinsulinemia, and hypertriglyceridemia, which is due to increased hepatic glucose production as well as reduced skeletal muscle glucose uptake and adipose tissue PPARγ activity. Herein, we tested the hypothesis that pharmacological PPARγ activation attenuates the diabetes-like syndrome associated with chronic mTOR inhibition. Rats treated with the mTOR inhibitor rapamycin (2 mg·kg−1·day−1) in combination or not with the PPARγ ligand rosiglitazone (15 mg·kg−1·day−1) for 15 days were evaluated for insulin secretion, glucose, insulin, and pyruvate tolerance, skeletal muscle and adipose tissue glucose uptake, and insulin signaling. Rosiglitazone corrected fasting hyperglycemia, attenuated the glucose and insulin intolerances, and abolished the increase in fasting plasma insulin and C-peptide levels induced by rapamycin. Surprisingly, rosiglitazone markedly increased the plasma insulin and C-peptide responses to refeeding in rapamycin-treated rats. Furthermore, rosiglitazone partially attenuated rapamycin-induced gluconeogenesis, as evidenced by the improved pyruvate tolerance and reduced mRNA levels of phospho enolpyruvate carboxykinase and glucose-6-phosphatase. Rosiglitazone also restored insulin's ability to stimulate glucose uptake and its incorporation into glycogen in skeletal muscle of rapamycin-treated rats, which was associated with normalization of Akt Ser473phosphorylation. However, the rapamycin-mediated impairments of adipose tissue glucose uptake and incorporation into triacylglycerol were unaffected by rosiglitazone. Our findings indicate that PPARγ activation ameliorates some of the disturbances in glucose homeostasis and insulin action associated with chronic rapamycin treatment by reducing gluconeogenesis and insulin secretion and restoring muscle insulin signaling and glucose uptake.
Influence of the microenvironment on cell fate determination and migration
Authors: Bloom Alexander B. , Zaman Muhammad H.
Published: March 2014

Several critical cell functions are influenced not only by internal cellular machinery but also by external mechanical and biochemical cues from the surrounding microenvironment. Slight changes to the microenvironment can result in dramatic changes to the cell's phenotype; for example, a change in the nutrients or pH of a tumor microenvironment can result in increased tumor metastasis. While cellular fate and the regulators of cell fate have been studied in detail for several decades now, our understanding of the extracellular regulators remains qualitative and far from comprehensive. In this review, we discuss the microenvironment influence on cell fate in terms of adhesion, migration, and differentiation and focus on both developments in experimental and computation tools to analyze cellular fate.
BRCA1 1675delA and 1135insA Account for One Third of Norwegian Familial Breast‐Ovarian Cancer and Are Associated with Later Disease Onset than Less Frequent Mutations
Authors: Borg Åke , Dørum Anne , Heimdal Ketil , Mæhle Lovise , Hovig Eivind , Møller Pål
Published: March 2014

A total of 845 women from breast‐ovarian cancer kindreds were enrolled in a clinical follow‐up program for early disease diagnosis; 35 women were prospectively identified with cancer. In order to estimate the role of genetic factors for cancer predisposition in this well‐defined set of patients, considered as representative for familial breast‐ovarian cancer in the Norwegian population, the BRCA1 gene was investigated for germline mutations. The entire coding region of BRCA1 was analysed using a protein truncation test, direct sequencing and a screen for known large genomic deletions and insertions. Twenty one (60%) of the 35 patients were identified as carriers of 11 distinct BRCA1 mutations. Two previously described founder mutations, 1675delA and 1135insA, were found to account for more than half (11/21) of all BRCA1 cases and for almost one third (11/35) of all breast and ovarian cancers. Supported by a previous population‐based analysis of these founder mutations in ovarian cancer, our findings suggest that a significant proportion of women at risk for developing inherited breast and ovarian cancer can be identified. This is particularly obvious in certain geographic regions where these founder mutations are prevalent. Women carrying the two founder mutations had a significantly older age of disease onset as compared to women with other BRCA1 mutations. This observation indicates that BRCA mutation penetrance estimates from populations with strong founder effects may be biased. One reason why some deleterious mutations are allowed to prevail in a population may be coupled to penetrance and the fact that they seldom induce disease in women in child‐bearing ages. Eleven out of 12 (92%) breast cancers in BRCA1 mutation carriers were estrogen receptor negative, versus 4 out of 9 (44%) in mutation negative patients (p = 0.03). Histopathological characteristics of the prospectively detected cancers indicated an unfavourable prognosis in mutation carriers.
Ethical, Social and Economic Issues in Familial Breast Cancer: A Compilation of Views from the E.C. Biomed II Demonstration Project
Authors: Steel Michael , Smyth Elizabeth , Vasen Hans , Eccles Diana , Evans Gareth , Møller Pål , Hodgson Shirley , Stoppa-Lyonnet Dominique , Chang-Claude Jenny , Caligo Maria , Morrison Patrick , Haites Neva
Published: March 2014

Demand for clinical services for familial breast cancer is continuing to rise across Europe. Service provision is far from uniform and, in most centres, its evolution has been determined by local conditions, specifically by local research interests, rather than by central planning. However, in a number of countries there is evidence of progress towards co‐ordinated development and audit of clinics providing risk assessment, counselling, screening and, in some cases, prophylactic intervention. Much important information should emerge from continued observation and comparative assessment of these developments.

In most countries for which relevant data are available, there is a distinct bias towards higher social class among those who avail themselves of clinic facilities (in line with findings from many other health‐promotion initiatives). This should be addressed when considering future organisation of clinical services.

Molecular genetic studies designed to identify the underlying mutations responsible for familial breast cancer are not generally regarded as part of the clinical service and are funded through research grants (if at all). Economic considerations suggest that there is a case for keeping this policy under review.

Familial cancers throw into sharp relief certain ethical and legal issues that have received much recent attention from government advisory bodies, patients’ representatives, professional commentators and the popular media. Two are of particular importance; first, the right to gain access to medical records of relatives, in order to provide accurate risk assessment for a given family member, versus the right to privacy in respect of personal medical information and, second, the obligation (or otherwise) to inform family members of their risk status if they have not actively sought that knowledge. The legal position seems to vary from country to country and, in many cases, is unclear. In view of pressures to establish uniform approaches to medical confidentiality across the EC, it is important to evaluate the experience of participants in this Demonstration Programme and to apply the principle of “non‐malfeasance” in formulating regu‐lations that should govern future practice in this field.

Data on economic aspects of familial breast cancer are remarkably sparse and outdated. As evidence accrues on the influence of screening and intervention programmes on morbidity and mortality, there is a strong case for evaluating the cost‐effectiveness of different models of service provision.
Utilisation of Prophylactic Mastectomy in 10 European Centres
Authors: Evans D. G. R. , Anderson E. , Lalloo F. , Vasen H. , Beckmann M. , Eccles D. , Hodgson S. , Møller P. , Chang-Claude J. , Morrison P. , Stoppa-Lyonnet D. , Steel M. , Haites N.
Published: March 2014

Increasingly women at high risk of breast cancer are opting for prophylactic surgery to reduce their risks. Data from 10 European centres that offer a risk counselling and screening service to women at risk show different approaches to the option of preventive surgery, although most centres adhere to a protocol including at least two risk counselling sessions and a psychological assessment. Thus far the combined centres have data on 174 women who have undergone prophylactic mastectomy with in excess of 400 women years of follow up. Operations were carried out on women with lifetime risks of 25–80%, with an average annual expected incidence rate of 1% per women. No breast cancers have occurred in this cohort. Long term follow up on an extended group of women will be necessary to truly address the risk of subsequent breast cancer and the psychological sequelae.
Costs and Benefits of Diagnosing Familial Breast Cancer
Authors: Heimdal Ketil , Mæhle Lovise , Møller Pål
Published: March 2014

Based on results from our surveillance program for women at risk for inherited breast cancer, we have calculated cost per year earned. Norwegian National Insurance Service reimbursement fees were used in the calculations. The calculated costs are based on empirical figures for expanding already established medical genetic departments and diagnostic outpatient clinics to undertake the work described. Cost per year earned was estimated at Euro 753 using our current practice of identifying the high‐risk women through a traditional cancer family clinic.

A strategy of identifying the high‐risk families through genetic testing of all incident breast and ovarian cancers for founder mutations in BRCA1, will increase the cost to Euro 832. Costs related more to genetic counseling and clinical follow‐up than to laboratory procedures. This potential economic limiting factor coincides with a shortage of personnel trained in genetic counseling. The number of relatives counseled to identify one healthy female mutation carrier (i.e. the uptake of genetic testing) is more important to cost‐effectiveness than family size. Costs will vary depending upon the penetrance of the mutations detected and the prevalence of founder mutations in the population examined. Prevalences of BRCA1 founder mutations in some high incidence areas of Norway may be sufficiently high to consider population screening. Unlike mutation screening of cancer genes, founder mutation analysis will not identify DNA variants of uncertain clinical significance. Identification of high‐risk families through founder mutation analysis of BRCA1 ensures that families with maximum risks are given first access to the limited resources of the high‐risk clinics. This may be the greatest contribution to increased cost effectiveness of such a strategy.

The assumptions underlying the calculations are discussed. The conclusion is that inherited breast cancer may be managed effectively for the cost of Euro 750–1,600 per year earned.
Genetic Counselling and Testing for Hereditary Breast and Ovarian Cancer: The Gent(le) Approach
Authors: De Vos M. , Poppe B. , Delvaux I. , Mortier G. , Claes K. , Messiaen L. , De Paepe A.
Published: March 2014

The counselling experience with 50 Flemish families in whom mutation analysis of the total coding region of the BRCA1 and BRCA2 gene has been initiated, is presented.

Genetic testing for breast‐ovarian cancer susceptibility is offered by a multidisciplinary team. During the counselling sessions, special attention is given to comprehensible and emotionally acceptable communi‐cation of genetic information and to the psychosocial evaluation of the counselee. The limitations of molecular testing and the controversy surrounding cancer prevention strategies are also discussed.

The overall acceptance of mutation testing is high. Some of the problems encountered are inaccuracy of the reported family history, poor retrieval of the medical records of affected family members and the reluctance of many patients to inform their relatives about the possibility of being tested.
Menstrual Cycle Dependent Variability for Serum Tumor Markers CEA, AFP, CA 19‐9, CA 125 and CA 15‐3 in Healthy Women
Authors: Erbağci Ayşe Binnur , Yilmaz Necat , Kutlar Irfan
Published: March 2014

Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19‐9, CA 125, CA 15‐3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase‐dependent difference was observed for CA 15‐3, midluteal concentrations (mean ± SEM; 26.33 ± 1.56 U/ml) higher than the midfollicular (mean ± SEM; 19.27 ± 1.49 U/ml) concentrations (p < 0.001). But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively).

CA 15‐3 antigen is a product of the MUC‐1 gene which is expressed in abundance by endometrial epithelial cells in the secretory phase of the menstrual cycle which may be the potential source of variability. The association of CA 125 levels with obesity suggests a possible role of adipose tissue in CA 125 metabolism. In conclusion our data suggest that in healthy women serum CA 15‐3 levels are significantly elevated in the midluteal phase of the menstrual cycle compared to midfollicular phase. Therefore, consideration of menstrual cycle dependent variability for CA 15‐3 appears indicated in interpretation of individual results.
The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction
Authors: Gonzalez Eric J. , Arms Lauren , Vizzard Margaret A.
Published: March 2014

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3–7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed. Altered visceral sensations from the urinary bladder (i.e., pain at low or moderate bladder filling) that accompany BPS/IC may be mediated by many factors including changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli (allodynia). The goals for this review are to describe chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor (transforming growth factor (TGF-β)/TGF-βtype 1 receptor) signaling that may be valuable LUT targets for pharmacologic therapy to improve urinary bladder function and reduce somatic sensitivity associated with urinary bladder inflammation.
Comparative Evaluation of Recombinant Protein Production in Different Biofactories: The Green Perspective
Authors: Merlin Matilde , Gecchele Elisa , Capaldi Stefano , Pezzotti Mario , Avesani Linda
Published: March 2014

In recent years, the production of recombinant pharmaceutical proteins in heterologous systems has increased significantly. Most applications involve complex proteins and glycoproteins that are difficult to produce, thus promoting the development and improvement of a wide range of production platforms. No individual system is optimal for the production of all recombinant proteins, so the diversity of platforms based on plants offers a significant advantage. Here, we discuss the production of four recombinant pharmaceutical proteins using different platforms, highlighting from these examples the unique advantages of plant-based systems over traditional fermenter-based expression platforms.
Differential Gene Expression Profiling of Enriched Human Spermatogonia after Short- and Long-Term Culture
Authors: Conrad Sabine , Azizi Hossein , Hatami Maryam , Kubista Mikael , Bonin Michael , Hennenlotter Jörg , Renninger Markus , Skutella Thomas
Published: March 2014

This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks) and long-term culture (up to more than 14 months) in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status ofin vitrocultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future.
Advances in Stem Cell Therapy for Erectile Dysfunction
Authors: Lin Ching-Shwun
Published: March 2014

Stem cell (SC) therapy for erectile dysfunction (ED) has been investigated in 35 published studies, with one being a small-scale clinical trial. Out of these 35 studies, 19 are concerned with cavernous nerve (CN) injury-associated ED while 10 with diabetes mellitus- (DM-) associated ED. Adipose-derived SCs (ADSCs) were employed in 18 studies while bone marrow SCs (BMSCs) in 9. Transplantation of SCs was done mostly by intracavernous (IC) injection, as seen in 25 studies. Allogeneic and xenogeneic transplantations have increasingly been performed but their immune-incompatibility issues were rarely discussed. More recent studies also tend to use combinatory therapies by modifying or supplementing SCs with angiogenic or neurotrophic genes or proteins. All studies reported better erectile function with SC transplantation, and the majority also reported improved muscle, endothelium, and/or nerve in the erectile tissue. However, differentiation or engraftment of transplanted SCs has rarely been observed; thus, paracrine action is generally believed to be responsible for SC’s therapeutic effects. But still, few studies actually investigated and none proved paracrine action as a therapeutic mechanism. Thus, based exclusively on functional outcome data shown in preclinical studies, two clinical trials are currently recruiting patients for treatment with IC injection of ADSC and BMSC, respectively.
Surface Hardening of Ti-15V-3Al-3Cr-3Sn Alloy after Cyclic Hydrogenation and Subsequent Solution Treatment
Authors: Hung Chia-Po , Wu Tair-I , Wu Jiann-Kuo
Published: March 2014

The as-received and preheated (1000°C-30 min. and 500°C-30 min.) sheets of Ti-15V-3Al-3Cr-3Sn alloy (Ti-153) were treated according to the predetermined process including a cyclic electrolytic hydrogenation (at 50 mA/cm2for 1 hr and at 5 mA/cm2for 10 hrs) combining a subsequent solution treatment to see the effects of various operating parameters on the evolution of microstructure and the variations of hardness. The hardening effect deriving from solid-solution strengthening of hydrogen eventually overrode that from precipitation hardening. The maximum hardness elevation was from 236.9 to 491.1 VHN.