bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical venous thrombosis following exogenous androgen use for bodybuilding
Authors: Sveinsson Olafur , Herrman Lars
Published: February 2013

There are only a few reports of patients developing cerebral venous sinus thrombosis (CVST) after androgen therapy. We present a young man who developed cortical venous thrombosis after using androgens to increase muscle mass. He was hospitalised for parasthesia and dyspraxia in the left hand followed by a generalised tonic–clonic seizure. At admission, he was drowsy, not fully orientated, had sensory inattention, pronation drift and a positive extensor response, all on the left side. The patient had been using anabolic steroids (dainabol 20 mg/day) for the last month for bodybuilding. CT angiography showed a right cortical venous thrombosis. Anticoagulation therapy was started with intravenous heparin for 11 days and oral anticoagulation (warfarin) thereafter. A control CT angiography 4 months later showed resolution of the thrombosis. He recovered fully.
Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in non-Hodgkin lymphoma and significant correlations with lactic acid dehydrogenase and β2-microglobulin
Authors: Zhang Zhuqing , Chen Kai , Yan Longchao , Yang Ziyi , Zhu Zhanmeng , Chen Chunlin , Zeng Jia , Wei Wei , Qi Xia , Ren Shuangyi , Zuo Yunfei
Published: February 2013

Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein (DC-SIGNR), a type II integral membrane protein and a member of the C-type lectins, has been reported to bind various strains of HIV-1, HIV-2, and simian immunodeficiency virus. Serum DC-SIGNR is not currently available for the detection of non-Hodgkin lymphoma (NHL). Using an enzyme-linked immunosorbent assay (ELISA), we assessed the serum levels of DC-SIGNR in 70 cancer patients and 100 healthy controls. Additionally, using immunohistochemistry, we determined the expression of DC-SIGNR in the lymph nodes. Using the ELISA, low serum levels of DC-SIGNR were detected in the patients (median, 4.513 ng·L−1; range, 1.066–9.232 ng·L−1; p = 0.0003). Serum concentrations of DC-SIGNR correlated significantly with age (p = 0.0077) and lactic acid dehydrogenase (p = 0.0046) and β2-microglobulin (p = 0.0491) levels. However, we found no statistically significant correlation between serum DC-SIGNR levels and clinical data such as sex, Ann Arbor stage, B symptoms, and histologic subtypes. Moreover, NHL patients with a lower level of serum DC-SIGNR expression in lymphatic endothelial cells also showed negative immunostaining levels. These results suggest that DC-SIGNR is a biological molecule that may be potentially useful in NHL clinical settings.
EFFECT OF EXCITATION WAVELENGTH ON THE RAMAN SPECTRUM OF HEXAGONAL DEFECTS IN 4H-SiC
Authors: HAN RU , FAN XIAOYA
Published: February 2013

The Raman spectra of 4H- SiC with hexagonal defect have been investigated as a function of the excitation wavelength. As the excitation wavelength increases, the excitation wavelength dependence of Raman spectrum of hexagonal defect is very different from that of the free defect zone in 4H- SiC . Four electronic Raman scattering peaks are seen to be significantly enhanced with longer wavelength excitation. In hexagonal defect, the optical modes ( E2( TO ), E1( TO ) and A1( LO )) and the second-order Raman spectrum are broadened and redshifted as the excitation wavelength increased. But the positions of these bands obtained from the free defect zone do not change within our experimental error. Structure defects are regarded as the origin of those abnormal phenomena in hexagonal defect, and the structure ordering of hexagonal defect may have some similarity with SiC monofilaments.
POINCARÉ SECTION ANALYSIS TO MEASURE SYNCHRONIZATION IN COUPLED HAMILTONIAN SYSTEMS
Authors: TIAN JING , QIU HAIBO , CHEN ZICHEN , CHEN YONG
Published: February 2013

As a novel synchronization phenomenon, measure synchronization (MS) in Hamiltonian systems is characterized by a commonly shared phase space that has invariant measure. Although there has been some discussions of the underlying mechanism, a general explanation of MS is still lacking. In this paper, we reveal the essence of MS by using Poincaré section analysis. A two coupled Bosonic Josephson junction model is employed to perform the analysis as an illustration. It is shown that coupled Hamiltonian systems exhibit separatrix crossing behavior at quasiperiodic MS transition. Moreover, using this analysis method we find that chaotic MS is the result of separatrix chaos. It is concluded that the Poincaré section technique is a general method to explain MS, and the direct correspondence between separatrix behavior and the MS transition is a universal property in coupled Hamiltonian systems.
A VERY HIGH AMPLITUDE SENSITIVITY OF A NEW MULTI-CORE HOLEY FIBER-BASED PLASMONIC SENSOR
Authors: POPESCU V. A.
Published: February 2013

The propagation characteristics in a new multi-core holey fiber-based plasmonic sensor are investigated using a finite element method. The fiber is made by a silica core with a small air hole in the center of the structure, surrounded by six air holes placed at the vertices of a hexagon, two layers of air holes arranged in a hexagonal way that are inserted in the SiO 2 core which is surrounded by a gold layer and a very thick distilled water layer. The structure is designed to have high amplitude sensitivity near the phase matching point corresponding to the maximum of the power fraction for a core guided supermode in the water and gold layers. The maximum of the imaginary part of the group refractive index is located to the same wavelength as the maximum of the amplitude sensitivity. The advantages of our design are a small value of FWHM parameter, a high value of the signal-to-noise ratio, a high value of the amplitude sensitivity (4040.9 RIU-1), a sensor resolution better than 2.5 × 10-6 RIU and a strong transmission loss of a core guided supermode at the resonant coupling due to efficient interaction with a plasmon mode.
ON THE CHAOS IN GENE NETWORKS
Authors: LIKHOSHVAI VITALY A. , FADEEV STANISLAV I. , KOGAI VLADISLAV V. , KHLEBODAROVA TAMARA M.
Published: February 2013

The methods for constructing "chaotic" nonlinear systems of differential equations modeling gene networks of arbitrary structure and dimensionality with various types of symmetry are considered. It has been shown that an increase in modality of the functions describing the control of gene expression efficiency allows for a decrease in the dimensionality of these systems with retention of their chaotic dynamics. Three-dimensional "chaotic" cyclic systems are considered. Symmetrical and asymmetrical attractors with "narrow" chaos having a Moebius-like structure have been detected in such systems. As has been demonstrated, a complete symmetry of the systems with respect to permutation of variables does not prevent the emergence of their chaotic dynamics.
EXPERIMENTAL QUANTIFICATION OF NON-GAUSSIANITY OF PHASE-RANDOMIZED COHERENT STATES
Authors: ALLEVI ALESSIA , OLIVARES STEFANO , BONDANI MARIA
Published: February 2013

We present the experimental investigation of the non-Gaussian nature of some mixtures of Fock states by reconstructing their Wigner function and exploiting two recently introduced measures of non-Gaussianity. In particular, we demonstrate the consistency between the different approaches and the monotonicity of the two measures for states belonging to the class of phase-randomized coherent states. Moreover, we prove that the exact behavior of one measure with respect to the other depends on the states under investigation and devise possible criteria to discriminate which measure is more useful for the characterization of the states in realistic applications.
STRUCTURE OF ENTROPY SOLUTIONS TO SCALAR CONSERVATION LAWS WITH STRICTLY CONVEX FLUX
Authors: ADIMURTHI  , GHOSHAL SHYAM SUNDAR , VEERAPPA GOWDA G. D.
Published: February 2013

We consider scalar conservation laws in one space dimension with convex flux and we establish a new structure theorem for entropy solutions by identifying certain shock regions of interest, each of them representing a single shock wave at infinity. Using this theorem, we construct a smooth initial data with compact support for which the solution exhibits infinitely many shock waves asymptotically in time. Our proof relies on Lax–Oleinik explicit formula and the notion of generalized characteristics introduced by Dafermos.
Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function
Authors: Ci Hong-Bo , Ou Zhi-Jun , Chang Feng-Jun , Liu Dong-Hong , He Guo-Wei , Xu Zhe , Yuan Hai-Yun , Wang Zhi-Ping , Zhang Xi , Ou Jing-Song
Published: February 2013

Mitral valve endothelial cells are important for maintaining lifelong mitral valve integrity and function. Plasma endothelial microparticles (EMPs) increased in various pathological conditions related to activation of endothelial cells. However, whether EMPs will increase in mitral valve disease and their relationship remains unclear. Here, 81 patients with mitral valve disease and 45 healthy subjects were analyzed for the generation of EMPs by flow cytometry. Human mitral valve endothelial cells (HMVECs) were treated with EMPs. The phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the association of eNOS and heat shock protein 90 (HSP90), and the generation of nitric oxide (NO) and superoxide anion (O2˙−) were measured. EMPs were increased significantly in patients with mitral valve disease compared with those in healthy subjects. EMPs were negatively correlated with mitral valve area in patients with isolated mitral stenosis. EMPs were significantly higher in the group with severe mitral regurgitation than those in the group with mild and moderate mitral regurgitation. Furthermore, EMPs were decreased dramatically in both Akt and eNOS phosphorylation and the association of HSP90 with eNOS in HMVECs. EMPs decreased NO production but increased O2˙− generation in HMVECs. Our data demonstrated that EMPs were significantly increased in patients with mitral valve disease. The increase of EMPs can in turn impair HMVEC function by inhibiting the Akt/eNOS-HSP90 signaling pathway. These findings suggest that EMPs may be a therapeutic target for mitral valve disease.
Endothelial cell-by-cell profiling reveals the temporal dynamics of VEGFR1 and VEGFR2 membrane localization after murine hindlimb ischemia
Authors: Imoukhuede P. I. , Dokun Ayotunde O. , Annex Brian H. , Popel Aleksander S.
Published: February 2013

VEGF receptor (VEGFR) cell surface localization plays a critical role in transducing VEGF signaling toward angiogenic outcomes, and quantitative characterization of these parameters is critical to advancing computational models for predictive medicine. However, studies to this point have largely examined intact muscle; thus, essential data on the cellular localization of the receptors within the tissue are currently unknown. Therefore, our aims were to quantitatively analyze VEGFR localization on endothelial cells (ECs) from mouse hindlimb skeletal muscles after the induction of hindlimb ischemia, an established model for human peripheral artery disease. Flow cytometry was used to measure and compare the ex vivo surface localization of VEGFR1 and VEGFR2 on CD31+/CD34+ECs 3 and 10 days after unilateral ligation of the femoral artery. We determined that 3 days after hindlimb ischemia, VEGFR2 surface levels were decreased by 80% compared with ECs from the nonischemic limb; 10 days after ischemia, we observed a twofold increase in surface levels of the modulatory receptor, VEGFR1, along with increased proliferating cell nuclear antigen, urokinase plasminogen activator, and urokinase plasminogen activator receptor mRNA expression compared with the nonischemic limb. The significant upregulation of VEGFR1 surface levels indicates that VEGFR1 indeed plays a critical role in the ischemia-induced perfusion recovery process, a process that includes both angiogenesis and arteriogenesis. The quantification of these dissimilarities, for the first time ex vivo, provides insights into the balance of modulatory (VEGFR1) and proangiogenic (VEGFR2) receptors in ischemia and lays the foundation for systems biology approaches toward therapeutic angiogenesis.
Cardiac myocyte exosomes: stability, HSP60, and proteomics
Authors: Malik Z. A. , Kott K. S. , Poe A. J. , Kuo T. , Chen L. , Ferrara K. W. , Knowlton A. A.
Published: February 2013

Exosomes, which are 50- to 100-nm-diameter lipid vesicles, have been implicated in intercellular communication, including transmitting malignancy, and as a way for viral particles to evade detection while spreading to new cells. Previously, we demonstrated that adult cardiac myocytes release heat shock protein (HSP)60 in exosomes. Extracellular HSP60, when not in exosomes, causes cardiac myocyte apoptosis via the activation of Toll-like receptor 4. Thus, release of HSP60 from exosomes would be damaging to the surrounding cardiac myocytes. We hypothesized that 1) pathological changes in the environment, such as fever, change in pH, or ethanol consumption, would increase exosome permeability; 2) different exosome inducers would result in different exosomal protein content; 3) ethanol at “physiological” concentrations would cause exosome release; and 4) ROS production is an underlying mechanism of increased exosome production. We found the following: first, exosomes retained their protein cargo under different physiological/pathological conditions, based on Western blot analyses. Second, mass spectrometry demonstrated that the protein content of cardiac exosomes differed significantly from other types of exosomes in the literature and contained cytosolic, sarcomeric, and mitochondrial proteins. Third, ethanol did not affect exosome stability but greatly increased the production of exosomes by cardiac myocytes. Fourth, ethanol- and hypoxia/reoxygenation-derived exosomes had different protein content. Finally, ROS inhibition reduced exosome production but did not completely inhibit it. In conclusion, exosomal protein content is influenced by the cell source and stimulus for exosome formation. ROS stimulate exosome production. The functions of exosomes remain to be fully elucidated.
A Theoretical Approach to Pseudogap and Superconducting Transitions in Hole-Doped Cuprates
Authors: Goswami Partha
Published: February 2013

We consider a two-dimensional fermion system on a square lattice described by a mean-field Hamiltonian involving the singlet id-density wave (DDW) order, assumed to correspond to the pseudo-gap (PG) state, favored by the electronic repulsion and the coexisting -wave superconductivity (DSC) driven by an assumed attractive interaction within the BCS framework. Whereas the single-particle excitation spectrum of the pure DDW state consists of the fermionic particles and holes over the reasonably conducting background, the coexisting states corresponds to Bogoliubov quasi-particles in the background of the delocalized Cooper pairs in the momentum space. We find that the two gaps in the single-particle excitation spectrum corresponding to PG and DSC, respectively, are distinct and do not merge into one “quadrature” gap if the nesting property of the normal state dispersion is absent. We show that the PG and DSC are representing two competing orders as the former brings about a depletion of the spectral weight available for pairing in the anti-nodal region of momentum space where the superconducting gap is supposed to be the largest. This indicates that the PG state perhaps could not be linked to a preformed pairing scenario. We also show the depletion of the spectral weight below at energies larger than the gap amplitude. This is an important hallmark of the strong coupling superconductivity.
Remodeling and Estimation for Sparse Partially Linear Regression Models
Authors: Zeng Yunhui , Wang Xiuli , Lin Lu
Published: February 2013

When the dimension of covariates in the regression model is high, one usually uses a submodel as a working model that contains significant variables. But it may be highly biased and the resulting estimator of the parameter of interest may be very poor when the coefficients of removed variables are not exactly zero. In this paper, based on the selected submodel, we introduce a two-stage remodeling method to get the consistent estimator for the parameter of interest. More precisely, in the first stage, by a multistep adjustment, we reconstruct an unbiased model based on the correlation information between the covariates; in the second stage, we further reduce the adjusted model by a semiparametric variable selection method and get a new estimator of the parameter of interest simultaneously. Its convergence rate and asymptotic normality are also obtained. The simulation results further illustrate that the new estimator outperforms those obtained by the submodel and the full model in the sense of mean square errors of point estimation and mean square prediction errors of model prediction.
Diet across the Lifespan and the Association with Breast Density in Adulthood
Authors: Lindgren Jessica , Dorgan Joanne , Savage-Williams Jennifer , Coffman Donna , Hartman Terryl
Published: February 2013

Studies have shown inconsistent results regarding the association between dietary factors across the lifespan and breast density and breast cancer in women. Breast density is a strong risk factor for breast cancer, and the mechanism through which it influences cancer risk remains unclear. Breast density has been shown to be modifiable, potentially through dietary modifications. The goal of this paper is to summarize the current studies on diet and diet-related factors across all ages, determine which dietary factors show the strongest association with breast density, the most critical age of exposure, and identify future directions. We identified 28 studies, many of which are cross-sectional, and found that the strongest associations are among vitamin D, calcium, dietary fat, and alcohol in premenopausal women. Longitudinal studies with repeated dietary measures as well as the examination of overall diet over time are needed to confirm these findings.
Epibenthic Assessment of a Renewable Tidal Energy Site
Authors: Sheehan Emma V. , Gall Sarah C. , Cousens Sophie L. , Attrill Martin J.
Published: February 2013

Concern over global climate change as a result of fossil fuel use has resulted in energy production from renewable sources. Marine renewable energy devices provide clean electricity but can also cause physical disturbance to the local environment. There is a considerable paucity of ecological data at potential marine renewable energy sites that is needed to assess potential future impacts and allow optimal siting of devices. Here, we provide a baseline benthic survey for the Big Russel in Guernsey, UK, a potential site for tidal energy development. To assess the suitability of proposed sites for marine renewable energy in the Big Russel and to identify potential control sites, we compared species assemblages and habitat types. This baseline survey can be used to select control habitats to compare and monitor the benthic communities after installation of the device and contribute towards the optimal siting of any future installation.
Lymph Node Metastasis after a Soft Tissue Sarcoma of the Leg: A Case Report and a Review of the Literature
Authors: Nelen S. D. , Vogelaar F. J. , Gilissen F. , Van der Linden J. C. , Bosscha K.
Published: February 2013

Introduction. Soft tissue sarcomas (STSs) represent 1 percent of all adult malignancies and sarcomas only rarely spread to the regional lymph nodes.Case Presentation. We present a case of a woman with a dermatofibrosarcoma protuberans and a sarcoma not therwise specified of the lower extremity. The patient had no distant metastasis during follow-up, but did develop a regional lymph nodemetastasis (RLNM) in the groin. We reviewed the literature about RLNM in STSs.Discussion. Reviewing the literature we see that within specific histological types RLNM occurs as often as distant metastasis. Furthermore RLNM occurs in over 10% for specific histological types and in 24% of all patients with a soft tissue sarcoma of the lower extremity. Except for radical lymphadenectomy with a 5-year survival rate of 46% there is no appropriate treatment.Conclusion. The risk for a RLNM in certain histological types and anatomical locations might transcend the risk for a distant lung metastasis.
A Bayesian Classifier Learning Algorithm Based on Optimization Model
Authors: Liu Sanyang , Zhu Mingmin , Yang Youlong
Published: February 2013

Naive Bayes classifier is a simple and effective classification method, but its attribute independence assumption makes it unable to express the dependence among attributes and affects its classification performance. In this paper, we summarize the existing improved algorithms and propose a Bayesian classifier learning algorithm based on optimization model (BC-OM). BC-OM uses the chi-squared statistic to estimate the dependence coefficients among attributes, with which it constructs the objective function as an overall measure of the dependence for a classifier structure. Therefore, a problem of searching for an optimal classifier can be turned into finding the maximum value of the objective function in feasible fields. In addition, we have proved the existence and uniqueness of the numerical solution. BC-OM offers a new opinion for the research of extended Bayesian classifier. Theoretical and experimental results show that the new algorithm is correct and effective.
MicroRNA-Related Genetic Variants Associated with Clinical Outcomes in Early-Stage Non–Small Cell Lung Cancer Patients
Authors: Pu Xia , Roth Jack A. , Hildebrandt Michelle A.T. , Ye Yuanqing , Wei Hua , Minna John D. , Lippman Scott M. , Wu Xifeng
Published: February 2013

Given the density of single-nucleotide polymorphisms (SNP) in the human genome and the sensitivity of single-nucleotide changes in microRNA (miRNA) functionality and processing, we asked whether polymorphisms within miRNA processing pathways and binding sites may influence non–small cell lung cancer (NSCLC) patients' prognosis. We genotyped 240 miRNA-related SNPs in 535 patients with stage I and II NSCLCs to determine associations with overall recurrence and survival as well as effect in specific treatment subgroups. After correcting for multiple comparisons, the G allele of FZD4:rs713065 displayed a significant association with decreased risk of death in surgery-only patients [HR, 0.46; 95% confidence interval (CI), 0.32–0.65]. DROSHA:rs6886834 variant A allele (HR, 6.38; 95% CI, 2.49–16.31) remained significant for increased risk of recurrence in the overall and surgery-only populations, respectively. FAS:rs2234978 G allele remained significantly associated with survival in all patients (HR, 0.59; 95% CI, 0.44–0.77), whereas borderline significant in subgroups (surgery-only: HR, 0.59; 95% CI, 0.42–0.84; surgery plus chemo: HR, 0.19; 95% CI, 0.07–0.46). Luciferase assays showed that the FAS SNP created a miR-651 functional binding site. Survival tree analysis was conducted to classify patients into distinct risk subgroups based on their risk genotype combinations. These results indicate that miRNA-related polymorphisms may be associated with NSCLC patients' clinical outcomes through altered miRNA regulation of target genes. Cancer Res; 73(6); 1867–75. ©2013 AACR.
Erlotinib Prolongs Survival in Pancreatic Cancer by Blocking Gemcitabine-Induced MAPK Signals
Authors: Miyabayashi Koji , Ijichi Hideaki , Mohri Dai , Tada Motohisa , Yamamoto Keisuke , Asaoka Yoshinari , Ikenoue Tsuneo , Tateishi Keisuke , Nakai Yousuke , Isayama Hiroyuki , Morishita Yasuyuki , Omata Masao , Moses Harold L. , Koike Kazuhiko
Published: February 2013

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the EGF receptor (EGFR) inhibitor erlotinib with gemcitabine has been the only molecular-targeted drug tested so far that has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen remains unknown. Here, we show that the combination is superior to gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout). We found that gemcitabine induced mitogen-activated protein kinase signaling, which was dramatically inhibited by erlotinib even in the Kras-activated PDAC cells in the mouse model. Mechanistic investigations suggested that gemcitabine induces EGFR ligand expression and ERBB2 activation by increasing heterodimer formation with EGFR, thereby maintaining high levels of ERBB2 protein in PDAC cells. Overall, our findings suggest a significant role of ERBB in PDAC treatment. Cancer Res; 73(7); 2221–34. ©2013 AACR.
Intrinsic Resistance to JAK2 Inhibition in Myelofibrosis
Authors: Kalota Anna , Jeschke Grace R. , Carroll Martin , Hexner Elizabeth O.
Published: February 2013

Purpose: Recent results have shown that myeloproliferative neoplasms (MPN) are strongly associated with constitutive activation of the Janus-activated kinase (JAK)2 tyrosine kinase. However, JAK2 inhibitors currently approved or under development for treating myeloproliferative neoplasms do not selectively deplete the malignant clone, and the inhibition of activity of the drug target (JAK2) has not been rigorously evaluated in the clinical studies. Therefore, in this study we developed an in vitro assay to gain insight into how effectively JAK2 activity is inhibited in the samples of patients.

Experimental Design: We treated primary cells from normal donors and patients with MPN with JAK2 inhibitors and measured phosphorylation of downstream targets STAT5 and STAT3 by flow cytometry. Obtained results were next correlated with JAK2 V617F allele burden and plasma cytokine level.

Results: We observed a dose-dependent decrease in pSTAT5 and pSTAT3 in ex vivo treated granulocytes. However, phosphorylation of STAT3 and STAT5 in cells from patients with myelofibrosis was significantly less inhibited when compared with cells from patients with polycythemia vera, essential thrombocythemia, and normal donors. Sensitivity to inhibition did not correlate with JAK2 V617F clonal burden. Mixing studies using plasma from patients with myelofibrosis did not transfer resistance to sensitive cells. Likewise, no single cytokine measured seemed to account for the observed pattern of resistance.

Conclusions:Taken together, these observations suggest that there are cell intrinsic mechanisms that define a priori resistance to JAK2 inhibition in myelofibrosis, and the lesion is localized upstream of STAT3 and STAT5. Clin Cancer Res; 19(7); 1729–39. ©2013 AACR.
EpCAM Modulates NF-κB Signaling and Interleukin-8 Expression in Breast Cancer
Authors: Sankpal Narendra V. , Fleming Timothy P. , Gillanders William E.
Published: February 2013

The epithelial cell adhesion molecule (EpCAM) is a 40-kD type I transmembrane protein that is overexpressed in human epithelial cancers and is currently the target of molecular therapy based on its overexpression at the cell surface. Recently, we and others have shown a role for EpCAM in cell signaling and carcinogenesis, and EpCAM expression seems to promote breast cancer invasion. Interleukin-8 (IL-8/CXCL-8) is an inflammatory cytokine that has recently been shown to modulate breast cancer invasion and angiogenesis. In preliminary experiments, we identified a correlation between EpCAM and IL-8 expression in primary human breast cancers. Specific ablation of EpCAM in breast cancer cell lines results in decreased IL-8 expression, and IL-8 contributes to EpCAM-dependent breast cancer invasion. Specific ablation of EpCAM is also associated with decreased NF-κB transcription factor activity, decreased phosphorylation of the NF-κB family member RELA, and increased IκBα protein expression. EpCAM modulates IL-8 expression at baseline, and following IL-1β stimulation, which is known to be a potent inducer of NF-κB in breast cancer. In functional rescue experiments, specific ablation of RELA or forced expression of the NF-κB inhibitor protein IκBα prevented EpCAM-dependent rescue of IL-8 promoter activity. These studies show for the first time that EpCAM can modulate NF-κB transcription factor activity and IL-8 expression in breast cancer and confirm the role of EpCAM signaling in modulating breast cancer invasion. Further study is required to define the molecular mechanism(s) of EpCAM signaling in breast cancer and to direct the rational development of molecular therapies targeting EpCAM. Mol Cancer Res; 11(4); 418–26. ©2013 AACR.
The HER2- and Heregulin β1 (HRG)–Inducible TNFR Superfamily Member Fn14 Promotes HRG-Driven Breast Cancer Cell Migration, Invasion, and MMP9 Expression
Authors: Asrani Kaushal , Keri Ruth A. , Galisteo Rebeca , Brown Sharron A.N. , Morgan Sarah J. , Ghosh Arundhati , Tran Nhan L. , Winkles Jeffrey A.
Published: February 2013

HER2 overexpression occurs in 15% to 20% of all breast cancers and is associated with increased metastatic potential and poor patient survival. Abnormal HER2 activation, either through HER2 overexpression or heregulin (HRG):HER3 binding, elicits the formation of potent HER2–HER3 heterodimers and drives breast cancer cell growth and metastasis. In a previous study, we found that fibroblast growth factor-inducible 14 (Fn14), a member of the TNF receptor superfamily, was frequently overexpressed in human HER2+ breast tumors. We report here that HER2 and Fn14 are also coexpressed in mammary tumors that develop in two different transgenic mouse models of breast cancer. In consideration of these findings, we investigated whether HER2 activation in breast cancer cells could directly induce Fn14 gene expression. We found that transient or stable transfection of MCF7 cells with a HER2 expression plasmid increased Fn14 protein levels. Also, HRG1-β1 treatment of MCF7 cells transiently induced Fn14 mRNA and protein expression. Both the HER2- and HRG1-β1–induced increase in Fn14 expression in MCF7 cells as well as basal Fn14 expression in HER2 gene-amplified AU565 cells could be reduced by HER2 kinase inhibition with lapatinib or combined HER2 and HER3 depletion using siRNA. We also report that Fn14-depleted, HER2-overexpressing MCF7 cells have reduced basal cell migration capacity and reduced HRG1-β1–stimulated cell migration, invasion, and matrix metalloproteinase (MMP)-9 expression. Together, these results indicate that Fn14 may be an important downstream regulator of HER2/HER3–driven breast cancer cell migration and invasion. Mol Cancer Res; 11(4); 393–404. ©2013 AACR.
Equivalent Benefit of Rapamycin and a Potent mTOR ATP-Competitive Inhibitor, MLN0128 (INK128), in a Mouse Model of Tuberous Sclerosis
Authors: Guo Yanan , Kwiatkowski David J.
Published: February 2013

Tuberous sclerosis complex (TSC) is a hamartoma syndrome in which brain, renal, and lung tumors develop and cause both morbidity and death. Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1. Rapamycin and related drugs have been shown to have clinical benefit for these tumors in patients with TSC and those with sporadic forms of TSC-related neoplasms. However, lifelong therapy seems to be required, as tumors are not eliminated by this treatment. We examined the potential benefit of MLN0128, a novel potent mTOR ATP-competitive inhibitor, as a therapeutic strategy for renal cystadenomas that develop in A/J Tsc2+/− mice. Rapamycin given by intraperitoneal injection at 3 mg/kg 3 times per week, and MLN0128 given by gavage at 0.75 mg/kg 5 times per week had equivalent effects in suppressing tumor development during a 4-week treatment period, with an approximate 99% reduction in microscopic tumor cell volume. Marked reduction in activation of mTOR complex (mTORC)1 and blockade of cell growth was seen with both drugs, whereas only MLN0128 treatment had effects in blocking mTORC2 and 4EBP1 phosphorylation. However, when either drug was discontinued and mice were observed for two additional months, there was dramatic recovery of tumor growth, with extensive proliferation. Hence, longlasting tumor growth control is not achieved with transient treatment with either drug, and MLN0128 and rapamycin have equivalent therapeutic benefit in this mouse model. Differences in side-effect profiles might make MLN0128 more attractive for treatment of patients with TSC-related tumors, but will require additional study in humans. Mol Cancer Res; 11(5); 467–73. ©2013 AACR.
Individual Saturated and Monounsaturated Fatty Acids Trigger Distinct Transcriptional Networks in Differentiated 3T3-L1 Preadipocytes
Authors: Shaw Brittany , Lambert Samuel , Wong Monica H.T. , Ralston Jessica C. , Stryjecki Carolina , Mutch David M.
Published: February 2013

Background/Aims: Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Methods: Differentiated preadipocytes were treated with either 250 µM PA, SA, PMA, or OA for 48 h. Gene expression was analyzed using microarrays and real-time RT-PCR. Data were compared with those of a previous study reporting AT gene expression in humans following the consumption of SFA- or MUFA-enriched diets. Results: Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Conclusions: Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids.
Neuroimaging and Biochemical Markers in the Three Variants of Primary Progressive Aphasia
Authors: Gil-Navarro S. , Lladó A. , Rami L. , Castellví M. , Bosch B. , Bargalló N. , Lomeña F. , Reñé R. , Montagut N. , Antonell A. , Molinuevo J.L. , Sánchez-Valle R.
Published: February 2013

Background/Aim: To investigate in variants of primary progressive aphasia (PPA) the association between current clinical and neuroimaging criteria and biochemical/genetic markers at the individual level. Methods: Thirty-two PPA patients were classified as non-fluent/agrammatic (nfvPPA), semantic (svPPA), or logopenic variant (lvPPA) or as unclassifiable (uPPA). In all patients, we evaluated the neuroimaging criteria (magnetic resonance imaging and/or single photon emission computed tomography/positron emission tomography) of each variant and studied serum progranulin levels, APOE genotype and Alzheimer’s disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested. Results: Ten of 15 (66%) nfvPPA, 5/5 (100%) svPPA and 7/7 (100%) lvPPA patients showed at least one positive neuroimaging-supported diagnostic criterion. All lvPPA and 3/5 (60%) uPPA patients presented AD-CSF biomarkers, which were absent in nfvPPA and svPPA cases. Four (27%) nfvPPA patients had dementia-causing mutations: 2 carried a GRN mutation and 2 the C9ORF72 hexanucleotide expansion. Conclusions: There was an excellent association between clinical criteria and neuroimaging-supported biomarkers in svPPA and lvPPA, as well as with AD-CSF biochemical markers in the lvPPA. Neuroimaging, biochemical and genetic findings in nfvPPA were heterogeneous. Incorporating biochemical/genetic markers into the PPA clinical diagnosis would allow clinicians to improve their predictions of PPA neuropathology, especially in nfvPPA and uPPA cases.
Resonance of Moral Shocks in Abolitionist Animal Rights Advocacy: Overcoming Contextual Constraints
Authors: Wrenn Corey Lee
Published: February 2013

Abstract

Jasper and Poulsen (1995) have long argued that moral shocks are critical for recruitment in the nonhuman animal rights movement. Building on this, Decoux (2009) argues that the abolitionist faction of the nonhuman animal rights movement fails to recruit members because it does not effectively utilize descriptions of suffering. However, the effectiveness of moral shocks and subsequent emotional reactions has been questioned. This article reviews the literature surrounding the use of moral shocks in social movements. Based on this review, it is suggested that the exploitation of emotional reactions to depictions of suffering can sometimes prove beneficial to recruitment, but successful use is contextually rooted in preexisting frameworks, ideology, and identity. It is concluded that a reliance on images and narratives might be misconstrued in a society dominated by nonhuman animal welfare ideology.
Philo and the Physiognomic Tradition
Authors: Lincicum David
Published: February 2013

Abstract

In the context of recent interest in physiognomy among students of ancient Judaism and Christianity, attention to Philo of Alexandria has been strangely lacking. But Philo does evince some knowledge of the practice of physiognomy. After brief orientating remarks, evidence of Philo’s acquaintance with physiognomic topoi is supplied, together with consideration of the weighty objections Philo has to the theoretical underpinnings of strict physiognomics. In the end, Philo may be said to operate with a certain “physiognomic consciousness” even if he does not have the psychological theory and trust in sense-perception necessary to sustain a more far-reaching commitment to the practice.
Role of Interactions between Aerosol Radiative Effect, Dynamics, and Cloud Microphysics on Transitions of Monsoon Intraseasonal Oscillations
Authors: Hazra Anupam , Goswami B. N. , Chen Jen-Ping
Published: February 2013

Extended-range prediction of monsoon intraseasonal oscillations (MISOs), crucial for agriculture and water management, is limited by their event-to-event variability. Here, the authors propose a hypothesis supported by a number of model simulations involving detailed cloud microphysical processes indicating that aerosols contribute significantly to the transitions from “break” to “active” phases of MISO. The role of aerosol indirect effect in the process of invigoration of precipitation is demonstrated with a high-resolution regional model for Indian summer monsoon breaks that are followed by an active condition (BFA) and contrasted with breaks that are not followed by an active condition (BNFA). The BFA are characterized by higher concentrations of absorbing aerosols that lead to a stronger north–south low-level temperature gradient and strong moisture convergence. Forced uplift beyond the freezing level initiates the cold-rain process involving mixed-phase microphysics and latent heat release at higher levels, thereby invigorating convection, enhancing precipitation, and resulting in an active condition. While more aerosols tend to reduce the cloud drop size and delay the warm rain, it is overcome by the higher moisture convergence during BFA and invigoration by cold-rain processes. The net production of rainfall is sensitive to cloud structure as it depends on the relative strength of the warm- and cold-rain initiation processes. The results indicate the importance of aerosols on transitions of MISO and a pathway by which they influence the transitions involving complex interactions between direct radiative forcing, large-scale dynamics, and cloud microphysics. Broader implications of these results in event-to-event variability of MISO and its predictability are also highlighted.
Implicit Theories of Relationships and Close Relationship Violence
Authors: Cobb Rebecca A. , DeWall C. Nathan , Lambert Nathaniel M. , Fincham Frank D.
Published: February 2013

People differ in what they think makes for a successful relationship, but it is unclear how these beliefs relate to the perpetration of violence. Four studies ( N = 2,591) examined the relationship between growth beliefs and the perpetration of violence in close relationships. Specifically, the current work tested the hypothesis that growth beliefs mitigate against close relationship violence, possibly due to increased satisfaction with sacrificing one’s own self-interest for the betterment of the relationship. Studies 1 and 2 provided cross-sectional and longitudinal evidence that growth beliefs predicted less perpetration of close relationship violence. Studies 3 and 4 showed that the relationship between growth beliefs and lower perpetration of violence was mediated by satisfaction with sacrifice within one’s relationship. All effects of growth beliefs remained significant after controlling for destiny beliefs. Discussion centers on the importance of implicit theories of relationships for understanding the perpetration of violence in close relationships.
Will I Marry if My Parents Can’t? Young Adults With LGB Parents Consider Marriage for Themselves
Authors: Goldberg Abbie E.
Published: February 2013

Although an emerging body of research has examined lesbian, gay, and bisexual (LGB) adults’ attitudes and feelings about marriage, very little research has explored how their offspring view marriage. The current exploratory, qualitative, interview-based study of 35 adolescents and emerging adults (ages 15-28 years; mean age = 21 years) with LGB parents examines their attitudes about and desire for marriage. Results revealed that many participants endorsed romantic ideas about marriage and hoped to someday marry themselves. Other participants expected to marry, but solely for “pragmatic” reasons (i.e., legal/financial protections). Some participants expressed concerns about the institution of marriage, and therefore rejected marriage for themselves—although some conceded that they might marry if and when all LGB people were able to marry. Finally, a small group of participants expressed a desire to marry, but struggled with the idea of marrying when their LGB parents could not. These findings reveal great diversity in the marital desires of young adults with LGB parents, and highlight the various social contexts that ultimately shape their beliefs and intentions surrounding marriage.
Emotional and social loneliness in later life
Authors: Liu Brittany S. , Rook Karen S.
Published: February 2013

The adverse effects of loneliness on health and well-being accelerate with age, making it important to understand the relationship experiences that underlie loneliness in later life. The current study distinguished between emotional and social loneliness and compared their associations with parallel categories of positive and negative social exchanges in a representative sample of older adults. Given the high rates of marital loss in later life, analyses included comparisons of currently and formerly married individuals. The results revealed that emotional support and its negative counterpart (insensitive behavior) are particularly consequential for emotional loneliness among married participants. Companionship was associated with emotional and social loneliness among married and formerly married participants, whereas its negative counterpart (rejection) appeared to be particularly consequential for social loneliness among formerly married participants. The results underscore the value of a differentiated approach to older adults’ loneliness and social exchanges.
Estimation and performance evaluation of optimal hedge ratios in the carbon market of the European Union Emissions Trading Scheme
Authors: Fan John Hua , Roca Eduardo , Akimov Alexandr
Published: February 2013

Following the introduction of the European Union Emissions Trading Scheme (EU-ETS), CO2 emissions have become a tradable commodity. As a regulated party, emitters are forced to take into account the additional cost of carbon emissions in their production costs structure. Given the high volatility in the carbon price, the importance of price risk management becomes unquestionable. This study is the first attempt that has been made to calculate hedge ratios and to investigate their hedging effectiveness in the EU-ETS carbon market by applying conventional, recently developed estimation models. These hedge ratios are then compared with those derived for other markets. In spite of the uniqueness and novelty of the carbon market, the results of the study are consistent with those found in other markets – that the hedge ratio is in the range of 0.5–1.0 and is still best estimated by simple regression models.
Limitations for Interpreting Failure on Individual Subtests of the Montreal Cognitive Assessment
Authors: Moafmashhadi Parastoo , Koski Lisa
Published: February 2013

Background:

The Montreal Cognitive Assessment (MoCA) is sensitive to mild forms of cognitive impairment in geriatric populations and asks questions under the subheadings visuospatial/executive, naming, attention, language, abstraction, delayed recall, and orientation. This study examined the extent to which these subsets of MoCA items evaluate their intended cognitive domains.

Methods:

Clinical data from 185 geriatric memory clinic outpatients who underwent cognitive screening and subsequent neuropsychological assessment were analyzed. Factor analysis of their neuropsychological test scores identified 5 cognitive domains memory, language, visuospatial ability, attention/processing speed, and cognitive control. Scores on MoCA subtests were examined for their correlations with individual factor scores and for their sensitivity and specificity in predicting impairment within each domain.

Results:

The MoCA subtest scores correlated significantly but modestly with neuropsychological test factor scores in their corresponding domains, for example, the correlation between 5-word recall and the memory factor was 0.46. However, subtest scores were poor predictors of impaired performance on the tests contributing to each cognitive domain. The best predictive accuracy was seen for the visuospatial/executive subtest that showed fair accuracy at predicting impairment on tests in the visuospatial domain. Other subtests showed unacceptably poor levels of accuracy when predicting impaired scores in their respective domains (60%-67%).

Conclusions:

In a sample of geriatric outpatients referred for cognitive assessment, performance on individual items and subtests of the MoCA yields insufficient information to draw conclusions about impairment in specific cognitive domains as determined by neuropsychological testing.
Estimating efficacy in the presence of non-ignorable non-trial interventions in the Helsinki Psychotherapy Study
Authors: Härkänen Tommi , Arjas Elja , Laaksonen Maarit A , Lindfors Olavi , Haukka Jari , Knekt Paul
Published: February 2013

In a randomised clinical trial with a longitudinal outcome, analyses of the efficacy of the study treatments may be complicated by both non-trial interventions, which have not been administered by the researcher, and sparsely measured outcome values. The delay between the change in outcome and the starting of the non-trial intervention may be much shorter than the time intervals between the actual measurements. We propose a model that accounts for the possible dynamic interdependence between the longitudinal outcome and time-to-event data. The model is based on discretising time into short intervals. This results in a missing data problem, which we tackle using Bayesian inference and data augmentation. The method is based on the assumption that decisions to initiate non-trial interventions are not confounded by unobservable factors. The Helsinki Psychotherapy Study data are used as an illustration. Different psychotherapies were compared, and possible episodes of psychotropic medication were viewed as non-trial interventions. Simulation studies suggest that our method provides reasonable estimates of the effects of both the study treatment and the non-trial intervention also showing some robustness against possible latent background factors. An application of marginal structural modelling, however, appeared to underestimate the differences between the treatments.