bluuebunny/crossref_metadata_2025 huggingface dataset:
EMBEDDINGS OF *-GRAPHS INTO 2-SURFACES
Authors: FRIESEN TYLER , MANTUROV VASSILY OLEGOVICH
Published: November 2013

This paper considers *-graphs in which all vertices have degree 4 or 6, and studies the question of calculating the genus of orientable 2-surfaces into which such graphs may be embedded. A *-graph is a graph endowed with a formal adjacency structure on the half-edges around each vertex, and an embedding of a *-graph is an embedding under which the formal adjacency relation on half-edges corresponds to the adjacency relation induced by the embedding. *-graphs are a natural generalization of four-valent framed graphs, which are four-valent graphs with an opposite half-edge structure. In [Embeddings of four-valent framed graphs into 2-surfaces, Dokl. Akad. Nauk424(3) (2009) 308–310], the question of whether a four-valent framed graph admits a ℤ2-homologically trivial embedding into a given surface was shown to be equivalent to a problem on matrices. We show that a similar result holds for *-graphs in which all vertices have degree 4 or 6. This gives an algorithm in quadratic time to determine whether a *-graph admits an embedding into the plane.
NEUTRINO COUPLING TO COSMOLOGICAL BACKGROUND: A REVIEW ON GRAVITATIONAL BARYO/LEPTOGENESIS
Authors: LAMBIASE GAETANO , MOHANTY SUBHENDRA , PRASANNA ARAGAM R.
Published: November 2013

In this paper, we review the theories of origin of matter–antimatter asymmetry in the universe. The general conditions for achieving baryogenesis and leptogenesis in a CPT conserving field theory have been laid down by Sakharov. In this review, we discuss scenarios where a background scalar or gravitational field spontaneously breaks the CPT symmetry and splits the energy levels between particles and antiparticles. Baryon or Lepton number violating processes in proceeding at thermal equilibrium in such backgrounds gives rise to Baryon or Lepton number asymmetry.
THE UNREASONABLE EFFECTIVENESS OF EXPONENTIALLY SUPPRESSED CORRECTIONS IN PRESERVING INFORMATION
Authors: PAPADODIMAS KYRIAKOS , RAJU SUVRAT
Published: November 2013

We point out that nonperturbative effects in quantum gravity are sufficient to reconcile the process of black hole evaporation with quantum mechanics. In ordinary processes, these corrections are unimportant because they are suppressed by e-S. However, they gain relevance in information-theoretic considerations because their small size is offset by the corresponding largeness of the Hilbert space. In particular, we show how such corrections can cause the von Neumann entropy of the emitted Hawking quanta to decrease after the Page time, without modifying the thermal nature of each emitted quantum. Second, we show that exponentially suppressed commutators between operators inside and outside the black hole are sufficient to resolve paradoxes associated with the strong subadditivity of entropy without any dramatic modifications of the geometry near the horizon.
CVA UNDER ALTERNATIVE SETTLEMENT CONVENTIONS AND WITH SYSTEMIC RISK
Authors: DURAND CYRIL , RUTKOWSKI MAREK
Published: November 2013

We propose a fairly general framework which allows one to perform Credit Value Adjustment (CVA) computations for a contract with bilateral counterparty risk in the presence of (a) systemic risk and (b) wrong-way or right-way risks. Our methodology focuses on the role of alternative settlement clauses, but it also aims to cover various features of margin agreements. We present a comparative analysis of numerical results that supports our initial conjecture that alternative specifications of settlement values have a nonnegligible impact on CVA computations for contracts with bilateral counterparty risk. Our conclusions emphasize the practical importance of more sophisticated models that are capable of fully reflecting the actual features of financial contracts, as well as the influence of the market environment.
DISCRETE WAVELET TRANSFORM OF FINITE SIGNALS: DETAILED STUDY OF THE ALGORITHM
Authors: RAJMIC PAVEL , PRUSA ZDENEK
Published: November 2013

The paper presents a detailed analysis of algorithms used for the forward and the inverse discrete wavelet transform (DTWT) of finite-length signals. The paper provides answers to questions such as "how many wavelet coefficients are computed from the signal at a given depth of the decomposition" or conversely, "how many signal samples are needed to compute a single wavelet coefficient at a given depth of the decomposition" or "how many coefficients at a given depth are influenced by the selected type of boundary treatment" or "how many samples of the input signal simultaneously influence two neighboring wavelet coefficients at a given depth of the decomposition". As a byproduct, the rigorous analysis of the algorithms gives details needed for the implementation. The paper is accompanied by several Matlab functions.
NAVIGATION METHODS FOR THE SKIING ROBOT
Authors: PETRIČ TADEJ , PETERNEL LUKA , GAMS ANDREJ , NEMEC BOJAN , ŽLAJPAH LEON
Published: November 2013

In this paper, we propose and evaluate methods for the local navigation using only visual perception for the skiing robot. Our skiing robot, capable of skiing using the carving technique, has no direct control on the velocity of skiing as it cannot break or accelerate, therefore well known navigation methods for nonholonomic mobile robots cannot be directly applied. We consider the following methods: an intuitive method of aiming at the closest gates, a human obstacle avoidance movement model, neural networks learning from a set of human demonstrations, and a global method that uses a predefined, spline-encoded path. The navigation performance of the robot on unknown ski courses is evaluated using two criteria: successful completion of the course and the time required to complete the course. Simulation results show the applicability and drawbacks of presented methods. Finally, the method using the neural networks was applied on a real-world skiing robot and we tested navigating a slalom course on both roller blades and skies.
TOWARDS UNDERSTANDING AUTISM RISK FACTORS: A CLASSIFICATION OF BRAIN IMAGES WITH SUPPORT VECTOR MACHINES
Authors: CHEN COLLEEN PAM , KEOWN CHRISTOPHER LEE , MÜLLER RALPH-AXEL
Published: November 2013

We demonstrate the use of support vector machine methods to classify autism neuroimaging data collected from multiple sites.
ON THE MINIMAL DISTANCE SPECTRAL RADIUS IN THE CLASS OF BICYCLIC GRAPHS
Authors: NATH MILAN , PAUL SOMNATH
Published: November 2013

Bicyclic graphs are connected graphs in which the number of edges equals the number of vertices plus one. The class of bicyclic graphs of order n, denoted by ℬn, can be partitioned into two subclasses: the class [Formula: see text] of graphs which contain induced ∞-graphs, and the class [Formula: see text] of graphs which contain induced θ-graphs. Bose et al. [2] have found the graph having the minimal distance spectral radius in [Formula: see text]. In this paper, we determine the graphs having the minimal distance spectral radius in [Formula: see text]. These results together give a complete characterization of the graphs having the minimal distance spectral radius in ℬn.
Age of the magmatism related to the inverted Stephanian–Permian basin of the Sallent area (Pyrenees)
Authors: Rodríguez-Méndez Lidia , Cuevas Julia , Esteban José Julián , Tubía José M. , Sergeev Sergei , Larionov Alexander
Published: November 2013

We have dated an alkaline diabase dyke from the Axial Zone of the Pyrenees near the village of Sallent (Spain), using a sensitive high-resolution ion microprobe (SHRIMP). The diabase dyke intrudes into Devonian rocks that constitute the basement of an inverted Stephanian–Permian basin. Five U–Pb analyses of zircon yield a concordant age of 259.2±3.2 Ma (2σ) for the intrusion of the dyke. This age links diabase dykes with the magmatism associated with the opening of the Stephanian–Permian basins scattered along the Pyrenees. Previous data from the largest Anayet and Midi d'Ossau volcanic massifs, located to the NW of the studied dyke, indicate that the Permian magmatism develops from late Autunian/early Saxonian to Wordian ages. Consequently, this new age broadens the time span of the Permian magmatism of the Pyrenees. The work relates the structure of the Stephanian–Permian basin and the magmatism in order to explain the transition to the new geodynamic setting prevailing in the Pyrenees during the Mesozoic.
Strain and foliation refraction patterns around buckle folds
Authors: Frehner Marcel , Exner Ulrike
Published: November 2013

Axial plane foliation associated with geological folds may exhibit a divergent or convergent fan. Commonly, the foliation is assumed to reflect the major principal finite strain orientation. Here, the strain orientation around numerically simulated single-layer buckle folds is analysed in detail. Four different strain measures are considered: (1) finite strain, (2) infinitesimal strain, (3) incremental strain (recording the strain history from a certain shortening value until the end), and (4) initially layer-perpendicular passive marker lines. In the matrix at the outer arc of the fold, all strain measures result in similar divergent fan patterns. Therefore, divergent foliation fans around natural folds cannot readily be associated with the finite strain orientation as they may reflect other strain measures. In the simulated folds, the convergent fans in the stronger layer show differences between the different strain measures, which are associated with a 90°-switch of the major principal strain from a layer-perpendicular to a layer-parallel orientation at the outer arc. A similar observation is made in one of three studied natural folds (near Ribadeo and Luarca, NW Spain). It is suggested that the convergent foliation fan pattern inside a fold is better suited for strain estimates than the divergent fan around a fold.
Intraluminal acid activates esophageal nodose C fibers after mast cell activation
Authors: Zhang Shizhong , Liu Zhenyu , Heldsinger Andrea , Owyang Chung , Yu Shaoyong
Published: November 2013

Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2–3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acid-induced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation.
Large intestine permeability is increased in patients with compensated liver cirrhosis
Authors: Pijls Kirsten E. , Koek Ger H. , Elamin Elhaseen E. , de Vries Hanne , Masclee Ad A. M. , Jonkers Daisy M. A. E.
Published: November 2013

Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Increased intestinal permeability has been found in patients with liver cirrhosis, but data on small and large intestine permeability and tight junctions (TJs) in patients with compensated cirrhosis are scarce. We aimed to investigate both small and large intestine permeability in patients with stable compensated cirrhosis compared with healthy controls and evaluated the expression of TJ proteins in mucosal biopsies at duodenal and sigmoid level. Intestinal permeability was assessed in 26 patients with compensated cirrhosis and 27 matched controls using a multisugar test. Duodenal and sigmoid biopsies were available from a subgroup for analyses of gene transcription and expression of key TJ proteins by qRT-PCR and ELISA, respectively. Median 0–5-h urinary sucrose excretion and lactulose/rhamnose ratio were comparable between patients with compensated cirrhosis and controls, whereas 5–24-h urinary sucralose/erythritol ratio was increased in these patients. Downregulation of gene transcription was found for claudin-3 in duodenal biopsies and claudin-4 in sigmoid biopsies, and at the protein level occludin expression was significantly increased in both duodenal and sigmoid biopsies. This study shows that gastroduodenal and small intestine permeability are not altered, whereas large intestine permeability is increased in patients with stable compensated cirrhosis. Only limited alterations were found regarding the expression of TJ proteins in both the small and large intestine.
Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption
Authors: Yoshimatsu Hiroki , Yonezawa Atsushi , Yao Yoshiaki , Sugano Kumiko , Nakagawa Shunsaku , Omura Tomohiro , Matsubara Kazuo
Published: November 2013

Riboflavin, also known as vitamin B2, is transported across the biological membrane into various organs by transport systems. Riboflavin transporter RFVT3 is expressed in the small intestine and has been suggested to localize in the apical membranes of the intestinal epithelial cells. In this study, we investigated the functional involvement of RFVT3 in riboflavin absorption using intestinal epithelial T84 cells and mouse small intestine. T84 cells expressed RFVT3 and conserved unidirectional riboflavin transport corresponding to intestinal absorption. Apical [3H]riboflavin uptake was pH-dependent in T84 cells. This uptake was not affected by Na+ depletion at apical pH 6.0, although it was significantly decreased at apical pH 7.4. The [3H]riboflavin uptake from the apical side of T84 cells was prominently inhibited by the RFVT3 selective inhibitor methylene blue and significantly decreased by transfection of RFVT3-small-interfering RNA. In the gastrointestinal tract, RFVT3 was expressed in the jejunum and ileum. Mouse jejunal and ileal permeabilities of [3H]riboflavin were measured by the in situ closed-loop method and were significantly reduced by methylene blue. These results strongly suggest that RFVT3 would functionally be involved in riboflavin absorption in the apical membranes of intestinal epithelial cells.
Tumor–Stroma Interaction: Revealing Fibroblast-Secreted Exosomes as Potent Regulators of Wnt-Planar Cell Polarity Signaling in Cancer Metastasis
Authors: Luga Valbona , Wrana Jeffrey L.
Published: November 2013

Cancer-associated fibroblasts (CAF) regulate tumor progression, but their role in cancer metastasis remains largely unexplored. Exosomes are secreted microvesicles that are emerging as potent mediators of cell–cell communication that are of particular importance in tumor–stroma interactions. The Wnt-planar cell polarity (PCP) pathway is the primary regulator of convergent extension cell movements during vertebrate development, but the role of this signaling pathway in cancer cell migration and metastasis has been unclear. Recently, we revealed that fibroblasts secrete exosomes that promote breast cancer cell (BCC) protrusive activity, motility, and metastasis by activating autocrine Wnt-PCP signaling in BCCs. Moreover, we showed that Wnt ligands produced by BCCs tether to fibroblast exosomes upon trafficking of exosomes in BCCs. These findings have several implications that motivate promising future research in the fields of tumor–stroma communication, exosome function, and Wnt-PCP signaling in cancer metastasis. Cancer Res; 73(23); 6843–7. ©2013 AACR.
Clinical and Biochemical Studies Support Smokeless Tobacco's Carcinogenic Potential in the Human Oral Cavity
Authors: Mallery Susan R. , Tong Meng , Michaels Gregory C. , Kiyani Amber R. , Hecht Stephen S.
Published: November 2013

In 2007, the International Agency for Research on Cancer presented compelling evidence that linked smokeless tobacco use to the development of human oral cancer. Although these findings imply vigorous local carcinogen metabolism, little is known about levels and distribution of phase I, II, and III (drug egress) enzymes in human oral mucosa. In this study here, we integrated clinical data, and imaging and histopathologic analyses of an oral squamous cell carcinoma that arose at the site of smokeless tobacco quid placement in a patient. Immunoblot and immunohistochemical (IHC) analyses were used to identify tumor and normal human oral mucosal smokeless tobacco-associated metabolic activation and detoxification enzymes. Human oral epithelium contains every known phase I enzyme associated with nitrosamine oxidative bioactivation with approximately 2-fold interdonor differences in protein levels. Previous studies have confirmed approximately 3.5-fold interdonor variations in intraepithelial phase II enzymes. Unlike the superficially located enzymes in nonreplicating esophageal surface epithelium, IHC studies confirmed that oral mucosal nitrosamine metabolizing enzymes reside in the basilar and suprabasilar region, which notably is the site of ongoing keratinocyte DNA replication. Clearly, variations in product composition, nitrosamine metabolism, and exposure duration will modulate clinical outcomes. The data presented here form a coherent picture consistent with the abundant experimental data that link tobacco-specific nitrosamines to human oral cancer. Cancer Prev Res; 7(1); 23–32. ©2013 AACR.
A Novel AKT1 Mutant Amplifies an Adaptive Melanoma Response to BRAF Inhibition
Authors: Shi Hubing , Hong Aayoung , Kong Xiangju , Koya Richard C. , Song Chunying , Moriceau Gatien , Hugo Willy , Yu Clarissa C. , Ng Charles , Chodon Thinle , Scolyer Richard A. , Kefford Richard F. , Ribas Antoni , Long Georgina V. , Lo Roger S.
Published: November 2013

BRAF inhibitor (BRAFi) therapy leads to remarkable anti melanoma responses, but the initial tumor shrinkage is commonly incomplete, providing a nidus for subsequent disease progression. Adaptive signaling may underlie early BRAFi resistance and influence the selection pattern for genetic variants, causing late, acquired resistance. We show here that BRAFi (or BRAFi + MEKi) therapy in patients frequently led to rebound phosphorylated AKT (p-AKT) levels in their melanomas early on-treatment. In cell lines, BRAFi treatment led to rebound levels of receptor tyrosine kinases (RTK; including PDGFRβ), phosphatidyl (3,4,5)-triphosphate (PIP3), pleckstrin homology domain recruitment, and p-AKT. PTEN expression limited this BRAFi-elicited PI3K–AKT signaling, which could be rescued by the introduction of a mutant AKT1 (Q79K) known to confer acquired BRAFi resistance. Functionally, AKT1Q79K conferred BRAFi resistance via amplification of BRAFi-elicited PI3K–AKT signaling. In addition, mitogen-activated protein kinase pathway inhibition enhanced clonogenic growth dependency on PI3K or AKT. Thus, adaptive or genetic upregulation of AKT critically participates in melanoma survival during BRAFi therapy.

Significance: This study provides a mechanistic link between early, adaptive and late, acquired BRAF inhibitor resistance in melanoma, with early BRAFi-induced signaling alterations shaping the subsequent evolutionary selective pressure. These findings argue for upfront, combined targeting of the mutant BRAF genotype and a pervasive drug-adaptive, AKT-dependent tumor response. Cancer Discov; 4(1); 69–79. ©2013 AACR.

See related commentary by Solit and Rosen, p. 27

This article is highlighted in the In This Issue feature, p. 1
Critical Illness-Related Corticosteroid Insufficiency in Children
Authors: Levy-Shraga Yael , Pinhas-Hamiel Orit
Published: November 2013

Adequate adrenocortical function is essential for survival in critical illness. Most critically ill patients display elevated plasma cortisol concentrations, which reflects activation of the hypothalamic-pituitary-adrenal axis and is considered to be a homeostatic adaptation. However, many critically ill patients have ‘relative' or ‘functional' adrenal insufficiency, which is characterized by an inadequate production of cortisol in relation to an increased demand during periods of severe stress. Recently, the term ‘critical illness-related corticosteroid insufficiency' (CIRCI) was coined. CIRCI occurs as a result of a decrease in adrenal steroid production or tissue resistance to glucocorticoids. An international task force of the American College of Critical Care Medicine issued recommendations for the diagnosis and management of this condition in adult patients. We review the prevalence, diagnosis, and therapeutic approach to adrenal insufficiency in critically ill children. We found a lack of consensus within the pediatric field as to the optimal approach to CIRCI, and call for an international task force to establish unified guidelines.
Factors of Response to Pegylated Interferon/Ribavirin Combination Therapy and Mechanism of Viral Clearance
Authors: Sugimoto Kayo , Kim Soo Ryang , El-Shamy Ahmed , Imoto Susumu , Ando Kenji , Kim Ke Ih , Tanaka Yasuhito , Yano Yoshihiko , Kim Soo Ki , Hasegawa Yutaka , Fujinami Aya , Ohta Mitsuhiro , Takashi Hatae , Hotta Hak , Hayashi Yoshitake , Kudo Masatoshi
Published: November 2013

Objectives: This study explores viral factors of the interferon (IFN) and ribavirin (RBV) resistance-determining region (IRRDR), the IFN sensitivity-determining region (ISDR) and the core protein, and host factor interleukin 28B associated with response to pegylated IFN (PEG-IFN) and RBV combination therapy, and the correlation of viral and host factors with IFN-λ1. Methods: A total of 58 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. The pretreatment factors associated with rapid virological response (RVR) and sustained virological response (SVR) were analyzed. Pretreatment IFN-λ1 serum levels were compared with the viral and host factors. Results: Univariate analysis showed that IRRDR ≥6 and ISDR ≥2 were significant pretreatment predictors of RVR, and multivariate analysis identified IRRDR ≥6 and hemoglobin as significant predictors of SVR. Pretreatment IFN-λ1 was significantly higher in the SVR group than in the non-SVR group and also in the IRRDR ≥6 group than in the IRRDR ≤5 group. Conclusions: IRRDR ≥6 was the only significant predictor of SVR and was correlated with IFN-λ1. High serum levels of IFN-λ1 may be conducive to effective PEG-IFN/RBV combination therapy because of the immunomodulatory system.
Usefulness of the Extracted-Overlay Function in CT/MR-Ultrasonography Fusion Imaging for Radiofrequency Ablation of Hepatocellular Carcinoma
Authors: Makino Yuki , Imai Yasuharu , Igura Takumi , Kogita Sachiyo , Sawai Yoshiyuki , Fukuda Kazuto , Hori Masatoshi , Kudo Masatoshi , Murakami Takamichi
Published: November 2013

Objectives: We developed a novel technique of the extracted-overlay function in CT/MR-ultrasonography (US) fusion imaging for radiofrequency ablation (RFA), in which only a tumor extracted from CT/MR images with a virtual ablative margin of arbitrary thickness is overlaid on US. The usefulness of this function is investigated in this preliminary report. Methods: The volume data of the extracted tumor with a virtual ablative margin were created on an image-processing workstation, and transported into a US unit equipped with a CT/MR-US fusion imaging system. After the positional registration of US and transported images, the extracted tumor with an ablative margin could be overlaid on US. In RFA, using this function, an electrode was inserted targeting the overlaid tumor with an ablative safety margin of 5 mm on US, and the treatment effect was evaluated by dynamic CT. Treatment results of 23 consecutive hepatocellular carcinomas (HCCs) that underwent RFA using this function were retrospectively analyzed. Results: Complete tumor ablation was achieved in 22 (95.7%) and 1 (4.3%) HCCs in 1 and 2 treatment sessions, respectively. Conclusions: Due to the visualization of an extracted tumor with an ablative safety margin on a US image, even during and after ablation, this function is useful for treatment planning and guidance of RFA.
Prediction of Response to Pegylated Interferon/Ribavirin Combination Therapy for Chronic Hepatitis C Genotypes 2a and 2b and High Viral Load
Authors: Kim Soo Ryang , El-Shamy Ahmed , Imoto Susumu , Kim Ke Ih , Sugimoto Kayo , Kim Soo Ki , Tanaka Yasuhito , Hatae Takashi , Hasegawa Yutaka , Fujinami Aya , Ohta Mitsuhiro , Hotta Hak , Kudo Masatoshi
Published: November 2013

Objective: We investigated the impact of host genetics represented by the single nucleotide polymorphism (SNP) of the IL28B gene and viral genetic variations within the nonstructural protein 5A (NS5A) [including the interferon (IFN)/ribavirin (RBV) resistance-determining region (IRRDR) and the IFN sensitivity-determining region (ISDR)] on the outcome of pegylated IFN and RBV (PEG-IFN/RBV) treatment. Methods: Sixty-six patients infected with hepatitis C virus (HCV)-2a or HCV-2b who received PEG-IFN/RBV for 24 weeks were examined. Results: In HCV-2a, the major genotype of IL28B SNP showed a tendency toward association with sustained virological response (SVR) and rapid virological response (RVR), and four or more mutations in IRRDR (IRRDR[2a] ≥4) and one or more mutations in ISDR plus its carboxyl-flanking region (ISDR/+C[2a] ≥1) were significantly associated with SVR and RVR. In HCV-2b, one or more mutations in the N-terminal part of IRRDR (IRRDR/N[2b] ≥1) were significantly associated with RVR. Multivariate analysis identified the major genotype of IL28B SNP and IRRDR[2a] ≥4 as independent predictive factors of SVR in HCV-2a, with IRRDR[2a] ≥4 being more powerful than the IL28B SNP. Also, IRRDR[2a] ≥4 in HCV-2a and IRRDR/N[2b] ≥1 in HCV-2b were significant determiners of RVR. Conclusion: The NS5A sequence heterogeneity and IL28B SNP are useful factors to predict the sensitivity to PEG-IFN/RBV therapy in HCV-2a and HCV-2b infections.
Degree of Decrease in Central Retinal Thickness Predicts Visual Acuity Response to Intravitreal Ranibizumab in Diabetic Macular Edema
Authors: Santos Ana Rita , Gomes Sara Cristina , Figueira João , Nunes Sandrina , Lobo Conceição Lopes , Cunha-Vaz José Guilherme
Published: November 2013

Purpose: To characterize factors that may be associated with optimal or suboptimal response to ranibizumab intravitreal injections in diabetic macular edema (DME). Methods: Fifty-nine eyes with DME treated with ranibizumab were included. All underwent best-corrected visual acuity (BCVA) assessment and optical coherence tomography (OCT) at baseline, 3 and 6 months. Central retinal thickness (CRT) was assessed at each visit, and OCT images were classified according to their morphological patterns. Results: A mean BCVA increase of 4.78 and 5.52 letters, and a CRT decrease of 80.25 and 106.12 µm were found after 3 and 6 months of treatment (p < 0.001). BCVA improvement was found to be dependent on baseline BCVA and the degree of CRT decrease. Twenty-six eyes (44%) showing a CRT decrease ≥20% improved BCVA by 10.3 ± 13.0 letters, whereas 33 eyes (56%) with a CRT decrease <20% had BCVA improvement of 1.8 ± 7.2 letters (odds ratio = 3.31). Conclusions: The degree of CRT decrease obtained by spectral-domain OCT identifies well the optimal responders to intravitreal ranibizumab and predicts BCVA improvement after treatment.
Treatment of Primary Breast Cancer at the Surgical Unit of the Charité 1984-1998
Authors: Winzer Klaus-Jürgen , Buchholz Anika , Guski Hans , Frohberg Hans-Dieter , Diekmann Felix , Possinger Kurt , Sauerbrei Willi
Published: November 2013

Background: We have analyzed the patient population of one clinic (Charité) over a period of 15 years. Besides the changes in the technical facilities and therapeutical guidelines during these years, this period also reflects the changes in the health system attributable to the reunification of East and West Germany. Until now only few analyses for breast cancer patients from the German speaking area have been reported. Patients and Methods: All 2,062 patients undergoing surgical treatment for breast cancer between 1984 and 1998 were documented and followed up until 2007. The analysis included 1,560 patients with a primary breast cancer who fulfilled certain inclusion criteria. The treatment strategies applied to this population are presented in 3 time periods (1984-1990, 1991-1993, and 1994-1998). The effects of prognostic factors on overall survival were investigated using univariate analyses. Results: The percentage of pT1 tumors changed from 50.7% in the first period to 63.1% in the third period. The percentage of node-negative patients hardly changed with time (on average 61.6%). However, the percentage of patients with less than 10 assessed nodes decreased from 48.4% to 6.7% and 2.5% for the 3 periods, respectively. Therapeutic strategies changed drastically. Survival rate increased substantially, most likely due to improved therapeutic strategies, but also for other reasons not considered in the analysis.
Successful Treatment with Nab-Paclitaxel and Gemcitabine after FOLFIRINOX Failure in a Patient with Metastasized Pancreatic Adenocarcinoma
Authors: Berger Anne K. , Weber Tim F. , Jäger Dirk , Springfeld Christoph
Published: November 2013

Background: Advanced pancreatic adenocarcinoma still remains associated with a desperate prognosis. Nevertheless, treatment options for patients with metastasized disease have improved considerably over the last few years. Recently, cytotoxic combination therapies such as the FOLFIRINOX regimen and combined nab-paclitaxel/gemcitabine have shown improved overall survival compared to gemcitabine alone. There is still no standard of care in second-line therapy for patients with disease progression. Case Report: We report the case of a 47-year-old patient who dramatically responded to second-line treatment with nab-paclitaxel and gemcitabine after primary progression to the FOLFIRINOX protocol. Conclusion: Second-line treatment after FOLFIRINOX is feasible for patients with good performance status. Our case report supports preclinical findings that suggest that pancreatic cancer is a heterogeneous disease. Further studies that characterize possible subgroups and identify predictive molecular markers to guide therapy are warranted.
Evaluation of Cardiotoxicity via Speckle-Tracking Echocardiography in Patients Treated with Anthracyclines
Authors: Dogru Atalay , Cabuk Devrim , Sahin Tayfun , Dolasik Ilhan , Temiz Suleyman , Uygun Kazim
Published: November 2013

Background: The aim of this study was to examine the cardiac effects of anthracycline therapy based on speckle-tracking echocardiography (STE) and to identify patients at risk for cardiotoxicity. Patients and Methods: The study included 35 breast cancer (BC) and 15 lymphoma patients who were treated with anthracycline-based chemotherapy. Conventional echocardiography and STE were performed 1 month prior to and 1 month after chemotherapy. Longitudinal strain analysis was performed via STE using automated functional imaging. Results: The ejection fraction (EF) and the fractional shortening values were significantly lower in the lymphoma group. There was a positive correlation between anthracycline dose and subclinical heart failure (p = 0.024). There was an increase in the myocardial performance index in both groups. After therapy, STE showed regional decreases in the longitudinal strain values in the BC group, but the global strain values did not differ. In the lymphoma group, the apical long-axis, the 4-chamber, and the global longitudinal strain values were significantly lower after therapy (p = 0.002, 0.041, and 0.004, respectively). The long-axis and global longitudinal strain values were significantly lower in the lymphoma patients with normal EF values (p = 0.01 and 0.05, respectively). Conclusion: Cardiotoxicity during the early phase of anthracycline treatment can be detected via STE prior to the observation of systolic function deterioration.
A Meta-Analysis of Internal Mammary Lymph Node Metastasis in Breast Cancer Patients
Authors: Li Zongtao , Gu Xiaomei , Tong Junwang , Liu Bingli , Sun Liqian , Gao Xiaozeng , Jiang Xiaohua
Published: November 2013

Background: Knowing the status of the internal mammary lymph (IML) nodes is important for accurate staging and appropriate selection of subsequent treatment in breast cancer. We conducted a meta-analysis to clarify the rate of IML node metastasis in breast cancer patients and discussed the importance of this finding. Methods: We retrieved articles from the literature that reported positive rates of IML node metastasis in breast cancer patients. The quality of the selected articles was assessed using the ‘Methodological Index for Non-Randomized Studies'. The heterogeneity was tested, and publication bias was assessed using a funnel plot. Finally, the positive rate of IML node metastasis in breast cancer patients was calculated using the random-effects model. Results: 15 articles met the inclusion criteria and a total of 4,248 patients were included in the analysis. Heterogeneity across the studies was statistically significant (p = 0.014); thus, the random-effects model was used and the calculated positive rate of IML node metastasis was 23% (95% confidence interval (CI), 0.21-0.25). Conclusions: Approximately 23% of the breast cancer patients had IML node metastases, for which the prognosis is generally poor. Accurate staging and integrated treatment are necessary to improve the survival of these patients.
miR-145 Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma in Part by Targeting c-Myc
Authors: Wang Feng , Xia Jin , Wang Nengchao , Zong Hong
Published: November 2013

Background: Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal cancer and crucial to tumorigenesis. Herein, we identified the role of miR-145 in esophageal squamous cell carcinoma (ESCC) development in vitro and in vivo. Material and Methods: miR-145 expression was investigated in 40 ESCC samples as well as 5 ESCC cell lines by real-time polymerase chain reaction. Crystal violet and transwell assays were conducted to explore the effects of miR-145 on the proliferation and invasion of human ESCC cell lines, respectively. The impact of overexpression of miR-145 on putative target c-Myc was subsequently confirmed via Western blot. Results: miR-145 expression was frequently downregulated in ESCC specimens and cell lines compared with adjacent normal tissues (p < 0.05). Overexpression of miR-145 suppressed (p < 0.05) ESCC cell proliferation and invasion, as well as the growth of xenograft tumors in mice. Overexpression of miR-145 significantly decreased (p < 0.05) the protein level of c-Myc which has previously been identified as a direct target of miR-145. Conclusion: Our results demonstrate that overexpression of miR-145 inhibits tumor growth in part by targeting c-Myc. Our findings revealed that miR-145 may act as a tumor suppressor in ESCC, and its dysregulation may be involved in the initiation and development of human ESCC.
Outcome of Standard and High-Risk Patients With Acute Anterior Circulation Stroke After Stent Retriever Thrombectomy
Authors: Gratz Pascal P. , Jung Simon , Schroth Gerhard , Gralla Jan , Mordasini Pasquale , Hsieh Kety , Heldner Mirjam R. , Mattle Heinrich P. , Mono Marie-Luise , Fischer Urs , Arnold Marcel , Zubler Christoph
Published: November 2013

Background and Purpose—

Stent retrievers have become an important tool for the treatment of acute ischemic stroke. The aim of this study was to analyze outcome and complications in a large cohort of patients with stroke treated with the Solitaire stent retriever. The study also included patients who did not meet standard inclusion criteria for endovascular treatment: low or high baseline National Institutes of Health Stroke Scale score, ≥80 years of age, extensive ischemic signs in middle cerebral artery territory, and time from symptom onset to endovascular intervention >8 hours.

Methods—

Consecutive patients with acute anterior circulation stroke treated with the Solitaire FR were analyzed. Data on characteristics of endovascular interventions, complications, and clinical outcome were collected prospectively. Patients who met standard inclusion criteria were compared with those who did not.

Results—

A total of 227 patients were included. Mean age was 68.2±14.7 years, and median National Institutes of Health Stroke Scale score on admission was 16 (range, 2–36). Reperfusion was successful (thrombolysis in cerebral infarction, 2b–3) in 70.9%. Outcome was favorable (modified Rankin Scale, 0–2) in 57.7% of patients who met standard inclusion criteria and 30.3% of those who did not. The rates for symptomatic intracranial hemorrhage were 3.7% and 13.1%, for death 11.4% and 33.8%, and for symptomatic intraprocedural complications 2.5% and 4.8%, respectively.

Conclusions—

Patients <80 years of age, without extensive pretreatment ischemic signs, and baseline National Institutes of Health Stroke Scale score ≤30 had high rates of favorable outcome and low periprocedural complication rates after Solitaire thrombectomy. Successful reperfusion was also common in patients not fulfilling standard inclusion criteria, but worse clinical outcomes warrant further research with a special focus on optimal patient selection.
Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease
Authors: Dichgans Martin , Malik Rainer , König Inke R. , Rosand Jonathan , Clarke Robert , Gretarsdottir Solveig , Thorleifsson Gudmar , Mitchell Braxton D. , Assimes Themistocles L. , Levi Christopher , O´Donnell Christopher J. , Fornage Myriam , Thorsteinsdottir Unnur , Psaty Bruce M. , Hengstenberg Christian , Seshadri Sudha , Erdmann Jeanette , Bis Joshua C. , Peters Annette , Boncoraglio Giorgio B. , März Winfried , Meschia James F. , Kathiresan Sekar , Ikram M. Arfan , McPherson Ruth , Stefansson Kari , Sudlow Cathie , Reilly Muredach P. , Thompson John R. , Sharma Pankaj , Hopewell Jemma C. , Chambers John C. , Watkins Hugh , Rothwell Peter M. , Roberts Robert , Markus Hugh S. , Samani Nilesh J. , Farrall Martin , Schunkert Heribert ,   Collaborators/second tier of authors:, Gschwendtner Andreas , Bevan Steve , Chen Yu-Ching , DeStefano Anita L. , Parati Eugenio A. , Quertermous Tom , Ziegler Andreas , Boerwinkle Eric , Holm Hilma , Fischer Marcus , Kessler Thorsten , Willenborg Christina , Laaksonen Reijo , Voight Benjamin F. , Stewart Alexandre F.R. , Rader Daniel J. , Hall Alistair S. , Kooner Jaspal S.
Published: November 2013

Background and Purpose—

Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases.

Methods—

Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (
P
<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype.

Results—

Common variants associated with CAD at
P
<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (
P
<5×10
−8
) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (
P
IS
=1.62×10
−7
) and ABO (
P
IS
=2.6×10
−4
), as well as at HDAC9 (
P
LAS
=2.32×10
−12
), 9p21 (
P
LAS
=3.70×10
−6
), RAI1-PEMT-RASD1 (
P
LAS
=2.69×10
−5
), EDNRA (
P
LAS
=7.29×10
−4
), and CYP17A1-CNNM2-NT5C2 (
P
LAS
=4.9×10
−4
).

Conclusions—

Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
Sound, Narrative and the Spaces in between: Disruptive Listening in Jerusalem’s Old City
Authors: Wood Abigail
Published: November 2013

This article explores the intertwined roles of sound performance, listening and narration as agentive modes of parsing conflicted spaces in Jerusalem’s Old City. Via a series of ethnographic case studies, I illustrate some of the everyday ways in which overlapping geographies are constructed and communicated in public and semi-public ‘civil’ spaces at the contested seams of Israel and Palestine. In performing music in the city, citing poetry or pronouncing judgments on the soundscape, inhabitants and visitors draw upon both sensory experiences and a broad corpus of literary, artistic, historical and narrative commentary on the city. Drawing on the work of Michael Jackson and Davide Panagia, I suggest that unnarratable sensory experiences such as these might expose moments when political subjectivity is reconfigured, challenging unitary narratives by highlighting the inherent complexity and ambiguity of everyday experience.
Staging Particular Difference: Politics of Space in the Palestinian Alternative Music Scene
Authors: Karkabi Nadeem
Published: November 2013

In recent years, an alternative popular music scene has emerged among young Palestinians on both sides of the Green Line. Musicians and their audiences produce a politicized counterculture that innovatively fuses local and international musical expressions as a form of protest that aims to challenge external and internal impositions of structural oppression and othering. This scene constitutes the struggle of young Palestinians against civil marginalization in Israel and military occupation in the occupied territories, as well as against social and religious controls within their own communities. Drawing on Foucault’s work on Heterotopia, this article analyzes the cultural and political significance of Palestinian festive spaces by tracing the networks and conditions under which partygoers either fail or must compromise the staging of festive resistance, or conversely, succeed in appropriating places for their purposes despite spatial and social constraints.
Israel’s J14 Social Protest Movement and Its Imaginings of ‘Home’: On Music, Politics and Social Justice
Authors: Belkind Nili
Published: November 2013

The J14 social protest movement in Israel (2011) began as a protest against the high cost of living, and most prominently, the inflated cost of housing. However, it quickly became the site of an emerging public discourse regarding the relationship between power and one’s home, whether material dwelling or the universe of meanings associated with home, homeland, citizenship, nationality and ethnicity. This article explores the ways in which expressive culture—musical, visual and discursive—provided the engine for envisioning and contesting new imaginaries of home and contextualizing political action within the protest. A focus on Jaffa, a mixed Jewish-Palestinian city, highlights the ways in which expressive culture negotiated inherent tensions surrounding the meanings of ‘home’ that were brought into the open in Israel’s marginalized peripheries.
Aerotactile Integration from Distal Skin Stimuli
Authors: Derrick Donald , Gick Bryan
Published: November 2013

Tactile sensations at extreme distal body locations can integrate with auditory information to alter speech perception among uninformed and untrained listeners. Inaudible air puffs were applied to participants’ ankles, simultaneously with audible syllables having aspirated and unaspirated stop onsets. Syllables heard simultaneously with air puffs were more likely to be heard as aspirated. These results demonstrate that event-appropriate information from distal parts of the body integrates in speech perception, even without frequent or robust location-specific experience. In addition, overall performance was significantly better for those with hair on their ankles, which suggests that the presence of hair may help establish signal relevance, and so aid in multi-modal speech perception.
Visual and Haptic Representations of Material Properties
Authors: Baumgartner Elisabeth , Wiebel Christiane B. , Gegenfurtner Karl R.
Published: November 2013

Research on material perception has received an increasing amount of attention recently. Clearly, both the visual and the haptic sense play important roles in the perception of materials, yet it is still unclear how both senses compare in material perception tasks. Here, we set out to investigate the degree of correspondence between the visual and the haptic representations of different materials. We asked participants to both categorize and rate 84 different materials for several material properties. In the haptic case, participants were blindfolded and asked to assess the materials based on haptic exploration. In the visual condition, participants assessed the stimuli based on their visual impressions only. While categorization performance was less consistent in the haptic condition than in the visual one, ratings correlated highly between the visual and the haptic modality. PCA revealed that all material samples were similarly organized within the perceptual space in both modalities. Moreover, in both senses the first two principal components were dominated by hardness and roughness. These are two material features that are fundamental for the haptic sense. We conclude that although the haptic sense seems to be crucial for material perception, the information it can gather alone might not be quite fine-grained and rich enough for perfect material recognition.
Multiscale Interactions in an Idealized Walker Circulation: Mean Circulation and Intraseasonal Variability
Authors: Slawinska Joanna , Pauluis Olivier , Majda Andrew J. , Grabowski Wojciech W.
Published: November 2013

A high-resolution cloud-resolving model (CRM) simulation is developed here for a two-dimensional Walker circulation over a planetary-scale domain of 40 000 km for an extended period of several hundred days. The Walker cell emerges as the time-averaged statistical steady state with a prescribed sinusoidal sea surface temperature (SST) pattern with a mean temperature of 301.15 K and a horizontal variation of 4 K. The circulation exhibits intraseasonal variability on a time scale of about 20 days with quasi-periodic intensification of the circulation and broadening of the convective regime. This variability is closely tied to synoptic-scale systems associated with expansion and contraction of the Walker circulation. An index for the low-frequency variability is developed using an empirical orthogonal function (EOF) analysis and by regressing various dynamic fields on this index. The low-frequency oscillation has four main stages: a suppressed stage with strengthened midlevel circulation, an intensification phase, an active phase with strong upper-level circulation, and a weakening phase. Various physical processes occurring at these stages are discussed as well as the impact of organized convective systems on the large-scale flow.