bluuebunny/crossref_metadata_2025 huggingface dataset:
Cluster Policies in Bulgaria: European Integration, Postsocialist Dynamics and Local Level Initiatives
Authors: SELLAR CHRISTIAN , EMILOVA MAKSIMILIANA , PETKOVA‐TANCHEVA CHRASTINA DIMITROVA , MCNEIL KATHLEEN
Published: September 2010

This article investigates public policies aimed at developing industrial clusters in Bulgaria by looking at initiatives at supranational, national and local levels. It argues that cluster policies have functioned as paths directing actions in the postsocialist transformation of Bulgaria. In doing so, it seeks answers to the following research questions: what are the connections between policy implementation, institutional changes and economic transformation at the national and local levels in Bulgaria; what is the role of the European Union in shaping these changes; and what is the role of local actors in shaping the policies and development trends within one specific cluster? Through an analysis of government policies, data and empirical research, the article shows how different groups (foreign consultants, local elites and national administrators) have understood the concepts of ‘clusters’ and ‘industrial districts’ in different ways, then used these concepts as a tool to access foreign resources. The analysis highlights both similarities and differences in cluster policies at the three levels considered.

Cet examen des politiques publiques de développement de pôles industriels en Bulgarie s’intéresse aux initiatives de niveaux supranational, national et local. Il affirme qu’au cours de la phase de transformation postsocialiste, ces politiques ont servi de mesures d’orientation de trajectoires. Parallèlement, l’étude cherche à répondre aux questions suivantes: quels sont les rapports entre mise en œuvre des politiques publiques, évolutions institutionnelles et transformations économiques tant au plan national que local? quel rôle l’Union européenne a‐t‐elle dans la configuration de ces changements, et quel poids les acteurs locaux ont‐ils dans la détermination des politiques et des axes de développement concernant un pôle particulier? En analysant les politiques gouvernementales, les faits et l’étude empirique, l’article montre que différents groupes (experts étrangers, élites locales et représentants de l’administration nationale) n’ont pas appréhendé de la même manière les concepts de ‘pôles’ (clusters) et de ‘districts industriels’, et qu’ils les ont ensuite utilisés afin d’accéder à des ressources d’origine étrangère. Ainsi, il est possible d’établir similitudes et divergences entre les politiques relatives aux pôles industriels, et ce, à chacun des trois niveaux étudiés.
Access to Primary and Preventive Care among Foreign‐Born Adults in Canada and the United States
Authors: Lebrun Lydie A. , Dubay Lisa C.
Published: September 2010

Objective. To conduct cross‐country comparisons and assess the effect of foreign birth on access to primary and preventive care in Canada and the United States.

Data Sources. Secondary data from the 2002 to 2003 Joint Canada–United States Survey of Health.

Study Design. Descriptive and comparative analyses were conducted, and logistic regression models were used to assess the effect of immigrant status and country of residence on access to care. Outcomes included measures of health care systems and processes, utilization, and patient perceptions.

Principal Findings. In adjusted analyses, immigrants in Canada fared worse than nonimmigrants regarding having timely Pap tests; in the United States, immigrants fared worse for having a regular doctor and an annual consultation with a health professional. Immigrants in Canada had better access to care than immigrants in the United States; most of these differences were explained by differences in socioeconomic status and insurance coverage across the two countries. However, U.S. immigrants were more likely to have timely Pap tests than Canadian immigrants, even after adjusting for potential confounders.

Conclusions. In both countries, foreign‐born populations had worse access to care than their native‐born counterparts for some indicators but not others. However, few differences in access to care were found when direct cross‐country comparisons were made between immigrants in Canada versus the United States, after accounting for sociodemographic differences.
Linear Morhpea, Nevus Comedonicus, and Lichen Striatus in a 5‐Year‐Old Girl
Authors: SINHA APARNA , NATARAJAN SIVAKUMAR
Published: September 2010

Abstract:  Linear morphea, lichen striatus, and nevus comedonicus are rare conditions. We describe a five‐year‐old girl in whom all three of these dermatoses are present.
TUNEL Assay for Identifying Ablated Myocardium
Authors: WINSTON BRION , NALESNIK MICHAEL , BAZAZ RAVEEN
Published: September 2010

The terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) assay identifies apoptosis and is used in transplant pathology to detect cardiac allograft rejection. We illustrate the use of TUNEL in identifying segments of ablated ventricular myocardium, and discuss its advantages over conventional histopathological stains. The TUNEL assay can be useful to investigators of catheter ablation therapy. (PACE 2010; 33:1548–1549)
Who Mobilizes? Participatory Democracy in Chávez's Bolivarian Revolution
Authors: Hawkins Kirk A.
Published: September 2010

This article assesses popular mobilization under the Chávez government's participatory initiatives in Venezuela using data from the AmericasBarometer survey of 2007. This is the first study of the so-called Bolivarian initiatives using nationally representative, individual-level data. The results provide a mixed assessment. Most of the government's programs invite participation from less active segments of society, such as women, the poor, and the less educated, and participation in some programs is quite high. However, much of this participation clusters within a narrow group of activists, and a disproportionate number of participants are Chávez supporters. This partisan bias probably reflects self-screening by Venezuelans who accept Chávez's radical populist discourse and leftist ideology, rather than vote buying or other forms of open conditionality. Thus, the Venezuelan case suggests some optimism for proponents of participatory democracy, but also the need to be more attuned to its practical political limits.
The 3‐ureidopropionase ofCaenorhabditis elegans, an enzyme involved in pyrimidine degradation
Authors: Janowitz Tim , Ajonina Irene , Perbandt Markus , Woltersdorf Christian , Hertel Patrick , Liebau Eva , Gigengack Ulrike
Published: September 2010

Pyrimidines are important metabolites in all cells. Levels of cellular pyrimidines are controlled by multiple mechanisms, with one of these comprising the reductive degradation pathway. In the model invertebrateCaenorhabditis elegans, two of the three enzymes of reductive pyrimidine degradation have previously been characterized. The enzyme catalysing the final step of pyrimidine breakdown, 3‐ureidopropionase (β‐alanine synthase), had only been identified based on homology. We therefore cloned and functionally expressed the 3‐ureidopropionase ofC. elegansas hexahistidine fusion protein. The purified recombinant enzyme readily converted the two pyrimidine degradation products: 3‐ureidopropionate and 2‐methyl‐3‐ureidopropionate. The enzyme showed a broad pH optimum between pH 7.0 and 8.0. Activity was highest at approximately 40 °C, although the half‐life of activity was only 65 s at that temperature. The enzyme showed clear Michaelis–Menten kinetics, with aKmof 147 ± 26 μmand aVmaxof 1.1 ± 0.1 U·mg protein−1. The quaternary structure of the recombinant enzyme was shown to correspond to a dodecamer by ‘blue native’ gel electrophoresis and gel filtration. The organ specific and subcellular localization of the enzyme was determined using a translational fusion to green fluorescent protein and high expression was observed in striated muscle cells. With the characterization of the 3‐ureidopropionase, the reductive pyrimidine degradation pathway inC. eleganshas been functionally characterized.

Structured digital abstract

 MINT‐7986015:3‐ureidopropionase(uniprotkb:Q19437) and3‐ureidopropionase(uniprotkb:Q19437)bind(MI:0407) byblue native page(MI:0276)
The Cumulative Effects of Forcing Function, Damping, and Mistuning on Blade Forced Response in a High Speed Centrifugal Compressor With Inlet Distortion
Authors: Kammerer Albert , Abhari Reza S.
Published: September 2010

The vibratory response amplitude of a blade under forced response conditions depends primarily on the aerodynamic excitation amplitude, on damping, and on the effects of mistuning. The work presented here targets to identify the individual contribution of these parameters to the resultant response amplitude depending on the mass flow and the resonance case. For this purpose, measurements were performed of the excitation amplitude, damping, and response amplitude for a high-speed centrifugal compressor. The inlet flow field was intentionally distorted in order to target specific excitation cases of the first main blade mode. For the compressor used, it was found that the overall damping of the first mode could be considered to be constant for any resonance case and mass flow. For this reason, case-to-case variations in the blade-averaged response amplitude were found to depend solely on the aerodynamic excitation amplitude due to inlet flow distortion. Based on an examination of the aerodynamic work distribution during resonance, zones of either excitation or damping work on the blade surface could be successfully identified. This enabled the conclusion to be drawn that energy transfer is a very localized phenomenon and may significantly change as the mass flow is altered, thereby introducing a redistribution of the blade excitation function. The effect of mistuning was shown to alter aerodynamic damping and response amplitude. However, the variation in aerodynamic damping of individual blades was relatively low, thus suggesting that blade-to-blade variation in response amplitude is primarily driven by energy localization in the sense typically experienced with coupled and mistuned structures.
Isozyme variation, morphology, and growth response to temperature in Pythium irregulare
Authors: Barr D. J. S. , Warwick S. I. , Desaulniers N. L.
Published: September 2010

Isozyme-based genetic diversity, morphological characters, and growth rate at different temperatures were compared in a worldwide collection of 125 isolates presumed to be Pythium irregulare Buisman. The isozyme data was analysed with previously published data for Pythium ultimum Trow and Pythium sylvaticum Campbell & Hendrix. UPGMA cluster analysis yielded a dendrogram with four distinct groups: P. ultimum, P. sylvaticum, and two for P. irregulare. Putative P. irregulare isolates were separated into 33 multilocus genotypes defined by 11 isozyme loci: group A contained 116 isolates in 25 genotypes, and group B, 8 isolates in 7 genotypes. One genotype with a single isolate was determined as P. sylvaticum. Based on the isozyme analysis, group B was considered a distinct taxonomic entity from group A, but lacked any unique morphological character. There was a wide range in oogonium and oospore sizes among different isolates of P. irregulare, with those in group B generally being larger. Some isolates in group A had well developed oogonial spines, but others were essentially spineless, whereas all those in group B were spineless. Both groups A and B contained isolates with distinctly aplerotic oospores and others with essentially plerotic oospores. Antheridial number and shape were highly variable both within and among isolates in the two groups. Growth rate over a range of temperatures varied among isolates in both groups and was not a reliable taxonomic criterion. The irregular shape of oogonia and, when present, oogonial spines were the only reliable characters for distinguishing P. irregulare isolates from other taxa. Key words: taxonomy, Oomycetes, Pythiaceae, Pythium ultimum, Pythium sylvaticum.
QUANTIFYING SLOW EVOLUTIONARY DYNAMICS IN RNA FITNESS LANDSCAPES
Authors: ŠULC PETR , WAGNER ANDREAS , MARTIN OLIVIER C.
Published: September 2010

We re-examine the evolutionary dynamics of RNA secondary structures under directional selection towards an optimum RNA structure. We find that the punctuated equilibria lead to a very slow approach to the optimum, following on average an inverse power of the evolutionary time. In addition, our study of the trajectories shows that the out-of-equilibrium effects due to the evolutionary process are very weak. In particular, the distribution of genotypes is close to that arising during equilibrium stabilizing selection. As a consequence, the evolutionary dynamics leave almost no measurable out-of-equilibrium trace, only the transition genotypes (close to the border between different periods of stasis) have atypical mutational properties.
Body temperature as a mouse pharmacodynamic response to bombesin receptor subtype-3 agonists and other potential obesity treatments
Authors: Metzger Joseph M. , Gagen Karen , Raustad Kate A. , Yang Liming , White Amanda , Wang Sheng-Ping , Craw Stephanie , Liu Ping , Lanza Thomas , Lin Linus S. , Nargund Ravi P. , Guan Xiao-Ming , Strack Alison M. , Reitman Marc L.
Published: September 2010

Treatment of rodents with a bombesin receptor subtype-3 (BRS-3) agonist reduces food intake and increases fasting metabolic rate, causing weight loss with continued treatment. In small mammals, core body temperature (Tb) is regulated in part by nutritional status, with a reduced Tbduring fasting. We report that fed Brs3 knockout mice have a lower Tb, which is discordant with their nutritional status. Treatment of wild-type mice with a BRS-3 agonist increased Tb, more so when the baseline Tbwas reduced such as by fasting or during the inactive phase of the light cycle. With repeated BRS-3 agonist dosing, the Tbincrease attenuated despite continued weight loss efficacy. The increase in Tbwas not prevented by inhibitors of prostaglandin E (PGE) production but was partially reduced by a β-adrenergic blocker. These results demonstrate that BRS-3 has a role in body temperature regulation, presumably secondary to its effect on energy metabolism, including effects on sympathetic tone. By making use of this phenomenon, the reversal of the fasting Tbreduction was developed into a sensitive single-dose pharmacodynamic assay for BRS-3 agonism and other antiobesity compounds acting by various mechanisms, including sibutramine, cannabinoid-1, and melanin-concentrating hormone-1 receptor blockers, and melanocortin, β3-adrenergic, and cholecystokinin-1 receptor agonists. These drugs increased both the fasted Tband the fasted, resting metabolic rates. The Tbassay is a robust, information-rich assay that is simpler and has a greater throughput than measuring metabolic rate and is a practical, effective tool for drug discovery.
Rostroventrolateral medullary neurons modulate glucose homeostasis in the rat
Authors: Verberne A. J. M. , Sartor D. M.
Published: September 2010

Several lines of evidence support the view that the premotor sympathetic input to the adrenal gland arises from the rostroventrolateral medulla (RVLM). The aim of this study was to determine whether RVLM neurons play a role in glucose homeostasis. We identified RVLM neurons that control epinephrine secretion by searching for medullospinal neurons that responded to neuroglucoprivation induced by systemic 2-deoxyglucose (2-DG) administration. We tested the effect of disinhibition of the RVLM on arterial blood pressure and plasma glucose concentration. RVLM medullospinal barosensitive neurons ( n = 17) were either unaffected or slightly inhibited by 2-DG. In contrast, we found a group ( n = 6) of spinally projecting neurons that were excited by 2-DG administration. These neurons were not barosensitive and had spinal conduction velocities in the unmyelinated range (<1 m/s). These neurons may mediate epinephrine secretion and participate in the counterregulatory responses to neuroglucoprivation. To test the hypothesis that activation of the RVLM leads to adrenomedullary activation and subsequent hyperglycemia, we applied the GABAA antagonist bicuculline to the RVLM and measured blood pressure, heart rate, and blood glucose in rats with intact adrenals or after bilateral adrenalectomy. Disinhibition of the RVLM resulted in hypertension, tachycardia, and hyperglycemia (4.9 ± 0.3 to 14.7 ± 0.9 mM, n = 5, P < 0.05). Adrenalectomy significantly reduced the hyperglycemic response but did not alter the cardiovascular responses. These data suggest that the RVLM is a key component of the neurocircuitry that is recruited in the counterregulatory response to hypoglycemia.
Transcriptional responses to thermal acclimation in the eurythermal fish Gillichthys mirabilis (Cooper 1864)
Authors: Logan Cheryl A. , Somero George N.
Published: September 2010

Thermal acclimation (acclimatization) capacity may be critical for determining how successfully an ectotherm can respond to temperature change, and adaptive shifts in gene expression may be pivotal for mediating these acclimatory responses. Using a cDNA microarray, we examined transcriptional profiles in gill tissue of a highly eurythermal goby fish, Gillichthys mirabilis , following 4 wk of acclimation to 9°C, 19°C, or 28°C. Overall, gill transcriptomes were not strikingly different among acclimation groups. Of the 1,607 unique annotated genes on the array, only 150 of these genes (9%) were significantly different in expression among the three acclimation groups (ANOVA, false discovery rate < 0.05). Principal component analysis revealed that 59% of the variation in expression among these genes was described by an expression profile that is upregulated with increasing acclimation temperature. Gene ontology analysis of these genes identified protein biosynthesis, transport, and several metabolic categories as processes showing the greatest change in expression. Our results suggest that energetic costs of macromolecular turnover and membrane-localized transport rise with acclimation temperature. The upregulation of several classes of stress-related proteins, e.g., heat shock proteins, seen in the species' response to acute thermal stress was not observed in the long-term 28°C-acclimated fish. The transcriptional differences found among the acclimation groups thus may reflect an acclimation process that has largely remedied the effects of acute thermal stress and established a new steady-state condition involving changes in relative energy costs for different processes. This pattern of transcriptional alteration in steady-state acclimated fish may be a signature of eurythermy.
Exploratory Movements Determine Cue Weighting in Haptic Length Perception of Handheld Rods
Authors: Debats Nienke B. , van de Langenberg Rolf W. , Kingma Idsart , Smeets Jeroen B. J. , Beek Peter J.
Published: September 2010

In the present study, we sought to unravel how exploratory movements affect length perception of rods that are held in and wielded by hand. We manipulated the mechanical rod properties—mass ( m), first moment of mass distribution (M), major principal moment of inertia ( I1)—individually, allowing us to assess the relative contribution of each of these mechanical variables to the perceptual judgment. Furthermore we developed a method to quantify the force components of the mechanical variables in the total of forces acting at the hand-rod interface, and we calculated each component's relative contribution. The laws of mechanics dictate that these relative force contributions depend on the characteristics of the exploratory movements performed. We found a clear relationship between the relative force contribution of the mechanical variables and their contribution to perceived rod length. This finding is the first quantitative demonstration that exploration style determines how much each mechanical variable influences length perception. Moreover, this finding suggested a cue weighting mechanism in which exploratory movements determine cue reliability (and thus cue weighting). We developed a cue combination model for which we first identified three length cues in the form of ratios between the mechanical variables. Second, we calculated the weights of these cues from the recorded rod movements. The model provided a remarkably good prediction of the experimental data. This strongly suggests that rod length perception by wielding is achieved through a weighted combination of three specific length cues, whereby the weighting depends on the characteristics of the exploratory movements.
Gene expression profiles linked to AT1angiotensin receptors in the kidney
Authors: Makhanova Natalia A. , Crowley Steven D. , Griffiths Robert C. , Coffman Thomas M.
Published: September 2010

To characterize gene expression networks linked to AT1angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT1Areceptor-deficient mice (KOs) at baseline and after 2 days of angiotensin II infusion (1,000 ng·kg−1·min−1). At baseline, 405 genes were differentially expressed (>1.5×) between WT and KO kidneys. Of these, >80% were upregulated in the KO group including genes involved in inflammation, oxidative stress, and cell proliferation. After 2 days of angiotensin II infusion in WT mice, expression of ≈805 genes was altered (18% upregulated, 82% repressed). Genes in metabolism and ion transport pathways were upregulated while there was attenuated expression of genes protective against oxidative stress including glutathione synthetase and mitochondrial superoxide dismutase 2. Angiotensin II infusion had little effect on blood pressure in KOs. Nonetheless, expression of >250 genes was altered in kidneys from KO mice during angiotensin II infusion; 14% were upregulated, while 86% were repressed including genes involved in immune responses, angiogenesis, and glutathione metabolism. Between WT and KO kidneys during angiotensin II infusion, 728 genes were differentially expressed; 10% were increased and 90% were decreased in the WT group. Differentially regulated pathways included those involved in ion transport, immune responses, metabolism, apoptosis, cell proliferation, and oxidative stress. This genome-wide assessment should facilitate identification of critical distal pathways linked to blood pressure regulation.
Iterative Processing for Superposition Mapping
Authors: Wo Tianbin , Noemm Meelis , Hao Dapeng , Hoeher Peter Adam
Published: September 2010

Superposition mapping (SM) is a modulation technique which loads bit tuples onto data symbols simply via
linear superposition. Since the resulting data symbols are often Gaussian‐like, SM has a good theoretical potential to approach
the capacity of Gaussian channels. On the other hand, the symbol constellation is typically nonbijective and its characteristic is
very different from that of conventional mapping schemes like QAM or PSK. As a result, its behavior is also quite different from
conventional mapping schemes, particularly when applied in the framework of bit‐interleaved coded modulation. In this paper, a
comprehensive analysis is provided for SM, with particular focus on aspects related to iterative processing.
Surgical Management of Calciphylaxis Associated with Primary Hyperparathyroidism: A Case Report and Review of the Literature
Authors: Bishop Jennifer , Brown Eric , Podesta Augusto , Troy Cathrine , Dong Xiang (Eric)
Published: September 2010

Calciphylaxis, or calcific uremic arteriolopathy, commonly affects people with end-stage renal disease and carries with it a high rate of morbidity and mortality. Here, we present the unusual case of a 56-year-old woman, with extensive medical problems, who developed calciphylaxis in the presence of primary hyperparathyroidism. Our patient initially presented with bilateral, exquisitely tender thigh lesions. The diagnosis of calciphylaxis was rendered histologically by extensive calcification of the subcutaneous blood vessels. Subsequent parathyroidectomy identified the presence of a hyperactive mediastinal parathyroid adenoma, weighing 0.62 grams. Postoperatively, the patient had normalization of hypercalcemia and parathyroid hormone levels, with subsequent healing of her thigh wounds. Currently, there have been sixteen cases described in the English literature, with only nine being offered a potentially therapeutic parathyroidectomy. It is contingent upon the vigilant physician to diagnose and properly manage this difficult yet treatable condition.
Red Ginseng Extract Facilitates the Early Differentiation of Human Embryonic Stem Cells into Mesendoderm Lineage
Authors: Kim Yoon Young , Ku Seung-Yup , Rosenwaks Zev , Liu Hung Ching , Oh Sun Kyung , Moon Shin Yong , Choi Young Min
Published: September 2010

Human embryonic stem cells (hESCs) have capacities to self‐renew and differentiate into all cell types in vitro. Red ginseng (RG) is known to have a wide range of pharmacological effects in vivo; however, the reports on its effects on hESCs are few. In this paper, we tried to demonstrate the effects of RG on the proliferation and differentiation of hESCs. Undifferentiated hESCs, embryoid bodies (EBs), and hESC‐derived cardiac progenitors (CPs) were treated with RG extract at 0.125, 0.25, and 0.5 mg/mL. After treatment of undifferentiated hESCs from day 2 to day 6 of culture, BrdU labeling showed that RG treatment increased the proliferation of hESCs, and the expression of Oct4 and Nanog was increased in RG‐treated group. To find out the effects of RG on early differentiation stage cells, EBs were treated with RG extract for 10 days and attached for further differentiation. Immunostaining for three germ layer markers showed that RG treatment increased the expressions of Brachyury and HNF3β on EBs. Also, RG treatment increased the expression of Brachyury in early‐stage and of Nkx2.5 in late‐stage hESC‐derived CPs. These results demonstrate facilitating effects of RG extract on the proliferation and early differentiation of hESC.
Differential Mechanisms of Acquired Resistance to Insulin-like Growth Factor-I Receptor Antibody Therapy or to a Small-Molecule Inhibitor, BMS-754807, in a Human Rhabdomyosarcoma Model
Authors: Huang Fei , Hurlburt Warren , Greer Ann , Reeves Karen A. , Hillerman Stephen , Chang Han , Fargnoli Joseph , Graf Finckenstein Friedrich , Gottardis Marco M. , Carboni Joan M.
Published: September 2010

Agents targeting insulin-like growth factor-I receptor (IGF-IR), including antibodies and small-molecule inhibitors, are currently in clinical development for the treatment of cancers including sarcoma. However, development of resistance is a common phenomenon resulting in failures of anticancer therapies. In light of this problem, we developed two resistant models from the rhabdomyosarcoma cell line Rh41: Rh41-807R, with acquired resistance to BMS-754807, a small-molecule dual-kinase inhibitor targeting IGF-IR and insulin receptor (IR), and Rh41-MAB391R, with resistance to MAB391, an IGF-IR–blocking antibody. In addition, tumor xenograft models were established from Rh41 and Rh41-807R cell lines. Gene expression and DNA copy number analyses of these models revealed shared as well as unique acquired resistance mechanisms for the two types of IGF-IR inhibitors. Each resistant model used different signaling pathways as a mechanism for proliferation. Platelet-derived growth factor receptor α (PDGFRα) was amplified, overexpressed, and constitutively activated in Rh41-807R cells and tumors. Knockdown of PDGFRα by small interfering RNA in Rh41-807R resensitized the cells to BMS-754807. Synergistic activities were observed when BMS-754807 was combined with PDGFRα inhibitors in the Rh41-807R model in vitro. In contrast, AXL expression was highly elevated in Rh41-MAB391R but downregulated in Rh41-807R. Notably, BMS-754807 was active in Rh41-MAB391R cells and able to overcome resistance to MAB391, but MAB391 was not active in Rh41-807R cells, suggesting potentially broader clinical activity of BMS-754807. This is the first study to define and compare acquired resistance mechanisms for IGF-IR–targeted therapies. It provides insights into the differential acquired resistance mechanisms for IGF-IR/IR small-molecule inhibitor versus anti–IGF-IR antibody. Cancer Res; 70(18); 7221–31. ©2010 AACR.
hnRNP A2/B1 Modulates Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines
Authors: Tauler Jordi , Zudaire Enrique , Liu Huaitian , Shih Joanna , Mulshine James L.
Published: September 2010

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been reported to be overexpressed in lung cancer and in other cancers such as breast, pancreas, and liver. However, a mechanism linking hnRNP A2/B1 overexpression and progression to cancer has not yet been definitively established. To elucidate this mechanism, we have silenced hnRNPA2/B1 mRNA in non–small-cell lung cancer cell lines A549, H1703, and H358. These cell lines present different levels of expression of epithelial-to-mesenchymal transition (EMT) markers such as E-cadherin, fibronectin, and vimentin. Microarray expression analysis was performed to evaluate the effect of silencing hnRNP A2/B1 in A549 cells. We identified a list of target genes, affected by silencing of hnRNP A2/B1, that are involved in regulation of migration, proliferation, survival, and apoptosis. Silencing hnRNP A2/B1 induced formation of cell clusters and increased proliferation. In the anchorage-independent assay, silencing hnRNP A2/B1 increased colony formation by 794% in A549 and 174% in H1703 compared with a 25% increase in proliferation, in both cell lines, in a two-dimensional proliferation assay. Silencing hnRNP A2/B1 decreased migration in intermediate cell line A549 and mesenchymal cell line H1703; however, no changes in proliferation were observed in epithelial cell line H358. Silencing hnRNP A2/B1 in A549 and H1703 cells correlated with an increase of E-cadherin expression and downregulation of the E-cadherin inhibitors Twist1 and Snai1. These data suggest that expression of hnRNP A2/B1 may play a role in EMT, in nonepithelial lung cancer cell lines A549 and H1703, through the regulation of E-cadherin expression. Cancer Res; 70(18); 7137–47. ©2010 AACR.
Modulation of Gene Expression and Tumor Cell Growth by Redox Modification of STAT3
Authors: Li Li , Cheung Shing-hu , Evans Emma L. , Shaw Peter E.
Published: September 2010

Reactive oxygen species (ROS) promote tumor cell proliferation and survival by directly modulating growth-regulatory molecules and key transcription factors. The signal transducer and activator of transcription 3 (STAT3) is constitutively active in a variety of tumor cell types, where the effect of ROS on the Janus kinase/STAT pathway has been examined. We report here that STAT3 is directly sensitive to intracellular oxidants. Oxidation of conserved cysteines by peroxide decreased STAT3 binding to consensus serum-inducible elements (SIE) in vitro and in vivo and diminished interleukin (IL)-6–mediated reporter expression. Inhibitory effects produced by cysteine oxidation in STAT3 were negated in redox-insensitive STAT3 mutants. In contrast, ROS had no effect on IL-6–induced STAT3 recruitment to the c-myc P2 promoter. Expression of a redox-insensitive STAT3 in breast carcinoma cells accelerated their proliferation while reducing resistance to oxidative stress. Our results implicate STAT3 in coupling intracellular redox homeostasis to cell proliferation and survival. Cancer Res; 70(20); 8222–32. ©2010 AACR.
Detailed Distribution of NK012, an SN-38–Incorporating Micelle, in the Liver and Its Potent Antitumor Effects in Mice Bearing Liver Metastases
Authors: Takahashi Amane , Ohkohchi Nobuhiro , Yasunaga Masahiro , Kuroda Jun-ichiro , Koga Yoshikatsu , Kenmotsu Hirotsugu , Kinoshita Taira , Matsumura Yasuhiro
Published: September 2010

Purpose: To clarify and compare the antitumor effects and specific biodistribution of NK012, an SN-38–incorporating polymeric micelle, in mice bearing multiple liver metastases of human colon cancer HT-29 cells with irinotecan hydrochloride (CPT-11).

Experimental Design: The maximum tolerable dose of NK012 (30 mg/kg) or CPT-11 (66.7 mg/kg) was i.v. administered three times every 4 days to mice bearing metastases to the liver colonized 7 days after the portal administration of HT-29 cells (n = 6). In vivo antitumor effects were evaluated by bioluminescence imaging and histopathologic examination. Drug biodistribution was analyzed by high-performance liquid chromatography and fluorescence microscopy (n = 3).

Results: NK012 eradicated the liver metastases and produced a significant longer survival rate than CPT-11 (P = 0.0006). High-performance liquid chromatography showed the prolonged distribution of NK012 and free SN-38 released from NK012 in the tumors, liver, and spleen for weeks after NK012 administration. On the other hand, the accumulation levels of CPT-11 and free SN-38 converted from CPT-11 rapidly decreased within 1 day after CPT-11 administration. In the liver metastases, fluorescence microscopy and immunohistochemistry showed that administered NK012 was distributed mainly adjacent to tumor vessels after 1 day. As for the normal liver, NK012 was distributed in Kupffer cells instead of hepatocytes for at least 7 days after administration.

Conclusion: This study suggests that NK012 is strongly effective against liver metastases and does not damage the liver despite the long retention time of NK012 in Kupffer cells. Clin Cancer Res; 16(19); 4822–31. ©2010 AACR.
Molecular Therapy Targeting Sonic Hedgehog and Hepatocyte Growth Factor Signaling in a Mouse Model of Medulloblastoma
Authors: Coon Valerie , Laukert Tamara , Pedone Carolyn A. , Laterra John , Kim K. Jin , Fults Daniel W.
Published: September 2010

The use of genetically engineered mice has provided insights into the molecular pathogenesis of the pediatric brain tumor medulloblastoma and revealed promising therapeutic targets. Ectopic expression of Sonic hedgehog (Shh) in cerebellar neural progenitor cells induces medulloblastomas in mice, and coexpression of hepatocyte growth factor (HGF) enhances Shh-induced tumor formation. To determine whether Shh + HGF–driven medulloblastomas were responsive to Shh signaling blockade and whether treatment response could be enhanced by combination therapy targeting both HGF and Shh signaling pathways, we carried out a survival study in mice. We induced medulloblastomas by retrovirus-mediated expression of Shh and HGF, after which we treated the mice systemically with (a) HGF-neutralizing monoclonal antibody L2G7, (b) Shh signaling inhibitor cyclopamine, (c) Shh-neutralizing monoclonal antibody 5E1, (d) L2G7 + cyclopamine, or (e) L2G7 + 5E1. We report that monotherapy targeting either HGF signaling or Shh signaling prolonged survival and that anti-HGF therapy had a more durable response than Shh-targeted therapy. The effect of L2G7 + 5E1 combination therapy on cumulative survival was equivalent to that of L2G7 monotherapy and that of L2G7 + cyclopamine therapy was worse. The principal mechanism by which Shh- and HGF-targeted therapies inhibited tumor growth was a potent apoptotic death response in tumor cells, supplemented by a weaker suppressive effect on proliferation. Our observation that combination therapy either failed to improve or even reduced survival in mice bearing Shh + HGF–induced medulloblastomas compared with monotherapy underscores the importance of preclinical testing of molecular-targeted therapies in animal models of tumors in which the targeted pathways are known to be active. Mol Cancer Ther; 9(9); 2627–36. ©2010 AACR.
From a “Common Principle of Equality” to “European Antidiscrimination Law”
Authors: de Witte Bruno
Published: September 2010

The principle of equality is an important part of the contemporary constitutional law of all European countries. It is therefore a “common” principle, and was, as such, also integrated in the legal system of the European Communities. However, this common principle of equality was modernized and modified by a series of specific antidiscrimination laws adopted in the European Union, mainly during the past decade. This contribution explores the ways in which those recent antidiscrimination laws have modified the traditional understanding of equality law in Europe and are giving “teeth” to the abstract principle of equality.
The Hollow Legal Shell of European Race Discrimination Policy: The EC Race Directive
Authors: Mason Luke
Published: September 2010

The “Race Directive,” along with the rest of the recent European Union expansion of its body of equality law, was welcomed with huge acclaim and fanfare, predictably by the Commission, but also by much academic writing. Now that this has subsided, it is necessary to engage in a sober analysis of the contents of the directive. Although the directive has been seen as embodying a huge shift in conceptions of equality and discrimination, and as part of an emerging European social citizenship, a closer examination of the provisions of the directive reveals something quite different: an ambivalence towards broader reaching conceptions of equality, a repeating of the mistakes of the past, and a series of delegations of key decisions regarding the potentially most progressive aspects of the legislation to other actors. This article suggests that whereas the directive contains many positive aspects, to a large extent it represents an exercise in passing the buck, given the hollowness of many of the seemingly expansive provisions. This means that our focus must shift onto member states and other actors, who have traditionally been conspicuously inactive in the field of race discrimination.
Structural evaluation of elastic core-spun yarns and fabrics under tensile fatigue loading
Authors: Adeli Behrang , Ali Akbar Ghareaghaji  , Shanbeh Mohsen
Published: September 2010

Nowadays the application of elastic core-spun yarns in fabric manufacturing and the clothing industry has increased tremendously. These yarns undergo tensile fatigue loading, a common phenomenon which occurs on some part of apparel such as the knee during wearing and use. In this research, cotton covered spandex filament core-spun yarns with 5 different draw ratios on the core part were subjected to 500, 1000 and 1500 tensile fatigue cyclic loads using a purpose-built instrument for fatigue behavior assessment. Also, the woven fabrics of these yarns were produced and underwent the same cyclic loadings. Tensile properties of fatigued yarns were measured by a tensile tester. The yarn deformation and displacement of core and sheath parts was traced via a microtomy technique and scanning electron microscopy (SEM) studies. Finally, the surface of the fatigued fabrics was studied by image processing to see any surface roughness and pilling due to straining. The results revealed the pronounced effect of draw ratio on the breaking strength and breaking elongation after cyclic loading. The obtained results showed that the samples produced by a 2.9 and 3.9 draw ratio of the core part had the highest and lowest level of breaking strength after 1500 tensile cyclic loading, respectively. The samples produced by a 2.9 draw ratio showed the highest decrease of breaking elongation after 1500 tensile cyclic loading. The likely mechanism of buckling behavior of core-spun yarns after experiencing strain energy is proposed. The results showed that after 1000 cyclic loads, the highest number of pills was countable on the fabric surface.
Fresh Faces, New Places: Moving Beyond Teacher-Researcher Perspectives in Hip-Hop-Based Education Research
Authors: Irby Decoteau J. , Hall H. Bernard
Published: September 2010

Grounded in critical and culturally relevant theory, hip-hop-based education (HHBE) research documents the use of hip-hop in educational settings. Despite the richness of the emerging field, overreliance on teacher-researcher perspectives leaves much to be desired. Little is known of the extent and ways HHBE is used by nonresearching K-12 teachers. The field of HHBE would be well served to begin exploring the practices of K-12 teachers in various school settings. To encourage such a move, this article demonstrates that a new set of educators whose identities and teaching contexts are not considered in the field are indeed interested in HHBE.
Passive Ranges of Motion of the Hips and Their Relationship with Pitching Biomechanics and Ball Velocity in Professional Baseball Pitchers
Authors: Robb Andrew J. , Fleisig Glenn , Wilk Kevin , Macrina Leonard , Bolt Becky , Pajaczkowski Jason
Published: September 2010

Background

Pelvis and trunk motions during baseball pitching are associated with ball velocity. Thus, limits in hip flexibility may adversely affect pitching biomechanics and the ability to generate ball velocity.

Hypotheses

Professional baseball pitchers will have less passive range of motion in the nondominant hip and the measured ranges of motion of both the nondominant and dominant hips will correlate with biomechanical parameters of the lower extremity among professional pitchers.

Study Design

Cross-sectional study; Level of evidence, 3.

Methods

Nineteen healthy professional baseball pitchers volunteered for testing. Fluid goniometry was used to measure passive range of motion of adduction (ADD), abduction (ABD), internal rotation, external rotation, total arc of rotation, and total arc of ADD + ABD. Pitching biomechanical data were collected using an automated 3-dimensional motion analysis system while participants threw fastballs.

Results

Pitchers possessed significantly less passive range of motion in the nondominant hip when compared with the dominant hip for all ranges. Total arc of rotation of the nondominant hip correlated with ball velocity (r = .50). Total arc of ADD + ABD in the nondominant hip and ABD in the nondominant hip were correlated with stride length (r = —.72 and. 70, respectively). Dominant hip ABD (r = .63), total arc of rotation in the nondominant hip (r = —.45), and total arc of ADD + ABD of the dominant hip (r = .44) were correlated with trunk separation. Total arc of ADD + ABD of the nondominant hip (r = —.52) and total arc of rotation of the dominant hip (r = —.44) were correlated with pelvic orientation.

Conclusion

Passive range of motion is smaller in the nondominant hip than the dominant hip among professional pitchers. The measured disparity between the hips is significantly correlated with various pitching biomechanical parameters of the trunk and pelvis. Future research is required to investigate a causal relationship between less hip passive range of motion and both ball velocity and pitching biomechanics.
Debonding of composites structural insulated sandwich panels
Authors: Mousa Mohammed A , Uddin Nasim
Published: September 2010

A new type of composites structural insulated panels (CSIPs) is presented in this article. These panels are proposed for structural floor and wall applications. The developed composite panels are made of low-cost orthotropic thermoplastic glass/polypropylene laminate as facesheets and expanded polystyrene foam as a core. CSIPs have a considerably high facesheet/core moduli ratio. The common mode of failure of these panels is facesheet/core debonding. Accordingly, this investigation presents models for interfacial tensile stress and critical wrinkling in-plane stress associated with debonding of CSIPs. The facesheet in compression was modeled as a beam on a Winkler foundation. The proposed models were validated using full-scale experimental testing for CSIPs floor and wall panels. Both type of panels failed by facesheet/ debonding with natural half-wavelength approximately equal to the core thickness.
Florence Nightingale in Absentia: Nursing and the 1893 Columbian Exposition
Authors: Selanders Louise C. , Crane Patrick
Published: September 2010

In 1893, Chicago hosted the Columbian Exposition. This event showcased America’s social, cultural, and scientific advances and its growing cultural parity with Western Europe. This was the first major exposition in which women played a prominent role. Integral to the fair was a series of Congresses that provided an international platform for discussion of social issues. The Congress on Hospitals, Dispensaries, and Nursing, a section of the International Congress of Charities, Correction, and Philanthropy, particularly focused on health care issues. Nursing leaders from Europe and North America participated. Although Florence Nightingale provided a major paper that was read at the Congress, she was unable to attend the event. The intent of this article is to examine the issues and themes debated at the 1893 Congress and identify how the influence of Nightingale effected these discussions and the development of Western nursing for the next half-century.
Alienation, authenticity and the self
Authors: Rae Gavin
Published: September 2010

While many commentators have held that the concept ‘alienation’ is of crucial importance when attempting to understand human existence, others have held that it is an inherently empty concept that we should abandon. In this article, I refute the latters’ charge by showing that each conception of ‘alienation’ is underpinned by a normative ontological conception of the preferable, or authentic, self and show that the concept ‘alienation’ has ethical, existential and socio-political uses. From this I conclude that, when properly understood, the concept ‘alienation’ can provide us with vital insights into human existence.
People Use Self-Control to Risk Personal Harm: An Intra-Interpersonal Dilemma
Authors: Rawn Catherine D. , Vohs Kathleen D.
Published: September 2010

People will smoke cigarettes, drink alcohol, binge eat, drink coffee, eat chili peppers, fail tests, steal, ingest illicit drugs, engage in violent and sadistic actions including killing, have sex, and seek to become HIV positive for the sake of interpersonal acceptance. The self-control for personal harm model reconceptualizes behaviors that have both urge and control components as demonstrating either successful or failed self-control, depending on the incipient urge. The model underscores the role of expected social rewards as an important incentive for which people sometimes engage in personally risky and aversive behaviors despite feeling that they would rather avoid the behaviors and attendant harm. Research from diverse perspectives converges to show that risky behaviors, which might on the surface appear to be self-control failures, can in fact require self-control exertion.