bluuebunny/crossref_metadata_2025 huggingface dataset:
NKX2.2 Suppresses Self-Renewal of Glioma-Initiating Cells
Authors: Muraguchi Teruyuki , Tanaka Shingo , Yamada Daisuke , Tamase Akira , Nakada Mitsutoshi , Nakamura Hideo , Hoshii Takayuki , Ooshio Takako , Tadokoro Yuko , Naka Kazuhito , Ino Yasushi , Todo Tomoki , Kuratsu Jun-ichi , Saya Hideyuki , Hamada Jun-ichiro , Hirao Atsushi
Published: December 2010

Glioblastoma (GBM) is the most aggressive and destructive form of brain cancer. Animal models that can unravel the mechanisms underlying its progression are needed to develop rational and effective molecular therapeutic approaches. In this study, we report the development of mouse models for spontaneous gliomas representing distinct progressive stages of disease that are governed by defined genetic alterations. Neural stem/progenitor cell (NPC)-specific constitutive Ras activation in vivo plus p53 deficiency led to development of primarily anaplastic astrocytoma (grade III), whereas combined loss of p53 plus p16Ink4a/p19Arf led to development of GBM (grade IV) at 100% penetrance within 6 weeks. These glioma models showed enhanced stem cell properties (stemness) accompanied by malignant progression. Notably, we determined that, in our models and in human specimens, downregulation of the homeodomain transcription factor NKX2.2, which is essential for oligodendroglial differentiation, was correlated with increased tumor malignancy. NKX2.2 overexpression by GBM-derived glioma-initiating cells (GIC) induced oligodendroglial differentiation and suppressed self-renewal capacity. By contrast, Nkx2.2 downregulation in mouse NPCs accelerated GBM formation. Importantly, the inhibitory effects of NXK2.2 on GIC self-renewal were conserved in human cells. Thus, our mouse models offer pathobiologically significant advantages to investigate the nature of brain tumors, with improved opportunities to develop novel mechanism-based therapeutic approaches. Cancer Res; 71(3); 1135–45. ©2010 AACR.
The Metastasis-Associated microRNA miR-516a-3p Is a Novel Therapeutic Target for Inhibiting Peritoneal Dissemination of Human Scirrhous Gastric Cancer
Authors: Takei Yoshifumi , Takigahira Misato , Mihara Keichiro , Tarumi Yuzo , Yanagihara Kazuyoshi
Published: December 2010

Although aberrant microRNA (miRNA) is expressed in different types of human cancer tissues, its pathophysiologic role and the relevance of tumorigenesis and metastasis are still largely unknown. Here, we defined miRNAs involved in cancer metastasis (metastamirs) using an established mouse model for peritoneal dissemination of human scirrhous gastric carcinoma cells. Highly metastatic derivatives (44As3 cells) were derived from the parental cells originally isolated from patients (HSC-44PE cells). Using microarray analysis to identify differentially expressed miRNAs in 44As3 and HSC-44PE cells, we focused on miR-516a-3p as a candidate antimetastatic miRNA (antimetastamir) whose functions in cancer had not been studied. We confirmed attenuated expression of miR-516a-3p in 44As3 cells compared with HSC-44PE cells by Northern blot analysis and quantitative reverse transcriptase PCR. Stable ectopic overexpression in 44As3-miR-516a-3p cells permitted identification of sulfatase 1 as a direct target of the miRNA, through use of the isobaric tagging reagent iTRAQ and the QSTAR Elite Hybrid LC-MS/MS system. Sulfatase 1 is known to remove 6-O-sulfates from heparan sulfate proteoglycans on the cell surface, causing release of membrane-bound Wnt ligands from cells. Consistent with this function, Western blot analyses revealed high levels of Wnt3a, Wnt5a, and nuclear β-catenin accumulation in 44As3 cells but relatively reduced levels in 44As3-miR-516a-3p cells. Notably, orthotopic inoculation of nude mice with 44As3-miR-516a-3p cells yielded significantly longer survival periods compared with mice inoculated with control 44As3 cells. Through atelocollagen-mediated delivery of an miR-516a-3p expression vector into orthotopic 44As3 tumors, we documented its feasibility as a treatment agent. Our findings define the miRNA miR-516-3p as an antimetastamir with potential therapeutic applications in blocking metastatic dissemination of gastric cancers. Cancer Res; 71(4); 1442–53. ©2010 AACR.
Recovery of Anoikis in Src-Transformed Cells and Human Breast Carcinoma Cells by Restoration of the SIRPα1/SHP-2 Signaling System
Authors: Hara Kazuo , Senga Takeshi , Biswas Md. Helal Uddin , Hasegawa Hitoki , Ito Satoko , Hyodo Toshinori , Hirooka Yoshiki , Niwa Yasumasa , Goto Hidemi , Hamaguchi Michinari
Published: December 2010

Src kinase dysregulation contributes to cancer progression but mechanistic understanding for this contribution remains incomplete. Signal regulatory protein α1 (SIRPα1) is a tumor suppressor that is constitutively suppressed in v-Src-transformed cells, where restoration of SIRPα1 expression inhibits anchorage-independent growth. In this study, we investigated the role of the protein tyrosine phosphatase-2 (SHP-2) in SIRPα1 activity. SHP-2 suppression resulted in a blockade of SIRPα1-mediated inhibition of anchorage-independent growth. Notably, we found that SIRPα1 did not act in v-Src-transformed cells by triggering cell growth arrest but by eliciting a suspension-selective apoptosis (anoikis), and that SHP-2 was required for this effect. Furthermore, we found that SHP-2 was crucial for recovery of stress fiber and focal contact formation by SIRPα1 in v-Src-transformed cells. Finally, we found that SIRPα1/SHP-2 signaling regulates anoikis in human breast carcinoma cells with activated c-Src. Taken together, our findings define SHP-2 as an essential component of tumor suppression and anoikis mediated by SIRPα1 in human breast carcinoma cells as well as in v-Src-transformed cells. Cancer Res; 71(4); 1229–34. ©2010 AACR.
Polo-Like Kinase 1 is a Therapeutic Target in High-Risk Neuroblastoma
Authors: Ackermann Sandra , Goeser Felix , Schulte Johannes H. , Schramm Alexander , Ehemann Volker , Hero Barbara , Eggert Angelika , Berthold Frank , Fischer Matthias
Published: December 2010

Purpose: High-risk neuroblastoma remains a therapeutic challenge for pediatric oncologists. The Polo-like kinase 1 (PLK1) is highly expressed in many human cancers and is a target of the novel small-molecule inhibitor BI 2536, which has shown promising anticancer activity in adult malignancies. Here, we investigated the effect of BI 2536 on neuroblastoma cells in vitro and in vivo to explore PLK1 as a potential target in high-risk neuroblastoma therapy.

Experimental Design: PLK1 transcript levels were analyzed by microarrays in 476 primary neuroblastoma specimens, and correlation with prognostic markers and patient outcome was examined. To explore the effect of PLK1 inhibition on neuroblastoma cells, 7 cell lines were treated with BI 2536 and changes in growth properties were determined. Furthermore, nude mice with IMR-32 and SK-N-AS xenografts were treated with BI 2536.

Results: PLK1 is highly expressed in unfavorable neuroblastoma and in neuroblastoma cell lines. Expression of PLK1 is associated with unfavorable prognostic markers such as stage 4, age >18 months, MYCN amplification, unfavorable gene expression-based classification, and adverse patient outcome (P < 0.001 each). On treatment with nanomolar doses of BI 2536, all neuroblastoma cell lines analyzed showed significantly reduced proliferation, cell cycle arrest, and cell death. Moreover, BI 2536 abrogated growth of neuroblastoma xenografts in nude mice.

Conclusions: Elevated PLK1 expression is significantly associated with high-risk neuroblastoma and unfavorable patient outcome. Inhibition of PLK1 using BI 2536 exhibits strong antitumor activity on human neuroblastoma cells in vitro and in vivo, opening encouraging new perspectives for the treatment of high-risk neuroblastoma. Clin Cancer Res; 17(4); 1–11. ©2010 AACR.
The struggle to professionalize: An ethnographic account of the occupational position of Advanced Nurse Practitioners
Authors: McMurray Robert
Published: December 2010

This article considers what happens when subordinate occupations challenge established roles and hierarchically organized professional divisions. Charting the struggles of a group of Advanced Nurse Practitioners to be recognized as a profession, the article considers the ways in which claims to licence, place and mandate are employed to negotiate new occupational spaces. Such spaces are shown to emerge as a consequence of the interplay of individual demands and favourable supply side conditions, the latter being required to support the development of new models of working in marginal positions. In a departure from accounts that place managerialism and entrepreneurialism in opposition to professionalism, the article shows how the executive authority that comes with entrepreneurial ownership can bolster professionalizing claims, disrupting and reversing hierarchically organized professional divisions. Identified as a context specific form of ordinal switching, the article considers whether such reversals herald a long-term shift in dominant—subordinate professional relations.
Experimental medicine in drug addiction: towards behavioral, cognitive and neurobiological biomarkers
Authors: Duka Theodora , Crombag Hans S , Stephens David N
Published: December 2010

Several theoretical frameworks have been developed to understand putative processes and mechanisms involved in addiction. Whilst these ‘theories of addiction’ disagree about importance and/or nature of a number of key psychological processes (e.g. the necessity of craving and/or the involvement of drug-value representations), a number of commonalities exist. For instance, it is widely accepted that Pavlovian associations between cues and environmental contexts and the drug effects acquired over the course of addiction play a critical role, especially in relapse vulnerability in detoxified addicts. Additionally, all theories of addiction (explicitly or implicitly) propose that chronic drug exposure produces persistent neuroplastic changes in neurobiological circuitries underlying critical emotional, cognitive and motivational processes, although disagreement exists as to the precise nature of these neurobiological changes and/or their psychological consequences. The present review, rather than limiting itself to any particular theoretical stance, considers various candidate psychological, neurobiological and/or behavioral processes in addiction and outlines conceptual and procedural approaches for the experimental medicine laboratory. The review discusses (1) extinction, renewal and (re)consolidation of learned associations between cues and drugs, (2) the drug reward value, (3) motivational states contributing to drug seeking and (4) reflective (top-down) and sensory (bottom-up) driven decision-making. In evaluating these psychological and/or behavioral processes and their relationship to addiction we make reference to putative underlying brain structures identified by basic animal studies and/or imaging studies with humans.
Hyperhomocysteinemia does not affect global DNA methylation and nicotinamide N-methyltransferase expression in mice
Authors: Bromberg Anna , Levine Joseph , Belmaker RH , Agam Galila
Published: December 2010

DNA methylation is coupled with one-carbon metabolism involving homocysteine/methionine interconversion. Correlation between plasma homocysteine levels and leukocyte global DNA methylation was reported but not always replicated. Nicotinamide N-methyltransferase (NNMT) is a determinant of plasma homocysteine levels. Findings suggest alteration of one-carbon metabolism in schizophrenia etiology; hyperhomocysteinemia was observed in schizophrenia. A recent study carried out by the authors of this paper found an association between NNMT and schizophrenia and decreased post-mortem brain NNMT mRNA levels. The present study assessed the interrelationship between brain and leukocytes global DNA methylation and plasma homocysteine levels, and between hyperhomocysteinemia and brain NNMT expression.

Mice were administered homocysteine in drinking water. Percentage global genome DNA methylation was measured using the cytosine-extension method, and NNMT expression was measured using real-time quantitative reverse transcriptase PCR (qRT-PCR). Homocysteine administration resulted in a 10-fold increase in plasma homocysteine. However, there was no change in global DNA methylation in lymphocytes or in the frontal cortex. No significant intra-individual correlation was found between global DNA methylation in leukocytes and frontal cortex, suggesting that leukocyte global DNA methylation may not serve as a marker for brain global DNA methylation. No difference was found in NNMT expression in homocysteine-treated mice compared with control mice.

In conclusion, relatively short-term hyperhomocysteinemia in mice does not reproduce or lead to alterations reported in one-carbon metabolism in disorders associated with lifelong elevated plasma homocysteine.
Changing Brains, Changing Perspectives
Authors: van den Bos Wouter , van Dijk Eric , Westenberg Michiel , Rombouts Serge A.R.B. , Crone Eveline A.
Published: December 2010

Adolescence is characterized by the emergence of advanced forms of social perspective taking and significant changes in social behavior. Yet little is known about how changes in social cognition are related to changes in brain function during adolescence. In this study, we investigated the neural correlates of social behavior during three phases of adolescence, carrying out functional magnetic resonance imaging of participants’ brains while they were Player 2 in the Trust Game. We found that with age, adolescents were increasingly sensitive to the perspective of the other player, as indicated by their reciprocal behavior. These advanced forms of social perspective-taking behavior were associated with increased involvement of the left temporo-parietal junction and the right dorsolateral prefrontal cortex. In contrast, young adolescents showed more activity in the anterior medial prefrontal cortex, a region previously associated with self-oriented processing and mentalizing. These findings suggest that the asynchronous development of these neural systems may underlie the shift from thinking about self to thinking about the other.
The emerging mediascape, same old theories? A case study of online news diffusion in Korea
Authors: Im Yung-Ho , Kim Eun-mee , Kim Kyungmo , Kim Yeran
Published: December 2010

This article aims to re-examine the main ideas of traditional diffusion study in the context of the internet. Two news stories, one initiated by an established news organization and one uploaded by an individual internet user, were selected for our case study. The study analyzed how a news story gets carried on through various websites of media organizations and individuals.We found that the original stories undergo transformations in terms of content and form over time in the diffusion process. The authors hence introduce a new concept, ‘seed news’, in order to explain this transformative online news diffusion phenomenon. The concept of seed news may subsume the manifold and dynamic process of diffusion, addition, displacement, evolution, and decline of the news story. It also comes to terms with the multifarious dimensions of transmission and the active interplay between the media and users, or among the users themselves.
Eosinophilic colitis: epidemiology, clinical features, and current management
Authors: Alfadda Abdulrahman A. , Storr Martin A. , Shaffer Eldon A.
Published: December 2010

Primary eosinophilic gastrointestinal disorders (EGIDs) represent a spectrum of inflammatory gastrointestinal disorders in which eosinophils infiltrate the gut in the absence of known causes for such tissue eosinophilia. EGIDs can be subgrouped as eosinophilic esophagitis (EE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC). The least frequent manifestation of EGIDs is EC. EC is a heterogeneous entity with a bimodal age distribution, presenting with either an acute self-limited bloody diarrhea in otherwise healthy infants or as a more chronic relapsing colitis in young adults. The pathophysiology of primary EC appears related to altered hypersensitivity, principally as a food allergy in infants and T lymphocyte-mediated (i.e. non-IgE associated) in young adults. In adults, symptoms include diarrhea, abdominal pain, and weight loss. Endoscopic changes are generally modest, featuring edema and patchy granularity. Although standardized criteria are not yet established, the diagnosis of EC depends on histopathology that identifies an excess of eosinophils. Therapeutic approaches are based on case reports and small case series, as prospective randomized controlled trials are lacking. Eosinophilic colitis in infants is a rather benign, frequently food-related entity and dietary elimination of the aggressor often resolves the disorder within days. Adolescent or older patients require more aggressive medical management including: glucocorticoids, anti-histamines, leukotriene receptors antagonists as well as novel approaches employing biologics that target interleukin-5 (IL-5) and IgE. This review article summarizes the current knowledge of EC, its epidemiology, clinical manifestations, diagnosis, and treatment.
Correlation between serum gastrin and cellular proliferation in Barrett’s esophagus
Authors: Green Daniel A. , Mlynarczyk Carrie M. , Vaccaro Benjamin J. , Capiak Kristina M. , Quante Michael , Lightdale Charles J. , Abrams Julian A.
Published: December 2010

Background: Patients with Barrett’s esophagus (BE) are commonly treated with proton-pump inhibitors (PPIs) to minimize the exposure of esophageal mucosa to stomach acid. However, the use of these medications can lead to significant hypergastrinemia in a subset of patients, which is concerning due to the known tumorigenic and proliferative effects of gastrin. The present pilot study aims to investigate a potential correlation between serum gastrin and cellular proliferation in BE.

Methods: We performed a cross-sectional analysis of patients with nondysplastic BE on PPI therapy. Fasting serum gastrin was measured on the same day as esophageal biopsies were obtained. These biopsies were then stained with Ki-67 nuclear antibody. Pearson’s correlation coefficient was calculated to assess the relationship between Ki-67 index and ln(gastrin).

Results: A total of 10 patients were included in the study. The mean age was 62.6 (±8.4) years and 5 patients were male. The median serum gastrin level was 45.2 pM (interquartile range [IQR] 33–113) and the median Ki-67 index was 49.6% (IQR 23–64). We found a statistically significant positive correlation between Ki-67 index and ln(gastrin) ( r = 0.64; p = 0.05).

Conclusions: In nondysplastic BE patients on PPI therapy, serum gastrin levels were significantly correlated with cellular proliferation. These pilot data lend support to a potential causal effect of gastrin on neoplastic progression in BE. Longitudinal studies of patients with BE are needed to determine whether hypergastrinemia is a risk factor for the development of dysplasia and adenocarcinoma or could be used as a biomarker for disease progression.
miR-ID: A novel, circularization-based platform for detection of microRNAs
Authors: Kumar Pavan , Johnston Brian H. , Kazakov Sergei A.
Published: December 2010

MicroRNAs (miRNAs) are important regulators of gene expression and have great potential as biomarkers, prognostic indicators, and therapeutic targets. Determining the expression patterns of these molecules is essential for elucidating their biogenesis, regulation, relation to disease, and response to therapy. Although PCR-based assays are commonly used for expression profiling of miRNAs, the small size, sequence heterogeneity, and (in some cases) end modifications of miRNAs constrain the performance of existing PCR methods. Here we introduce miR-ID, a novel method that avoids these constraints while providing superior sensitivity and sequence specificity at a lower cost. It also has the unique ability to differentiate unmodified small RNAs from those carrying 2′-OMe groups at their 3′-ends while detecting both forms. miR-ID is comprised of the following steps: (1) circularization of the miRNA by a ligase; (2) reverse transcription of the circularized miRNA (RTC), producing tandem repeats of a DNA sequence complementary to the miRNA; and (3) qPCR amplification of segments of this multimeric cDNA using 5′-overlapping primers and a nonspecific dye such as SYBR Green. No chemically modified probes (e.g., TaqMan) or primers (e.g., LNA) are required. The circular RNA and multimeric cDNA templates provide unmatched flexibility in the positioning of primers, which may include straddling the boundaries between these repetitive miRNA sequences. miR-ID is based on new findings that are themselves of general interest, including reverse transcription of small RNA circles and the use of 5′-overlapping primers for detection of repetitive sequences by qPCR.
Reforming Ratification
Authors: Yap Ji Lian
Published: December 2010

This paper considers recent company law reform proposals in Hong Kong in relation to the ratification of breaches of directors' duties, and also makes suggestions for further reform. In the course of this discussion, comparisons will be made with the corresponding position under the UK Companies Act 2006. Finally, several wider observations in relation to the consequences of codification of common law principles and the divergence between English and Hong Kong company law will be offered. The aim is to suggest directions for future reform in the important but somewhat inaccessible area of ratification of breaches of directors' duties. While this paper seeks to consider these issues in the light of Hong Kong, the discussion would be of interest to those from other common law jurisdictions who are examining the issue of ratification or looking with interest at the recent United Kingdom company law reform efforts and considering whether to adopt them locally.
Expression of functional KISS1 and KISS1R system is altered in human pituitary adenomas: evidence for apoptotic action of kisspeptin-10
Authors: Martínez-Fuentes Antonio J , Molina Marcelo , Vázquez-Martínez Rafael , Gahete Manuel D , Jiménez-Reina Luis , Moreno-Fernández Jesús , Benito-López Pedro , Quintero Ana , de la Riva Andrés , Diéguez Carlos , Soto Alfonso , Leal-Cerro Alfonso , Resmini Eugenia , Webb Susan M , Zatelli Maria C , degli Uberti Ettore C , Malagón María M , Luque Raul M , Castaño Justo P
Published: December 2010

Context

KISS1 was originally identified as a metastasis-suppressor gene able to inhibit tumor progression. KISS1 gene products, the kisspeptins, bind to a G-protein-coupled receptor (KISS1R, formerly GPR54), which is highly expressed in placenta, pituitary, and pancreas, whereas KISS1 mRNA is mainly expressed in placenta, hypothalamus, striatum, and pituitary.

Objective and design

KISS1/KISS1R pituitary expression profile, coupled to their anti-tumoral capacities, led us to hypothesize that this system may be involved in the biology of pituitary tumors. To explore this notion, expression levels of KISS1R and KISS1 were evaluated in normal and adenomatous pituitaries. Additionally, functionality of this system was assessed by treating dispersed pituitary adenoma cells in primary culture with kisspeptin-10 and evaluating intracellular calcium kinetics and apoptotic rate.

Results

Both KISS1 and KISS1R were expressed in normal pituitary, whereas this simultaneous expression was frequently lost in pituitary tumors, where diverse patterns of KISS1/KISS1R expression were observed that differed among distinct types of pituitary adenomas. Measurement of calcium kinetics revealed that kisspeptin-10 elicits a remarkable increase in [Ca2+]i in individual cells from four out of the five GH-producing adenomas studied, whereas cells derived from non-functioning pituitary adenomas (NFPA, n=45) did not respond. In contrast, kisspeptin-10 treatment increased the apoptotic rate in cells derived from both GH-producing and NFPA.

Conclusions

These results provide primary evidence that KISS1 and KISS1R expression can be differentially lost in pituitary tumor subtypes, where this system can exert functional, proapoptotic actions, and thereby offer novel insights to investigate the biology and therapeutic options to treat these tumors.
Effect of particle shape on density and permeability of sands
Authors: Göktepe A. B. , Sezer A.
Published: December 2010

Particle shape is widely considered to be one of the most important factors affecting the behaviour of granular soils. This effect may change, based on variations in the grain size distribution. Therefore the effect of particle shape on the behaviour of granular soils should be investigated in soils of similar gradations. In this study, 20 different sands of five origins are initially subjected to image analyses in order to obtain data concerning shape characteristics. Then Proctor tests at three energy levels are conducted to obtain the densification characteristics of these soils. Basic statistical analyses are employed to obtain the distributions that the particle shape characteristics best fit. Empirical equations are developed to estimate the relative density of sands. Constant-head permeability tests are performed to determine the most suitable empirical formula for estimating the coefficient of permeability for granular soils. A new method for obtaining the shape coefficient for the Kozeny–Carman equation is proposed. Overall, relationships between a number of particle shape and fractal dimension parameters, as well as several statistics related to the relative density and permeability of soils, are investigated within an experimental framework.
A new approach to rapid 3D modelling of rock mass structure
Authors: Turanboy A. , Ülker E.
Published: December 2010

The prediction of rock mass behaviour is an important task in many engineering projects, as the behaviour of rock masses can be controlled by the presence of discontinuities. Being able to map the structure of a rock mass is crucial to understanding its potential behaviour. This understanding can positively impact on the safety and efficiency of an engineering project. In this research, rock masses were modelled and analysed using linear mathematical transformations and isometric perspective methods to achieve meaningful three-dimensional results. The rock mass fracture representation is based on explicit modelling of rock faces. The developed model can improve safety and productivity through its application in the determination and analysis of rock mass structure for geological and geotechnical assessment. Based on the methods explained here, a software system was developed for analysing the geometric characteristics of discontinuities in a rock mass. In this model, discontinuities in a rock mass can be visualised both individually and in combination, and cross-sections can be generated at any desired location. In addition, intersection lines between discontinuities can be generated as dip direction vectors. The natural structure attained by using this developed model agrees well with field measurements.
The Basis of Epistemology: How the Mind Understands and Develops Meaning
Authors: Brooks Eugene M.
Published: December 2010

The neurophysiological mechanism of meaning is explained as being essentially the same as that of consciousness. While consciousness and meaning are not the same semantically, at the physiological level, the difference between the two functions is mainly that, in the case of meanings, the underlying qualities are not available to consciousness and unlike consciousness, meanings are understood by the individual as being in the mind instead of in the environment. With the presupposition of the Identity Theory, both consciousness and meaning reduce to Understandings within the mind. They are similar “mental” (physical) constructions.
Efficient online handwritten Chinese character recognition system using a two-dimensional functional relationship model
Authors: Chang Yun , Lee Jia , Rijal Omar , Bakar Syed
Published: December 2010

Efficient online handwritten Chinese character recognition system using a two-dimensional functional relationship model

This paper presents novel feature extraction and classification methods for online handwritten Chinese character recognition (HCCR). TheX-graph andY-graph transformation is proposed for deriving a feature, which shows useful properties such as invariance to different writing styles. Central to the proposed method is the idea of capturing the geometrical and topological information from the trajectory of the handwritten character using theX-graph and theY-graph. For feature size reduction, the Haar wavelet transformation was applied on the graphs. For classification, the coefficient of determination (R2p) from the two-dimensional unreplicated linear functional relationship model is proposed as a similarity measure. The proposed methods show strong discrimination power when handling problems related to size, position and slant variation, stroke shape deformation, close resemblance of characters, and non-normalization. The proposed recognition system is applied to a database with 3000 frequently used Chinese characters, yielding a high recognition rate of 97.4% with reduced processing time of 75.31%, 73.05%, 58.27% and 40.69% when compared with recognition systems using the city block distance with deviation (CBDD), the minimum distance (MD), the compound Mahalanobis function (CMF) and the modified quadratic discriminant function (MQDF), respectively. High precision rates were also achieved.
Reduction in the number of LUT elements for control units with code sharing
Authors: Barkalov Alexander , Titarenko Larysa , Bieganowski Jacek
Published: December 2010

Reduction in the number of LUT elements for control units with code sharing

Two methods are proposed targeted at reduction in the number of look-up table elements in logic circuits of compositional microprogram control units (CMCUs) with code sharing. The methods assume the application of field-programmable gate arrays for the implementation of the combinational part of the CMCU, whereas embedded-memory blocks are used for implementation of its control memory. Both methods are based on the existence of classes of pseudoequivalent operational linear chains in a microprogram to be implemented. Conditions for the application of the proposed methods and examples of design are shown. Results of conducted experiments are given.
Development and optimization of metoprolol succinate gastroretentive drug delivery system
Authors: Boldhane Sanjay , Kuchekar Bhanudas
Published: December 2010

Development and optimization of metoprolol succinate gastroretentive drug delivery system

Metoprolol succinate (MS) gastroretentive (GR) controlled release system was formulated to increase gastric residence time leading to improved drug bioavailability. Box-Behnken model was followed using novel combinations of sodium alginate (SA), sodium carboxymethylcellulose (NaCMC), magnesium alumino metasilicate (MAS) as independent variables. Floating lag time (Flag),t25,t50,t75, diffusion exponent as dependent variables revealed that the amount of SA, NaCMC and MAS have a significant effect (p< 0.05) ont25,t50,t75and Flag. MSGR tablets were prepared and evaluated for mass, thickness, hardness, friability, drug content and floating property. Tablets were studied for dissolution for 24 h and exhibited controlled release of MS with floating for 16 h. The release profile of the optimized batch MS01 fitted first-order kinetics (R2= 0.9868,n= 0.543), indicating non-Fickian diffusion or anomalous transport by diffusion and swelling.
A novel analytical approach for reducing the consumption of organic solvents in the charge transfer-based spectrophotometric analysis: Application in the analysis of certain antihypertensive drugs
Authors: Darwish Ibrahim , Mahmoud Ashraf , Al-Majed Abdul-Rahman
Published: December 2010

A novel analytical approach for reducing the consumption of organic solvents in the charge transfer-based spectrophotometric analysis: Application in the analysis of certain antihypertensive drugs

The present study describes the development of a novel analytical approach that can reduce by 50-fold the consumption of organic solvents in the charge transfer (CT)-based spectrophotometric analysis. The proposed approach employed 96-microwell assay plates for carrying out the reaction. The CT reaction between the electron-donating analyte and electron-accepting reagent was performed in microwells (200-μL of organic solvent) and the color signals were measured with a microwell-plate reader. Optimum conditions for the proposed approach were established for two antihypertensive drugs, namely ramipril (RML) and lisinopril (LSL) as model compounds for the electron-donating analytes, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a π-electron acceptor. Under the optimum conditions, Beer's law was obeyed in the concentration range of 6-100 and 6-60 μg mL-1for RML and LSL, respectively. The limits of detection were 0.97 and 1.10 μg mL-1for RML and LSL, respectively. The precision of the methods was satisfactory; the values of relative standard deviations did not exceed 1.1 %. The proposed approach was successfully applied to the analysis of pharmaceutical dosage forms with good accuracy and precision. The results were comparable with those of the reported methods. The approach described herein is of great practical value in pharmaceutical analysis because it reduces the exposure of analysts to the toxic effects of organic solvents, lowers the analysis cost by 50-fold, and it has a high throughput property. Although the approach was validated for RML and LSL, the same methodology could be used for any electron-donating analyte for which a CT-reaction can be performed.
J. S. Mill and the Art of Compromise
Authors: Cejudo Rafael
Published: December 2010

J. S. Mill and the Art of Compromise

The wordcompromisemeans a kind of agreement and a concession to something harmful or wrong. I argue that particularly this second sense is quite relevant in the ethics of political action. John Stuart Mill focused upon this issue in hisThoughts on Parliamentary Reform 1859.I outline Mill's doctrine on compromise looking at the external and internal features of an acceptable measure of compromise. These features provide a set of conditions necessary in order for compromise to take place, but they do not guarantee sufficient conditions. In order to assess Mill's political coherence and to draw a general distinction between strategic and ethical compromises the paper concludes by considering two compromise measures that Mill adopted while he was a Member of Parliament.
Moral Judgments, Moral Virtues, and Moral Norms
Authors: Popper Miroslav
Published: December 2010

Moral Judgments, Moral Virtues, and Moral Norms

The paper consists of two basic parts. In the first, contemporary approaches to moral judgments and their relations with moral virtues and moral norms are analyzed. The focus is on comparing the role of the emotions and reason, and conscious and unconscious processes in forming and/or justifying moral judgments. The second part examines views on the current broader socio-political situation in Western countries and points to the growing feelings of insecurity among people mainly due to the fact that traditional ways of life have been losing solid ground, settled (social) norms and ethical systems are weakening and at the same time the social trust in various state institutions and bureaucratic structures involved in power is decreasing. In conclusion the author argues for the potential of the ethic of autonomy that would lead to still greater cooperation in globalized ethic, primarily thanks to our moral emotions and moral judgments.
Calling Citizens to a Moral Way of Life: A Dutch Example of Moralized Politics
Authors: Ossewaarde Marinus
Published: December 2010

Calling Citizens to a Moral Way of Life: A Dutch Example of Moralized Politics

This article offers a sociological analysis of the moral revisions that accompany welfare state reforms in the Netherlands. It is argued that Dutch welfare state reforms after the Cold War rely on moral discourses in particular and moral language in general to legitimize and effectuate policy measures. The Dutch reformers have been pursuing a set of strategies of moralization designed to adjust the Dutch welfare state to the new, post-Cold War situation, in which social policies are redesigned to support the operation of global markets. This article seeks to show how this "moral revision" has been taking place by consulting data sources provided by Dutch media, policy documents, council reports, advices, speeches, and newspaper interviews. This implies that special attention is paid to the rhetoric, language, tones, symbolism, metaphors and moral images used and propagated by moral revisionists, elites and media, their definitions of the prevailing moral situation and of the desired one, their formulation of desired values and norms and the ways in which moral panics are aroused. Three recent Dutch policy innovations, namely the national debate on norms and values, the Charter Responsible Citizenship and the family policy memorandum, are interpreted as political strategies to re-engineer the new morality that can sustain a reformed state.
Social Conformity and Response Bias Revisited: The Influence of "Others" on Japanese Respondents
Authors: Kondo Chisuzu , Saito Chiaki , Deguchi Ayaka , Hirayama Miki , Acar Adam
Published: December 2010

Social Conformity and Response Bias Revisited: The Influence of "Others" on Japanese Respondents

This study was undertaken to investigate the impact of other respondents' answers on individual responses in survey studies. The study employed four different conditions and manipulated the direction and the level of social pressure. The results have confirmed that social desirability bias hugely impacts individual answers. It was found that respondents are seven times more likely to choose a socially unacceptable option if majority of the preceding respondents also have chosen the same option. Additionally, the existence of an interviewer during data collection was found to be a factor pressuring respondents to give more socially acceptable responses.
Racism and Its Presuppositions: Towards a Pragmatic Ethics of Social Change
Authors: Lanre-Abass B.
Published: December 2010

Racism and Its Presuppositions: Towards a Pragmatic Ethics of Social Change

Racism has been described as a litmus test or a barium meal which reveals other disorders and injustices within the body politic. It presupposes the legitimacy of racial classifications and the metaphysical reality of races and therefore provides a vital area of scrutiny for philosophical traditions. This paper examines racism and its anti-social effects both on the individual and the society at large. It argues that racism is generally driven by fear and hatred hence all forms of racism are dangerous, socially harmful and morally wrong in practice. The paper recommends ways of overcoming the evil of racism by emphasizing social intelligence and self-realization as moral ideals drawing on John Dewey's pragmatism in ethics. It concludes by stressing Dewey's moral pragmatism as a potent instrument of social change.
Some of the Main Factors of Innovative Renewal of Companies' Operations
Authors: Hustič Igor , Mulej Matjaž
Published: December 2010

Some of the Main Factors of Innovative Renewal of Companies' Operations

Problems cannot be solved by the mentality that has caused them, such as neglecting the non-technological innovation. Often, innovative renewal of companies' operations is urgently needed. Overcoming the consequences of the global economic and financial crisis cannot be successful without innovation of the values, culture, business ethics and norms of all their important stakeholders. We suggest a new synergy of methods aimed at renewal of business processes in an innovative way by using the dialectical systems theory approach. We combine BSC, ISO 9000, the method ‘learning company’ and USOMID. Literature so far has not made it clear that those approaches can complement each other and jointly contribute to renewal of business operations according to the requirement of the requisite holism.
Entrepreneurial Conative Component of Competences: the Case of Slovenia
Authors: Kovač Darko , Meško Maja , Bertoncelj Andrej
Published: December 2010

Entrepreneurial Conative Component of Competences: the Case of Slovenia

Competitive pressures, globalization and economic growth have brought Slovenian enterprises to enhance the role of entrepreneurial competences. The present paper aims to study conative component of entrepreneurial competences as a crucial part of human capital in Slovenian enterprises. The focus of this paper is any eventual disparity of non-teachable attributes of conative component of competences of Slovene enterpreneuer with learned ones rather than the concept of entrepreneurship itself. Authors seperate entrepreneurial competences into three components: cognitive, affective and conative. The purpose of this study is to assess the entrepreneurial conative traits and to investigate the correlation between different conative components of entrepreneurial competences and compare the results to their job-related self-expetations. The conative component of entrepreneurial competences was measures with the Kolbe A™ Index. The study was conducted with 43 Slovenian entrepreneuers from three different enterprises. Independet sample t-test and Pearson's correlation were used to test research aims. SPSS 16.0 was used to analyse the data. The results show conative components of Slovenian entrepreneurial competences, difference between them and individual's job-related self expectations and that the correlation between conative components exist.
Higher Education Demand Factors and the Demand for Tourism Education in Slovenia
Authors: Čepar Žiga , Bojnec Štefan
Published: December 2010

Higher Education Demand Factors and the Demand for Tourism Education in Slovenia

This paper investigates the higher education demand in Slovenia, which is investigated in general and in the field of tourism, using regression analysis on selected time-series data. We find a positive and significant association between the higher education demand in general and the demographic and socio-economic circumstances. Demographic trends in general slow down or even decrease the demand for higher education, while socio-economic factors mostly encourage the demand for higher education. However, unfavourable demographic factors are already prevailing over the favourable socio-economic factors, meaning that growth rates of absolute demand for higher education are starting to decline. We analyze the movements of demand for higher education in the field of tourism in recent years and compare them to the movements of the demand for higher education in general and to the movements of the demand for tourism in Slovenia. The demand for tourist services is a factor that encourages demands for higher education in the field of tourism. Finally, we derive some conclusions about higher education demand determinants in Slovenia in general and in the field of tourism, and propose some recommendations for national educational policy.
Stem Cells of Adult Organisms in Biology and Medicine
Authors: Kawiak Jerzy
Published: December 2010

The life span of adult cells is restricted, becoming senescent and eventually undergoing apoptosis. Cells are replaced by new ones which originate from a population of stem cells. An example is provided by the hemopoietic system in the bone marrow. In an adult body, stem cells may be identified by markers present in both embryonic and tissue-specific stem cells. Oct3/4, CXCR4, Nanog, CD133 and CD34 are examples of such markers. The stem cells share several properties, such as they may: 1) replicate and give rise to new stem cells, 2) differentiate into heterogenous tissue and organ specific cells and, finally, 3) stem cells are self-protected against various toxic agents and radiation. In adult tissues, stem cells reside in specialized sites (niches), for example in the bone marrow, skin, digestive tract epithelium, and skeletal muscles. Stem cells residing in these stem cell niches are anchored there by chemokines and adhesion molecules. Stroma-Derived Factor-1 (SDF-1), α-chemokine and stem-cell expressed receptor CXCR4 play an important role in the retention of stem cells in such niches. Several stress factors may attenuate the SDF-1-CXCR4 axis in the bone marrow, which leads to the release of stem cells from their niches into circulation. Another important stem cell niche-anchoring mechanism is the interaction of Wnt (a ligand) with Frizzled LRP (receptor). The recently accumulated evidence suggests that malignancy arises from an arrest in maturation and mutation of stem cells. Cancer stem cells are responsible for tumor growth, its relapse and metastasis.The first direct evidence for the existence of cancer stem cells came from observations of acute myeloblastic leukemia. Currently, cell populations enriched for cancer stem cells have been isolated from several tumors. The cancer stem cells represent less than 1% of tumor cells in the mouse models.
Hutsulshchyna and Public Progress
Authors: Kibych Anna
Published: December 2010

Hutsulshchyna and Public Progress

The article describes the public-demographic changes in Hutsulshchyna in the light of political and economic surroundings of a changing Ukraine. There are indications proving that structural shifts in Hutsuls' ethnic culture, caused by cultural globalization, are about to happen. Preservation of ethnographic features in present-day conditions, as well as Hutsuls' adaptation to new social realities, appears to become a complex socio-cultural problem of this region of Ukraine.
Spatial Diversification of the Balance on the Labour Market in Rural areas in Poland
Authors: Stanny Monika
Published: December 2010

Spatial Diversification of the Balance on the Labour Market in Rural areas in Poland

The purpose of the study is to present the spatial diversification of the level of the balance on the local labour market in the rural areas. The spatial unit of the analysis is constituted by rural communes (gminas) and the rural areas of the urban-rural communes in Poland according to the administrative division into town and village. This means that the research concerns the spatial diversification observed according to 2,171 units. It was accepted in the research that a balanced labour market occurs where favourable demographic structures are located around the largest regional centres in Poland. This is connected with the development of the communes' non-agricultural economic functions and a strong dependence on urban markets.
Tectonic evolution of the southeastern part of the Pohorje Mountains (Eastern Alps, Slovenia)
Authors: Kirst Frederik , Sandmann Sascha , Nagel Thorsten , Froitzheim Nikolaus , Janák Marian
Published: December 2010

Tectonic evolution of the southeastern part of the Pohorje Mountains (Eastern Alps, Slovenia)

Field relations and deformation structures in the southeastern part of the Pohorje Mountains constrain the tectonic evolution of the Austroalpine high-pressure/ultrahigh pressure (HP/UHP) terrane. The Slovenska Bistrica Ultramafic Complex (SBUC) forms a large (ca. 8 × 1 km size) body of serpentinized harzburgite and dunite including minor garnet peridotite and is associated with partly amphibolitized eclogite bodies. The SBUC occurs in the core of an isoclinal, recumbent, northward closing antiform and is mantled by metasedimentary rocks, mostly gneisses and a few marbles, including isolated eclogite/amphibolite lenses. Before this folding, the SBUC formed the deepest part of the exposed terrane. We interpret the SBUC to be derived from near-MOHO, uppermost mantle which was intruded by gabbros in the subsurface of a Permian rift zone. During Cretaceous intracontinental subduction, the SBUC was most likely part of the footwall plate which experienced HP to UHP metamorphism and was folded during exhumation. In the Miocene, the Pohorje Pluton intruded and, subsequently, the metamorphic rocks together with the pluton were deformed probably due to east-west extension and contemporaneous north-south shortening, thus forming an antiformal metamorphic core complex.