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Deregulation
Kinds of Deregulation Selected AbstractsTHE SUSTAINED IMPACTS OF TAXI DEREGULATIONECONOMIC AFFAIRS, Issue 1 2010Sean D. Barrett The Irish High Court decision in 2000 to deregulate entry to the taxi sector brought a large increase in taxi numbers and reduced waiting times for customers. These developments were sustained through to 2008 with increased output and reduced waiting times. In view of these lasting successes, arguments that taxi deregulation is unwise and unsustainable are examined. [source] TAXI DEREGULATION AND TRANSACTION COSTSECONOMIC AFFAIRS, Issue 2 2006Christian Seibert Deregulation of taxi markets has the potential to deliver significant benefits. However, it presents the problem of transaction costs and in particular problems linked with imperfect information and co-ordination. This article argues that the use of a centralised intermediary in deregulated taxi markets can overcome these problems so that the benefits of competition are maximised, without the need for government fare regulation. [source] Managing the Bank-System Crisis in Coordinated Market Economies: Institutions and Blame Avoidance Strategies in Sweden and JapanGOVERNANCE, Issue 1 2006TORSTEN SVENSSON Sweden and Japan represent two different positions regarding policymaking when faced with similar crises of the bank systems. Different institutional settings led the main actors to different paths of reactions in order to avoid blame. In the Japanese case, the very close relationship between private banks and the Ministry of Finance, in combination with the lesser degree of widespread perceptions of a system crisis, made it more urgent as well as possible to conceal the actual state of affairs for the politicians. Confronted with the threat of losing power over the financial administration to a new agency, the ministry postponed the reforms in order to conceal the deep financial problems. The institutional setting was different in Sweden. Deregulation had separated the government from the administration of banks. Among the public deteriorating economic conditions were easily connected to the banks. This brought about political unity. It was possible to put the blame on the banks and take the credit for the efforts to tidy up the mess without losing credibility. [source] Advanced and intelligent technologies for reliable operation of power systems and electricity marketsIEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 5 2008Ryuichi Yokoyama Senior Member Abstract Deregulation of power industries is still progressing in many countries, aiming at reduction of the electricity price, diversity of customer diverse choices, services and promotion of new business and keeping supply reliability. Many countries are testing this notion in anticipation of lower power prices through open competition. In such a competitive situation, it is necessary for suppliers to take on the responsibility of keeping supply reliability at the load end in order to prevent outages, for instance, independent power producers (IPP) placing distributed generations (DGs) close to the load or conventional utilities utilizing advanced and intelligent system operation/control technologies that are costly. Usually, customers pay one price for power that is good enough for ordinary use, therefore not necessarily highly consistent in quality of voltage, current, frequency or reliability. However, if customers desire better quality power, additional fees are added according to the particular characteristics desired, thus customers are supplied with this type of better power that they choose. Under such a worldwide new trend in power systems and markets, this article is edited for the purpose of introducing the most advanced technologies and the newest issues related to reliable and stable operations of power markets and systems in the competitive environment. © 2008 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source] CARMA1-mediated NF-,B and JNK activation in lymphocytesIMMUNOLOGICAL REVIEWS, Issue 1 2009Marzenna Blonska Summary:, Activation of transcription factor nuclear factor-,B (NF-,B) and Jun N-terminal kinase (JNK) play the pivotal roles in regulation of lymphocyte activation and proliferation. Deregulation of these signaling pathways leads to inappropriate immune response and contributes to the development of leukemia/lymphoma. The scaffold protein CARMA1 [caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1] has a central role in regulation of NF-,B and the JNK2/c-Jun complex in both B and T lymphocytes. During last several years, tremendous work has been done to reveal the mechanism by which CARMA1 and its signaling partners, B cell CLL-lymphoma 10 and mucosa-associated lymphoid tissue 1, are activated and mediate NF-,B and JNK activation. In this review, we summarize our findings in revealing the roles of CARMA1 in the NF-,B and JNK signaling pathways in the context of recent advances in this field. [source] Unbalanced expression of licensing DNA replication factors occurs in a subset of mantle cell lymphomas with genomic instabilityINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Magda Pinyol Abstract DNA licensing is a crucial process for chromosome replication control. Deregulation of the licensing factors Cdt1, Cdc6 and the licensing inhibitor geminin has been associated with DNA replication defects and chromosomal instability. We examined the expression of these factors, in mantle cell lymphoma (MCL) and non-neoplastic lymphoid samples, and analysed the potential role of their deregulation in genomic instability. Geminin, Cdt1 and Cdc6 were coordinately expressed in non-neoplastic tissues and most MCL in relationship to the proliferative activity of the cells. However, 6 (18%) tumours showed an unbalanced "licensing signature" characterized by a higher expression of Cdt1 and Cdc6 than the negative regulator geminin. Tumours with this unbalanced signature and p53/p14ARF alterations had significantly higher number of chromosome abnormalities than lymphomas with p53/p14ARF alterations but with a normal licensing signature. No aberrations of Cdct1, Cdc6, and geminin genes were detected in cases with unbalanced licensing. However, tumours with p53/ARF inactivation and unbalanced licensing signature had significantly higher cyclin D1 levels than tumours with normal licensing signature. These results suggest that an unbalanced mRNA expression of licensing regulatory genes may play a role in the pathogenesis of the chromosomal instability of a subset of MCL with inactivation of the p53/p14ARF pathway. © 2006 Wiley-Liss, Inc. [source] Deregulation of Stat5 expression and activation causes mammary tumors in transgenic miceINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Elena Iavnilovitch Abstract Members of the signal transducers and activators of transcription (Stat) family regulate essential cellular growth and survival functions in normal cells and have also been implicated in tumorigenesis. We have studied the potential role of Stat5 in mammary tumorigenesis by targeting Stat5 variants to the mammary gland of transgenic mice using regulatory sequences of the ,-lactoglobulin gene. Mammary-directed expression of the wild-type Stat5, constitutively activated Stat5 and carboxyl-terminally truncated dominant negative Stat5 forms resulted in mammary tumors with incidence rates of up to 22% and latency periods of 8,12 months. Undifferentiated carcinomas most frequently occurred in mice expressing the carboxyl-terminally truncated Stat5. The more differentiated papillary and micropapillary adenocarcinomas were primarily found in mice overexpressing the native and constitutively active transgenes. Higher levels of translation initiation factor 4E (eIF4E) and cyclin D1 expression but lower levels of activated Stat3 were found in tumors of mice expressing the constitutively active Stat5 when compared to mice expressing the wild-type or truncated forms. A higher expression of the estrogen receptor (ER,) was observed in carcinomas compared to other phenotypes. The ability of both forms of Stat5, the transactivating form and the dominant negative form, to participate in oncogenesis indicates that there is more than one mechanism by which Stat5 contributes to this process. The transactivation function of Stat5 is involved in the determination of tumors with a more differentiated phenotype. © 2004 Wiley-Liss, Inc. [source] Nuclear localization signals and human diseaseIUBMB LIFE, Issue 7 2009Laura M. McLane Abstract In eukaryotic cells, the physical separation of the genetic material in the nucleus from the translation and signaling machinery in the cytoplasm by the nuclear envelope creates a requirement for a mechanism through which macromolecules can enter or exit the nucleus as necessary. Nucleocytoplasmic transport involves the specific recognition of cargo molecules by transport receptors in one compartment followed by the physical relocation of that cargo into the other compartment through regulated pores that perforate the nuclear envelope. The recognition of protein cargoes by their transport receptors occurs via amino acid sequences in cargo proteins called nuclear targeting signals. Both nuclear import and export of proteins are highly regulated processes that control, not only what cargo can enter and/or exit the nucleus, but also when in the cell cycle and in what cell type, the cargo can be transported. Deregulation of the nuclear transport of specific cargoes has been linked to numerous cancers and developmental disorders highlighting the importance of understanding the mechanisms underlying nucleocytoplasmic transport and particularly the modulation of the specific interactions between transporter receptors and nuclear targeting signals within target cargo proteins. © 2009 IUBMB IUBMB Life 61(7): 697,706, 2009 [source] Using RFPs to manage your bank relationshipJOURNAL OF CORPORATE ACCOUNTING & FINANCE, Issue 1 2006James S. Sagner Who is in charge of your firm's relationship with its bank,your company or the bank? Deregulation of the financial services industries has made access to banking services more difficult. And many companies find they have to award credit and noncredit business to retain their banks' goodwill. What is more, the finance function is often no longer the sole gatekeeper for all banking contact. But companies,and finance,can get back in control by using requests for proposals (RFPs) to manage the bank relationship. This article shows how to do that. © 2006 Wiley Periodicals, Inc. [source] Deregulation of E-cadherin,catenin complex in precancerous lesions of gastric adenocarcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2003ANNIE ON-ON CHAN Abstract Background and Aim: Decrease in expression of the E-cadherin,catenin complex is an important element in gastric carcinogenesis. However, the expression of the complex in gastric precancerous lesions has not been well studied. The present study aimed to examine the serial change in expression of E-cadherin,catenin complex in the precancerous lesions of gastric cancer patients. Methods: Gastrectomy specimens of 40 patients with gastric cancer were retrieved. Areas with chronic gastritis, atrophic gastritis, intestinal metaplasia and adenocarcinoma were identified and immunostained for ,-catenin, ,-catenin and E-cadherin. The results were scored semiquantitatively by two independent pathologists using a validated scoring system. Results: A significant decrease in score was observed in 5% (1/22) of ,-catenin, 0% (0/22) of ,-catenin and 9% (2/22) of E-cadherin in chronic atrophic gastritis patients, and in 28% (5/18) of ,-catenin, 67% (10/15) of ,-catenin and 57% (8/14) of E-cadherin in intestinal metaplasia patients. The scoring of ,-catenin, ,-catenin and E-cadherin correlated with each other. Forty-three percent of patients had concordant changes of scores along the gastritis,adenocarcinoma sequence. There was no association between Helicobacter pylori status and E-cadherin,catenin complex expression. Conclusion: Deregulation of the E-cadherin,catenin complex was observed in the majority of precancerous lesions in patients with gastric adenocarcinoma, which has potential diagnostic and therapeutic implications. © 2003 Blackwell Publishing Asia Pty Ltd [source] The Competitive Dynamics of Geographic Deregulation in Banking: Implications for Productive EfficiencyJOURNAL OF MONEY, CREDIT AND BANKING, Issue 5 2008DOUGLAS D. EVANOFF market entry; bank mergers; banking deregulation; cost X-efficiency Deregulation of geographic restrictions in banking over the past 20 years has intensified both potential and actual competition in the industry. The accumulating empirical evidence suggests that potential efficiency gains associated with consolidating banks are often not realized. We evaluate the impact of this increased competition on the productive efficiency of non-merging banks confronted with new entry in their local markets and find that the incumbent banks respond by improving cost efficiency. Thus, studies evaluating the impact of bank mergers on the efficiency of the combining parties alone may be overlooking the most significant welfare-enhancing aspect of merger activity. [source] The Natural Gas Market: 60 Years of Regulation and Deregulation by Paul W. MacAvoy.JOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 1 2003$35.00, 176 pp., CT: Yale University, New Haven [source] Deregulation and the Racial Composition of AirlinesJOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 2 2001Jacqueline Agesa Economic theory suggests that the enhanced product market competition of deregulation reduces employers' ability to discriminate when hiring. Recent studies of the effect of deregulation on racial employment in the naturally competitive trucking industry find that deregulation increased minority employment. This study examines the effect of deregulation on racial employment in the airline industry. Because deregulation transformed airlines from wasteful service competition to rigorous price competition, deregulation's effect on racial hiring in this continuously competitive industry is not apparent. This study finds that deregulation only modestly changed the racial composition of major airline occupations, which suggests that the change in market structure as a result of deregulation may largely determine the effect of regulatory reform on the racial composition of an industry. © 2001 by the Association for Public Policy Analysis and Management. [source] Upregulation of Serotonin Transporter by Alcohol in Human Dendritic Cells: Possible Implication in Neuroimmune DeregulationALCOHOLISM, Issue 10 2009Dakshayani Kadiyala Babu Background:, Alcohol is the most widely abused substance and its chronic consumption causes neurobehavioral disorders. It has been shown that alcohol affects the function of immune cells. Dendritic cells (DC) serve as the first line of defense against infections and are known to accumulate neurotransmitters such as 5-hydroxytryptamine (5-HT). The enzyme monoamine oxidase-A (MAO-A) degrades 5-HT that is associated with clinical depression and other neurological disorders. 5-HT is selectively transported into neurons through the serotonin transporter (SERT), which is a member of the sodium- and chloride-dependent neurotransmitter transporter (SLC6) family. SERT also serves as a receptor for psychostimulant recreational drugs. It has been demonstrated that several drugs of abuse such as amphetamine and cocaine inhibit the SERT expression; however, the role of alcohol is yet to be elucidated. We hypothesize that alcohol can modulate SERT and MAO-A expression in DC, leading to reciprocal downregulation of 5-HT in extracellular medium. Methods:, Dendritic cells were treated with different concentrations (0.05% to 0.2%v/v) of alcohol for 24,72 hours and processed for SERT and MAO-A expression using Q-PCR and Western blots analysis. In addition, SERT function in DC treated with alcohol both in the presence and absence of imipramine, a SERT inhibitor was measured using 4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide uptake assay. 5-HT levels in culture supernatant and intracellular 5-hydroxy indole acetic acid (5-HIAA) and cyclic AMP were also quantitated using ELISA. Results:, Dendritic cells treated with 0.1% alcohol for 24 hours showed significant upregulation of SERT and MAO-A expression compared with untreated DC. We also observed that 0.1% alcohol enhanced the function of SERT and decreased extracellular 5-HT levels compared with untreated DC cultures, and this was associated with the elevation of intracellular 5-HIAA and cyclic AMP levels. Conclusions:, Our study suggests that alcohol upregulates SERT and MAO-A by elevating cyclic AMP, which may lead to decreased concentration of 5-HT in the extracellular medium. As 5-HT is a major neurotransmitter and an inflammatory mediator, its alcohol-mediated depletion may cause both neurological and immunological deregulation. [source] A novel strategy to inhibit FAK and IGF-1R decreases growth of pancreatic cancer xenograftsMOLECULAR CARCINOGENESIS, Issue 2 2010Donghang Zheng Abstract Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments that target only one of the pathways. Ablation of IGF-1R signaling by siRNA showed minimal effects on the survival and growth of pancreatic cancer cells. An increased activity of FAK pathway was seen in these cells after IGF-1R knockdown. Further inhibition of FAK pathway using Y15 significantly decreased cell survival, adhesion, and promoted apoptosis. The combination of Y15 treatment and IGF-1R knockdown also showed significant antitumor effect in vivo. The current study demonstrates the importance of dual inhibition of both these signaling pathways as a novel strategy to decrease both in vitro and in vivo growth of human pancreatic cancer. © 2009 Wiley-Liss, Inc. [source] Analysis of gastrointestinal physiology using a novel intestinal transit assay in zebrafishNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2009H. A. Field Abstract, Gastrointestinal function depends upon coordinated contractions to mix and propel food through the gut. Deregulation of these contractions leads to alterations in the speed of material transit through the gut, with potentially significant consequences. We have developed a method for visualizing intestinal transit, the physiological result of peristaltic contractions, in larval zebrafish. This method allows direct, non-invasive observation of luminal content as it traverses the gut. Using this method, we characterized gastrointestinal transit in zebrafish larvae at 7 days postfertilization. In addition, we used this transit assay to assess the physiological consequences of reduced or absent enteric neurones on intestinal transit in larval zebrafish. This may facilitate the use of the zebrafish for investigating the effect of compounds and candidate genes on gastrointestinal motility. [source] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma developmentPATHOLOGY INTERNATIONAL, Issue 5 2010Masatoshi Shigoka MicroRNAs (miRNAs) belong to a class of the endogenously expressed non-coding small RNAs which primarily function as gene regulators. Growing evidence suggests that miRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. The miR-17-92 cluster especially is markedly overexpressed in several cancers, and is associated with the cancer development and progression. In this study, we have demonstrated that miR-92a is highly expressed in hepatocellular carcinoma (HCC). In addition, the proliferation of HCC-derived cell lines was enhanced by miR-92a and inhibited by the anti-miR-92a antagomir. On the other hand, we have found that the relative amount of miR-92a in the plasmas from HCC patients is decreased compared with that from the healthy donors. Interestingly, the amount of miR-92a was elevated after surgical treatment. Thus, although the physiological significance of the decrease of miR-92a in plasma is still unknown, deregulation of miR-92 expression in cells and plasma should be implicated in the development of HCC. [source] Deregulation and Subequilibrium in the Australian Dairy Processing IndustryTHE ECONOMIC RECORD, Issue 233 2000HRISTOS DOUCOULIAGOS The Australian dairy processing industry is currently undergoing a program of substantial regulatory reform. In this paper we assess the impact of this deregulation on the production and cost systems of the industry. This is undertaken using a translog restricted cost function, for the period 1969 to 1996, with labour, milk and energy as the variable inputs and capital as the one fixed input. We find that this industry has undergone significant changes in terms of factor demand and cost structures associated with the introduction of new technology. [source] The Impact of Deregulation and Financial Innovation on Consumers: The Case of the Mortgage MarketTHE JOURNAL OF FINANCE, Issue 1 2010KRISTOPHER S. GERARDI ABSTRACT We develop a technique to assess the impact of changes in mortgage markets on households, exploiting an implication of the permanent income hypothesis: The higher a household's expected future income, the higher its desired consumption, ceteris paribus. With perfect credit markets, desired consumption matches actual consumption and current spending forecasts future income. Because credit market imperfections mute this effect, the extent to which house spending predicts future income measures the "imperfectness" of mortgage markets. Using micro-data, we find that since the early 1980s, mortgage markets have become less imperfect in this sense, and securitization has played an important role. [source] Deregulation of Aurora kinase gene expression in human testicular germ cell tumoursANDROLOGIA, Issue 4 2010E. Baldini Summary The Aurora kinases regulate chromosome segregation and cytokinesis, and alterations in their expression associate with cell malignant transformation. In this study, we demonstrated by qRT-PCR analysis of 14 seminomas that Aurora-A mRNA was, with respect to control tissues, augmented in five of 14 tumour tissues by 2.17 ± 0.30 fold (P < 0.05) and reduced in 9 to 0.38 ± 0.10 (P < 0.01). Aurora-B mRNA was increased in 11 tumour tissues by 4.33 ± 0.82 fold (P < 0.01) and reduced in 3 to 0.41 ± 0.11 fold. Aurora-C mRNA was reduced to 0.20 ± 0.32 fold (P < 0.01) in 13 seminomas and up-regulated in one case. Western blot experiments, performed on protein extracts of nine seminomas and six normal testes, showed an up-regulation of Aurora-B protein by 10.14 ± 3.51 fold (P < 0.05), while Aurora-A protein was found increased in four seminomas by 2.16 ± 0.43 (P < 0.05), unchanged in three and reduced in two tumour tissues. Aurora-C protein was increased by 9.2 ± 2.90 fold (P < 0.05), suggesting that post-transcriptional mechanisms modulate its expression. In conclusion, we demonstrated that expression of Aurora kinases is deregulated in seminomas, suggesting that they may play a role in the progression of testicular cancers. [source] Evaluating the British Model of Electricity DeregulationANNALS OF PUBLIC AND COOPERATIVE ECONOMICS, Issue 3 2004by Stephen Thomas It was expected that replacement of monopolies in some areas by markets and price-setting in monopoly areas using a simple incentive formula would mean that regulation of the industry would be ,light'. This article examines how regulation has turned out in practice. It concludes that the promise of ,light' regulation has not been fulfilled. Regulation of competitive markets is a major regulatory activity, incentive regulation has evolved into a complex and intrusive form of rate-of-return, while regulation of industry structure has allowed the industry to descend into a concentrated, vertically integrated structure, at odds with the aims of the reforms. [source] HP24 MICRORNA EXPRESSION PROFILES IN BARRETT'S OESOPHAGUSANZ JOURNAL OF SURGERY, Issue 2007D. I. Watson Purpose The genetic changes that drive the metaplastic change from squamous oesophagus (NO) towards Barrett's oesophagus (BO) and cancer are unclear. microRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and contribute to cellular differentiation and identity. We sought to determine the role of miRNAs in BO. Methodology Biopsies of NO, BO and cardia were taken from 7 patients and RNA was extracted. miRNA expression profiles of 300 miRNAs were determined by microarray. Guided by the array results, real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) for 8 selected miRNAs enabled their expression to be studied in tissues from another 15 patients. Results Array data revealed that 39 miRNAs were significantly differentially expressed between NO, BO and cardia. A tissue-specific expression profile was confirmed by RT-PCR, with miR-21, 143, 145, 194 and 215 significantly up regulated in BO and cardia (columnar) vs. NO (squamous). A trend towards increased miR-21 expression from NO to BO and adenocarcinoma was observed (p = 0.1). Interestingly, high expression of miR-143, 194 and 215 was seen in BO vs. NO (p < 0.0001), but with subsequent downregulation in cancers (p = 0.1). In contrast, miR-203 and 205 were highly expressed in NO and low in BO and cardia. A database search revealed that these miRNAs potentially target (proto-)oncogenes and tumour suppressor genes. Conclusions Differences in miRNA expression are present between NO, BO, cardia and cancer. Deregulation of certain miRNAs, and their predicted effect on the expression of target genes, might contribute to the metaplastic and neoplastic process in the oesophagus and could serve as novel biomarkers to classify diseased tissues. [source] The Impact of APROC on Taiwan's Economy: A CGEAnalysis of DeregulationASIAN ECONOMIC JOURNAL, Issue 1 2002Shiu-Tung Wang The Taiwan Government defines the Asia-Pacific Regional Operations Center (APROC) project as designed ,to transform Taiwan into a regional economic center through overall liberalization and internationalization'. From this definition and the targets of APROC as set by the Taiwan Government, it is not difficult to see that deregulation is one of the basic means of achieving its goals. In this paper, we use a computable general equilibrium (CGE) model to evaluate the possible effects of this deregulation. The effects of deregulation on the economy go through four channels in the model: (i) deregulation liberalizes the market; (ii) deregulation moderates factor market distortion; (iii) deregulation attracts foreign investment, speeds up capital accumulation and enlarges capital stock in Taiwan; and (iv) deregulation attracts foreign investment and hence improves technology. Six simulations are conducted in this paper. All of the simulations show positive effects on Taiwan's economy as a whole, while for individual sectors the effects are various. [source] Deregulation of wholesale petrol prices: what happened to capital city petrol prices?AUSTRALIAN JOURNAL OF AGRICULTURAL & RESOURCE ECONOMICS, Issue 1 2010Alistair Davey Wholesale petrol prices were deregulated in August 1998. This paper will quantify the effect associated with the deregulation of wholesale petrol prices on relative retail prices for unleaded petrol in Adelaide, Melbourne and Sydney. This is done through Box,Jenkins autoregressive integrated moving average methodology coupled with Box and Tiao intervention analysis. Weekly price data will be used for Adelaide, Melbourne, and Sydney. It finds that from the beginning of 1999, deregulation coincided with relatively lower retail petrol prices for all three cities. In the absence of any other possible alternative explanation for the simultaneous fall in relative retail petrol prices across all three cities, it is concluded that this change was most likely associated with deregulation. These results suggest that regulation of wholesale petrol prices were ineffectual in terms of constraining capital city retail petrol prices at the very least and may have actually contributed towards relatively higher retail petrol prices. This also suggests that future policy interventions designed to constrain prices in the downstream petroleum industry should be very carefully considered. [source] Deregulation, Competitive Pressures and the Emergence of IntermodalismAUSTRALIAN JOURNAL OF PUBLIC ADMINISTRATION, Issue 3 2002Sophia Everett Deregulation has dramatically altered the face of Australian industry and associated services throughout the last decade or so. In the transport sector, in particular, changes have been significant and deregulation has led to pervasive changes in market structure, to the actual ownership of infrastructure and to a shift in strategic focus from a public utility to one of commercial viability and market orientation. Competitive pressures in the transport sector as a result of deregulation have meant that traditional public sector organisations such as railways and ports have been transformed. A major impact of these developments has been that transport operators, in an endeavour either to maintain or capture market share, have been forced to restructure and refocus and, in the face of growing competition, have been forced to reinvent themselves and move increasingly towards the provision of an integrated intermodal service. Rail operators are now no longer simple linehaul operators in container or bulk freight markets but have become market,focused third,party service providers of a range of integrated functions. [source] Integrated genomic and expression profiling in mantle cell lymphoma: identification of gene-dosage regulated candidate genesBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2008Margit Schraders Summary Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) translocation and several other cytogenetic aberrations, including heterozygous loss of chromosomal arms 1p, 6q, 11q and 13q and/or gains of 3q and 8q. The common intervals of chromosomal imbalance have been narrowed down using array-comparative genomic hybridization (CGH). However, the chromosomal intervals still contain many genes potentially involved in MCL pathogeny. Combined analysis of tiling-resolution array-CGH with gene expression profiling on 11 MCL tumours enabled the identification of genomic alterations and their corresponding gene expression profiles. Only subsets of genes located within given cytogenetic anomaly-intervals showed a concomitant change in mRNA expression level. The genes that showed consistent correlation between DNA copy number and RNA expression levels are likely to be important in MCL pathology. Besides several ,anonymous genes', we also identified various fully annotated genes, whose gene products are involved in cyclic adenosine monophosphate-regulated pathways (PRKACB), DNA damage repair, maintenance of chromosome stability and prevention of rereplication (ATM, ERCC5, FBXO5), energy metabolism (such as genes that are involved in the synthesis of proteins encoded by the mitochondrial genome) and signal transduction (ARHGAP29). Deregulation of these gene products may interfere with the signalling pathways that are involved in MCL tumour development and maintenance. [source] Epigenetic regulation of the non-canonical Wnt pathway in acute myeloid leukemiaCANCER SCIENCE, Issue 2 2010Vanesa Martín Wnt5a is a member of the Wnt family of proteins that signals through the non-canonical Wnt/Ca2+pathway to suppress cyclin D1. Deregulation of this pathway has been found in animal models suggesting that it acts as tumour suppressor in acute myeloid leukemia (AML). Although DNA methylation is the main mechanism of regulation of the canonical Wnt pathway in AML, the role of WNT5A abnormalities has never been evaluated in this clinical setting. The methylation status of WNT5A promoter,exon 1 was analyzed by methylation-specific PCR and sequencing in eleven AML-derived cell lines and 252 AML patients. We observed WNT5A hypermethylation in seven cell lines and in 43% (107/252) of AML patients. WNT5A methylation was associated with decreased WNT5A expression (P < 0.001) that was restored after exposure to 5-Aza-2'-deoxycytidine. Moreover, WNT5A hypermethylation correlated with upregulation of CYCLIN D1 expression (P < 0.001). Relapse (15%vs 37%, P < 0.001) and mortality (61%vs 79%, P = 0.004) rates were lower for patients in the non-methylated group. Disease-free survival and overall survival at 6 and 7 years, respectively, were 60% and 27% for unmethylated patients and 20% and 0% for hypermethylated patients (P = 0.0001 and P = 0.04, respectively). Interestingly, significant differences were also observed when the analysis was carried out according to cytogenetic risk groups. We demonstrate that WNT5A, a putative tumor suppressor gene in AML, is silenced by methylation in this disease and that this epigenetic event is associated with upregulation of CYCLIN D1 expression and confers poor prognosis in patients with AML. (Cancer Sci 2009) [source] ATP-Noncompetitive Inhibitors of CDK,Cyclin ComplexesCHEMMEDCHEM, Issue 1 2009Mar Orzáez Dr. Abstract Progression through the cell division cycle is controlled by a family of cyclin-dependent kinases (CDKs), the activity of which depends on their binding to regulatory partners (cyclins A,H). Deregulation of the activity of CDKs has been associated with the development of infectious, neurodegenerative, and proliferative diseases such as Alzheimer's, Parkinson's, or cancer. Most cancer cells contain mutations in the pathways that control the activity of CDKs. This observation led this kinase family to become a central target for the development of new drugs for cancer therapy. A range of structurally diverse molecules has been shown to inhibit the activity of CDKs through their activity as ATP antagonists. Nevertheless, the ATP binding sites on CDKs are highly conserved, limiting the kinase specificity of these inhibitors. Various genetic and crystallographic approaches have provided essential information about the mechanism of formation and activation of CDK,cyclin complexes, providing new ways to implement novel research strategies toward the discovery of new, more effective and selective drugs. Herein we review the progress made in the development of ATP-noncompetitive CDK,cyclin inhibitors. [source] Deregulation of cell-death pathways as the cornerstone of skin diseasesCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2010N. Zutterman Summary Deregulation of cell-death pathways plays a key role in the pathogenesis of various skin diseases. The different types of cell death are mainly defined by morphological criteria, and include apoptosis, autophagic cell death, and necrosis. The process of apoptosis is well characterized at the molecular level and involves the activation of two main pathways, the intrinsic and extrinsic pathways, converging into the execution of apoptosis by intracellular cysteine proteases, called caspases. The relevance and implication of these apoptotic pathways in the pathophysiology of skin diseases, such as toxic epidermal necrolysis, graft-versus-host disease and skin cancer, has been extensively studied. The role of autophagic cell death in progression of skin tumours and response to cytotoxic drugs is only beginning to be elucidated. [source] Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signalingDEVELOPMENTAL DYNAMICS, Issue 5 2008Jennifer L. Fogel Abstract Although Hedgehog (HH) signaling plays a critical role in patterning the ventral midbrain, its role in early midbrain specification is not known. We examined the midbrains of sonic hedgehog (Shh) and smoothened (Smo) mutant mice where HH signaling is respectively attenuated and eliminated. We show that some ventral (Evx1+) cell fates are specified in the Shh,/, mouse in a Ptc1 - and Gli1 -independent manner. HH-independent ventral midbrain induction was further confirmed by the presence of a Pax7 -negative ventral midbrain territory in both Shh,/, and Smo,/, mice at and before embryonic day (E) 8.5. Midbrain signaling centers are severely disrupted in the Shh,/, mutant. Interestingly, dorsal markers are up-regulated (Wnt1, Gdf7, Pax7), down-regulated (Lfng), or otherwise altered (Zic1) in the Shh,/, midbrain. Together with the increased cell death seen specifically in Shh,/, dorsal midbrains (E8.5,E9), our results suggest specific regulation of dorsal patterning by SHH, rather than a simple deregulation due to its absence. Developmental Dynamics 237:1359-1372, 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||||||||