A nonantisense sequence-selective effect of a phosphorothioate oligodeoxynucleotide directed against the epidermal growth factor receptor in A431 cells

The overexpression of epidermal growth factor receptor (EGFr) has been implicated as a causative factor and a poor prognostic marker in a number of carcinomas. Therefore, strategies that down-regulate EGFr expression may be therapeutically useful. We designed antisense ODNs complementary to the initiation codon region of the EGFr mRNA and evaluated their efficacy in several tumor-derived cells, including the A431 cell line that express amplified levels of EGFr. A 15-mer phosphorothioate (PS) antisense ODN (erbB1AS15) induced a concentration-dependent reduction in proliferation that was accompanied by a change in the morphology of A431 cells into more tightly clustered and discrete colonies. A 15-mer sense (PS) control oligodeoxynucleotide (ODN) and a phosphodiester (PO) version of erbB1AS15 had little or no effect on cell number of morphology, and erbB1AS15 (PS) did not induce these effects in control cell lines expressing lower levels of EGFr. The effects of erbB1AS15 (PS) on A431 cells were not mediated by a true antisense mechanism in that there was no reduction in the level of EGFr mRNA or protein over a 24-hr period, as determined by Northern and Western blotting, respectively. However, autophosphorylation of the receptor was significantly reduced by erbB1AS15 (PS) and not by control ODNs. The results of further studies suggested that this effect was mediated by a direct, dose-dependent inhibition of the EGFr tyrosine kinase enzyme and was not due to impairment of either ligand-binding or receptor dimerization. These data suggest that erbB1AS15 (PS) can inhibit proliferation and alter the morphology of A431 cells by a sequence-selective, but nonantisense mechanism affecting receptor tyrosine kinase activity.

Monopoly in the UK:what determines whether the MMC finds against the investigated firms?

This paper draws on data from 73 UK Monopolies and Mergers Commission reports on monopoly between 1973 and 1995. It shows that there is a roughly two in three chance that the Commission will come to an adverse conclusion against the investigated firms in a given case. 75–80% of decisions can be explained purely in terms of the market share of the leading firm and knowledge of the broad nature of the alleged anti-competitive practice. An adverse finding is most likely in cases involving exclusive dealing, and least likely where other vertical restraints are involved.

Length, lexicality, and articulatory suppression in immediate recall:evidence against the articulatory loop

Influential models of short-term memory have attributed the fact that short words are recalled better than longer words in serial recall (the length effect) to articulatory rehearsal. Crucial for this link is the finding that the length effect disappears under articulatory suppression. We show, instead, that, under suppression, the length effect is abolished or reversed for real words but remains robust for nonwords. The latter finding is demonstrated in a variety of conditions: with lists of three and four nonwords, with nonwords drawn from closed and open sets, with spoken and written presentation, and with written and spoken output. Our interpretation is that the standard length effect derives from the number of phonological units to be retained. The length effect is abolished or reversed under suppression because this condition encourages reliance on lexical-semantic representations. Using these representations, longer words can more easily be reconstructed from degraded phonology than shorter words. © 2005 Elsevier Inc. All rights reserved.

Language against the odds, or rather not:the weak central coherence hypothesis and language

EV is a child with a talent for learning language combined with Asperger syndrome. EV’s talent is evident in the unusual circumstances of her acquisition of both her first (Bulgarian) and second (German) languages and the unique patterns of both receptive and expressive language (in both the L1 and L2), in which she shows subtle dissociations in competence and performance consistent with an uneven cognitive profile of skills and abilities. We argue that this case provides support for theories of language learning and usage that require more general underlying cognitive mechanisms and skills. One such account, the Weak Central Coherence (WCC) hypothesis of autism, provides a plausible framework for the interpretation of the simultaneous co-occurrence of EV’s particular pattern of cognitive strengths and weaknesses. Furthermore, we show that specific features of the uneven cognitive profile of Asperger syndrome can help explain the observed language talent displayed by EV. Thus, rather than demonstrating a case where language learning takes place despite the presence of deficits, EV’s case illustrates how a pattern of strengths within this profile can specifically promote language learning.

Have the GIPSI settled down? Breaks and multivariate stochastic volatility models for, and not against, the European financial integration

We investigate the integration of the European peripheral financial markets with Germany, France, and the UK using a combination of tests for structural breaks and return correlations derived from several multivariate stochastic volatility models. Our findings suggest that financial integration intensified in anticipation of the Euro, further strengthened by the EMU inception, and amplified in response to the 2007/2008 financial crisis. Hence, no evidence is found of decoupling of the equity markets in more troubled European countries from the core. Interestingly, the UK, despite staying outside the EMU, is not worse integrated with the GIPSI than Germany or France. © 2013 Elsevier B.V.

Hand in hand:privatising five star hotels in Egypt through the stock market will enhance the latter's role as well as set an example of the benefits that could be gained from privatisation

This thesis examines the possibility of privatising public owned five star hotels in Egypt through its stock market in order to give a boost to the Egyptian privatisation programme and to help activate its stock market. To explore these aspects, two main technical exercises were executed. First the writer constructed, for the first time in Egypt, a daily price index for Cairo Stock Exchange and an index for the tourism sector, in order to analyze the efficiency of the capital market. This technical analysis showed that Cairo stock exchange is inefficient, stagnant and undergoes minimal fluctuations, especially when compared to other developed and emerging markets. Second, given the importance and complexity of the valuation of SOEs prior to their privatisation, a sample of three five star hotels that could be prime candidates for privatisation via the stock market in Egypt were selected and a detailed financial analysis for the three hotels was concluded. The result was a valuation range for the three hotels using various valuation methods. Nevertheless it was found out that the final value of hotels will be determined by the market itself. Depite the inefficiency of Cairo Stock Exchange, the thesis did not rule out privatisation through the stock market. On the contrary it cited several examples of developing countries that were able to successfully privatise some of their SOEs via their rudimentary capital markets. Finally, the thesis recommended that five star hotels could be pefect candidates for privatisation via the stock market in Egypt. This is because five star hotels are profitable, privately managed, non strategic and not highly capital intensive businesses. In addition, they do not suffer from overstaffing and the industry in which they operate i.e. tourism sector, has high growth prospects and is of an international nature. Therefore it is anticipated that privatisation of five star hotels can attract a lot of investors because of the relatively high returns. This in turn will help activate and popularize the capital market in Egypt. At the same time the benefits of privatisation would be more visible which will give more momentum to the privatisation programme and make it more politically acceptable.

Ethnic conflict and war crimes in the Balkans:the narratives of denial in post-conflict Serbia

In the years following the fall of Slobodan Milo evic, Serbian social, cultural and political responses to the wars of the 1990s have fallen under intense international scrutiny. But is this scrutiny justfied, and how can these responses be better understood? Jelena Obradovic engages with ideas about post-conflict societies, memory, cultural trauma, and national myths of victimhood and justified war to shed light upon Serbian denial and justification of war crimes - for example, Serbia's reluctant cooperation with the International Criminal Tribunal for the former Yugoslavia (ICTY). Rather than treating denial as a failure to come to terms with the past or as resurgent nationalism, Obradovic argues that the justification of atrocities are often the result of a societal need to understand and incorporate violent events within culturally acceptable boundaries.

Evaluation of DNA enzymes targeted against the RNA component of human telomerase

Glioblastoma Multiforme (GBM) is a highly malignant form of brain cancer for which there is currently no effective cure. Consequently, developing new therapies and elucidating effective targets is crucial for this fatal disease. In recent years, DNA enzymes, deoxyribonucleic acid molecules with enzymatic activity, have emerged. In the same manner as ribozymes, DNA enzymes are able to effect cleavage of RNA in a sequence-specific manner, and operate with catalytic efficiency. In this study, two DNA enzymes were designed to target the template region of human telomerase RNA (hTR), utilising the 10-23 and 8-17 catalytic motifs elucidated by Santoro and Joyce (1997). Telomerase is an RNA-dependent DNA polymerase, which stabilises telomere lengths by adding hexameric repeats (TTAGGG in humans) to chromosome termini, thus preventing the telomere shortening that usually occurs during mitotic cell division. Telomerase activity, whilst absent in normal somatic tissues, is present in almost 90% of all tumours. Thus, there is speculation that telomerase may be the much sought universal target for therapeutic intervention in cancer. In vitro cleavage assays showed both DNA enzymes to be catalytically competent. Unmodified phosphodiester (PO) backbone DNA enzymes were rapidly degraded in the presence of serum, with a half-life of 10 minutes. The common approach of introducing phosphorothioate (PS) linkages was used in an effort to overcome this instability. As a result of concurrent activity and stability studies on the DNA enzymes with various numbers of PS linkages, the DNA enzymes with a PO core and PS arms were chosen for use in further cell work. The cleavage activity of both was shown to be specific and affected by temperature, pH, MgCI2 concentration and enzyme concentration. Both DNA enzyme motifs reduced telomerase activity in cell lysates, as assessed by the telomerase repeat amplification protocol (TRAP) with an IC50 of 100nM. DNA enzymes being polyanionic molecules do not readily cross biological barriers. Cellular association of naked DNA enzyme was inefficient at less than 2%. Cellular delivery of the DNA enzymes was effectively improved using commercial cationic lipid formulations. However, the lipid-mediated delivery of DNA enzymes to U87-MG cells over a 4-hour period did not significantly inhibit cell proliferation compared to controls. This is possibly due to an expected lag period between the inhibition of telomere maintenance and cell death. Therefore, biodegradable polymer microspheres were investigated as a potential delivery option for prolonged and sustained delivery. In vitro release profiles showed that after an initial burst, sustained release of DNA enzymes was observed over 35 days. Finally, the efficacy and specificity of the DNA enzymes were demonstrated in a luciferase based reporter assay. Specific inhibition of luciferase expression was displayed at 10nM. Thus DNA enzymes have potential against endogenous cellular targets.

Web-Based Information Systems in the Stock Market Financial Information Domain

The information domain is a recognised sphere for the influence, ownership, and control of information and it's specifications, format, exploitation and explanation (Thompson, 1967). The article presents a description of the financial information domain issues related to the organisation and operation of a stock market. We review the strategic, institutional and standards dimensions of the stock market information domain in relation to the current semantic web knowledge and how and whether this could be used in modern web based stock market information systems to provide the quality of information that their stakeholders want. The analysis is based on the FINE model (Blanas, 2003). The analysis leads to a number of research questions for future research.

Swimming against the tide: A study of a youth enrichment program seeking to empower inner-city Black youth

Serious inequities in our K-12 public education system, particularly in regard to the quality of education in predominately Black inner-city schools, are well-documented in the literature (Freeman, 1998; Ross, 1998). Moreover, there is general agreement that the most effective means of ameliorating that situation is through well-thought-out after-school programs and partnership initiatives (Beck, 1993; Gardner et al., 2001). ^ The purpose of this qualitative study was to examine the programmatic interventions of a youth enrichment program for inner-city Black youth currently in place at the Overtown Youth Center (OYC) in Miami, Florida, in order to: (a) discern those factors that support its claim that it is making a difference in students’ lives, (b) explore how any such factors are implemented, and (c) determine whether its interventions have served to equalize the playing field for these youth. ^ Two primary methods of data collection were used for this study. The first was participant observation conducted over the course of two years through a partnership initiative established and led by this author. The second was through in-depth interviews of the Center’s founder, staff, and students. Secondary methods used were the recording of informal conversations and the analysis of written documents. ^ Analysis of the data yielded four features of the Center that are indispensible to the students’ growth. The center provides the youth with (a) physical and psychological safety, (b) supportive relationships, (c) exposure to cultural and educational opportunities, and (d) assistance in building self-esteem. ^ The most significant finding of the study was that OYC has been successful at making a difference in students’ lives and at increasing their aspirations to attend college. By addressing the full spectrum of their needs, the Center has given them many of the necessary tools with which to compete and thereby helped equalize their opportunities to succeed in school and in life. ^ The study also noted a number of challenges for the Center to examine. The main issues that need to be addressed more seriously are staff turnover, staff indifference, nepotism, inconsistent student attendance, and insufficient focus on racial issues and African-American-centered education. Meeting those challenges would engender even greater positive outcomes.^

From Bilingualism to Interlinguistics: The Case Against the Deficit Model of Language Acquisition

The article argues against an ahistorical deficit model of Spanish/English bilingualism in educational practice based on interlinguistic research. The bidirectional facilitative effects of Hispanic bilingualism allow Spanish-speaking minorities to exploit their language background while learning academic English and integrating their language and culture into the American mainstream.