Functional studies of a germ-line polymorphism at codon 47 within the p53 gene.

A rare germ-line polymorphism in codon 47 of the p53 gene replaces the wild-type proline (CCG) with a serine (TCG). Restriction analysis of 101 human samples revealed the frequency of the rare allele to be 0% (n = 69) in Caucasians and 4.7% (3/64, n = 32) among African-Americans. To investigate the consequence of this amino acid substitution, a cDNA construct (p53 mut47ser) containing the mutation was introduced into a lung adenocarcinoma cell line (Calu-6) that does not express p53. A growth suppression similar to that obtained after introduction of a wild-type p53 cDNA construct was observed, in contrast to the result obtained by introduction of p53 mut143ala. Furthermore, expression of neither p53 mut47ser nor wild-type p53 was tolerated by growing cells. In transient expression assays, both mut47ser and wild-type p53 activated the expression of a reporter gene linked to a p53 binding sequence (PG13-CAT) and inhibited the expression of the luciferase gene under the control of the Rous sarcoma virus promoter (RSVluc). In the same assay, mut143ala did not activate the expression of PG13-CAT and produced only a slight inhibitory effect on RSVluc. These findings indicate that the p53 variant with a serine at codon 47 should be considered as a rare germ-line polymorphism that does not alter the growth-suppression activity of p53.

Cadmium uptake and induction of metallothionein synthesis in a renal epithelial cell line (LLC-PK1).

LLC-PK1 cells, an established cell line from pig kidney with proximal tubule properties, were cultivated in vitro at confluence on plastic dishes. They were then exposed (apical side) to inorganic cadmium (CdCl2, 5 microM) for periods ranging between 1 to 24 h. Analysis of the cell supernatant after homogenisation and ultracentrifugation indicated that Cd taken up in the first 3 h was bound to cytosolic high molecular weight proteins, but was redistributed to low molecular weight proteins at later stages. Induction of Cd-metallothionein (Cd-Mt) synthesis, as judged from Cd-Mt binding to a specific anti-Cd-Mt antibody and from the rate of 35S-cys incorporation into a specific protein fraction, was apparent 3-6 h after the addition of Cd to the incubation medium.

Abnormal Returns of Dividend Announcements during a Boom and a Recession. Empirical Evidence from U.S. from the years of 2000 - 2002 and 2005 - 2007, including Finnish Extra Dividends

This study examines the short time price effect of dividend announcements during a boom and a recession. The data being used here is gathered from the years of 2000 - 2002 when it was a recession after the techno bubble burst and from the years 2005 - 2007 when investors experienced large capital gains all around the world. The data consists of dividend increases and intact observations. The aim is to find out differences in abnormal returns between a boom and a recession. Second, the study examines differences between different dividend yield brackets. Third, Finnish extra dividends, mainly being delivered to shareholders in 2004 are included to the empirical test. Generally stated, the aim is to find out do investors respect dividends more during a recession than a boom and can this be proved by using dividend yield brackets. The empirical results from U.S shows that the abnormal returns of dividend increase announcements during the recession in the beginning of this decade were larger than during the boom. Thus, investors seem to respect dividend increases more when stock prices are falling. Substantial abnormal returns of dividend increases during the time period of 2005 - 2007 could not be found. The results from the overall samples state that the abnormal returns during the recession were positively slightly higher than during the boom. No clear and strong evidence was found between different dividend yield brackets. In Finland, there were substantial abnormal returns on the announcement day of the extra dividends. Thus, indicating that investors saw the extra dividends as a good thing for shareholders' value. This paper is mostly in line with the theory that investors respect dividends more during bad times than good times.

Improvement of Operational Efficiency effectiveness (OEE) using Six Sigma DMAIC Methodology — Case Bottomer line AD2378

Overall Equipment Effectiveness (OEE) is the key metric of operational excellence. OEE monitors the actual performance of equipment relative to its performance capabilities under optimal manufacturing conditions. It looks at the entire manufacturing environment measuring, in addition to the equipment availability, the production efficiency while the equipment is available to run products, as well as the efficiency loss that results from scrap, rework, and yield losses. The analysis of the OEE provides improvement opportunities for the operation. One of the tools used for OEE improvement is Six Sigma DMAIC methodology which is a set of practices originally developed to improve processes by eliminating defects. It asserts the continuous efforts to reduce variation in process outputs as key to business success, as well as the possibility of measurement, analysis, improvement and control of manufacturing and business processes. In the case of the Bottomer line AD2378 in Papsac Maghreb Casablanca plant, the OEE figures reached 48.65 %, which is below the accepted OEE group performance. This required immediate actions to achieve OEE improvement. This Master thesis focuses on the application of Six Sigma DMAIC methodology in the OEE improvement on the Bottomer Line AD2378 in Papsac Maghreb Casablanca plant. First, the Six Sigma DMAIC and OEE usage in operation measurement will be discussed. Afterwards, the different DMAIC phases will allow the identification of improvement focus, the identification of OEE low performance causes and the design of improvement solutions. These will be implemented to allow further tracking of improvement impact on the plant operations.

Abnormal Return of Dividend Announcements during a Boom and a Recession. Empirical evidence from the years of 2002 - 2002 and 2005 - 2007, including the Finnish extra dividends

Tutkimuksen tavoitteena on tutkia epänormaalien tuottojen esiintymistä nousu- ja laskusuhdanteen aikana osingonilmoituspäivän ympärillä. Osinkoilmoitukset ovat kerätty Yhdysvaltojen markkinalta (NYSE) ajanjaksoilta 2000 - 2002, jolloin pörssit laskivat teknokuplan jälkeen ja 2005 - 2007, jolloin sijoittajat kokivat suuria kurssivoittoja. Osinkoilmoitushavainnot koostuvat yhtiöistä, jotka nostivat tai pitivät osinko per osake paikallaan. Tavoitteena on tutkia eroja epänormaaleissa tuotoissa näiden kahden ajanjakson välillä. Toiseksi, tavoitteena on tutkia miten epänormaalit tuotot poikkeavat toisistaan eri osinkotuottoluokissa. Kolmanneksi, tavoitteena on tutkia esiintyikö markkinoilla epänormaaleja tuottoja kun suomalaiset yritykset ilmoittivat ylimääräisistä osingoista, pääasiassa vuonna 2004. Yksinkertaisesti ja lyhyesti sanottuna tavoitteena on tutkia arvostavatko sijoittajat osinkoja enemmän laskukauden vai nousukauden aikana. Rahoitusteorian mukaan sijoittajien tulisi arvostaa laskukauden aikana enemmän yhtiöitä, jotka pystyvät maksamaan huonosta taloustilanteesta huolimatta hyvää osinkoa. Empiiriset testit Yhdysvalloista osoittavat, että osingon nostamisesta johtuvat epänormaalit tuotot olivat suuremmat laskusuhdanteen aikana kuin noususuhdanteen aikana. Tämä on linjassa teorian kanssa. Osingon-nostot aiheuttivat nousukauden aikana vähäisiä epänormaaleja tuottoja. Selviä eroja eri osingontuottoluokkien välillä ei pystytty havaitsemaan. Tulokset yhdistetystä aineistosta osoittavat, että sijoittajat kokivat vähäisiä positiivisia epänormaaleja tuottoja laskukauden aikana. Nousukautena tuotot olivat lähellä nollaa. Suomen markkinoilla havaittiin selvä epänormaalituotto osingonilmoituspäivänä. Tulokset ovat pääpiirteittäin linjassa teorian kanssa. Sijoittajat arvostavat osinkoja hieman enemmän lasku- kuin noususuhdanteen aikana.

PROM-OPEN: PROMOTING OPEN SCIENCE IN AN ON-LINE E-LEARNING ENVIRONMENT

Peer-reviewed

Monotherapy or Polytherapy for First-Line Treatment of SE?

Status epilepticus (SE) is one of the most frequent neurologic emergencies, and a rapid and effective treatment is warranted. Current guidelines recommend a stepwise approach using a sequence of different antiepileptic drugs with benzodiazepines (BZD) being the first treatment proposed. To provide the more effective treatment as soon as possible, some authors have suggested using a combined polytherapy as first-line treatment. Strong evidence supports the use of benzodiazepines, mostly lorazepam and midazolam as initial monotherapy treatment for SE. Insufficient data are available to support the use of nonsedating antiepileptic drugs as phenytoin, valproic acid, or levetiracetam without a previous benzodiazepine administration. Studies assessing the role of a combined initial therapy are rare, if not missing. Moreover, owing the wide range of SE etiologies, a "one fits all" initial polytherapy seems difficult to achieve. After reviewing the available evidence, guidelines, and current practices regarding monotherapy and polytherapy as first-line treatment in SE in adults, the authors propose a rational algorithm for early antiseizure treatment in SE.

Identification of new transformation products during enzymatic treatment of tetracycline and erythromycin antibiotics at laboratory scale by an on-line turbulent flow liquid-chromatography coupled to a high resolution mass spectrometer LTQ-Orbitrap

This work describes the formation of transformation products (TPs) by the enzymatic degradation at laboratory scale of two highly consumed antibiotics: tetracycline (Tc) and erythromycin (ERY). The analysis of the samples was carried out by a fast and simple method based on the novel configuration of the on-line turbulent flow system coupled to a hybrid linear ion trap – high resolution mass spectrometer. The method was optimized and validated for the complete analysis of ERY, Tc and their transformation products within 10 min without any other sample manipulation. Furthermore, the applicability of the on-line procedure was evaluated for 25 additional antibiotics, covering a wide range of chemical classes in different environmental waters with satisfactory quality parameters. Degradation rates obtained for Tc by laccase enzyme and ERY by EreB esterase enzyme without the presence of mediators were ∼78% and ∼50%, respectively. Concerning the identification of TPs, three suspected compounds for Tc and five of ERY have been proposed. In the case of Tc, the tentative molecular formulas with errors mass within 2 ppm have been based on the hypothesis of dehydroxylation, (bi)demethylation and oxidation of the rings A and C as major reactions. In contrast, the major TP detected for ERY has been identified as the “dehydration ERY-A”, with the same molecular formula of its parent compound. In addition, the evaluation of the antibiotic activity of the samples along the enzymatic treatments showed a decrease around 100% in both cases

Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.

Cost-effectiveness of Tenofovir / Emtricitabine / Efavirenz versus Zidovudine / Lamivudine / Efavirenz as fist-line regimens for the treatment of HIV-infected patients in low-income settings

The Highly Active Antiretroviral Therapy (HAART) is the combination of at least three antiretroviral compounds. The combination purpose is to reduce the likelihood of drug resistance. However in the long-term the resistance to the first-line combination occurs and leads to treatment failure. Thus, a second-line and even a third-line regimen are recommended in the long run. [...] [P. 5] The two treatment alternatives under comparison: Tenofovir (300 mg) CO-formulated with Emtricitabine (200 mg) and Efavirenz (600 mg) currently known under the brand name Atripla (R) was introduced in July 2006 in the United States market. The excellent safety profile and ease of use make this combination a perfect first-line regimen in low-income settings. Therefore, this treatment option was recommended in WHO 2006 reviewed guidelines. Unfortunately, Tenofovir and Emtricitabine compounds are still costly and not yet widely available. For a matter of simplification this regimen is referred in this report as "the recent" therapy. Initially, we had in mind to consider the most frequently used first-line regimen in low-income countries (Stavudine / Larnivudme / Nevirapine) as a comparator for this economic evaluation. Unfortunately, according to the literature review results (see Annex 3); there was no data available comparing head to head the effectiveness of this regimen with the recent one. Instead, we selected a less frequently but commonly used first-line regimen in low-income countries as a comparator: Zidovudine, Lamivudine, Efavirenz. This combination has extensive experience in durability, safety and toxicity and seems to be an optimal choice for a first-line regimen according to the clinical trial group 384 team. Furthermore, Zidovudine, one of the compounds of this combination is now recommended as one of the preferred NNRTI [Non Nucleoside Reverse Transcriptase Inhibitors] options to be considered by countries instead of Stavudine (the most used NNRTI in limited-income countries). As this combination has been included in the WHO guidelines as a first-line therapy since 2003 when WHO launched the "3 by 5" scaling-up initiative, this combination of drugs is referred in this report as the "old" therapy. Objectives: The primary objective of this economic evaluation is to compare the two first-line HAARTs introduced above, in a low-income setting context. Both of these combinations are recommended by the 2006 WHO guidelines as potential first-line regimens. The secondary objective is to provide a simplified and comprehensible cost-effectiveness modeling tool in order to help policy makers, in resource-limited settings, make decisions about which first-line HAART to fund using the scarce resources available. [P. 6-7]

On-line life history calendar and sensitive topics : A pilot study

The use of the life history calendar (LHC) or the event history calendar as tools for collecting retrospective data has received increasing attention in many fields of social science and medicine. However, little research has examined the use of this method with web-based surveys. In this study, we adapted this method to an on-line setting to collect information about young adults' life histories, sexual behaviors, and substance use. We hypothesized that the LHC method would help respondents to date sensitive and non-sensitive events more precisely than when using a conventional questionnaire. We conducted an experimental design study comparing university students' responses to an on-line LHC and a conventional on-line question list. A test-retest design in which the respondents completed the survey again two weeks later was also applied to test the precision and reliability of the participants' dating of events. The results showed that whereas the numbers of sensitive and non-sensitive events were generally similar for the two on-line questionnaires, the responses obtained with the LHC were more consistent across the two administrations. Analyses of the respondents' on-line behavior while completing the LHC confirmed that respondents used the LHC's graphic interface to correct and reedit previous answers, thus decreasing data errors. (C) 2015 Elsevier Ltd. All rights reserved.

Change points detection in crime-related time series: an on-line fuzzy approach based on a shape space representation

The extension of traditional data mining methods to time series has been effectively applied to a wide range of domains such as finance, econometrics, biology, security, and medicine. Many existing mining methods deal with the task of change points detection, but very few provide a flexible approach. Querying specific change points with linguistic variables is particularly useful in crime analysis, where intuitive, understandable, and appropriate detection of changes can significantly improve the allocation of resources for timely and concise operations. In this paper, we propose an on-line method for detecting and querying change points in crime-related time series with the use of a meaningful representation and a fuzzy inference system. Change points detection is based on a shape space representation, and linguistic terms describing geometric properties of the change points are used to express queries, offering the advantage of intuitiveness and flexibility. An empirical evaluation is first conducted on a crime data set to confirm the validity of the proposed method and then on a financial data set to test its general applicability. A comparison to a similar change-point detection algorithm and a sensitivity analysis are also conducted. Results show that the method is able to accurately detect change points at very low computational costs. More broadly, the detection of specific change points within time series of virtually any domain is made more intuitive and more understandable, even for experts not related to data mining.

On-line teaching and Copyright : Any Hopes for an EU Harmonized Playground?

Education never fails to be mentioned ¿ and, often, mentioned first ¿ as a public interest that justifies an exception to copyright. Educational purposes were already present in the first version of the Berne Convention of 18862 and have remained there (although in revised language) ever since. The WIPO Copyright Treaty of 19963 expressly referred to education in its Preamble, when ¿Recognizing the need to maintain a balance between the rights of authors andthe larger public interest, particularly education, research and access to information, as reflected in the Berne Convention¿ (emphasis added). And morerecently, the EU Directive on Copyright in the Information Society4 stressed its goal ¿to promote learning and culture by protecting works and other subjectmatter while permitting exceptions or limitations in the public interest for the purpose of education and teaching¿ (Recital 14, emphasis added).

Optimización y aproximación al problema de la regresión simbólica a través de Straight Line Programs (SLP's) y algoritmos genéticos : Entrenamiento genético de SLP's

El problema de la regresión simbólica consiste en el aprendizaje, a partir de un conjunto muestra de datos obtenidos experimentalmente, de una función desconocida. Los métodos evolutivos han demostrado su eficiencia en la resolución de instancias de dicho problema. En este proyecto se propone una nueva estrategia evolutiva, a través de algoritmos genéticos, basada en una nueva estructura de datos denominada Straight Line Program (SLP) y que representa en este caso expresiones simbólicas. A partir de un SLP universal, que depende de una serie de parámetros cuya especialización proporciona SLP's concretos del espacio de búsqueda, la estrategia trata de encontrar los parámetros óptimos para que el SLP universal represente la función que mejor se aproxime al conjunto de puntos muestra. De manera conceptual, este proyecto consiste en un entrenamiento genético del SLP universal, utilizando los puntos muestra como conjunto de entrenamiento, para resolver el problema de la regresión simbólica.

Power line communication in motor cables of variable-speed electric drives − analysis and

Data transmission between an electric motor and a frequency converter is required in variablespeed electric drives because of sensors installed at the motor. Sensor information can be used for various useful applications to improve the system reliability and its properties. Traditionally, the communication medium is implemented by an additional cabling. However, the costs of the traditional method may be an obstacle to the wider application of data transmission between a motor and a frequency converter. In any case, a power cable is always installed between a motor and a frequency converter for power supply, and hence it may be applied as a communication medium for sensor level data. This thesis considers power line communication (PLC) in inverter-fed motor power cables. The motor cable is studied as a communication channel in the frequency band of 100 kHz−30 MHz. The communication channel and noise characteristics are described. All the individual components included in a variable-speed electric drive are presented in detail. A channel model is developed, and it is verified by measurements. A theoretical channel information capacity analysis is carried out to estimate the opportunities of a communication medium. Suitable communication and forward error correction (FEC) methods are suggested. A general method to implement a broadband and Ethernet-based communication medium between a motor and a frequency converter is proposed. A coupling interface is also developed that allows to install the communication device safely to a three-phase inverter-fed motor power cable. Practical tests are carried out, and the results are analyzed. Possible applications for the proposed method are presented. A speed feedback motor control application is verified in detail by simulations and laboratory tests because of restrictions for the delay in the feedback loop caused by PLC. Other possible applications are discussed at a more general level.