MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair.

Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links. It was reported earlier that FANCD2 co-localizes with NBS1. However, the functional connection between FANCD2 and MRE11 is poorly understood. In this study, we show that inhibition of MRE11, NBS1 or RAD50 leads to a destabilization of FANCD2. FANCD2 accumulated from mid-S to G2 phase within sites containing single-stranded DNA (ssDNA) intermediates, or at sites of DNA damage, such as those created by restriction endonucleases and laser irradiation. Purified FANCD2, a ring-like particle by electron microscopy, preferentially bound ssDNA over various DNA substrates. Inhibition of MRE11 nuclease activity by Mirin decreased the number of FANCD2 foci formed in vivo. We propose that FANCD2 binds to ssDNA arising from MRE11-processed DNA double-strand breaks. Our data establish MRN as a crucial regulator of FANCD2 stability and function in the DNA damage response.

Critical flux and fouling in ultrafiltration of proteins

In this thesis different parameters influencing critical flux in protein ultrafiltration and membrane foul-ing were studied. Short reviews of proteins, cross-flow ultrafiltration, flux decline and criticalflux and the basic theory of Partial Least Square analysis (PLS) are given at the beginning. The experiments were mainly performed using dilute solutions of globular proteins, commercial polymeric membranes and laboratory scale apparatuses. Fouling was studied by flux, streaming potential and FTIR-ATR measurements. Critical flux was evaluated by different kinds of stepwise procedures and by both con-stant pressure and constant flux methods. The critical flux was affected by transmembrane pressure, flow velocity, protein concentration, mem-brane hydrophobicity and protein and membrane charges. Generally, the lowest critical fluxes were obtained at the isoelectric points of the protein and the highest in the presence of electrostatic repulsion between the membrane surface and the protein molecules. In the laminar flow regime the critical flux increased with flow velocity, but not any more above this region. An increase in concentration de-creased the critical flux. Hydrophobic membranes showed fouling in all charge conditionsand, furthermore, especially at the beginning of the experiment even at very low transmembrane pressures. Fouling of these membranes was thought to be due to protein adsorption by hydrophobic interactions. The hydrophilic membranes used suffered more from reversible fouling and concentration polarisation than from irreversible foul-ing. They became fouled at higher transmembrane pressures becauseof pore blocking. In this thesis some new aspects on critical flux are presented that are important for ultrafiltration and fractionation of proteins.

The representation of EFL teachers’ views on the role of English as a Lingua Franca

El creciente número de hablantes no nativos de inglés en el mundo constituye la base a partir de la cual se han hecho recientes afirmaciones alrededor de la necesidad de enfatizar el papel del inglés como lingua franca en las clases de inglés. Este artículo investiga la visión de los profesores catalanes de inglés al respecto mediante un cuestionario centrado en aspectos como la preferencia de profesores nativos o no nativos, el conocimiento cultural idóneo para el profeso- rado de inglés, y la variedad de inglés escogida. Los resultados indican que el profesorado está influido por la supremacía del hablante nativo y una visión del inglés todavía restringida a las comunidades de hablantes nativos, con algunas diferencias significativas encontradas entre distintos grupos de profesores.

Non-native English-speaking English language teachers: history and research

Although the majority of English language teachers worldwide are non-native English speakers, no research was conducted on these teachers until recently. After the pioneering work of Robert Phillipson in 1992 and Peter Medgyes in 1994, nearly a decade had to elapse for more research to emerge on the issues relating to non-native English teachers. The publication in 1999 of George Braine's book Nonnative educators in English language teaching appears to have encouraged a number of graduate students and scholars to research this issue, with topics ranging from teachers' perceptions of their own identity to students' views and aspects of teacher education. This article compiles, classifies, and examines research conducted in the last two decades on this topic, placing a special emphasis on World Englishes concerns, methods of investigation, and areas in need of further attention.

Isotope ratio mass spectrometry as a tool for source inference in forensic science: a critical review

Isotope ratio mass spectrometry (IRMS) has been used in numerous fields of forensic science in a source inference perspective. This review compiles the studies published on the application of isotope ratio mass spectrometry (IRMS) to the traditional fields of forensic science so far. It completes the review of Benson et al. [1] and synthesises the extent of knowledge already gathered in the following fields: illicit drugs, flammable liquids, human provenancing, microtraces, explosives and other specific materials (packaging tapes, safety matches, plastics, etc.). For each field, a discussion assesses the state of science and highlights the relevance of the information in a forensic context. Through the different discussions which mark out the review, the potential and limitations of IRMS, as well as the needs and challenges of future studies are emphasized. The paper elicits the various dimensions of the source which can be obtained from the isotope information and demonstrates the transversal nature of IRMS as a tool for source inference.

A situated analysis of football goalkeepers' experiences in critical game situations.

This study described elite football (soccer) goalkeepers' activity and performance in critical game situations. The 11 best French players (M age = 15.5 yr., SD = 0.5) participated in the study. Interviews focused on goalkeepers' experiences were conducted to identify meaningful events involved in failed actions. Players formulated 23 critical game situations. Verbatim encoding using a thematic analysis indicated that four main categories (coming off the line, goal-line clearance, one-on-one, and diving) represented the most critical situations encountered during matches. The relations among experience and action, inner states, background, attention contents, and intentions were elucidated. The discussion is grounded on the properties of such critical game situations and their implications for improving goalkeepers' performance.

Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.

BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.

Using a blog to create and support a Community of Inquiry in Secondary Education

Understanding how blogs can support collaborative learning is a vital concern for researchers and teachers. This paper explores how blogs may be used to support Secondary Education students’ collaborative interaction and how such an interaction process can promote the creation of a Community of Inquiry to enhance critical thinking and meaningful learning. We designed, implemented and evaluated a science case-based project in which fifteen secondary students participated. Students worked in the science blogging project during 4 months. We asked students to be collaboratively engaged in purposeful critical discourse and reflection in their blogs in order to solve collectively science challenges and construct meaning about topics related to Astronomy and Space Sciences. Through student comments posted in the blog, our findings showed that the blog environment afforded the construction of a Community of Inquiry and therefore the creation of an effective online collaborative learning community. In student blog comments, the three presences for collaborative learning took place: cognitive, social, and teaching presence. Moreover, our research found a positive correlation among the three presences –cognitive, social and teaching– of the Community of Inquiry model with the level of learning obtained by the students. We discuss a series of issues that instructors should consider when blogs are incorporated into teaching and learning. We claim that embedded scaffolds to help students to argue and reason their comments in the blog are required to foster blog-supported collaborative learning.

Prediction in forensic science: a critical examination of common understandings

In this commentary, we argue that the term 'prediction' is overly used when in fact, referring to foundational writings of de Finetti, the correspondent term should be inference. In particular, we intend (i) to summarize and clarify relevant subject matter on prediction from established statistical theory, and (ii) point out the logic of this understanding with respect practical uses of the term prediction. Written from an interdisciplinary perspective, associating statistics and forensic science as an example, this discussion also connects to related fields such as medical diagnosis and other areas of application where reasoning based on scientific results is practiced in societal relevant contexts. This includes forensic psychology that uses prediction as part of its vocabulary when dealing with matters that arise in the course of legal proceedings.

Disaster recovery of business critical 3-tiered ERP applications: Disaster Recovery of Nokia Groups SAP R/3

Nykyaikaisessa liiketoimintaympäristössä yritysten kriittisiksi resursseiksi ovat muodostuneet liiketoimintaa tukevat tietojärjestelmät. Mahdollisuus hyödyntää näitä resursseja riippuu ko. liiketoiminnalle kriittisten järjestelmien luotettavuudesta ja hyödynnettävien sovellusten saatavuudesta. Eräs tilanne jossa järjestelmien kyky tukea todellisia liiketoimintaprosesseja vaarantuu on katastrofi. Vaikutukseltaan katastrofi voi olla paikallinen tai kattaa laajojakin alueita. Eri tyyppisiin katastrofeihin on varauduttava niiden edellyttämin tavoin. Eräs kriittisten tietojärjestelmien arkkitehtuuriin vaikuttanut trendi 90-luvulla on ollut client/server lähestymistapa. Client/server paradigman mukaan sovellus jaetaan tasoihin siten että esitys-, sovellus- ja tietokantakerrokset voidaan erottaa fyysisesti toisistaan näiden silti muodostaessa loogisesti yhtenäisen kokonaisuuden. Liiketoiminnan näkökulmasta 90- luvun mullistavia IT-uutuuksia olivat toiminnanohjausjärjestelmät, joiden avulla oli mahdollista hallita koko tuotantoketjua ja muita prosessikokonaisuuksia lähes reaaliajassa. Monikerroksisten toiminnanohjausjärjestelmien luotettavuus on osoittautunut haastavavaksi sillä kaikkien kerrosten suojaaminen kaikilta mahdollisilta katastrofeilta täydellisesti on nykyisellä teknologialla mahdotonta. Kompromissien tekemiseksi on oltava selvillä kunkin menetetyn prosessin aiheuttamista taloudellisista ja liiketoiminnallisista vaikutuksista. Tämän vuoksi juuri toiminnanohjausjärjestelmät ovat mielenkiintoisia, vaikuttavathan ne liiketoimintaprosesseihin läpi koko yrityksen prosessiketjun. Monikerroksisten client/server arkkitehtuuriin pohjautuvien toiminnanohjausjärjestelmien suojaamisessa katastrofeilta onkin sovellettava useita tekniikoita ja teknologioita, ja yhdistettävä kokonaisuus prosessikehykseen. Näin voidaan luoda suunnitelmallinen osa IT strategiaa, joka ottaa kantaa liiketoiminnan jatkuvuuteen katastrofitilanteessa ja mahdollistaa nopean ja täydellisen palautumisen kaikissa olosuhteissa.

Assessment of critical competences required in managing end-user driven businesses in a global forest products compa

Työn pääasiallisena tavoitteena on selvittää ydinosaamista, jota tarvitaan kansainvälisen metsäteollisuusyrityksen loppukäyttäjävetoisessa liiketoiminnassa. Lisäksi tavoitteena on laatia kompetenssimalli, jota voidaan käyttää mm. rekrytoinnissa, koulutuksen ja työnkierron suunnittelussa. Tarkoituksena on tarkastella sekä tällä hetkellä että tulevaisuudessa tarvittavia ydinosaamisia. Työ keskittyy myyntihenkilöiden kompetenssien kuvaamiseen. Kirjallisuuden ja asiantuntijoiden haastattelujen avulla on selvitetty. kompetensseihin liittyviä asioita ja käsitteitä, kuten organisaation oppiminen, innovaatiot sekä asiakaslähtöisyys. Tämän jälkeen on kartoitettu case-yrityksen kartonkiyksikön myyntihenkilökunnan kompetensseja. Kompetenssikartoitus on tehty teemahaastattelujen avulla sekä lisäksi on käytetty työn aikana laadittua kompetenssimatriisia. Saatuja tuloksia on verrattu yhden asiakkaan näkemyksiin. Tulosten mukaan kolme tärkeintä tämän hetken kompetenssia ovat: holistinen näkemys asioista, suhteiden rakentaminen ja kielitaito. Tulevaisuuden tärkeimpiä kompetensseja puolestaan ovat: asiakaslähtöisyys, sähköinen kaupankäynti ja suhteiden rakentaminen. Lopuksi on käsitelty yleisiä metsäteollisuuden tulevaisuuden haasteita sekä annettu joitain kehitysideoita kompetenssien kehittämistä varten.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.