PAX5 activates the transcription of the human telomerase reverse transcriptase gene in B cells.

Telomerase is an RNA-dependent DNA polymerase that synthesizes telomeric DNA. Its activity is not detectable in most somatic cells but it is reactivated during tumorigenesis. In most cancers, the combination of hTERT hypermethylation and hypomethylation of a short promoter region is permissive for low-level hTERT transcription. Activated and malignant lymphocytes express high telomerase activity, through a mechanism that seems methylation-independent. The aim of this study was to determine which mechanism is involved in the enhanced expression of hTERT in lymphoid cells. Our data confirm that in B cells, some T cell lymphomas and non-neoplastic lymph nodes, the hTERT promoter is unmethylated. Binding sites for the B cell-specific transcription factor PAX5 were identified downstream of the ATG translational start site through EMSA and ChIP experiments. ChIP assays indicated that the transcriptional activation of hTERT by PAX5 does not involve repression of CTCF binding. In a B cell lymphoma cell line, siRNA-induced knockdown of PAX5 expression repressed hTERT transcription. Moreover, ectopic expression of PAX5 in a telomerase-negative normal fibroblast cell line was found to be sufficient to activate hTERT expression. These data show that activation of hTERT in telomerase-positive B cells is due to a methylation-independent mechanism in which PAX5 plays an important role.

Characterizing the impact of minor cannula design modification.

OBJECTIVE: Bench evaluation of the hydrodynamic behavior of venous cannulas is a valuable technique for the analysis of their performance during cardiopulmonary bypass (CPB). The aim of this study was to investigate the effect of the internal diameter of the extracorporeal connecting tube of venous cannulas on flow rate (Q), pressure drop (delta P), and cannula resistance (delta P/Q²) values, using a computer assisted test bench.¦METHODS: An in vitro circuit was set up with silicone tubing between the test cannula encased in a movable reservoir, and a static reservoir. The delta P, defined as the difference between the drainage pressure and the preload pressure, was measured using high-fidelity Millar pressure transducers. Q was measured using an ultrasonic flowmeter. Data display and data recording were controlled using virtual instruments in a stepwise fashion.¦RESULTS: The 27 F smartcanula® with a 9 mm connecting tube diameter showed 17% less resistance compared to that with an 8 mm connecting tube diameter. Q values were 7.22±0.1 and 7.81±0.04 L/min for cannulas with 8 mm and 9 mm connecting tube diameters, respectively. The delta P/Q² ratio values were 72% lower for the Medtronic cannula with a 9 mm connecting tube diameter compared to that with an 8 mm connecting tube diameter. Q values for the Medtronic cannula were 3.94±0.23 and 6.58±0.04 L/min with 8 mm and 9 mm connecting tube diameters, respectively. The 27 F smartcanula® showed 13% more flow rate compared to the 28 F Medtronic cannula using the unpaired Student t-test (p<0.0001).¦CONCLUSIONS: Our results demonstrated that Q was increased but delta P and delta P/Q² values were significantly decreased when the connecting tube diameter was increased for venous cannulas. The connecting tube diameter significantly affected the resistance to liquid flow through the cannula. Smartcanulas® outperform Medtronic cannulas.

Reinforcement learning utilizes proxemics: an avatar learns to manipulate the position of people in immersive virtual reality

A reinforcement learning (RL) method was used to train a virtual character to move participants to a specified location. The virtual environment depicted an alleyway displayed through a wide field-of-view head-tracked stereo head-mounted display. Based on proxemics theory, we predicted that when the character approached within a personal or intimate distance to the participants, they would be inclined to move backwards out of the way. We carried out a between-groups experiment with 30 female participants, with 10 assigned arbitrarily to each of the following three groups: In the Intimate condition the character could approach within 0.38m and in the Social condition no nearer than 1.2m. In the Random condition the actions of the virtual character were chosen randomly from among the same set as in the RL method, and the virtual character could approach within 0.38m. The experiment continued in each case until the participant either reached the target or 7 minutes had elapsed. The distributions of the times taken to reach the target showed significant differences between the three groups, with 9 out of 10 in the Intimate condition reaching the target significantly faster than the 6 out of 10 who reached the target in the Social condition. Only 1 out of 10 in the Random condition reached the target. The experiment is an example of applied presence theory: we rely on the many findings that people tend to respond realistically in immersive virtual environments, and use this to get people to achieve a task of which they had been unaware. This method opens up the door for many such applications where the virtual environment adapts to the responses of the human participants with the aim of achieving particular goals.

Food allergy: Evaluation of the quality of life in Swiss children

Background: Food allergy in children, an increasingly prevalent disease, significantly affects the quality of life. Its impact can be analyzed by the recently validated French version of the Food Allergy Quality of Life Questionnaire (FAQLQ). Objectives: The aim of our study was to evaluate the quality of life in a small sample of Swiss children with IgE-mediated food allergy. Methods: Information were collected with the questionnaire among 0-12 years old children and their parents during a scheduled allergy visit, and analysed in term of emotional impact, food anxiety and social and food limitations. Patients were divided according to the questionnaire in three age groups: group 1 from 0 to 3 years, group 2 from 4 to 6 years and group 3 from 7 up to 12 years. Results: 30 food allergic patients were included, with a girl/boy ratio of 1:1.14. Median age was 6 years. 56% suffered from or had a history of eczema, 23% of rhino-conjunctivitis, 30% of asthma, and 13% reported a drug allergy. None had insect venom allergy. 57% were known to be allergic to one food, 20% to two foods, 20% to 3 foods and 3% had 3 or more food allergies. Tree nuts (51% of all allergies) as well as eggs (28 %) were the major allergies. Emotional impact had a total score of 1.54 but showed differences between age groups. In group 1 it was lower with 0.23, in group 2 the score was 2.03 and 1.77 in group 3. Food anxiety total score was 1.9; 0.76 in group 1, 2.31 in group 2 and 2.23 in group 3. Social and food limitations showed similar results with a total score of 1.73 and 1.23 in group 1, 2.05 in group 2 and 1.68 for group 3. Conclusion: Food allergy affects the quality of life of Swiss children. Our preliminary results on a small sample are comparable to previously published data. We show that the impact of food allergy on daily life increases when the child starts school and social activities.

Distraction osteogenesis in the management of severe maxillary hypoplasia in cleft lip and palate patients.

The aim of this study was to systematically review literature reporting on the use of external distraction osteogenesis (DO) and internal DO in the treatment of severe maxillary hypoplasia in cleft and palate patients. Literature research has been performed using the PubMed database of the National Library of Medicine and National Institutes of Health from 1966 to August 2007. We used cleft lip and palate and distraction osteogenesis as key words. Of the 104 articles found, we only considered the Anglo-Saxon literature, which reported on the correction of the maxillary hypoplasia with DO techniques. A total of 32 studies reported on anteroposterior external DO (27 studies on rigid external device and 5 on face mask), 17 studies reported on anteroposterior internal DO, and 3 studies reported on transverse internal DO have been retained for this review. Despite the heterogeneity and methodological limitations of most of the studies, results showed that external DO with rigid external device and internal DO resulted to be a more reliable and accurate technique than the face mask in the management of severe maxillary hypoplasia in patients with cleft lip and palate. The current review demonstrated that external and internal DO in the treatment of severe maxillary hypoplasia in cleft and palate patients (1) is a reproducible and valuable alternative to standard orthognathic surgery procedures, (2) allows for a global improvement in facial aesthetic, (3) allows a maxillary correction in patients during the period of mixed dentition, and (4) allows either for an unchanged or better velopharyngeal function.

Determination of the critical activities of a public-private intermediary organization with the help of value chain analysis

Tämän diplomityön tavoitteena oli selvittää arvoketjuanalyysin avulla toiminnot, joilla voittoatavoittelemattoman, julkisen osakeyhtiön toimintaa voitaisiin kuvata. Tarkoituksena oli selvittää mainitut toiminnot yleisesti ja luoda malli kohdeyrityksen arvoketjusta ja sen toiminnoista. Tutkielma jakautuu teoreettiseen ja empiiriseen osaan. Ensimmäinen pohjautuu aikaisempaan tutkimukseen ja kirjallisuuteen sidosryhmistä, arvon muodostumisesta ja arvoketjuanalyysistä. Jälkimmäinen on laadullista tapaustutkimusta. Empiriassa mallinnettiin Lappeenranta Innovation Oy:nsisäisiä toimintoja ja sidosryhmien odotuksia. Empiirinen tutkimus perustui kohdeyrityksen omistajille ja henkilöstölle tehtyihin haastatteluihin sekä yrityksen toiminnan päivittäiseen seurantaan. Johtopäätöksenätodettiin, että julkisen, voittoa tavoittelemattoman yrityksen toiminnot on mahdollista kuvata arvoketjuanalyysin avulla. Alan ja yrityksen asettamat erityispiirteet toivat haasteita määrittelylle, mutta silti arvoketju antoi selkeän tavan kohdeyrityksen toimintojen mallintamiselle.

Photographic rectification of the graphic documentation of historical and archaeological heritage: The case of the southern facade of the Praetorium tower in Tarragona (Tarraco, Hispania Citerior)

This article details the use of photographic rectification as support for the graphic documentation of historical and archaeological heritage and specifically the southern facade of the Torre del Pretori (Praetorium Tower) in Tarragona. The Praetorium Tower is part of a larger monumental complex and one of the towers that connected different parts of the Tarraco Provincial Forum, the politic-administrative centre of the ancient capital of Hispania Citerioris. It is therefore a valuable example of the evolution of Roman urban architecture. The aim of this project is to provide accurate graphic documentation of the structure to facilitate the restoration and conservation of the tower, as well as to provide a more profound architectural and archaeological understanding of the Roman forum. The use of photographic rectification enabled us to overcome the spatial and time difficulties involved in collecting data caused by the size and location of the building. Specific software made it easier to obtain accurate two-dimensional images. For this reason, in our case, photographic rectification helped us to make a direct analysis of the monument and facilitated interpretation of the architectural stratigraphy. We currently separate the line of research into two concepts: the construction processes and the architecture of the building. The documentation collected permitted various analyses: the characterisation of the building modules, identification of the tools used to work the building materials, etc. In conclusion, the use of orthoimages is a powerful tool that permits the systematic study of a Roman building that has evolved over the centuries and is now in a modern urban context.

Critères de qualité en radiothérapie des cancers de la tête et du cou sous l'égide de l'Intergroupe ORL Quality criteria in radiotherapy for head and neck cancers under the aegis of Head and Neck Intergroup.

The aim of radiotherapy is to deliver enough radiation to the tumor in order to achieve maximum tumour control in the irradiated volume with as few serious complications as possible with an irradiation dose as low as possible to normal tissue. The quality of radiotherapy is essential for optimal treatment and quality control is to reduce the bias in clinical trials avoiding possible major deviations. The assurance and quality control programs have been developed in large european (EORTC, GORTEC) and american cooperative groups (RTOG) of radiation oncology since the 1980s. We insist here on the importance of quality assurance in radiotherapy and the current status in this domain and the criteria for quality control especially for current clinical trials within GORTEC are discussed here.

Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling.

Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄), an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂) levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP)-9 as well as modulating transforming growth factor (TGF)-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.

Customization, transparency and proximity: a user- centered content strategy applied to the design of a virtual library website

We present a case study of the redesign of the organizational presentation and content of the Virtual Library website at the Universitat Oberta de Catalunya (Open University of Catalonia, UOC), based on a user-centered design strategy. The aim of the redesign was to provide users with more intuitive, usable and understandable content (textual content, resources and services) by implementing criteria of customization, transparency and proximity. The study also presents a selection of best practices for applying these criteria to the design of other library websites.

Causes of health expenditure growth : the predominance of changes in medical practices over population ageing

The increase in total health care expenditures in France can be explained by three distinct factors : the purely demographic effect (namely, the increase in the proportion of elderly people, given that health expenditure is an increasing function of age) ; the changes in morbidity at a given age ; the changes in practices, for a given age and morbidity level (e.g technological progress). The aim of this paper is basically to disentangle, evaluate and interpret the respective effects of these three factors. [Extrait introduction p. 3]

The role of culture in international students' image formation: the emergence of expected and perceived university image

Tämän tutkimuksen tavoitteena oli selvittää, vaikuttaako kansainvälisen opiskelijan kulttuuritausta opiskelijan odotetun ja koetun yliopistoimagon muodostumiseen. Jotta kulttuurin vaikutuksia yliopistoimagoon voitiin tutkia, tutkimuksessa tunnistettiin yliopistoimagon muodostumiseen oleellisesti vaikuttavat tekijät. Kulttuurin roolia organisaation imagon muodostumisessa ei ole tutkittu aiemmissa tieteellisissä julkaisuissa. Näin ollen tämän tutkimuksen voidaan katsoa edistäneen nykyistä imagotutkimusta. Tutkimuksen kohdeyliopistona oli Lappeenrannan teknillinen yliopisto (LTY). Tutkimuksen empiirinen osa toteutettiin kvantitatiivisena Internet - pohjaisena kyselytutkimuksena tilastollisen analyysin menetelmin. Otos (N=179) koostui kaikista Lappeenrannan teknillisessä yliopistossa lukuvuonna 2005-2006 opiskelleista kansainvälisistä opiskelijoista. Kyselyyn vastasi 68,7 % opiskelijoista. Johtopäätöksenä voidaan todeta, että kulttuurilla ei ole merkittävää vaikutusta yliopistoimagon muodostumiseen. Tutkimuksessa saatiin selville, että yliopiston Internet-sivujen laatu vaikuttaa positiivisesti odotetun yliopistoimagon muodostumiseen, kun taas koettuun yliopistoimagoon vaikuttavat positiivisesti odotettu yliopistoimago, pedagoginen laatu sekä opetusympäristö. Markkinoinnin näkökulmasta tulokset voidaan vetää yhteen toteamalla, että yliopistojen ei tarvitsisi räätälöidä tutkimuksessa tunnistettuja imagoon vaikuttavia tekijöitä eri kulttuureistatulevia opiskelijoita varten.

Customization, transparency and proximity: a user- centered content strategy applied to the design of a virtual library website

We present a case study of the redesign of the organizational presentation and content of the Virtual Library website at the Universitat Oberta de Catalunya (Open University of Catalonia, UOC), based on a user-centered design strategy. The aim of the redesign was to provide users with more intuitive, usable and understandable content (textual content, resources and services) by implementing criteria of customization, transparency and proximity. The study also presents a selection of best practices for applying these criteria to the design of other library websites.

The Effectiveness of Currency Hedging Strategies. Case: Imatra Boards Business Unit of Stora Enso Corp.

Tutkimus tarkastelee vaihtoehtoisia termiinisuojaustrategioita metsäteollisuuden alan tulosyksikössä. Jälkitestauksen tarkoituksena on arvioida vaihtoehtoisten strategioiden tuloksellisuutta suojata case-yrityksen kassavirtoja seuraavan kolmen arviointikriteerin avulla: yksittäisten vieraan valuutan määräisten kassavirtojen vaihtelu; koko vieraan valuutan määräisen kassavirran vaihtelu; suojausvoitot ja -tappiot. Tutkimuksen teoreettinen viitekehys tarkastelee yrityksen päätöksentekoa, valuuttariskien suojausprosessia sekä esittelee yrityksen vaihtoehtoisia suojausstrategioita. Tutkimuksen empiirinen aineisto pohjautuu case- yrityksen historiallisiin myyntilukuihin ja on kerätty yrityksen tietojärjestelmästä. Muu tutkimuksessa käytetty dataon kerätty eri tietokannoista. Tutkimuksen tulokset osoittavat, että suojaaminen vähentää kassavirtojen vaihtelua. Suojaamisen taloudelliset tulokset ovat kuitenkin erittäin riippuvaisia valitusta suojausstrategiasta, joka voi johtaa merkittäviin suojausvoittoihin, mutta yhtä hyvin myos merkittäviin tappioihin. Johdon näkemykset ja riskitoleranssi määrittelevät mitä strategiaa yrityksessä tullaan viime kädessä noudattamaan.

Dispersal ability modulates the strength of the latitudinal richness gradient in European beetles.

Aim A debate exists as to whether present-day diversity gradients are governed by current environmental conditions or by changes in environmental conditions through time. Recent studies have shown that latitudinal richness gradients might be partially caused by incomplete post-glacial recolonization of high-latitude regions; this leads to the prediction that less mobile taxa should have steeper gradients than more mobile taxa. The aim of this study is to test this prediction. Location Europe. Methods We first assessed whether spatial turnover in species composition is a good surrogate for dispersal ability by measuring the proportion of wingless species in 19 European beetle clades and relating this value to spatial turnover (beta sim) of the clade. We then linearly regressed beta sim values of 21 taxa against the slope of their respective diversity gradients. Results A strong relationship exists between the proportion of wingless species and beta sim, and beta sim was found to be a good predictor of latitudinal richness gradients. Main conclusions Results are consistent with the prediction that poor dispersers have steeper richness gradients than good dispersers, supporting the view that current beetle diversity gradients in Europe are affected by post-glacial dispersal lags.