Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

The meaning of marriage for men during the transition to fatherhood : the Swiss context

In Europe, Switzerland presents an unusual pattern of marriage with a very high proportion of couples who begin to cohabit without being married, but with a very low proportion of nonmarital births. A lot of couples marry before the conception of the child or during the pregnancy. In this article we focus on the point of view of men vis-agrave-vis the marriage and its meanings. Qualitative investigations show that men strongly desire marriage for several reasons, from their desire to participate in child rearing to the fear of having their paternity denied by Swiss institutions

Tractament de dades i geolocalització: proper bus Barcelona

Desenvolupament d'una aplicació per a mòbils Android que permeti conèixer les parades de bus més properes i el temps que falta perquè arribi cada línia de bus, mitjançant la geolocalització de l'usuari, un mapa de parades o un codi QR. Obtenció i tractament de les dades de parades i línies, així com obtenció en temps real de les properes arribades mitjançant "web scraping" (simulació de navegació d'un usuari per extreure dades dels webs) de les pàgines dels operadors.

Anàlisi del patrimoni proper com a recurs en la didàctica de les ciències socials

La pregunta inicial d’aquesta investigació rau en si el patrimoni proper és un recurs que facilita l’aprenentatge de les ciències socials als nens i nenes. Per tal de donar resposta a aquesta qüestió, s’ha estudiat la relació entre el patrimoni local i l’interès que genera. Per realitzar-ho, es van concretar uns ítems que han estat analitzats a partir d’un estudi de casos. Els participants d’aquesta investigació han estat un grup d’alumnes d’Educació Primària, els quals van realitzar una proposta didàctica on s’utilitzava el patrimoni proper com a eix vertebrador. També, han participat en aquesta investigació mestres d’escoles de Sant Celoni, els quals han expressat les vivències viscudes amb els seus alumnes en activitats que impliquen el patrimoni local. Finalment, s’ha analitzat la informació aportada per tots els participants i s’ha arribat a unes conclusions.

Com ha de ser una activitat científica efectiva basada en l'experimentació i l'estudi de l'entorn proper? Estudi de casos i proposta de criteris a tenir en compte en el disseny d’activitats científiques escolars en l’entorn

Actualment moltes fonts d'informació ens descriuen i argumenten com han de ser les activitats científiques a l'escola per garantir l'aprenentatge significatiu de l'alumnat, i d'altres estudis ens mostren com han de ser les activitats escolars en l'entorn; però no hi ha estudis que ens descriguin i argumentin com han de ser les activitats científiques escolars basades en l'experimentació i l'estudi de l'entorn proper. Així doncs, aquesta investigació s'endinsa per solucionar un problema actual que és: com ha de ser una bona activitat científica escolar basada en l'experimentació i l'estudi de l'entorn proper? En resposta a això, aquest treball es basa en una investigació avaluativa que analitza diversos projectes de ciències basats en l'entorn a partir de l'observació d'uns criteris específics elaborats, per una banda a partir de les idees d'experts sobre com ha de ser una bona activitat científica i com ha de ser una activitat escolar d'entorn efectiva; i per altra banda a partir de les idees extretes de les entrevistes fetes a mestres promotores de projectes científics escolars innovadors centrats i duts a terme en l'entorn proper.

Less is more ? The Commission proposal on access to EU documents and the proper limits of transparency

Transparency is now seen as a key tool of democratic governance. The European Union's commitment to transparency is now at the centre of a crucial debate between the Commission and the Parliament on the future of citizen's right of access to information. This article presents the main characteristics of the current regime and questions the pertinence of the proposed changes in light of the international drive at modernising access to information laws and the attempt at identifying the ̳proper limits of transparency'. The questions raised range from the identification of what can be accessed to the definition of exemption and the protection of competing interests.

Hitsaussuojakaasujen tehokas ja taloudellinen käyttö

Suojakaasun päätehtävänä on suojata hitsaustapahtumaa ympäröivän ilman vaikutukselta. Päätehtävän lisäksi suojakaasullavoidaan vaikuttaa suoraan tai välillisesti lähes kaikkiin hitsauksen asioihin, joista laatu, tehokkuus ja taloudellisuus muodostuvat. Suojakaasuja tarvitsevat hitsausmenetelmät ovat: kaasukaarihitsausprosessit (MIG/MAG-, TIG- ja plasmahitsaus), laserhitsaus sekä näiden yhdistelmät eli hybridihitsausmenetelmät sekä MIG-juotto. Hitsaussuojakaasujen peruskaasu tänä päivänä on argon, johon hitsausprosessista tai materiaalistariippuen sekoitetaan hiilidioksidia, heliumia, vetyä tai happea. Pääsääntöisesti hitsaussuojakaasut ovat kahden komponentin kaasuja, mutta 3-komponenttikaasut ovat yleistymässä. Sopivalla suojakaasuseostuksella saadaan erittäin merkittävä hyöty tuottavuuden lisääntyessä ja laadun parantuessa. Suojakaasujen oikealla toimitusmuodolla on merkittävä vaikutus kokonaiskustannuksiin. Uudet, kehittyneet sekoitinlaitteet mahdollistavat tarkat osakomponenttien sekoittamiset hitsauspaikalla. Seokset ovat jatkuvasti analysoitavissa ja jäljitettävissä. Suojakaasujen kierrätys on erityisesti kalliiden kaasujen, kuten helium ja argon, kohdalta tulevaisuuden haaste ja mahdollisuus. Suojakaasulla on suuri merkitys hitsauksen tuottavuuteen, taloudellisuuteen ja myös hitsausympäristöön ja työturvallisuuteen. Robottihitsauksen lisääntyminen asettaa vaatimuksia, joihinoikein valitulla suojakaasulla voidaan myönteisesti vaikuttaa. Tehokashitsaus on valmistusprosessin tärkeä osa, jossa oikein valituilla suojakaasuilla saavutetaan merkittävä tuottavuuden lisäys vaikuttamalla kaariominaisuuksiin, tunkeumaan, roiskeisiin, nopeuteen, hitsimetallurgiaan, lämmöntuontiin ja hitsausympäristöön. Diplomityössä tutkittiin casena Peikko Finland Oy:n suojakaasujärjestelmät, niiden tehokkuus, toimivuus ja sopivuus konepajan tuotantoon ja erityisesti robottihitsaukseen.

Does the working environment influence health care professionals' values, meaning in life and religiousness? Palliative care units compared with maternity wards.

CONTEXT: Increased altruism, self-transcendence, and quests for meaning in life (MiL) have been found in palliative care (PC) patients and their families who experience the finiteness of life. Similar changes were observed in healthy subjects who were experimentally confronted with their mortality. OBJECTIVES: The study investigated how daily experiences of the transitoriness of life influence PC health care professionals' (HCPs) values, MiL, and religiousness. METHODS: In a cross-sectional study, the Schwartz Value Survey, the Schedule for Meaning in Life Evaluation, and the Idler Index of Religiosity were used to investigate personal values, MiL, and private religiousness. HCPs working in PC (confronted with death) were compared with a control group of HCPs working at maternity wards (MWs) using multivariate models. Differences were considered to be statistically significant at P < 0.05. RESULTS: Seventy PC- and 70 MW-HCPs took part in the study (response rate 74.0%). No differences between the groups were found in overall MiL satisfaction scores. PC-HCPs were significantly more religious than MW-HCPs; they listed spirituality and nature experience more often as areas in which they experience MiL. Furthermore, hedonism was more important for PC-HCPs, and they had higher scores in openness-to-change values (stimulation and self-direction). MW-HCPs were more likely to list family as a MiL area. They assigned more importance to health and scored higher in conservation values (conformity and security). Duration of professional experience did not influence these results. CONCLUSION: Basic differences in values, MiL, and religiousness between PC-HCPs and MW-HCPs might have influenced the choice of working environment because no effect of job duration was observed. Longitudinal research is needed to confirm this hypothesis.

Viilun käsittelyn laadullinen saanto

Työn tavoitteena oli selvittää viilun käsittelyn laadullista saantoa vanerin valmistusprosessissa sekä laadulliseen saantoon vaikuttavia tekijöitä viilun käsittelyyn liittyviä työpisteitä tutkimalla. Kirjallisuusosassa tarkasteltiin vanerin valmistusprosessia, viilun ominaisuuksia erityisesti laadun osalta, standardin mukaisia laatuluokkia, saantoon vaikuttavia tekijöitä sekä tuotannonohjauksen periaatteita viilun valmistuksessa. Kokeellinen osa perustui tuotannonraportointijärjestelmästä saataviin tietoihin sekä haastattelu- ja seurantatutkimuksiin eräällä vaneritehtaalla. Kokeellisessa osassa käytiin läpi viilun käsittelyyn liittyvät työvaiheet viilun leikkauksesta ja lajittelusta viilun liimoitukseen ja ladontaan saakka. Lisäksi tutkittiin käytössä olevan viilun lajittelujärjestelmän tuloksen oikeellisuutta viilun laadutuksessa, saumauksen onnistumista, viilun paikkauksen laadullista onnistumista sekä ladonnan onnistumista viilun käsittelyn nykytilan selvittämiseksi. Tutkimuksen tulosten perusteella pohdittiin lajittelussa tapahtuvaa laadullisen saannon tulosta kohdeyrityksessä sekä esitettiin joukko kehitysehdotuksia, joilla viilutuotantoa voidaan selkeyttää ja parantaa tulevaisuudessa.

The Articulation of Different Life Domains among Female Senior Managers and Their Subjective Well-Being : Focusing on Meaning Constructions in Everyday Life

Work-life issues have become a major concern across Western societies with the objective to promote women's careers and well-being. However, despite growing attempts to increase the number of women in senior management positions in European countries, such as Switzerland, they remain highly underrepresented. Inspired from the cultural approach in psychology, this article focuses on these women's concrete everyday life to understand how they articulate different life domains and how this influences their subjective well-being. A narrative approach based on reflexivity is adopted to analyze women's activity. Results show meaning intertwinements between life priorities that are often conflicting. Two psychological functions are identified: the feeling of control and the letting go of control. Each of these contributes to women's subjective well-being through the use of diversified supports, but their structuring roles appear only in relation to one another. Results are discussed in the light of existing literature and of their implications.

Maintenance process development for remote administration of network servers

Maintenance is a part of system development and it is possible to develop operation models for accomplishing maintenance tasks. These models can be applied to individual maintenance tasks, maintenance projects and version management. Beneficial operation models makes maintenance more effective and they assist in managing various changes. The purpose of this thesis was to develop a maintenance process which can be used to remote administer network servers. This consisted of defining those operation models and technical specifications which enable to set up, manage changes, maintain and monitor resources of information systems that are located in several different sites. At first in this thesis the needs of the process were determined and requirements were defined based on those needs. The meaning of processes in maintenance of information systems, maintenance workflows and challenges were studied. Then current practical problems and disadvantages of maintenance work were analyzed in order to focus the development to proper issues. Because available operation models did not cover all the recent needs, new maintenance process which fulfilled the requirements was developed.

Meaning in life and perceived quality of life in Switzerland: results of a representative survey in the German, French and Italian regions.

BACKGROUND: The concept of meaning in life (MIL) has become a central one in recent years, particularly in psycho-oncology and palliative care. The Schedule for Meaning in Life Evaluation (SMILE) has been developed to allow individuals to choose the life areas that they consider to be important for their own MIL. This approach relates to the "World Health Organisation" definition of quality of life (QOL) as an individual's perception of his own position. The aims of this study were (i) to assess MIL in a representative sample of the Swiss population according to the three linguistic regions and (ii) to evaluate whether MIL constitutes a significant determinant of the perceived QOL. METHODS: A telephone survey of the Swiss population, performed by a professional survey company, was conducted between November and December 2013. The interview included the SMILE, perceived QOL (0-10) and health status (1-5), and various sociodemographic variables. In the SMILE, an index of weighting (IOW, 20-100), an index of satisfaction (IOS, 0-100), and a total SMILE index (IOWS, 0-100) are calculated from the areas mentioned by the participants as providing MIL. RESULTS: Among the 6671 telephonic contacts realized, 1015 (15 %) participants completed the survey: 405 French, 400 German and 210 Italian participants. "Family" (80.2 %), "occupation/work" (51 %), and "social relations" (43.3 %) were the most cited MIL-relevant categories. Italian participants listed "health" more frequently than German and French participants (50.4 % vs 31.5 % and 24.8 % respectively, χ(2) = 12.229, p = .002). Age, gender, education, employment, and marital status significantly influenced either the MIL scores or the MIL-relevant categories. Linear regression analyses indicate that 24.3 % of the QOL variance (p = .000) is explained by health status (B = .609, IC = .490-.728, p = .000), MIL (B = .034, IC = .028-.041, p = .000) and socioeconomic status (F = 11.01, p = .000). CONCLUSION: The major finding of our analysis highlights the positive and significant influence of MIL on the perceived QOL in a representative sample of a general, multilingual and multicultural population. This result indicates that the existential dimension is not only determinant for QOL in some critical life events, as shown e.g. in psycho-oncology and palliative care, but also in everyday life.