Inactivated Parapoxvirus ovis induces a transient increase in the expression of proinflammatory, Th1-related, and autoregulatory cytokines in mice

The immunostimulatory properties of inactivated Parapoxvirus ovis (iPPVO) have long been investigated in different animal species and experimental settings. In this study, we investigated the effects of iPPVO on cytokine expression in mice after intraperitoneal inoculation. Spleen and sera collected from iPPVO-treated mice at intervals after inoculation were submitted to cytokine mRNA determination by real-time PCR (qPCR), serum protein concentration by ELISA, and interferon (IFN)-α/β activity by bioassay. The spleen of iPPVO-treated animals showed a significant increase in mRNA expression of all cytokines assayed, with different kinetics and magnitude. Proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and IL-8 mRNA peaked at 24 hours postinoculation (hpi; 5.4-fold increase) and 48 hpi (3- and 10-fold increases), respectively. A 15-fold increase in IFN-γ and 6-fold IL-12 mRNA increase were detected at 48 and 24 hpi, respectively. Increased expression of autoregulatory cytokines (Th2), mainly IL-10 and IL-4, could be detected at later times (72 and 96 hpi) with peaks of 4.7- and 4.9-fold increases, respectively. IFN-I antiviral activity against encephalomyocarditis virus was demonstrated in sera of treated animals between 6 and 12 hpi, with a >90% reduction in the number of plaques. Measurement of serum proteins by ELISA revealed increased levels of IL-1, TNF-α, IL-12, IFN-γ, and IL-10, with kinetics similar to those observed by qPCR, especially for IL-12 and IFN-γ. These data demonstrate that iPPVO induced a transient and complex cytokine response, initially represented by Th1-related cytokines followed by autoregulatory and Th2 cytokines.

Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

Association between the increase in brain temperature and physical performance at different exercise intensities and protocols in a temperate environment

There is evidence that brain temperature (Tbrain) provides a more sensitive index than other core body temperatures in determining physical performance. However, no study has addressed whether the association between performance and increases in Tbrain in a temperate environment is dependent upon exercise intensity, and this was the primary aim of the present study. Adult male Wistar rats were subjected to constant exercise at three different speeds (18, 21, and 24 m/min) until the onset of volitional fatigue. Tbrain was continuously measured by a thermistor inserted through a brain guide cannula. Exercise induced a speed-dependent increase in Tbrain, with the fastest speed associated with a higher rate of Tbrain increase. Rats subjected to constant exercise had similar Tbrain values at the time of fatigue, although a pronounced individual variability was observed (38.7-41.7°C). There were negative correlations between the rate of Tbrain increase and performance for all speeds that were studied. These results indicate that performance during constant exercise is negatively associated with the increase in Tbrain, particularly with its rate of increase. We then investigated how an incremental-speed protocol affected the association between the increase in Tbrain and performance. At volitional fatigue, Tbrain was lower during incremental exercise compared with the Tbrain resulting from constant exercise (39.3±0.3 vs 40.3±0.1°C; P<0.05), and no association between the rate of Tbrain increase and performance was observed. These findings suggest that the influence of Tbrain on performance under temperate conditions is dependent on exercise protocol.

Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

High levels of LDL-C combined with low levels of HDL-C further increase platelet activation in hypercholesterolemic patients

High levels of low-density lipoprotein cholesterol (LDL-C) enhance platelet activation, whereas high levels of high-density lipoprotein cholesterol (HDL-C) exert a cardioprotective effect. However, the effects on platelet activation of high levels of LDL-C combined with low levels of HDL-C (HLC) have not yet been reported. We aimed to evaluate the platelet activation marker of HLC patients and investigate the antiplatelet effect of atorvastatin on this population. Forty-eight patients with high levels of LDL-C were enrolled. Among these, 23 had HLC and the other 25 had high levels of LDL-C combined with normal levels of HDL-C (HNC). A total of 35 normocholesterolemic (NOMC) volunteers were included as controls. Whole blood flow cytometry and platelet aggregation measurements were performed on all participants to detect the following platelet activation markers: CD62p (P-selectin), PAC-1 (GPIIb/IIIa), and maximal platelet aggregation (MPAG). A daily dose of 20 mg atorvastatin was administered to patients with high levels of LDL-C, and the above assessments were obtained at baseline and after 1 and 2 months of treatment. The expression of platelets CD62p and PAC-1 was increased in HNC patients compared to NOMC volunteers (P<0.01 and P<0.05). Furthermore, the surface expression of platelets CD62p and PAC-1 was greater among HLC patients than among HNC patients (P<0.01 and P<0.05). Although the expression of CD62p and PAC-1 decreased significantly after atorvastatin treatment, it remained higher in the HLC group than in the HNC group (P<0.05 and P=0.116). The reduction of HDL-C further increased platelet activation in patients with high levels of LDL-C. Platelet activation remained higher among HLC patients regardless of atorvastatin treatment.

Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca2+]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca2+]i. Pre-incubation with Resv significantly reduced the change in [Ca2+]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca2+]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.

Thick Section Laser Beam Welding of Structural Steels: Methods for Improving Welding Efficiency

Laser beam welding (LBW) is applicable for a wide range of industrial sectors and has a history of fifty years. However, it is considered an unusual method with applications typically limited to welding of thin sheet metal. With a new generation of high power lasers there has been a renewed interest in thick section LBW (also known as keyhole laser welding). There was a growing body of publications during 2001-2011 that indicates an increasing interest in laser welding for many industrial applications, and in last ten years, an increasing number of studies have examined the ways to increase the efficiency of the process. Expanding the thickness range and efficiency of LBW makes the process a possibility for industrial applications dealing with thick metal welding: shipbuilding, offshore structures, pipelines, power plants and other industries. The advantages provided by LBW, such as high process speed, high productivity, and low heat input, may revolutionize these industries and significantly reduce the process costs. The research to date has focused on either increasing the efficiency via optimizing process parameters, or on the process fundamentals, rather than on process and workpiece modifications. The argument of this thesis is that the efficiency of the laser beam process can be increased in a straightforward way in the workshop conditions. Throughout this dissertation, the term “efficiency” is used to refer to welding process efficiency, specifically, an increase in efficiency refers an increase in weld’s penetration depth without increasing laser power level or decreasing welding speed. These methods are: modifications of the workpiece – edge surface roughness and air gap between the joining plates; modification of the ambient conditions – local reduction of the pressure in the welding zone; modification of the welding process – preheating of the welding zone. Approaches to improve the efficiency are analyzed and compared both separately and combined. These experimentally proven methods confirm previous findings and contribute additional evidence which expand the opportunities for laser beam welding applications. The focus of this research was primarily on the effects of edge surface roughness preparation and pre-set air gap between the plates on weld quality and penetration depth. To date, there has been no reliable evidence that such modifications of the workpiece give a positive effect on the welding efficiency. Other methods were tested in combination with the two methods mentioned above. The most promising - combining with reduced pressure method - resulted in at least 100% increase in efficiency. The results of this thesis support the idea that joining those methods in one modified process will provide the modern engineering with a sufficient tool for many novel applications with potential benefits to a range of industries.

Tuottavuuden, vaikuttavuuden ja kustannusvaikuttavuuden arviointi alueellisesti integroiduissa sosiaali- ja terveyspalveluissa – palvelujen käyttöön perustuva malli ja esimerkkejä

Yli puolet kuntien vuosibudjeteista kuluu sosiaali- ja terveyspalveluihin. Jatkossa väestö ikääntyy ja huoltosuhteen muutos tulee niukentamaan kuntien resursseja ja lisäämään palvelujen tarvetta. Näin ollen vaikuttavien ja kustannustehokkaiden ratkaisumallien luominen on ensiarvoisen tärkeää. Tutkimuksen tavoitteena on rakentaa malli, jota voidaan hyödyntää tuottavuuden, vaikuttavuuden ja kustannusvaikuttavuuden jatkuvassa seurannassa alueellisissa sosiaali- ja terveyspalveluissa ja testata mallia esimerkkitapauksilla. Pääpaino on vaikuttavuudessa ja kustannusvaikuttavuudessa. Aiemman tutkimuksen perusteella tuottavuuden, vaikuttavuuden ja kustannusvaikuttavuuden mittaamiseen on useita lähestymistapoja. Tässä tutkimuksessa tuottavuutta arvioidaan panosten ja tuotosten suhteella, vaikuttavuutta palvelujen käytöllä ja kustannusvaikuttavuutta palvelujen käytön kustannuksilla. Kirjallisuudesta nousee esille selkeä tarve yli perinteisten organisaatiorajojen menevälle jatkuvalle vaikuttavuuden seurannalle. Aikaisempi tutkimus kattaa kertaluontoisia selvityksiä, joissa usein mittarit ovat operatiivisella tasolla, toimialasidonnaisia tai vaikeasti mitattavissa. Tutkimus on suunnittelutiedettä. Tutkimuksen lopputuloksena syntyy sosiaali- ja terveyspalvelujen käyttömalli (sote-palvelujen käyttömalli), jota varten toteutetaan tietokanta ja raportointikerros. Sote-palvelujen käyttömallia testataan tässä tutkimuksessa kolmella eri organisaatioyksiköllä ja asiakasryhmällä, jotka ovat strategisesti merkittäviä tutkittavalle organisaatiolle ja asiakasryhmiin on kohdennettu selkeä kehittämistoimenpide (kuntoutukseen panostaminen ja vammaisten sekä vanhusten laitoshoidon purku). Sote-palvelujen käyttömalli tuottaa tietoa kehittämistoimenpiteiden tuottavuudesta, vaikuttavuudesta ja kustannusvaikuttavuudesta. Sote-palvelujen käyttömallin todetaan soveltuvan tutkittavaan organisaatioon ja sote-palvelujen käyttömalli on sielläjatkuvassa käytössä. Sote-palvelujen käyttömalli on siirrettävissä myös muihin soteorganisaatioihin ja laajennettavissa myös muihin sosiaali- ja terveyspalveluihin ja niitä lähellä oleviin palveluihin.

Modifioidun MAG-kaarihitsausprosessin hyödyntäminen railotilavuuden pienentämisessä mekanisoidussa orbitaalihitsauksessa.

Länsimaisen työn hinta luo jatkuvan paineen hitsauksen tuottavuuden parantamiseen. MIG/MAG-hitsauksen tuottavuutta voidaan parantaa tehostamalla hitsausprosessia, vähentämällä hitsien lukumäärää ja pienentämällä hitsiaineen tarvetta. Eri virtalähdevalmistajat tuovat markkinoille hitsausprosesseja hitsauksen tehostamiseen, joilla pystytään korvata vähemmän tuottavia hitsaustyövaiheita. Hitsien lukumäärän vähentäminen on rakenteen suunnitteluun liittyvä tekijä ja hitsiaineen tarpeen pienentäminen voidaan toteuttaa railogeometrian muutoksilla tai tuotteen sopivalla suunnittelulla. Diplomityössä on tutkittu 30 mm paksujen S355 rakenneteräsputkien hitsauksen tuottavuuden kasvattamista käyttäen nykyaikaisia modifioituja kaarihitsausprosesseja ja railotilavuutta pienentämällä. Työssä vertailtiin 30o ja 60o railokulmalla tehtyjä liitoksia. Railogeometrian muutoksen lisäksi diplomityössä vertailtiin eri menetelmien tehokkuutta putken pohjapalon hitsauksessa.

Kustannusriskien hallinnan kehittäminen julkisissa liikenneväylähankkeissa

Tämän tutkimuksen keskeisempänä tavoitteena on kehittää kustannusriskien tunnistamista ja hallintaa julkisen organisaation liikenneväylähankkeissa. Hankkeiden kustannusarvioinnin epävarmuustekijöiden tunnistaminen ja minimointi varhaisessa vaiheessa nähdään keinona parantaa organisaation kokonaistuottavuutta ja -taloudellisuutta. Kyseinen diplomityö on tutkimusmenetelmältään laadullinen tapaustutkimus, jossa kustannusriskejä pyritään ymmärtämään ilmiöinä ja luomaan uutta tietoa. Työn empiirisenä aineistona on viisi eri liikenneväylähanketta. Kustannusriskien taustalla olevien tekijöiden tunnistamista varten on haastateltu näiden viiden väylähankkeen kustannushallinnan ydinhenkilöitä. Tähän menetelmään kiteytyy työn uutuusarvo aihepiirin aiempaan tutkimukseen verrattuna. Tutkimuksen keskeisin tulos on kustannusriskien tunnistustaulukko, jota ehdotetaan käytettävän kustannusarviointiin epävarmuutta aiheuttavien tekijöiden tunnistamiseen. Kustannusarvioinnin epävarmuustekijöiden minimointia varten tarkistustaulukossa on lueteltu kunkin kustannusriskin hallintaan ehdotettu hallintakeino. Tunnistustaulukkoa voidaan käyttää missä tahansa suunnitteluvaiheessa ja tarvittaessa päivittää tulevaisuudessa.

Improving productivity by developing knowledge management practices for a consulting company

The objective of the research was to identify knowledge conversion states in consultancy sales and delivery processes for the company’s one business unit, to know where to store certain types of information and knowledge, and to create best practices for the company’s knowledge management activities in the selected business processes. The used research methodology was action research. The current business processes were analyzed by interviewing people involved in them. The results were documented and catego- rized, and based on them the target states of the processes were developed. Knowledge man- agement activities were integrated to the business processes. The main findings of the research were that roles and responsibilities in the processes were not clear to people, information systems did not fully support individuals and time was wasted searching for information and knowledge. There were also many variations of how the processes actually realized, which affected the overall quality of the process. The conclusions of the research were that knowledge management activities should be high- lighted in businesses where knowledge workers are the main assets of the company. Knowledge management practices can be supported by company culture, leadership and in- formation systems. However, one main factor is each individual’s willingness to share knowledge. By integrating knowledge management activities to business processes and hav- ing information systems supporting knowledge management, individual productivity can be improved.

Physiological potential of rice seeds treated with rhizobacteria or the insecticide thiamethoxam

Development of new technologies, aiming at increasing productivity in different crops, involves constant research on the effectiveness and application of these techniques in seed treatment. In this study, it was aimed at evaluating physiological potential of rice seeds treated with plant growth-promoting rhizobacteria (PGPR) (strains DFs185, DFs223, DFs306, DFs416), or with two dosages of the insecticide thiamethoxam. The variables assessed were: germination (G); first count of germination (FCG); cold test (CT); length of seedlings aerial parts (LAP), root system (LRS), and total length (TL); emergence speed index (ESI); emergence (E), at 14 days; and dry phytomass (DP). Treatments have had a positive effect on percentage of G, FCG and E. The strain DFs185 has promoted increase in percentage emergence, for five of the six lots assessed. The variables: LAP; LRS; TL; ESI; and DP have undergone low or none influence of treatments; and there has been no toxic effect of rhizobacteria or insecticide thiamethoxam. In the cold test, a negative effect of treatments has been detected. Seed treatment with rhizobacteria, as well as with thiamethoxam, improve quality of low quality rice seeds. The strain DFs185 is promising for treating rice seeds, once it stimulates seed germination and emergence.

Organizational creativity – Hegemonic and alternative discourses

SUMMARY Organizational creativity – hegemonic and alternative discourses Over the course of recent developments in the societal and business environment, the concept of creativity has been brought into new arenas. The rise of ‘creative industries’ and the idea of creativity as a form of capital have attracted the interests of business and management professionals – as well as academics. As the notion of creativity has been adopted in the organization studies literature, the concept of organizational creativity has been introduced to refer to creativity that takes place in an organizational context. This doctoral thesis focuses on organizational creativity, and its purpose is to explore and problematize the hegemonic organizational creativity discourse and to provide alternative viewpoints for theorizing about creativity in organizations. Taking a discourse theory approach, this thesis, first, provides an outline of the currently predominant, i.e. hegemonic, discourse on organizational creativity, which is explored regarding themes, perspectives, methods and paradigms. Second, this thesis consists of five studies that act as illustrations of certain alternative viewpoints. Through these exemplary studies, this thesis sheds light on the limitations and taken-for-granted aspects of the hegemonic discourse and discusses what these alternative viewpoints could offer for the understanding of and theorizing for organizational creativity. This study leans on an assumption that the development of organizational creativity knowledge and the related discourse is not inevitable or progressive but rather contingent. The organizational creativity discourse has developed in a certain direction, meaning that some themes, perspectives, and methods, as well as assumptions, values, and objectives, have gained a hegemonic position over others, and are therefore often taken for granted and considered valid and relevant. The hegemonization of certain aspects, however, contributes to the marginalization of others. The thesis concludes that the hegemonic discourse on organizational creativity is based on an extensive coverage of certain themes and perspectives, such as those focusing on individual cognitive processes, motivation, or organizational climate and their relation to creativity, to name a few. The limited focus on some themes and the confinement to certain prevalent perspectives, however, results in the marginalization of other themes and perspectives. The negative, often unintended, consequences, implications, and side effects of creativity, the factors that might hinder or prevent creativity, and a deeper inquiry into the ontology and epistemology of creativity have attracted relatively marginal interest. The material embeddedness of organizational creativity, in other words, the physical organizational environment as well as the human body and its non-cognitive resources, has largely been overlooked in the hegemonic discourse, although thereare studies in this area that give reason to believe that they might prove relevant for the understanding of creativity. The hegemonic discourse is based on an individual-centered understanding of creativity which overattributes creativity to an individual and his/her cognitive capabilities, while simultaneously neglecting how, for instance, the physical environment, artifacts, social dynamics and interactions condition organizational creativity. Due to historical reasons, quantitative as well as qualitative yet functionally- oriented studies have predominated the organizational creativity discourse, although studies falling into the interpretationist paradigm have gradually become more popular. The two radical paradigms, as well as methodological and analytical approaches typical of radical research, can be considered to hold a marginal position in the field of organizational creativity. The hegemonic organizational creativity discourse has provided extensive findings related to many aspects of organizational creativity, although the con- ceptualizations and understandings of organizational creativity in the hegemonic discourse are also in many respects limited and one-sided. The hegemonic discourse is based on an assumption that creativity is desirable, good, necessary, or even obligatory, and should be encouraged and nourished. The conceptualiza- tions of creativity favor the kind of creativity which is useful, valuable and can be harnessed for productivity. The current conceptualization is limited to the type of creativity that is acceptable and fits the managerial ideology, and washes out any risky, seemingly useless, or negative aspects of creativity. It also limits the possible meanings and representations that ‘creativity’ has in the respective discourse, excluding many meanings of creativity encountered in other discourses. The excessive focus on creativity that is good, positive, productive and fits the managerial agenda while ignoring other forms and aspects of creativity, however, contributes to the dilution of the notion. Practices aimed at encouraging the kind of creativity may actually entail a risk of fostering moderate alterations rather than more radical novelty, as well as management and organizational practices which limit creative endeavors, rather than increase their likelihood. The thesis concludes that although not often given the space and attention they deserve, there are alternative conceptualizations and understandings of organizational creativity which embrace a broader notion of creativity. The inability to accommodate the ‘other’ understandings and viewpoints within the organizational creativity discourse runs a risk of misrepresenting the complex and many-sided phenomenon of creativity in organizational context. Keywords: Organizational creativity, creativity, organization studies, discourse theory, hegemony