Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain.

Telmisartan is an angiotensin II receptor blocker with peroxisome proliferator-activated receptor-gamma agonistic properties. Telmisartan prevents weight gain and decreases food intake in models of obesity and in glitazone-treated rodents. This study further investigates the influence of telmisartan and pioglitazone and their association on weight gain and body composition by examining their influence on neuroendocrine mediators involved in food intake. Male C57/Black 6 mice were fed a high-fat diet, weight matched, and randomized in 4 treatment groups: vehicle, pioglitazone, telmisartan, and pioglitazone-telmisartan. Weight gain, food and water intake, body composition, plasma leptin levels, and the hypothalamic expression of neuroendocrine mediators were analyzed. Additional studies were performed with irbesartan and in angiotensin II 1(A) receptor-knockout mice. Telmisartan abolished weight and fat gain in vehicle- and pioglitazone-treated mice while decreasing food intake, the hypothalamic expression of the agouti-related protein, and plasma leptin levels. Modifications in neuropeptide Y and proopiomelanocortin were not consistent with changes in food intake. The effects on weight gain and expression of the agouti-related protein were intermediate with irbesartan. The effects of telmisartan on weight gain were even more pronounced in angiotensin II 1(A) receptor-knockout mice. This study confirms the anorexigenic effects of telmisartan in mice fed a high-fat diet and suggests for the first time a functional role of telmisartan on hypothalamic orexigenic agouti-related protein regulation. These anorexigenic properties abolish both weight gain and body composition modifications in fat-fed and glitazone-treated mice. The anorexigenic properties are independent from the angiotensin II 1(A) receptor.

ICT Action Plan Meeting the high-level skills needs of enterprise in Ireland

The technology sector in Ireland is thriving. Employment, through indigenous and multinational technology firms continues to grow strongly year on year. All of the top 10 multinational technology companies have a significant presence in Ireland and the indigenous software sector’s exports are worth well in excess of €1 billion annually. Five of the top 10 exporters in Ireland are technology companies, and the sector is responsible for approximately one-third of Ireland’s total turnover. Since January 2011, over 80 jobs a week have been announced in the sector. This is on foot of 6% employment growth in 2009 and 4% in 2010. A recent global competitiveness report ranks Ireland as the top destination in the world by quality and value of investments. With a growing multinational technology presence in Ireland and a vibrant and innovative indigenous software sector, the future prospects for Ireland’s technology sector are bright.

Viral-mediated overexpression of mutant huntingtin to model HD in various species.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin (Htt) gene. Despite intensive efforts devoted to investigating the mechanisms of its pathogenesis, effective treatments for this devastating disease remain unavailable. The lack of suitable models recapitulating the entire spectrum of the degenerative process has severely hindered the identification and validation of therapeutic strategies. The discovery that the degeneration in HD is caused by a mutation in a single gene has offered new opportunities to develop experimental models of HD, ranging from in vitro models to transgenic primates. However, recent advances in viral-vector technology provide promising alternatives based on the direct transfer of genes to selected sub-regions of the brain. Rodent studies have shown that overexpression of mutant human Htt in the striatum using adeno-associated virus or lentivirus vectors induces progressive neurodegeneration, which resembles that seen in HD. This article highlights progress made in modeling HD using viral vector gene transfer. We describe data obtained with of this highly flexible approach for the targeted overexpression of a disease-causing gene. The ability to deliver mutant Htt to specific tissues has opened pathological processes to experimental analysis and allowed targeted therapeutic development in rodent and primate pre-clinical models.

Beta-adrenoceptor stimulation increases neuropeptide Y release from sympathetic nerves in intact rats.

This study was undertaken to assess in conscious normotensive rats the effects of beta-adrenoceptor stimulation on plasma neuropeptide Y (NPY) levels. Wistar rats were subjected to adrenal demedullation on the right side and were either adrenalectomized or sham-operated on the left side. Eleven days later, the conscious rats were infused i.v. for 30 min with either isoproterenol (10 ng/min) or its vehicle. Plasma NPY levels were significantly lower (23.8 +/- 2.6 pM, means +/- S.E.M., n = 12, P < 0.01) in vehicle-treated medullectomized rats than in corresponding sham-operated controls (36.7 +/- 4.1 pM, n = 12). The medullectomized rats infused with isoproterenol showed plasma NPY levels (36.7 +/- 3.3 pM, n = 11) comparable to those of sham-operated rats having received the vehicle. These data therefore demonstrate that plasma NPY levels are lower in rats without adrenal medulla and that in these animals isoproterenol increases NPY release, most likely by activating pre-synaptic beta-adrenoceptors.

Iowa Rail Route Alternatives Analysis, June 1998

The development of new rail systems in the first part of the 21st century is the result of a wide range of trends that are making it increasingly difficult to maintain regional mobility using the two dominant intercity travel modes, auto and air. These trends include the changing character of the economic structure of industry. The character of the North American industrial structure is moving rapidly from a manufacturing base to a service based economy. This is increasing the need for business travel while the increase in disposable income due to higher salaries has promoted increased social and tourist travel. Another trend is the change in the regulatory environment. The trend towards deregulation has dramatically reduced the willingness of the airlines to operate from smaller airports and the level of service has fallen due to the creation of hub and spoke systems. While new air technology such as regional jets may mitigate this trend to some degree in medium-size airports, smaller airports will continue to lose out. Finally, increasing environmental concerns have reduced the ability of the automobile to meet intercity travel needs because of increased suburban congestion and limited highway capacity in big cities. Against this background the rail mode offers new options due to first, the existing rail rights-of-way offering direct access into major cities that, in most cases, have significant capacity available and, second, a revolution in vehicle technology that makes new rail rolling stock faster and less expensive to purchase and operate. This study is designed to evaluate the potential for rail service making an important contribution to maintaining regional mobility over the next 30 to 50 years in Iowa. The study evaluates the potential for rail service on three key routes across Iowa and assesses the impact of new train technology in reducing costs and improving rail service. The study also considers the potential for developing the system on an incremental basis. The service analysis and recommendations do not involve current Amtrak intercity service. That service is presumed to continue on its current route and schedule. The study builds from data and analyses that have been generated for the Midwest Rail Initiative (MWRI) Study. For example, the zone system and operating and capital unit cost assumptions are derived from the MWRI study. The MWRI represents a cooperative effort between nine Midwest states, Amtrak and the Federal Railroad Administration (FRA) contracting with Transportation Economics & Management Systems, Inc. to evaluate the potential for a regional rail system. The 1 The map represents the system including the decision on the Iowa route derived from the current study. Iowa Rail Route Alternatives Analysis TEMS 1-2 system is to offer modern, frequent, higher speed train service to the region, with Chicago as the connecting hub. Exhibit 1-1 illustrates the size of the system, and how the Iowa route fits in to the whole.

Diagnostic Tools for Identifying Sleepy Drivers in the Field, RB21-012, 2013

The overarching goal of this project was to identify and evaluate cognitive and behavioral indices that are sensitive to sleep deprivation and may help identify commercial motor vehicle drivers (CMV) who are at-risk for driving in a sleep deprived state and may prove useful in field tests administered by officers. To that end, we evaluated indices of driver physiognomy (e.g., yawning, droopy eyelids, etc.) and driver behavioral/cognitive state (e.g. distracted driving) and the sensitivity of these indices to objective measures of sleep deprivation. The measures of sleep deprivation were sampled on repeated occasions over a period of 3.5-months in each of 44 drivers diagnosed with Obstructive Sleep Apnea (OSA) and 22 controls (matched for gender, age within 5 years, education within 2 years, and county of residence for rural vs. urban driving). Comprehensive analyses showed that specific dimensions of driver physiognomy associated with sleepiness in previous research and face-valid composite scores of sleepiness did not: 1) distinguish participants with OSA from matched controls; 2) distinguish participants before and after PAP treatment including those who were compliant with their treatment; 3) predict levels of sleep deprivation acquired objectively from actigraphy watches, not even among those chronically sleep deprived. Those findings are consistent with large individual differences in driver physiognomy. In other words, when individuals were sleep deprived as confirmed by actigraphy watch output they did not show consistently reliable behavioral markers of being sleep deprived. This finding held whether each driver was compared to him/herself with adequate and inadequate sleep, and even among chronically sleep deprived drivers. The scientific evidence from this research study does not support the use of driver physiognomy as a valid measure of sleep deprivation or as a basis to judge whether a CMV driver is too fatigued to drive, as on the current Fatigued Driving Evaluation Checklist.. Fair and accurate determinations of CMV driver sleepiness in the field will likely require further research on alternative strategies that make use of a combination of information sources besides driver physiognomy, including work logs, actigraphy, in vehicle data recordings, GPS data on vehicle use, and performance tests.

Prosody and pragmatics in parenthetical insertions in catalan

This paper analyses the role of prosody in parenthetical insertions, a type of structure that is extremely common in both speech and writing. The materials under study come from a corpus of spontaneous speech acts in Central Catalan (with varying degrees of spontaneity) from which a corpus of oral parenthetical insertions has been compiled. The prototypical prosodic features of a parenthetical insertion in Catalan are: prosodic autonomy, limited extension, production in between pauses or final pause, tendency towards acceleration, fall in intensity, lower pitch range and, finally, falling or rising melodic pattern. While the final fall is the most frequent pattern in spontaneous conversations with a high degree of confidence between interlocutors, a final rising structure is found in interviews in which the degree of confidence between participants is smaller, their roles are unequal, and the interviewed constructs a narrative discourse. We thus suggest that the pitch contour of parenthetical insertions is related to formality and discourse typology (in this case, narrative vs. dialogue). Bearing in mind the discursive functions performed by these insertions, we propose a typology which classifies them with regards to two main functions: completion of information, and modalisation.

Cardiovascular effects in patrol officers are associated with fine particulate matter from brake wear and engine emissions

Background: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variability parameters, and levels of serum proteins associated with inflammation, hemostasis and thrombosis. This study investigated sources potentially responsible for cardiovascular and hematological effects in highway patrol troopers. Results: Nine healthy young non-smoking male troopers working from 3 PM to midnight were studied on four consecutive days during their shift and the following night. Sources of in-vehicle PM2.5 were identified with variance-maximizing rotational principal factor analysis of PM2.5-components and associated pollutants. Two source models were calculated. Sources of in-vehicle PM2.5 identified were 1) crustal material, 2) wear of steel automotive components, 3) gasoline combustion, 4) speed-changing traffic with engine emissions and brake wear. In one model, sources 1 and 2 collapsed to a single source. Source factors scores were compared to cardiac and blood parameters measured ten and fifteen hours, respectively, after each shift. The "speed-change" factor was significantly associated with mean heart cycle length (MCL, +7% per standard deviation increase in the factor score), heart rate variability (+16%), supraventricular ectopic beats (+39%), % neutrophils (+7%), % lymphocytes (-10%), red blood cell volume MCV (+1%), von Willebrand Factor (+9%), blood urea nitrogen (+7%), and protein C (-11%). The "crustal" factor (but not the "collapsed" source) was associated with MCL (+3%) and serum uric acid concentrations (+5%). Controlling for potential confounders had little influence on the effect estimates. Conclusion: PM2.5 originating from speed-changing traffic modulates the autonomic control of the heart rhythm, increases the frequency of premature supraventricular beats and elicits proinflammatory and pro-thrombotic responses in healthy young men. [Authors]

Graph theory reveals dysconnected hubs in 22q11DS and altered nodal efficiency in patients with hallucinations.

Schizophrenia is postulated to be the prototypical dysconnection disorder, in which hallucinations are the core symptom. Due to high heterogeneity in methodology across studies and the clinical phenotype, it remains unclear whether the structural brain dysconnection is global or focal and if clinical symptoms result from this dysconnection. In the present work, we attempt to clarify this issue by studying a population considered as a homogeneous genetic sub-type of schizophrenia, namely the 22q11.2 deletion syndrome (22q11.2DS). Cerebral MRIs were acquired for 46 patients and 48 age and gender matched controls (aged 6-26, respectively mean age = 15.20 ± 4.53 and 15.28 ± 4.35 years old). Using the Connectome mapper pipeline (connectomics.org) that combines structural and diffusion MRI, we created a whole brain network for each individual. Graph theory was used to quantify the global and local properties of the brain network organization for each participant. A global degree loss of 6% was found in patients' networks along with an increased Characteristic Path Length. After identifying and comparing hubs, a significant loss of degree in patients' hubs was found in 58% of the hubs. Based on Allen's brain network model for hallucinations, we explored the association between local efficiency and symptom severity. Negative correlations were found in the Broca's area (p < 0.004), the Wernicke area (p < 0.023) and a positive correlation was found in the dorsolateral prefrontal cortex (DLPFC) (p < 0.014). In line with the dysconnection findings in schizophrenia, our results provide preliminary evidence for a targeted alteration in the brain network hubs' organization in individuals with a genetic risk for schizophrenia. The study of specific disorganization in language, speech and thought regulation networks sharing similar network properties may help to understand their role in the hallucination mechanism.

Particulate matter exposure in cars is associated with cardiovascular effects in healthy young men

Exposure to fine airborne particulate matter (PM(2.5)) is associated with cardiovascular events and mortality in older and cardiac patients. Potential physiologic effects of in-vehicle, roadside, and ambient PM(2.5) were investigated in young, healthy, nonsmoking, male North Carolina Highway Patrol troopers. Nine troopers (age 23 to 30) were monitored on 4 successive days while working a 3 P.M. to midnight shift. Each patrol car was equipped with air-quality monitors. Blood was drawn 14 hours after each shift, and ambulatory monitors recorded the electrocardiogram throughout the shift and until the next morning. Data were analyzed using mixed models. In-vehicle PM(2.5) (average of 24 microg/m(3)) was associated with decreased lymphocytes (-11% per 10 microg/m(3)) and increased red blood cell indices (1% mean corpuscular volume), neutrophils (6%), C-reactive protein (32%), von Willebrand factor (12%), next-morning heart beat cycle length (6%), next-morning heart rate variability parameters, and ectopic beats throughout the recording (20%). Controlling for potential confounders had little impact on the effect estimates. The associations of these health endpoints with ambient and roadside PM(2.5) were smaller and less significant. The observations in these healthy young men suggest that in-vehicle exposure to PM(2.5) may cause pathophysiologic changes that involve inflammation, coagulation, and cardiac rhythm.

Methods of Telecommunication Technology Forecasting

This master's thesis coversthe concepts of knowledge discovery, data mining and technology forecasting methods in telecommunications. It covers the various aspects of knowledge discoveryin data bases and discusses in detail the methods of data mining and technologyforecasting methods that are used in telecommunications. Main concern in the overall process of this thesis is to emphasize the methods that are being used in technology forecasting for telecommunications and data mining. It tries to answer to some extent to the question of do forecasts create a future? It also describes few difficulties that arise in technology forecasting. This thesis was done as part of my master's studies in Lappeenranta University of Technology.

Civil society organisations participating in ISO TC 228 and ISO TC 229: the INTERNORM project and its future

This paper presents the first results of the INTERNORM pilot project funded by the University of Lausanne (2010 - 2014) to support the involvement of civil society organisations (CSO) in two ISO technical committees (TC), the ISO TC 228 on "tourism and related services" and the ISO TC 229 on "nanotechnologies". It analyses how a distinct participatory mechanism can influence the institutional environment of technical diplomacy in which standards are shaped. The project is an attempt to respond to the democratic deficit attested in the field of international standardisation, formally open to civil society participation, but still largely dominated by expert knowledge and market players. Many international standards have direct implications on society as a whole, but CSOs (consumers and environmental associations, trade unions) are largely under-represented in negotiation arenas. The paper draws upon international relations literature on new institutional forms in global governance and studies of participation in science and technology to address three questions: to which extent do CSOs identify participation in standardisation as worth of their mobilisation? How is the pluralisation of knowledge and expertise supporting CSO position during the deliberation? To which extent can CSO access and influence standardisation beyond their consultative role? It argues that there are significant limitations to the rise of civil society participation in such global governance mechanisms. Despite high entry costs into technical diplomacy, participation is not so much a matter of upstream engagement, or of procedure and resources only, than of opportunistic CSOs mobilization, of distinct thematic incentives and concrete outcomes to be expected in standardisation arenas or in the broader use of international standards.

A Technology Intelligence Process for a High Technology Company

Tämä diplomityö määrittelee teknologiaseurantaprosessin, jolla korkean teknologian yritys voi ohjata toimintaansa. Korkean teknologian yrityksille on olennaista seurata teknologian kehitystä. Tällaiset yritykset tarvitsevat hyvin määritellyn järjestelmän, jolla ne voivat seurata ja ennustaa teknologista kehitystä.Työssä esitetään, että teknologiaseuranta ja kilpailuseuranta (competitive intelligence) ovat business intelligencen osa-alueita, jotka täydentävät ja tukevat toisiaan. Tärkeä havainto on, että business intelligence -prosessi on ennen kaikkea organisaation oppimisprosessi. Tästä seuraa, että minkä tahansa BI-prosessin tulisi perustua niihin prosesseihin, joiden avulla organisaatiot oppivat. Työssä esitetään myös, miten business intelligence, tietojohtaminen (knowledge management) ja organisaatioiden oppiminen liittyvät toisiinsa.Teknologiaseuranta on elintärkeä toiminto korkean teknologian yritykselle; sitä tarvitaan monella strategisen johtamisen osa-alueella, ainakin teknologia-, markkinointi- ja henkilöstöjohtamisessa. Teknologiaseurannan havaitaan myös olevan korkean teknologian yritykselle erittäin tärkeä ydinosaamisalue, jota ei voi kokonaan ulkoistaa.Työssä esitellään teknologiaseurantaprosessi, joka perustuu yleiselle business intelligence -prosessille ja siitä johdetulle kilpailuseurantaprosessille. Työssä myös esitetään ehdotus siitä, kuinka teknologiaseuranta voitaisiin järjestää korkean teknologian yrityksessä. Esitetty ratkaisu perustuu Community of practice -käsitteeseen. Community of practice on vapaaehtoisuuteen perustuva tiimi, jonka jäseniä yhdistää kiinnostus johonkin asiaan ja oppimishalu. Esimerkkiyrityksessä on tunnistettu selkeä tarve yhtenäiseen ja koordinoituun teknologiaseurantaan. Työssä esitetään alustava teknologiaseurantaprosessi esimerkkiyritykselle ja tunnistetaan teknologiaseurantaprosessin asiakkaat ja tekijät.

Electric Motor and Frequency Converter Markets in Latin America and Especially in the Mining Industry of Chile

Latinalaisen Amerikan osuus maailmantaloudesta on pieni verrattuna sen maantieteelliseen kokoon, väkilukuun ja luonnonvaroihin. Aluetta pidetään kuitenkin yhtenä tulevaisuuden merkittävistä kasvumarkkinoista. Useissa Latinalaisen Amerikan maissa on teollisuutta, joka hyödyntää luonnonvaroja ja tuottaa raaka-aineita sekä kotimaan että ulkomaiden markkinoille. Tällaisia tyypillisiä teollisuudenaloja Latinalaisessa Amerikassa ovat kaivos- ja metsäteollisuus sekä öljyn ja maakaasun tuotanto. Näiden teollisuudenalojen tuotantolaitteiden ja koneiden valmistusta ei Latinalaisessa Amerikassa juurikaan ole. Ne tuodaan yleensä Pohjois-Amerikasta ja Euroopasta. Tässä diplomityössä tutkitaan sähkömoottorien ja taajuusmuuttajien markkinapotentiaalia Latinalaisessa Amerikassa. Tutkimuksessa perehdytään Latinalaisen Amerikan maiden kansantalouksien tilaan sekä arvioidaan sähkömoottorien ja taajuusmuuttajien markkinoiden kokoa tullitilastojen avulla. Chilen kaivosteollisuudessa arvioidaan olevan erityistä potentiaalia. Diplomityössä selvitetään ostoprosessin kulkua Chilen kaivosteollisuudessa ja eri asiakastyyppien roolia siinä sekä tärkeimpiä päätöskriteerejä toimittaja- ja teknologiavalinnoissa.

Software methods for HTML files protection in local / corporate networks: review and implementation

Tässä luomistyössä on esitetty tutkimus informaation suojaamisen menetelmien osalta paikallisissa ja ryhmäkuntaisissa verkoissa. Tutkimukseen kuuluu nykyaikaisten kryptagraafisten järjestelmien, Internetin/Intranetin ohjelmointikeinojen ja pääsyoikeuksien jakelumenetelmien analyysi. Tutkimusten perusteella on laadittu ohjelmiston prototyyppi HTML-tiedostojen suojaamista varten. Ohjelmiston laatimisprosessi on sisältänyt vaatimusten, järjestelmän ja suojelukomponenttien suunnittelun ja protytyypin testauksen. Ohjelmiston realisoinnin jälkeen kirjoitettiin käyttöohjeet. Ohjelmiston prototyyppi suojaa informaatiota HTML-tiedoston koko käytön aikana ja eri yrityksissä voidaan käyttää sitä pienien laajennuksien jälkeen.