Role of rhinovirus load in the upper respiratory tract and severity of symptoms in lung transplant recipients.

BACKGROUND: Rhinovirus is the most common cause of respiratory viral infections and leads to frequent respiratory symptoms in lung transplant recipients. However, it remains unknown whether the rhinovirus load correlates with the severity of symptoms. OBJECTIVES: This study aimed to better characterize the pathogenesis of rhinoviral infection and the way in which viral load correlates with symptoms. STUDY DESIGN: We assessed rhinovirus load in positive upper respiratory specimens of patients enrolled prospectively in a cohort of 116 lung transplant recipients. Rhinovirus load was quantified according to a validated in-house, real-time, reverse transcription polymerase chain reaction in pooled nasopharyngeal and pharyngeal swabs. Symptoms were recorded in a standardised case report form completed at each screening/routine follow-up visit, or during any emergency visit occurring during the 3-year study. RESULTS: Rhinovirus infections were very frequent, including in asymptomatic patients not seeking a specific medical consultation. Rhinovirus load ranged between 4.1 and 8.3 log copies/ml according to the type of visit and clinical presentation. Patients with highest symptom scores tended to have higher viral loads, particularly those presenting systemic symptoms. When considering symptoms individually, rhinovirus load was significantly higher in the presence of symptoms such as sore throat, fever, sputum production, cough, and fatigue. There was no association between tacrolimus levels and rhinovirus load. CONCLUSIONS: Rhinovirus infections are very frequent in lung transplant recipients and rhinoviral load in the upper respiratory tract is relatively high even in asymptomatic patients. Patients with the highest symptom scores tend to have a higher rhinovirus load.

Loss of the RNA polymerase III repressor MAF1 confers obesity resistance.

MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences.

Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.

Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases.

Cherenkov mesons as in-medium quark energy loss

We recently showed that a heavy quark moving sufficiently fast through a quark-gluon plasma may lose energy by Cherenkov-radiating mesons [1]. Here we review our previous holographic calculation of the energy loss in N=4 Super Yang-Mills and extend it to longitudinal vector mesons and scalar mesons. We also discuss phenomenological implications for heavy-ion collision experiments. Although the Cherenkov energy loss is an O(1/Nc) effect, a ballpark estimate yields a value of dE/dx for Nc=3 which is comparable to that of other mechanisms.

Cherenkov mesons as in-medium quark energy loss

We recently showed that a heavy quark moving sufficiently fast through a quark-gluon plasma may lose energy by Cherenkov-radiating mesons [1]. Here we review our previous holographic calculation of the energy loss in N=4 Super Yang-Mills and extend it to longitudinal vector mesons and scalar mesons. We also discuss phenomenological implications for heavy-ion collision experiments. Although the Cherenkov energy loss is an O(1/Nc) effect, a ballpark estimate yields a value of dE/dx for Nc=3 which is comparable to that of other mechanisms.

A New Mechanism of Quark Energy Loss

We show that a heavy quark moving sufficiently fast through a quark-gluon plasma may lose energy by Cherenkov-radiating mesons. We demonstrate that this takes place in all strongly coupled, large-Nc plasmas with a gravity dual. The energy loss is exactly calculable in these models despite being an O(1/Nc)-effect. We discuss phenomenological implications for heavy-ion collision experiments.

Development of rotating drum under mechanical and thermal load

A variable temperature field sets exacting demands to the structure under mechanical load. Most of all the lifetime of the rotating drum structure depends on temperature differences between parts inside the drum. The temperature difference was known because of the measurements made before. The list of demands was created based on customers’ needs. The limits of this paper were set to the inner structure of the drum. Creation of ideas for the inner structure was started open minded. The main principle in the creation process was to create new ideas for the function of the product with the help of sub-functions. The sub-functions were created as independent as possible. The best sub-functions were combined together and the new working principles were created based on them. Every working principle was calculated separately and criticized at the end of the calculation process. The main objective was to create the new kind of structure, which is not based too much to the old, inoperative structure. The affect of own weight of the inner structure to the stress values was quite small but it was also taken into consideration when calculating the maximum stress value of the structure. Because of very complex structures all of the calculations were made with the help of the ProE – Mechanica software. The fatigue analyze was made also for the best structure solution.

Teollisuusverkon stabiilisuus saarekekäyttöön siirryttäessä

Työn aluksi on käsitelty sähkövoimajärjestelmien stabiilisuutta yleisesti. Myös teollisuuden sähköverkkojen erityispiirteitä on tarkasteltu. Teollisuusverkkojen komponentteja koskevassa selvityksessä eri laitteet on käsitelty siten, että niiden tärkeimmät ominaisuudet verkon erilaisissa muutostilanteissa tulevat esille. Tahtigeneraattorit ja epätahtikoneet on käsitelty yksityiskohtaisesti. Tutkimuksessa on esitelty teollisuusverkon saarekekäyttöön johtavia syitä, saarekkeeseen siirtymisen kriteereitä ja saarekekäytön toteutustapoja. Tehonvajaussuojaukseen liittyen on tutustuttu kuormanpudotusjärjestelyihin. Myös höyryverkon kuormien tasausten mahdollisuuksiin on luotu katsaus. Verkostolaskentaa käsittelevässä luvussa on keskitytty sopivan laskentamallin luomiseen liittyviin menetelmiin ja rajoituksiin. Lisäksi on kerrottu työn käytännön osan laskentamallin luomisen keskeiset periaatteet. Työn lopuksi on suoritettu simulointeja, joissa on tutkittu erään teollisuusverkon stabiilisuutta saarekekäyttöön siirryttäessä Calpos-verkostolaskentaohjelmistolla.

Load and Performance Testing of Web Applications on Service Based Environments

Suorituskyky- ja kuormitustestien tekeminen sovelluksille on erittäin tärkeä osa tuotantoprosessia nykypäivänä. Myös Web-sovelluksia testataan yhä enemmän. Tarve suorituskyky- ja kuormitustestien tekemiselle on selvä. Testattavan ympäristön tämänhetkinen, mutta myös tulevaisuuden toimivuus taataan oikein tehdyillä testeillä ja niitä seuraavilla korjaustoimenpiteillä. Suurten käyttäjämäärien testaaminen manuaalisesti on kuitenkin hyvin vaikeaa. Sirpaleisen ympäristön, kuten palveluihin perustuvien Web-sovellusympäristöjen testaaminen on haaste. Tämän työn aiheena on arvioida työkaluja ja menetelmiä, joilla raskaita teollisia Web-sovelluksia voidaan testata. Tavoitteena on löytää testausmenetelmiä, joilla voidaan luotettavasti simuloida suuria käyttäjämääriä. Tavoitteena on myös arvioida erilaisten yhteyksien ja protokollien vaikutusta Web-sovelluksen suorituskykyyn.