Aktiivisten magneettilaakereiden tilasäädön mallinnus ja simulointi

Aktiivisten magneettilaakereiden avulla on mahdollista kannatella ferromagneettisia kappaleita, kuten sähkökoneiden roottoreita, ilman fyysistä kontaktia. Magneettilaakerit tarjoavat monia etuja, kuten esimerkiksi kitkattomuuden, verrattuina perinteisiin mekaanisiin laakereihin. Nämä edut vielä korostuvat suurnopeuskäytöissä, jotka ovat magneettilaakereiden pääasiallisia käyttökohteita. Tässä työssä esitellään magneettilaakereihin liittyvät erusteoriat ja niiden sovellustavat. Tämän jälkeen tarkastellaanmagneettilaakereiden kanssa käytettäviä säätöratkaisuja ja esitetään niille soveltuvat viritysmenetelmät. Teorioiden pohjalta rakennetaan täydellinen magneettilaakerijärjestelmän simulointimalli säätöratkaisuineen ja suoritetaan järjestelmän toimintaa kuvaavia simulointeja. Simuloinneissa saadut tulokset pyritään vielä varmentamaan suorittamalla mittauksia koelaitteistolla ja vertaamalla saatuja tuloksia keskenään.

The micro-architecture estimation by TBS discriminate women with and without osteoporotic fracture independently of age, BMI and BMD: The Osteo-Mobile Vaud cohort study.

Introduction: « Osteo-Mobile Vaud » is a mobile osteoporosis (OP) screening program. The women > 60 years living in the region Vaud will be offered OP screening with new equipment installed in a bus. The main goal is to evaluate the fracture risk with the combination of clinical risk factors (CRF) and informations extracted by a single DXA: bone mineral density (BMD), vertebral fracture assessment (VFA), and micro-architecture (MA) evaluation. MA is yet evaluable in daily practice by the Trabecular Bone Score (TBS) measure. TBS is a novel grey-level texture measurement reflecting bone MA based on the use of experimental variograms of 2D projection images. TBS is very simple to obtain, by reanalyzing a lumbar DXA-scan. TBS has proven to have diagnosis and prognosis value, partially independent of CRF and BMD. A 55-years follow- up is planned. Method: The Osteo-Mobile Vaud cohort (1500 women, > 60 years, living in the region Vaud) started in July 2010. CRF for OP, lumbar spine and hip BMD, VFA by DXA and MA evaluation by TBS are recorded. Preliminary results are reported. Results: In July 31th, we evaluated 510 women: mean age 67 years, BMI 26 kg/m². 72 women had one or more fragility fractures, 39 had vertebral fracture (VFx) grade 2/3. TBS decreases with age (-0.005 / year, p<0.001), and with BMI (-0.011 per kg/m², p<0.001). Correlation between BMD and site matched TBS is low (r=0.4, p<0.001). For the lowest T-score BMD, odds ratio (OR, 95% CI) for VFx grade 2/3 and clinical OP Fx are 1.8 (1.1-2.9) and 2.3 (1.5-3.4). For TBS, age-, BMI- and BMD adjusted ORs (per SD decrease) for VFx grade 2/3 and clinical OP Fx are 1.9 (1.2-3.0) and 1.8 (1.2-2.7). The TBS added value was independent of lumbar spine BMD or the lowest T-score (femoral neck, total hip or lumbar spine). Conclusion: As in the already published studies, these preliminary results confirm the partial independence between BMD and TBS. More importantly, a combination of TBS and BMD may increase significantly the identification of women with prevalent OP Fx. For the first time we are able to have complementary information about fracture (VFA), density (BMD), and micro-architecture (TBS) from a simple, low ionizing radiation and cheap device: DXA. The value of such informations in a screening program will be evaluated.

Expanding view of phenotype and oxidative stress in Friedreich's ataxia patients with and without idebenone

Summary: Friedreich's ataxia (FRDA), the most common autosomal recessive ataxia, is characterised by progressive ataxia with dysarthria of speech, loss of deep-tendon reflexes, impaired vibratory and proprioceptive sensations and corticospinal weakness with a Babinski's sign. Patients eventually also develop kyphoscoliosis, cardiomyopathy and diabetes mellitus. The disease is a GAA repeat disorder resulting in severely reduced levels of frataxin, with secondary increased sensitivity to oxidative stress. The anti-oxidative drug, idebenone, is effective against FRDA-associated cardiomyopathy. We provide detailed clinical, electrophysiological and biochemical data from 20 genetically confirmed FRDA patients and have analysed the relation-ship between phenotype, genotype and malondialdehyde (MDA), which is a marker of superoxide formation. We assessed the effects of idebenone biochemically by measuring blood M DA and clinically by serial measurements of the International Cooperative Ataxia Rating Scale (ICARS). The GAA repeat length influenced the age at onset (p <0.001), the severity of ataxia (p= 0.02), the presence of cardiomyopathy (p =0.04) and of low-frequency hearing loss (p = 0.009). Multilinear regression analysis showed (p = 0.006) that ICARS was dependent on the two variables of disease duration (p = 0.01) and size of the GAA expansion (p = 0.02). We found no correlation to bilateral palpebral ptosis visual impairment, diabetes mellitus or skeletal deformities, all of which appear to be signs of disease progression rather than severity. We discuss more thoroughly two underrecognised clinical findings: palpebral ptosis and GAA length-dependent low-frequency hearing loss. The average ICARS remained unchanged in 10 patients for whom follow-up on treatment was available (mean 2.9 years), whereas most patients treated with idebenone reported an improvement in dysarthria (63%), hand dexterity (.58%) and fatigue (47%) after taking the drug for several weeks or months. Oxidative stress analysis showed an unexpected increase in blood MDA levels in patients on idebenone (p = 0.04), and we discuss the putative underlying mechanism for this result, which could then explain the unique efficacy of idebenone in treating the FRDA-associated cardiomyopathy, as opposed to other antioxidative drugs. Indeed, idebenone is not only a powerful stimulator of complexes II and III of the respiratory chain, but also an inhibitor of complex I activity, then promoting superoxide formation. Our preliminary clinical observations are the first to date supporting an effect of idebenone in delaying neurological worsening. Our MDA results point to the dual effect of idebenone on oxidative stress and to the need for controlled studies to assess its potential toxicity at high doses on the one hand, and to revisit the exact mechanisms underlying the .physiopathology of Friedreich's ataxia on the other hand, while recent reports suggest non-oxidative pathophysiology of the disease.

A mathematical study of fuzzy logic; an algebraic approach

Fuzzy set theory and Fuzzy logic is studied from a mathematical point of view. The main goal is to investigatecommon mathematical structures in various fuzzy logical inference systems and to establish a general mathematical basis for fuzzy logic when considered as multi-valued logic. The study is composed of six distinct publications. The first paper deals with Mattila'sLPC+Ch Calculus. THis fuzzy inference system is an attempt to introduce linguistic objects to mathematical logic without defining these objects mathematically.LPC+Ch Calculus is analyzed from algebraic point of view and it is demonstratedthat suitable factorization of the set of well formed formulae (in fact, Lindenbaum algebra) leads to a structure called ET-algebra and introduced in the beginning of the paper. On its basis, all the theorems presented by Mattila and many others can be proved in a simple way which is demonstrated in the Lemmas 1 and 2and Propositions 1-3. The conclusion critically discusses some other issues of LPC+Ch Calculus, specially that no formal semantics for it is given.In the second paper the characterization of solvability of the relational equation RoX=T, where R, X, T are fuzzy relations, X the unknown one, and o the minimum-induced composition by Sanchez, is extended to compositions induced by more general products in the general value lattice. Moreover, the procedure also applies to systemsof equations. In the third publication common features in various fuzzy logicalsystems are investigated. It turns out that adjoint couples and residuated lattices are very often present, though not always explicitly expressed. Some minor new results are also proved.The fourth study concerns Novak's paper, in which Novak introduced first-order fuzzy logic and proved, among other things, the semantico-syntactical completeness of this logic. He also demonstrated that the algebra of his logic is a generalized residuated lattice. In proving that the examination of Novak's logic can be reduced to the examination of locally finite MV-algebras.In the fifth paper a multi-valued sentential logic with values of truth in an injective MV-algebra is introduced and the axiomatizability of this logic is proved. The paper developes some ideas of Goguen and generalizes the results of Pavelka on the unit interval. Our proof for the completeness is purely algebraic. A corollary of the Completeness Theorem is that fuzzy logic on the unit interval is semantically complete if, and only if the algebra of the valuesof truth is a complete MV-algebra. The Compactness Theorem holds in our well-defined fuzzy sentential logic, while the Deduction Theorem and the Finiteness Theorem do not. Because of its generality and good-behaviour, MV-valued logic can be regarded as a mathematical basis of fuzzy reasoning. The last paper is a continuation of the fifth study. The semantics and syntax of fuzzy predicate logic with values of truth in ana injective MV-algerba are introduced, and a list of universally valid sentences is established. The system is proved to be semanticallycomplete. This proof is based on an idea utilizing some elementary properties of injective MV-algebras and MV-homomorphisms, and is purely algebraic.

Interoperability of learning objects copyright in the LUISA semantic learning management system

Semantic Web technology is able to provide the required computational semantics for interoperability of learning resources across different Learning Management Systems (LMS) and Learning Object Repositories (LOR). The EU research project LUISA (Learning Content Management System Using Innovative Semantic Web Services Architecture) addresses the development of a reference semantic architecture for the major challenges in the search, interchange and delivery of learning objects in a service-oriented context. One of the key issues, highlighted in this paper, is Digital Rights Management (DRM) interoperability. A Semantic Web approach to copyright management has been followed, which places a Copyright Ontology as the key component for interoperability among existing DRM systems and other licensing schemes like Creative Commons. Moreover, Semantic Web tools like reasoners, rule engines and semantic queries facilitate the implementation of an interoperable copyright management component in the LUISA architecture.

Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.

IMPORTANCE: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. CONCLUSIONS AND RELEVANCE: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.

Representation of Sound Objects within Early-Stage Auditory Areas: A Repetition Effect Study Using 7T fMRI.

Environmental sounds are highly complex stimuli whose recognition depends on the interaction of top-down and bottom-up processes in the brain. Their semantic representations were shown to yield repetition suppression effects, i. e. a decrease in activity during exposure to a sound that is perceived as belonging to the same source as a preceding sound. Making use of the high spatial resolution of 7T fMRI we have investigated the representations of sound objects within early-stage auditory areas on the supratemporal plane. The primary auditory cortex was identified by means of tonotopic mapping and the non-primary areas by comparison with previous histological studies. Repeated presentations of different exemplars of the same sound source, as compared to the presentation of different sound sources, yielded significant repetition suppression effects within a subset of early-stage areas. This effect was found within the right hemisphere in primary areas A1 and R as well as two non-primary areas on the antero-medial part of the planum temporale, and within the left hemisphere in A1 and a non-primary area on the medial part of Heschl's gyrus. Thus, several, but not all early-stage auditory areas encode the meaning of environmental sounds.

Endoscopic laryngotracheal cleft repair without tracheotomy or intubation.

OBJECTIVES: The objectives of this study are to present the technique and results of endoscopic repair of laryngotracheoesophageal clefts (LTEC) extending caudally to the cricoid plate into the cervical trachea and to revisit the classification of LTEC. METHODS: The authors conducted a retrospective case analysis consisting of four infants with complete laryngeal clefts (extending through the cricoid plate in three cases and down into the cervical trachea in one case) treated endoscopically by CO2 laser incision of the mucosa and two-layer endoscopic closure of the cleft without postoperative intubation or tracheotomy. RESULTS: All four infants resumed spontaneous respiration without support after a mean postoperative period of 3 days with continuous positive airway pressure (CPAP). They accepted oral feeding within 5 postoperative days (range, 3-11 days). No breakdown of endoscopic repair was encountered. After a mean follow up of 48 months (range, 3 mos to 7 y), all children have a good voice, have no sign of residual aspiration, but experience a slight exertional dyspnea. CONCLUSION: This limited experience on the endoscopic repair of extrathoracic LTEC shows that a minimally invasive approach sparing the need for postoperative intubation or tracheotomy is feasible and safe if modern technology (ultrapulse CO2 laser, endoscopic suturing, and postoperative use of CPAP in the intensive care unit) is available.

Reconstruction of 3D Planar Objects with Partial Occlusion

Kolmiulotteisten kappaleiden rekonstruktio on yksi konenäön haastavimmista ongelmista, koska kappaleiden kolmiulotteisia etäisyyksiä ei voida selvittää yhdestä kaksiulotteisesta kuvasta. Ongelma voidaan ratkaista stereonäön avulla, jossa näkymän kolmiulotteinen rakenne päätellään usean kuvan perusteella. Tämä lähestymistapa mahdollistaa kuitenkin vain rekonstruktion niille kappaleiden osille, jotka näkyvät vähintään kahdessa kuvassa. Piilossa olevien osien rekonstruktio ei ole mahdollista pelkästään stereonäön avulla. Tässä työssä on kehitetty uusi menetelmä osittain piilossa olevien kolmiulotteisten tasomaisten kappaleiden rekonstruktioon. Menetelmän avulla voidaan selvittää hyvällä tarkkuudella tasomaisista pinnoista koostuvan kappaleen muoto ja paikka käyttäen kahta kuvaa kappaleesta. Menetelmä perustuu epipolaarigeometriaan, jonka avulla selvitetään molemmissa kuvissa näkyvät kappaleiden osat. Osittain piilossa olevien piirteiden rekonstruointi suoritetaan käyttämäen stereonäköä sekä tietoa kappaleen rakenteesta. Esitettyä ratkaisua voitaisiin käyttää esimerkiksi kolmiulotteisten kappaleiden visualisointiin, robotin navigointiin tai esineentunnistukseen.

Fulvestrant with or without selumetinib, a MEK 1/2 inhibitor, in breast cancer progressing after aromatase inhibitor therapy: A multicentre randomised placebo-controlled double-blind phase II trial, SAKK 21/08.

BACKGROUND: Second line endocrine therapy has limited antitumour activity. Fulvestrant inhibits and downregulates the oestrogen receptor. The mitogen-activated protein kinase (MAPK) pathway is one of the major cascades involved in resistance to endocrine therapy. We assessed the efficacy and safety of fulvestrant with selumetinib, a MEK 1/2 inhibitor, in advanced stage breast cancer progressing after aromatase inhibitor (AI). PATIENTS AND METHODS: This randomised phase II trial included postmenopausal patients with endocrine-sensitive breast cancer. They were ramdomised to fulvestrant combined with selumetinib or placebo. The primary endpoint was disease control rate (DCR) in the experimental arm. ClinicalTrials.gov Indentifier: NCT01160718. RESULTS: Following the planned interim efficacy analysis, recruitment was interrupted after the inclusion of 46 patients (23 in each arm), because the selumetinib-fulvestrant arm did not reach the pre-specified DCR. DCR was 23% (95% confidence interval (CI) 8-45%) in the selumetinib arm and 50% (95% CI 27-75%) in the placebo arm. Median progression-free survival was 3.7months (95% CI 1.9-5.8) in the selumetinib arm and 5.6months (95% CI 3.4-13.6) in the placebo arm. Median time to treatment failure was 5.1 (95% CI 2.3-6.7) and 5.6 (95% CI 3.4-10.2) months, respectively. The most frequent treatment-related adverse events observed in the selumetinib-fulvestrant arm were skin disorders, fatigue, nausea/vomiting, oedema, diarrhoea, mouth disorders and muscle disorders. CONCLUSIONS: The addition of selumetinib to fulvestrant did not show improving patients' outcome and was poorly tolerated at the recommended monotherapy dose. Selumetinib may have deteriorated the efficacy of the endocrine therapy in some patients.

Liver Glucokinase A456V induces potent hypoglycemia without dyslipidemia through a paradoxical induction of the catalytic subunit of glucose-6-phosphatase

Recent reports point out the importance of the complex GK-GKRP in controlling glucose and lipid homeostasis. Several GK mutations affect GKRP binding, resulting in permanent activation of the enzyme. We hypothesize that hepatic overexpression of a mutated form of GK, GKA456V, described in a patient with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and could provide a model to study the consequences of GK-GKRP deregulation in vivo. GKA456V was overexpressed in the liver of streptozotocin diabetic mice. Metabolite profiling in serum and liver extracts, together with changes in key components of glucose and lipid homeostasis, were analyzed and compared to GK wild-type transfected livers. Cell compartmentalization of the mutant but not the wild-type GK was clearly affected in vivo, demonstrating impaired GKRP regulation. GKA456V overexpression markedly reduced blood glucose in the absence of dyslipidemia, in contrast to wild-type GK-overexpressing mice. Evidence in glucose utilization did not correlate with increased glycogen nor lactate levels in the liver. PEPCK mRNA was not affected, whereas the mRNA for the catalytic subunit of glucose-6-phosphatase was upregulated ~4 folds in the liver of GKA456V-treated animals, suggesting that glucose cycling was stimulated. Our results provide new insights into the complex GK regulatory network and validate liver-specific GK activation as a strategy for diabetes therapy.

Gamma-ray emission from massive young stellar objects

Context.Massive stars form in dense and massive molecular cores. The exact formation mechanism is unclear, but it is possible that some massive stars are formed by processes similar to those that produce the low-mass stars, with accretion/ejection phenomena occurring at some point of the evolution of the protostar. This picture seems to be supported by the detection of a collimated stellar wind emanating from the massive protostar IRAS 16547-4247. A triple radio source is associated with the protostar: a compact core and two radio lobes. The emission of the southern lobe is clearly non-thermal. Such emission is interpreted as synchrotron radiation produced by relativistic electrons locally accelerated at the termination point of a thermal jet. Since the ambient medium is determined by the properties of the molecular cloud in which the whole system is embedded, we can expect high densities of particles and infrared photons. Because of the confirmed presence of relativistic electrons, inverse Compton and relativistic Bremsstrahlung interactions are unavoidable. Aims.We aim to make quantitative predictions of the spectral energy distribution of the non-thermal spots generated by massive young stellar objects, with emphasis on the particular case of IRAS 16547-4247. Methods.We study the high-energy emission generated by the relativistic electrons which produce the non-thermal radio source in IRAS 16547-4247. We also study the result of proton acceleration at the terminal shock of the thermal jet and make estimates of the secondary gamma rays and electron-positron pairs produced by pion decay. Results.We present spectral energy distributions for the southern lobe of IRAS 16547-4247, for a variety of conditions. We show that high-energy emission might be detectable from this object in the gamma-ray domain. The source may also be detectable in X-rays through long exposures with current X-ray instruments. Conclusions.Gamma-ray telescopes such as GLAST, and even ground-based Cherenkov arrays of new generation can be used to study non-thermal processes occurring during the formation of massive stars.