Glucose tolerance is negatively associated with circulating progenitor cell levels

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Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion

Aims/hypothesis Insulin secretion in pancreatic islets is dependent upon mitochondrial function and production of ATP. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator-1 alpha (protein PGC-1 alpha; gene PPARGC1A) is a master regulator of mitochondrial genes and its expression is decreased and related to impaired oxidative phosphorylation in muscle from patients with type 2 diabetes. Whether it plays a similar role in human pancreatic islets is not known. We therefore investigated if PPARGC1A expression is altered in islets from patients with type 2 diabetes and whether this expression is influenced by genetic (PPARGC1A Gly482Ser polymorphism) and epigenetic (DNA methylation) factors. We also tested if experimental downregulation of PPARGC1A expression in human islets influenced insulin secretion. Methods The PPARGC1A Gly482Ser polymorphism was genotyped in human pancreatic islets from 48 non-diabetic and 12 type 2 diabetic multi-organ donors and related to PPARGC1A mRNA expression. DNA methylation of the PPARGC1A promoter was analysed in pancreatic islets from ten type 2 diabetic and nine control donors. Isolated human islets were transfected with PPARGC1A silencing RNA (siRNA). Results PPARGC1A mRNA expression was reduced by 90% (p < 0.005) and correlated with the reduction in insulin secretion in islets from patients with type 2 diabetes. After downregulation of PPARGC1A expression in human islets by siRNA, insulin secretion was reduced by 41% (p <= 0. 01). We were able to ascribe reduced PPARGC1A expression in islets to both genetic and epigenetic factors, i.e. a common PPARGC1A Gly482Ser polymorphism was associated with reduced PPARGC1A mRNA expression (p < 0.00005) and reduced insulin secretion (p < 0.05). In support of an epigenetic influence, the PPARGC1A gene promoter showed a twofold increase in DNA methylation in diabetic islets compared with non-diabetic islets (p < 0.04). Conclusions/Interpretation We have shown for the first time that PPARGC1A might be important in human islet insulin secretion and that expression of PPARGC1A in human islets can be regulated by both genetic and epigenetic factors

Kadun eri ratkaisujen vaikutukset ylläpitokustannuksiin

Tässä opinnäytetyössä tarkastellaan katujen ylläpitokustannuksia Helsingin kaupungissa. Työn toimeksiantajana on Helsingin kaupunki. Ohjaajina toimivat Helsingin kaupungin ylläpitoinsinööri Tuomas Lautaniemi ja Hämeen ammattikorkeakoulun liikennealan lehtori Rami Tervo. Työn tavoitteena oli kehittää Helsingin kaupungille apuväline ylläpitokustannusten arviointiin katusuunnittelun yhteydessä. Apuvälineeksi on toteutettu Excel-taulukko, joka laskee kadun eri ratkaisujen ja ominaisuuksien perusteella arvion vuosittaisista ylläpitokustannuksista. Tämän taulukon on tarkoitus antaa tarkempaa arviota katusuunnitelman yhteydessä ilmoitettaviin ylläpitokustannuksiin kuin ennen. Suurimmat katujen ylläpitoa hankaloittavat ratkaisut ovat kadunvarsipysäköinti, kolmitasoratkaisut (jalankulun, pyöräilyn ja ajoradan erottaminen eri tasoihin) ja ahtaat katutilat. Kadun ylläpitokustannuksiin vaikuttavat myös monet sellaiset asiat, joihin ei suunnittelulla voida vaikuttaa. Kadun eri rakenteellisten ominaisuuksien vaikutuksetkin ovat hyvin moninaisia ja usein vaikutukset vaihtelevat kohteittain. Näiden takia taulukon antama ylläpitokustannusarvio on vain karkea arvio kadun vuosittaisista ylläpitokustannuksista.In this thesis project maintenance costs of streets were examined by the perspective of the city of Helsinki. The commissioner of this thesis was the city of Helsinki. The supervisors included maintenance engineer Tuomas Lautaniemi from the city of Helsinki and traffic and transport management lecturer Rami Tervo from Häme University of Applied Sciences. The goal of this project was to develop an assistive device to the city of Helsinki which would help estimate the maintenance costs of streets. The assistive device was implemented using an Excel-table which calculates estimated annual maintenance costs for a specific street based on solutions and features of the street. The function of this Excel-table is to provide more exact maintenance costs shown in the street plan than before. The biggest challenges in the maintenance of streets are street parking, three-level solutions (walking, cycling and roadway are separated into different levels) and the narrow street space. The maintenance costs of streets are influenced by many factors which cannot be affected by planning. The effects of structural solutions on streets are multifold and often they change by location. This is why the estimated annual maintenance costs of a street are only a very rough estimates

Calibration and sensitivity of the Virgo detector during its second science run

The Virgo detector is a kilometer-length interferometer for gravitational wave detection located near Pisa (Italy). During its second science run (VSR2) in 2009, six months of data were accumulated with a sensitivity close to its design. In this paper, the methods used to determine the parameters for sensitivity estimation and gravitational wave reconstruction are described. The main quantities to be calibrated are the frequency response of the mirror actuation and the sensing of the output power. Focus is also put on their absolute timing. The monitoring of the calibration data as well as the parameter estimation with independent techniques are discussed to provide an estimation of the calibration uncertainties. Finally, the estimation of the Virgo sensitivity in the frequency-domain is described and typical sensitivities measured during VSR2 are shown.Comment: 30 pages, 23 figures, 1 table. Published in Classical and Quantum Gravity (CQG), Corrigendum include

Virgo calibration and reconstruction of the gravitational wave strain during VSR1

Virgo is a kilometer-length interferometer for gravitational waves detection located near Pisa. Its first science run, VSR1, occured from May to October 2007. The aims of the calibration are to measure the detector sensitivity and to reconstruct the time series of the gravitational wave strain h(t). The absolute length calibration is based on an original non-linear reconstruction of the differential arm length variations in free swinging Michelson configurations. It uses the laser wavelength as length standard. This method is used to calibrate the frequency dependent response of the Virgo mirror actuators and derive the detector in-loop response and sensitivity within ~5%. The principle of the strain reconstruction is highlighted and the h(t) systematic errors are estimated. A photon calibrator is used to check the sign of h(t). The reconstructed h(t) during VSR1 is valid from 10 Hz up to 10 kHz with systematic errors estimated to 6% in amplitude. The phase error is estimated to be 70 mrad below 1.9 kHz and 6 micro-seconds above.Comment: 8 pages, 8 figures, proceedings of Amaldi 8 conference, to be published in Journal of Physics Conference Series (JPCS). Second release: correct typo

Scientific Objectives of Einstein Telescope

The advanced interferometer network will herald a new era in observational astronomy. There is a very strong science case to go beyond the advanced detector network and build detectors that operate in a frequency range from 1 Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors will be able to probe a range of topics in nuclear physics, astronomy, cosmology and fundamental physics, providing insights into many unsolved problems in these areas.Comment: 18 pages, 4 figures, Plenary talk given at Amaldi Meeting, July 201

Personalized Management of Hyperglycemia in Type 2 Diabetes: Reflections from a Diabetes Care Editors' Expert Forum

In June 2012, 13 thought leaders convened in a Diabetes Care Editors' Expert Forum to discuss the concept of personalized medicine in the wake of a recently published American Diabetes Association/European Association for the Study of Diabetes position statement calling for a patient-centered approach to hyperglycemia management in type 2 diabetes. This article, an outgrowth of that forum, offers a clinical translation of the underlying issues that need to be considered for effectively personalizing diabetes care. The medical management of type 2 diabetes has become increasingly complex, and its complications remain a great burden to individual patients and the larger society. The burgeoning armamentarium of pharmacological agents for hyperglycemia management should aid clinicians in providing early treatment to delay or prevent these complications. However, trial evidence is limited for the optimal use of these agents, especially in dual or triple combinations. In the distant future, genotyping and testing for metabolomic markers may help us to better phenotype patients and predict their responses to antihyperglycemic drugs. For now, a personalized ("n of 1") approach in which drugs are tested in a trial-and-error manner in each patient may be the most practical strategy for achieving therapeutic targets. Patient-centered care and standardized algorithmic management are conflicting approaches, but they can be made more compatible by recognizing instances in which personalized A1C targets are warranted and clinical circumstances that may call for comanagement by primary care and specialty clinicians

The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE:The study protocol

Background: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods: IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients' demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions: IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease's awareness