Genome-wide association study of kidney function decline in individuals of European descent.

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.Kidney International advance online publication, 10 December 2014; doi:10.1038/ki.2014.361.

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.

Spectral analysis of the angular distribution function of back reflectors for thin film silicon solar cells

Nowadays, one of the most important challenges to enhance the efficiency of thin film silicon solar cells is to increase the short circuit intensity by means of optical confinement methods, such as textured back-reflector structures. In this work, two possible textured structures to be used as back reflectors for n-i-p solar cells have been optically analyzed and compared to a smooth one by using a system which is able to measure the angular distribution function (ADF) of the scattered light in a wide spectral range (350-1000 nm). The accurate analysis of the ADF data corresponding to the reflector structures and to the μc-Si:H films deposited onto them allows the optical losses due to the reflector absorption and its effectiveness in increasing light absorption in the μc-Si:H layer, mainly at long wavelengths, to be quantified.

Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Gas exchanges in peach palms as a function of the spad chlorophyll meter readings

The close relationship between the chlorophyll-meters readings and the total chlorophyll and nitrogen contents in leaves, has allowed their evaluation both in annual and perennial species. Besides, some physiological events such as the CO2 assimilation have also been estimated by chlorophyll meters. This work was carried out aiming to evaluate the gas exchanges of peach palms as a function of the chlorophyll SPAD-Meter readings. Three year-old peach palms from Yurimaguas, Peru were studied in Ubatuba, SP, Brazil, spaced 2 x 1 m in area under a natural gradient of organic matter which allowed four plots to be considered, according to the peach palms leaves colors, from light yellow to dark green. The SPAD readings and the stomatal frequency of leaflets were evaluated. The photosynthetic photon flux density (PPFD, μmol m-2 s-1), the leaf temperature (Tleaf, ºC), the CO2 assimilation (A, μmol m-2 s-1), the stomatal conductance (g s, mol m-2 s-1), the transpiration (E, mmol m-2 s-1) and the intercellular CO2 concentration (Ci, μmol mol-1) were evaluated with a portable infrared gas analyzer (LCA-4, ADC BioScientific Ltd., Great Amwell, U.K.). A linear increase in the CO2 assimilation as a function of the SPAD readings (y = -0.34 + 0.19x, R² = 0.99), indicates that they can be a rapid and cheap complementary method to evaluate in peach palms some important physiological events, such as CO2 assimilation.

Exercise efficiency relates with mitochondrial content and function in older adults.

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty-eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1-h submaximal test (55% V˙O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with (31)P-MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

Design for Customer Needs: Utilization of Quality Function Deployment in Product Development

Kansainvälisen kaupan kiristyessä yrityksien kyky täyttää asiakasketjunsa lailliset, sosiaaliset ja toiminnalliset asiakastarpeet tulee punnituksi. Globaalisuuden lisääntyessä asiakasketju voi sisältää toimintoja samanaikaisesti yli sadassa maassa. Jotta asiakasketjun tarpeet voidaan sisällyttää tuotteeseen tehokkaasti yhä useammat yritykset ovat siirtyneet käyttämään Quality Function Deployment nimistä projektijohto- ja laatutyökalua. Quality Function Deployment työkalu auttaa yritystä muuntamaan sisäisten ja ulkoisten asiakkaittensa tarpeet, tuotefunktioiksi ja tuotespesifikaatioiksi. Näin tehdessä voidaan uuden tuotteen kehitysaikaa ja hintaa alentaa merkittävästi suunnittelmalla tuote alunalkaen paremmin. QFD:tä on käytetty useissa yrityksissä Aasiassa, Pohjois-Amerikassa ja Euroopassa, sen kehittämisen jälkeen Japanissa 1960 luvulla. Tämä diplomityö antaa teoreettisen ja käytännön kuvauksen siitä miten QFD:tä kannatta käyttää ja mitä sen avulla voidaan saavuttaa vastaten kysymykseen "miten minä, ja yritykseni hyötyy jos käytän QFD:tä".

Toiminnanohjauksen kehittäminen toteutusaikataulun avulla

Tässä työssä tarkastellaan projektiin liittyvää toiminnanohjausta. Tutkimusongelmana on, kuinka toiminnanohjausta voitaisiin kehittää aikataulutuksen avulla. Työn yhtenä tavoitteena on luoda kokonaiskuva aikataulutuksen nykytilanteesta. Toisena tavoitteena on kartoittaa ajankohtaiset ongelmat. Kolmantena tavoitteena on luoda malli aikataulun laatimiselle kalanterin valmistuksessa.Kirjallisuustutkimuksen perusteella luotiin kuva projektiliiketoiminnasta ja projektinhallintaan sisältyvästä aikataulunhallinnasta. Haastattelututkimuksen perusteella luotiin kokonaiskuva projektin aikataulutuksesta ja siihen liittyvistä ongelmista. Tutkimusta täydennettiin analysoimalla erään projektin suunniteltua aikataulua ja toteutunutta aikataulua. Toiminnanohjauksen aikataulutustehtävä on muuttumassa yhä tarkeämmäksi toimittaessa resurssien äärirajoilla. Ajankohtaisia kysymyksiä ovat: toteutusaikataulun laatimistekniikka, projektin osittaminen, optimi suunnittelujärjestys ja kriittinen polku.Tutkimuksen perusteella kehitettiin toteutusaikataulun suunnittelun malli ja malliaikataulu. Mallin keskeiset osat ovat: projektin osittaminen tehtäviin, tärkeimpien tehtävien määrittäminen tarkempaa ohjausta varten, tehtävien välisten riippuvuuksien määrittäminen, tehtävien limitysmahdollisuuksien ja ajallisen keston arviointi, aikataulun esittäminen janakaaviona ja ulkoisten tekijöiden, kuten hankinnan asettamien vaatimusten huomioiminen malliaikataulussa. Malliaikataulua tullaan soveltamaan seuraavaan sopivaan toimitusprojektiin.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively];walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.