Submanifolds with constant Moebius curvature and flat normal bundle

We classify isometric immersions $f\colon M^{n}\to \mathbb{R}^{n+p}$, $n \geq 5$ and $2p \leq n$, with constant Moebius curvature and flat normal bundle.Comment: 28 page

Association between community noise and children's cognitive and behavioral development: a prospective cohort study

BACKGROUND: Noise exposure has been associated with adverse cognitive and behavioral outcomes in children, but evidence on longitudinal associations between community noise and child development in low- and middle-income countries is rare. We investigated associations between community noise and behavioral and cognitive development in preschool children in Sao Paulo. METHODS: We linked child development data from the Sao Paulo Western Region Birth Cohort with average (Lden) and night-time (Lnight) community noise exposure at children's home, estimated by means of a land use regression model using various predictors (roads, schools, greenness, residential and informal settlements). Outcomes were the Strengths and Difficulties Questionnaire (SDQ) and Regional Project on Child Development Indicators (PRIDI) at 3 years of age and the Child Behavior Checklist (CBCL) and International Development and Early Learning Assessment (IDELA) at 6 years of age. We investigated the relationship between noise exposure and development using cross-sectional and longitudinal regression models. RESULTS: Data from 3385 children at 3 years of age and 1546 children at 6 years of age were analysed. Mean Lden and Lnight levels were 70.3 dB and 61.2 dB, respectively. In cross-sectional analyses a 10 dB increase of Lden above 70 dB was associated with a 32% increase in the odds of borderline or abnormal SDQ total difficulties score (OR = 1.32, 95% CI: 1.04; 1.68) and 0.72 standard deviation (SD) increase in the CBCL total problems z-score (95% CI: 0.55; 0.88). No cross-sectional association was found for cognitive development. In longitudinal analyses, each 10 dB increase was associated with a 0.52 SD increase in behavioral problems (95% CI: 0.28; 0.77) and a 0.27 SD decrease in cognition (95%-CI: 0.55; 0.00). Results for Lnight above 60 dB were similar. DISCUSSION: Our findings suggest that community noise exposure above Lden of 70 dB and Lnight of 60 dB may impair behavioral and cognitive development of preschool children

Land use regression modelling of community noise in São Paulo, Brazil

Noise pollution has negative health consequences, which becomes increasingly relevant with rapid urbanization. In low- and middle-income countries research on health effects of noise is hampered by scarce exposure data and noise maps. In this study, we developed land use regression (LUR) models to assess spatial variability of community noise in the Western Region of Sao Paulo, Brazil.We measured outdoor noise levels continuously at 42 homes once or twice during one week in the summer and the winter season. These measurements were integrated with various geographic information system variables to develop LUR models for predicting average A-weighted (dB(A)) day-evening-night equivalent sound levels (Lden) and night sound levels (Lnight). A supervised mixed linear regression analysis was conducted to test potential noise predictors for various buffer sizes and distances between home and noise source.Noise exposure levels in the study area were high with a site average Lden of 69.3 dB(A) ranging from 60.3 to 82.3 dB(A), and a site average Lnight of 59.9 dB(A) ranging from 50.7 to 76.6 dB(A). LUR models had a good fit with a R(2) of 0.56 for Lden and 0.63 for Lnight in a leave-one-site-out cross validation. Main predictors of noise were the inverse distance to medium roads, count of educational facilities within a 400 m buffer, mean Normalized Difference Vegetation Index (NDVI) within a 100 m buffer, residential areas within a 50 m (Lden) or 25 m (Lnight) buffer and slum areas within a 400 m buffer. Our study suggests that LUR modelling with geographic predictor data is a promising and efficient approach for noise exposure assessment in low- and middle-income countries, where noise maps are not available

Land use regression modelling of NO2 in São Paulo, Brazil

BACKGROUND: Air pollution is a major global public health problem. The situation is most severe in low- and middle-income countries, where pollution control measures and monitoring systems are largely lacking. Data to quantify the exposure to air pollution in low-income settings are scarce. METHODS: In this study, land use regression models (LUR) were developed to predict the outdoor nitrogen dioxide (NO2) concentration in the study area of the Western Region Birth Cohort in Sao Paulo. NO2 measurements were performed for one week in winter and summer at eighty locations. Additionally, weekly measurements at one regional background location were performed over a full one-year period to create an annual prediction. RESULTS: Three LUR models were developed (annual, summer, winter) by using a supervised stepwise linear regression method. The winter, summer and annual models explained 52 %, 75 % and 66 % of the variance (R(2)) respectively. Cross-holdout validation tests suggest robust models. NO2 levels ranged from 43.2 mug/m(3) to 93.4 mug/m(3) in the winter and between 28.1 mug/m(3) and 72.8 mug/m(3) in summer. Based on our annual prediction, about 67 % of the population living in the study area is exposed to NO2 values over the WHO suggested annual guideline of 40 mug/m(3) annual average. CONCLUSION: In this study we were able to develop robust models to predict NO2 residential exposure. We could show that average measures, and therefore the predictions of NO2, in such a complex urban area are substantially high and that a major variability within the area and especially within the season is present. These findings also suggest that in general a high proportion of the population is exposed to high NO2 levels

Impaired Lysosome Reformation in Chloroquine-Treated Retinal Pigment Epithelial Cells

PURPOSE: To model the in vivo effects of chloroquine on the retinal pigment epithelium in experimentally tractable cell culture systems and determine the effects of mild chloroquine treatment on lysosome function and turnover. METHODS: Effects of low-dose chloroquine treatment on lysosomal function and accessibility to newly endocytosed cargo were investigated in primary and embryonic stem cell-derived RPE cells and ARPE19 cells using fluorescence and electron microscopy of fluorescent and gold-labeled probes. Lysosomal protein expression and accumulation were measured by quantitative PCR and Western blotting. RESULTS: Initial chloroquine-induced lysosome neutralization was followed by partial recovery, lysosomal expansion, and accumulation of undegraded endocytic, phagocytic, and autophagic cargo and inhibition of cathepsin D processing. Accumulation of enlarged lysosomes was accompanied by a gradual loss of accessibility of these structures to the endocytic pathway, implying impaired lysosome reformation. Chloroquine-induced accumulation of pro-cathepsin D, as well as the lysosomal membrane protein, LAMP1, was reproduced by treatment with protease inhibitors and preceded changes in lysosomal gene expression. CONCLUSIONS: Low-dose chloroquine treatment inhibits lysosome reformation, causing a gradual depletion of lysosomes able to interact with cargo-carrying vacuoles and degrade their content. The resulting accumulation of newly synthesized pro-cathepsin D and LAMP1 reflects inhibition of normal turnover of lysosomal constituents and possibly lysosomes themselves. A better understanding of the mechanisms underlying lysosome reformation may reveal new targets for the treatment of chloroquine-induced retinopathy

Migration Routes of New World Sanderlings (Calidris alba)

We color-marked Sanderlings (Calidris alba Pallas) at 19 locations in 6 countries in the New World and coordinated a network of volunteers to locate banded individuals in migration over a five-year period. The observers reported 252 independent sightings of birds in countries different from the country of banding. Sanderlings that migrate north to the Arctic from Chile and Peru travel principally through the central corridor (Texas and northward) of the United States and Canada; smaller numbers follow the Pacific coast. A few migrate north from the Pacific coast of South America along the Atlantic coast of the United States. Southbound from the Arctic to coastal Chile and Peru, many individuals switch eastward to stopovers on the Atlantic coast, including birds that migrated north along the U.S. Pacific coast. Sanderlings banded in Brazil during the nonbreeding period appear only on the U.S. Atlantic coast in migration. Our results emphasize the individual nature of migration. We found considerable heterogeneity in migratory behavior among individuals that spend the nonbreeding season together on the same beaches. Individuals from widely separated nonbreeding sites often shared similar pathways. In this species and perhaps in others, no simple single migratory route connects breeding with nonbreeding regions

Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction

PURPOSE: We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. METHODS: We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing. RESULTS: AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation. CONCLUSIONS: We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation

Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction

Funding Information: Supported by Funda??o para a Ciência e Tecnologia (FCT) ? Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union?s Horizon 2020 programme under grant agreement No. 811087. Funding Information: Supported by Fundação para a Ciência e Tecnologia (FCT) – Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union’s Horizon 2020 programme under grant agreement No. 811087. Publisher Copyright: Copyright 2021 The AuthorsPURPOSE. We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. METHODS. We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing. RESULTS. AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation. CONCLUSIONS. We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation.publishersversionpublishe