542 research outputs found
Case studies of landscape and environmental impact evaluation of roundabouts
This paper is a follow-up to a previous one that presented a new method for evaluating the landscape and environmental impact of roundabouts borrowed from building technology and based on the needs, requirements and performance expected from an object rather than on prescriptions for and descriptions of its dimensions and quality. The proposed method aims at defining criteria to set up an information structure based on a need and performance approach capable of evaluating impacts on the landscape and environmental integration. After a brief résumé of the above-mentioned principles, two applications are presented in order to highlight two practical developments. The roundabouts on which the applications are focused are located in an urban and in a rural environment respectively in the Northern part of Italy. Obviously their analysis cannot be considered comprehensive of all possible cases but it covers a large proportion of them. Differences between the two roundabouts are many and they concern, besides the landscape and environment, geometrical dimensions, type of flow, presence of weekday users (pedestrians and bikers). The final evaluation sheets are presented and through them it is relatively easy to single out the problems and drawbacks of the roundabouts from the landscape point of view
Landscape and Environmental Impact Evaluation of Roundabouts
The interest of researchers and practitioners on roundabout solutions has been growing increasingly
in the last decades. The often large areas occupied by this type of intersections require special attention on
the use of ground and the preservation of the natural, environmental and architectural heritage. This aim also
presents the opportunity for evaluating their impact on the landscape and environment. The paper proposes a
new method developed for roundabout evaluation (but generalizable to other infrastructures and fields) borrowed
from building technology and based on the needs, requirements and performance expected from an object rather
than on prescriptions for and descriptions of its dimensions and quality. Applications on two roundabouts are
presented in order to highlight practical developments. Their final evaluation sheets are presented and through
them it is relatively easy to single out the problems and drawbacks of the roundabouts from the landscape point
of view
Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors.
Background: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors
(SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer’s disease (AD)
living at home.
Methods: The study was conducted in two different outpatient neurological clinics. 338 patients with probable
ADwere treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician’s judgment and were
observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating
cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1),
three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed
and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated
with SSRIs).
Results: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and
treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score
from baseline to nine months showed that depressed patients not treated worsened in comparison with those
not depressed and not treated with SSRIs (mean change −0.8±2.3 vs 0.04±2.9; p = 0.02) and patients
depressed and treated with SSRI (mean change −0.8±2.3 vs 0.1±2.5; p = 0.03).
Conclusions: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the
negative effects of depression on cognition
Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application
Background
The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A).
Results
The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection.
Conclusions
E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquÃmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin
"Delirium Day": a nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool.
Versatility of MicroRNA Biogenesis
MicroRNAs (miRNAs) are short single-stranded RNA molecules that regulate gene expression. MiRNAs originate from large primary (pri) and precursor (pre) transcripts that undergo various processing steps along their biogenesis pathway till they reach their mature and functional form. It is not clear, however, whether all miRNAs are processed similarly. Here we show that the ratio between pre-miRNA and mature miRNA forms varies between different miRNAs. Moreover, over-expression of several factors involved in miRNA biogenesis, including Exportin-5, Drosha, NF90a, NF45 and KSRP, displayed bidirectional effects on pre/mature miRNA ratios, suggesting their intricate biogenesis sensitivity. In an attempt to identify additional factors that might explain the versatility in miRNA biogenesis we have analyzed the contribution of two hnRNP family members, hnRNPH1 and hnRNPR. Knock-down or over-expression of these genes suggested that hnRNPR inhibits, whereas hnRNPH1 facilitates, miRNA processing. Overall, our results emphasize that miRNA biogenesis is versatile
Surface Plasmon Resonance Reveals a Different Pattern of Proinsulin Autoantibodies Concentration and Affinity in Diabetic Patients
Type 1 diabetes mellitus (DM) is characterized by autoimmune aggression against pancreatic beta cells resulting in absolute deficiency of insulin secretion. The first detectable sign of emerging autoimmunity during the preclinical asymptomatic period is the appearance of diabetes-related autoantibodies. In children at risk for type 1 DM, high-affinity Insulin autoantibodies reactive to proinsulin, are associated with diabetes risk. Autoantibodies are usually measured by radioligand binding assay (RBA) that provides quasi-quantitative values reflecting potency (product between concentration and affinity) of specific autoantibodies. Aiming to improve the characterization of the specific humoral immune response, we selected surface plasmon resonance (SPR) as an alternative method to measure proinsulin autoantibodies (PAA). This novel technology has allowed real time detection of antibodies interaction and kinetic analysis. Herein, we have employed SPR to characterize the PAA present in sera from 28 childhood-onset (mean age 8.31±4.20) and 23 adult-onset diabetic patients (≥65 years old, BMI<30) in terms of concentration and affinity. When evaluating comparatively samples from both groups, childhood-onset diabetic patients presented lower PAA concentrations and higher affinities (median 67.12×10−9 M and 3.50×107 M−1, respectively) than the adults (median 167.4×10−9 M and 0.84×107 M−1, respectively). These results are consistent with those from the reference method RBA (Standard Deviation score median 9.49 for childhood-onset group and 5.04 for adult-onset group) where the binding can be directly related to the intrinsic affinity of the antibody, suggesting that there is a different etiopathogenic pathway between both types of clinical presentation of the disease. This technology has shown to be a useful tool for the characterization of PAAs parameters as an alternative to radioimmunoassay, with high versatility and reproducibility associated to low occupational and environmental risk. However, this technology is not eligible for routine marker screening, but this is a powerful technique for a fine description of the thermodynamic parameters of antigen-antibody interaction
PHAT XX. AGB Stars and Other Cool Giants in M31 Star Clusters
The presence of asymptotic giant branch (AGB) stars in clusters provides key constraints for stellar models, as has been demonstrated with historical data from the Magellanic Clouds. In this work, we look for candidate AGB stars in M31 star clusters from the Panchromatic Hubble Andromeda Treasury survey. Our photometric criteria selects stars brighter than the tip of the red giant branch, which includes the bulk of the thermally pulsing AGB stars as well as early-AGB stars and other luminous cool giants expected in young stellar populations (e.g., massive red supergiants, and intermediate-mass red helium-burning stars). The AGB stars can be differentiated, a posteriori, using the ages already estimated for our cluster sample. 937 candidates are found within the cluster aperture radii, half ( 3c450) of which are very likely cluster members. Cross-matching with additional databases reveals two carbon stars and 10 secure variables among them. The field-corrected age distribution reveals the presence of young supergiants peaking at ages smaller than 108 yr, followed by a long tail of AGB stars extending up to the oldest possible ages. This long tail reveals the general decrease in the numbers of AGB stars from initial values of 3c 50
7 10-6 M 99-1 at 108 yr down to 3c 5
7 10-6 M 99-1 at 1010 yr. Theoretical models of near-solar metallicity reproduce this general trend, although with localized discrepancies over some age intervals, whose origin is not yet identified. The entire catalog is released together with finding charts to facilitate follow-up studies
MicroRNAs in pulmonary arterial remodeling
Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH
- …