Early Cognitive/Social Deficits and Late Motor Phenotype in Conditional Wild-Type TDP-43 Transgenic Mice

Frontotemporal Dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases associated to mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43). To investigate in depth the behavioral phenotype associated with this proteinopathy, we used as a model transgenic (Tg) mice conditionally overexpressing human wild-type TDP 43 protein (hTDP-43-WT) in forebrain neurons. We previously characterized these mice at the neuropathological level and found progressive neurodegeneration and other features that evoke human TDP-43 proteinopathies of the FTD/ALS spectrum. In the present study we analyzed the behavior of mice at multiple domains, including motor, social and cognitive performance. Our results indicate that young hTDP-43-WT Tg mice (1 month after post-weaning transgene induction) present a normal motor phenotype compared to control littermates, as assessed by accelerated rotarod performance, spontaneous locomotor activity in the open field test and a mild degree of spasticity shown by a clasping phenotype. Analysis of social and cognitive behavior showed a rapid installment of deficits in social interaction, working memory (Y-maze test) and recognition memory (novel object recognition test) in the absence of overt motor abnormalities. To investigate if the motor phenotype worsen with age, we analyzed the behavior of mice after long-term (up to 12 months) transgene induction. Our results reveal a decreased performance on the rotarod test and in the hanging wire test, indicating a motor phenotype that was absent in younger mice. In addition, long-term hTDP-43-WT expression led to hyperlocomotion in the open field test. In sum, these results demonstrate a time-dependent emergence of a motor phenotype in older hTDP-43-WT Tg mice, recapitulating aspects of clinical FTD presentations with motor involvement in human patients, and providing a complementary animal model for studying TDP-43 proteinopathies.Fil: Alfieri, Julio Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Silva Pinto, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Müller Igaz, Lionel Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Optimization of Finite-Differencing Kernels for Numerical Relativity Applications

A simple optimization strategy for the computation of 3D finite-differencing kernels on many-cores architectures is proposed. The 3D finite-differencing computation is split direction-by-direction and exploits two level of parallelism: in-core vectorization and multi-threads shared-memory parallelization. The main application of this method is to accelerate the high-order stencil computations in numerical relativity codes. Our proposed method provides substantial speedup in computations involving tensor contractions and 3D stencil calculations on different processor microarchitectures, including Intel Knight Landing

From gridmap-file to VOMS: managing authorization in a Grid environment

Grids are potentially composed of several thousands of users from different institutions sharing their computing resources (or using resources provided by third parties). Controlling access to these resources is a difficult problem, as it depends on the policies of the organizations the users belong to and of the resource owners. Moreover, a simple authorization implementation, based on a direct user registration on the resources, is not applicable to a large scale environment. In this paper, we describe the solution to this problem developed in the framework of the European DataGrid [M. Draoli, G. Mascari, R. Piccinelli, Project Presentation, DataGrid-11-NOT-0103-_1] and DataTAG [http://www.datatag.org/] projects: the Virtual Organization Membership Service (VOMS) [R. Alfieri, et al., Managing Dynamic User Communities in a Grid of Autonomous Resources, TUBT005, in: Proceedings of the CHEP 2003, 2003]. VOMS allows a fine grained control of the use of the resources both to the users' organizations and to the resource owners

Valorisation of municipal and tannery sludge via hydrothermal liquefaction: Effect of the substrate chemical composition on yield and quality of bio-crude

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Autofluorescence image reconstruction and virtual staining for in-vivo optical biopsying

Modern photonic technologies are emerging, allowing the acquisition of in-vivo endoscopic tissue imaging at a microscopic scale, with characteristics comparable to traditional histological slides, and with a label-free modality. This raises the possibility of an ‘optical biopsy’ to aid clinical decision making. This approach faces barriers for being incorporated into clinical practice, including the lack of existing images for training, unfamiliarity of clinicians with the novel image domains and the uncertainty of trusting ‘black-box’ machine learned image analysis, where the decision making remains inscrutable. In this paper, we propose a new method to transform images from novel photonics techniques (e.g. autofluorescence microscopy) into already established domains such as Hematoxilyn-Eosin (H-E) microscopy through virtual reconstruction and staining. We introduce three main innovations: 1) we propose a transformation method based on a Siamese structure that simultaneously learns the direct and inverse transformation ensuring domain back-transformation quality of the transformed data. 2) We also introduced an embedding loss term that ensures similarity not only at pixel level, but also at the image embedding description level. This drastically reduces the perception distortion trade-off problem existing in common domain transfer based on generative adversarial networks. These virtually stained images can serve as reference standard images for comparison with the already known H-E images. 3) We also incorporate an uncertainty margin concept that allows the network to measure its own confidence, and demonstrate that these reconstructed and virtually stained images can be used on previously-studied classification models of H-E images that have been computationally degraded and de-stained. The three proposed methods can be seamlessly incorporated on any existing architectures. We obtained balanced accuracies of 0.95 and negative predictive values of 1.00 over the reconstructed and virtually stained image-set on the detection of color-rectal tumoral tissue. This is of great importance as we reduce the need for extensive labeled datasets for training, which are normally not available on the early studies of a new imaging technology.The authors would like to thank all pathologists that generated the BIOPOOL dataset (FP7-ICT-296162) that has been used for this work and specially to M. Saiz, A. Gaafar, S. Fernandez, A. Saiz, E. de Miguel, B. Catón, J. J. Aguirre, R. Ruiz, Ma A. Viguri, and R. Rezola

Similar long-term results of mitral valve repair for anterior compared with posterior leaflet prolapse

ObjectiveThe results of mitral valve repair for anterior leaflet prolapse have been less gratifying than those reported for posterior leaflet prolapse. We compared the long-term durability of 2 different surgical techniques: the edge-to-edge repair, which is used for the treatment of anterior leaflet prolapse, and quadrangular resection, which has been adopted for correction of posterior leaflet prolapse.MethodsFrom 1991 through April 2004, 133 patients with anterior leaflet prolapse and 605 with posterior leaflet prolapse caused by degenerative mitral disease underwent valve repair. The edge-to-edge repair was used for correction of anterior leaflet prolapse, and quadrangular resection of the posterior leaflet, with or without sliding plasty, was used for correction of posterior leaflet prolapse. All patients received a concomitant annuloplasty procedure.ResultsNo hospital deaths occurred in the anterior leaflet prolapse group, whereas 2 (0.3%) patients died in the posterior leaflet prolapse group (P = .7). Follow-up was 100% and 97.2% complete in the anterior and posterior leaflet prolapse groups, respectively. At 10 years, overall survival was 91% ± 4.06% for anterior leaflet prolapse and 93.5% ± 1.81% for posterior leaflet prolapse (P = .18), and freedom from cardiac death was 95.8% ± 2.83% for anterior leaflet prolapse and 97.4% ± 0.95% posterior leaflet prolapse (P = .27). Freedom from reoperation was 96% ± 2.3% in the anterior leaflet prolapse group and 96.5% ± 1.18% in the posterior leaflet prolapse group (P = .37). At follow-up (mean, 4.5 ± 3.12 years; range, 1 month-13.2 years), New York Heart Association functional class I or II was documented in 93.2% of patients in the anterior leaflet prolapse group and 92.8% in the posterior leaflet prolapse group (P = .98).ConclusionsThe long-term results of the edge-to-edge repair in the setting of anterior leaflet prolapse are similar to those obtained with quadrangular resection for the treatment of posterior leaflet prolapse

Cardiac surgery in 260 octogenarians: a case series

Background: The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years' period. Methods: A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period). Results: Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 - 36.450) was the unique independent predictor of mortality. Conclusions: Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected

Ultrastructure of Sheep Primordial Follicles Cultured in the Presence of Indol Acetic Acid, EGF, and FSH

The aim of this study was to investigate the ultrastructural characteristics of primordial follicles after culturing of sheep ovarian cortical slices in the presence of indol acetic acid (IAA), Epidermal Growth Factor (EGF), and FSH. To evaluate ultrastructure of primordial follicles cultured in MEM (control) or in MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for transmission electron microscopy. Except in the control, primordial follicles cultured in supplemented media for 6 d were ultrastructurally normal. They had oocyte with intact nucleus and the cytoplasm contained heterogeneous-sized lipid droplets and numerous round or elongated mitochondria with intact parallel cristae were observed. Rough endoplasmic reticulum (RER) was rarely found. The granulosa cells cytoplasm contained a great number of mitochondria and abundant RER. In conclusion, the presence of IAA, EGF, and FSH helped to maintain ultrastructural integrity of sheep primordial follicles cultured in vitro