Failure to Recover from Proactive Semantic Interference Differentiates Amnestic Mild Cognitive Impairment and PreMCI from Normal Aging after Adjusting for Initial Learning Ability

Background: There is increasing evidence that the failure to recover from proactive semantic interference (frPSI) may be an early cognitive marker of preclinical Alzheimer’s disease (AD). However, it is unclear whether frPSI effects reflect deficiencies in an individual’s initial learning capacity versus the actual inability to learn new semantically related targets. Objective: The current study was designed to adjust for learning capacity and then to examine the extent to which frPSI, proactive semantic interference (PSI) and retroactive semantic interference (RSI) effects could differentiate between older adults who were cognitively normal (CN), and those diagnosed with either Pre-Mild Cognitive Impairment (PreMCI) or amnestic MCI (aMCI). Methods: We employed the LASSI-L cognitive stress test to examine frPSI, PSI and RSI effects while simultaneously controlling for the participant’s initial learning capacity among 50 CN, 35 aMCI, and 16 PreMCI participants who received an extensive diagnostic work-up. Results: aMCI and PreMCI participants showed greater frPSI deficits (50% and 43.8% respectively) compared to only 14% of CNparticipants. PSI effects were observed for aMCI but not PreMCI participants relative to their CN counterparts. RSI failed to differentiate between any of the study groups. Conclusion: By using participants as their own controls and adjusting for overall learning and memory, it is clear that frPSI deficits occur with much greater frequency in individuals at higher risk for Alzheimer’s disease (AD), and likely reflect a failure of brain compensatory mechanisms.Fil: Curiel, Rosie E.. University of Miami; Estados UnidosFil: Crocco, Elizabeth A.. University of Miami; Estados UnidosFil: Raffo, Arlene. University of Miami; Estados UnidosFil: Guinjoan, Salvador Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Nemeroff, Charles B.. University of Miami; Estados UnidosFil: Penate, Ailyn. Mount Sinai Medical Center; Estados Unidos. University of Miami; Estados UnidosFil: Piña, Daema. University of Miami; Estados UnidosFil: Loewenstein, David A.. Mount Sinai Medical Center; Estados Unidos. University of Miami; Estados Unido

Developing a re-configurable architecture for the remote operation of marine autonomous systems

In this experience report, we explain how we take advantage of microservices’ inherent modular nature to accomplish a highly adaptable software architecture that can deal with the trials and tribulations often occurring in marine research environments. We will show the National Oceanography Centre’s journey to develop a web system to remotely operate marine autonomous vehicles from anywhere in the world with an internet connection and how, due to new unforeseen requirements, we took the microservice pattern into a new direction to allow for standalone offline operations of Autonomous Underwater Vehicles (AUV) from research ships in some of the most challenging environments in the world

New lives for old reverse osmosis (RO) membranes

The overall objective of the present work was to estimate by membrane autopsy the level of performances degradation of old reverse osmosis (RO) membranes/modules in order to envisage their reuse A mechanistic approach using the Spiegler-Kedem-Karchalsky model helps us to observe that the old RO membrane acquired a convective mass transfer We defined a novel Peclet number (denoted Pe') usable to distinguish between diffusional and convective mass transfer We observed that for the old membrane Pe' numbers are always higher than 1. Furthermore, SEM/AFM and EDX experiments show crystals and bacteria particles as fouling agents, roughness increase for the old membrane (from 73 to 220 nm) due to foulants deposition EDX experiments demonstrated that FexOy crystals are dominant SP measurements help us to observe a displacement of the isoelectric point (IEP) for the virgin membrane from 2.7 +/- 0.3 to 4 6 +/- 0 3 in comparison to the old one showing chemical modifications of the inner active layer suspected due to biofouling residuals In the last part and for the first time. module materials reuse Occurred in the place of their incineration as geotextile in proper home garden. Crown Copyright (C) 2009 Published by Elsevier B V All rights reserved

Fluorine-labeled Dasatinib Nanoformulations as Targeted Molecular Imaging Probes in a PDGFB-driven Murine Glioblastoma Model

Dasatinib, a new-generation Src and platelet-derived growth factor receptor (PDGFR) inhibitor, is currently under evaluation in high-grade glioma clinical trials. To achieve optimum physicochemical and/or biologic properties, alternative drug delivery vehicles may be needed. We used a novel fluorinated dasatinib derivative (F-SKI249380), in combination with nanocarrier vehicles and metabolic imaging tools (microPET) to evaluate drug delivery and uptake in a platelet-derived growth factor B (PDGFB)-driven genetically engineered mouse model (GEMM) of high-grade glioma. We assessed dasatinib survival benefit on the basis of measured tumor volumes. Using brain tumor cells derived from PDGFB-driven gliomas, dose-dependent uptake and time-dependent inhibitory effects of F-SKI249380 on biologic activity were investigated and compared with the parent drug. PDGFR receptor status and tumor-specific targeting were non-invasively evaluated in vivo using 18F-SKI249380 and 18F-SKI249380-containing micellar and liposomal nanoformulations. A statistically significant survival benefit was found using dasatinib (95 mg/kg) versus saline vehicle (P < .001) in tumor volume-matched GEMM pairs. Competitive binding and treatment assays revealed comparable biologic properties for F-SKI249380 and the parent drug. In vivo, Significantly higher tumor uptake was observed for 18F-SKI249380-containing micelle formulations [4.9 percentage of the injected dose per gram tissue (%ID/g); P = .002] compared to control values (1.6%ID/g). Saturation studies using excess cold dasatinib showed marked reduction of tumor uptake values to levels in normal brain (1.5%ID/g), consistent with in vivo binding specificity. Using 18F-SKI249380-containing micelles as radiotracers to estimate therapeutic dosing requirements, we calculated intratumoral drug concentrations (24–60 nM) that were comparable to in vitro 50% inhibitory concentration values. 18F-SKI249380 is a PDGFR-selective tracer, which demonstrates improved delivery to PDGFB-driven high-grade gliomas and facilitates treatment planning when coupled with nanoformulations and quantitative PET imaging approaches