Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice

© 2015 Elsevier Inc. The accumulation of extracellular amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aβ in the brain and in the peripheral blood and thus, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid or cardiolipin over 3. weeks. This treatment reduced significantly the amount of Aβ in the plasma and the brain levels of Aβ were lighter affected. Nevertheless, this dosing regimen did modulate tau phosphorylation and glycogen synthase kinase 3 activities in the brain, suggesting that the targeting of circulating Aβ may be therapeutically relevant in AD.CIBERNED (an initiative of ISCIII) and the Plan Nacional DGCYT (SAF2009-12249-C02-01) and by an Institutional grant from the 'Fundación Areces'Peer Reviewe

Peripheral amyloid levels present gender differences associated with aging in AβPP/PS1 mice

The accumulation of amyloid-β (Aβ) peptide is one of the major neuropathological hallmarks of Alzheimer's disease (AD). We have analyzed whether the progression of amyloidosis differentially affects males and females along aging in AβPP/PS1 transgenic mice. The levels of peripheral amyloid, Aβ40 and Aβ42, are not modified in either sex until 9 months of age. After that, however, there is an increase in amyloid levels in plasma among females and a decrease among males. These findings could be essential to design gender-specific strategies in other in vivo experiments or even in AD treatments. Supplementary Figure 1. A) Percentage of the cases of AβPP/PS1 transgenic mice (males and females) that show bladder disturbances. In dark affected individuals, in grey no evidence of any disturbance. Image of a healthy bladder (B) and a swollen bladder (C). D) Western blot analysis of some biochemical markers in the mice brains; 6 and 15 months, male, female, transgenic and wild type.This work was supported by grants from the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED; an initiative of the ISCIII). In addition, work in FW’s lab was supported by grants from the “Plan Nacional”, “Dirección General de Ciencia y Tecnología -DGCYT-” SAF2012-39148-C03-01; CAMS2010/BMD-231-(2010-14) and EU-FP7-2009-CT222887, and an Institutional grant from the “Fundacion Areces”.Peer Reviewe

Males vs females: differences in the AB accumulation

Background: The accumulation of extracellular amyloid-beta (Aß) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). For the analysis of Aß-peptide aggregation, different mouse models (single or double transgenic mice) have been used to follow the evolution of AD-amyloidosis, and to test potential treatments. So far, cerebellum tissue has not been deeply analyzed to check the amyloidosis in these transgenic models. Besides, sex influence hasn't been systematically studied in these models, even it has been described important gender differences in the evolution of AD in human population. We have checked whether the progression of amyloidosis in a double transgenic mouse, APP/PS1, is susceptible to aging and differentially affects males and females. Methods: Aß levels were measured by ELISA in plasma and tissue samples. Cortex and cerebellum tissue of transgenic males and females from 6 to 15 months of age were processed to be analyzed. In addition, fixed hemibrains brain were coronally sectioned and used to perform immunohistochemistry and immunofluorescence studies.Peer reviewe

A novel achromatic Fresnel lens for high concentrating photovoltaic systems

In this paper we present a novel manufacturing method to produce achromatic Fresnel lenses for photovoltaic application. These achromatic lenses are capable of reaching a concentration factor three times higher than that attained by a conventional Silicone-on-Glass (SOG) Fresnel lens. The manufacturing method presented to fabricate the achromatic lens, which we refer to as Achromatic Doublet on Glass (ADG) Fresnel lens, is simple, cost-effective and highly scalable. A comprehensive ray-tracing analysis and its comparison with experimental results is presented in this work

Automatic regrouping of strata in the Goodness-of-Fit chi-square test

Pearson's chi-square test is widely employed in social and health sciences to analyse categorical data and contingency tables. For the test to be valid, the sample size must be large enough to provide a minimum number of expected elements per category. This paper develops functions for regrouping strata automatically, thus enabling the goodness-of-fit test to be performed within an iterative procedure. The usefulness and performance of these functions is illustrated by means of a simulation study and the application to different datasets. Finally, the iterative use of the functions is applied to the Continuous Sample of Working Lives, a dataset that has been used in a considerable number of studies, especially on labour economics and the Spanish public pension system

Evolución histórica de las enfermedades causadas por micobacterias no pigmentadas de crecimiento rápido en un Hospital Universitario

Non-pigmented rapidly growing mycobacteria (NPRGM) are a group of organisms of increasing interest due to the growing number of potential patients and the difficulties for a proper treatment in many of them. However, the evolution of these diseases in a long period of time and its evolutionary changes has been described only in a scanty number of reports. Material and methods. We performed a retrospective study between January 1st 2004 and December 31st 2017 in order to evaluate the clinical significance and types of diseases caused by NPRGM. Patients with isolates of NPRGM during this period were selected for the study, and clinical charts were reviewed using a predefined protocol. Results. During this period we identified 59 patients (76 clinical samples) with isolates of NPRGM, with 12 cases of clinical disease and one patient with doubtful significance (including 6 respiratory tract infections, 2 catheter infections, 1 skin and soft tissue infection, 1 disseminated infection, 1 conjunctivitis, 1 prosthetic joint infection and 1 mastitis). Fifty percent of M. chelonae isolates, 37.5% of M. abscessus isolates and 23.33% of M. fortuitum isolates were clinically significant. None of the isolates of other species were significant. Conclusions. Most isolates in respiratory samples were contaminants/colonizations. M. abscessus was the main etiological agent in respiratory syndromes, whereas M. chelonae and M. fortuitum were more frequently associated with other infections, especially clinical devices and skin and soft tissue infections.Las micobacterias no pigmentadas de crecimiento rápido (MNPCR) son un grupo de organismos de interés creciente debido al número cada vez mayor de pacientes potenciales y a las dificultades en el tratamiento. Sin embargo, el número de estudios que analizan la evolución de estos casos a lo largo de un periodo de tiempo largo es escaso. Material and métodos. Se realizó un estudio retrospectivo entre el 1 de enero de 2004 y el 31 de diciembre de 2017 para evaluar el significado clínico y los tipos de enfermedades causados por MNPCR. Se seleccionaron para ello aquellos pacientes con aislamientos de MNPCR, y se revisaron las historias clínicas mediante un protocolo predefinido. Resultados. Se identificaron 59 pacientes (76 muestras) con aislamientos de MNPCR, de los cuales 12 presentaron enfermedad y uno tuvo un significado dudoso (incluyendo 6 infecciones respiratorias, 2 infecciones asociadas a catéter, 1 infección de piel y partes blandas, 1 infección diseminada, 1 conjuntivitis, 1 infección de prótesis osteoarticular y 1 mastitis). El 50 % de los aislamientos de Mycobacterium chelonae, el 37,5 % de Mycobacterium abscessus y el 23,33 % de Mycobacterium fortuitum fueron clínicamente significativos. Ninguno de los aislamientos de otras especies fue significativo La mayoría de los aislamientos de muestras respiratorias resultaron ser contaminantes/ colonizaciones. M. abscessus fue el principal agente etiológico en las infecciones respiratorias, mientras que M. chelonae y M. fortuitum fueron asociados con mayor frecuencia a otras infecciones, especialmente infecciones de piel y partes blandas e infecciones asociadas a dispositivos biomédico

Design and modeling of a cost-effective achromatic Fresnel lens for concentrating photovoltaics

This paper presents a novel Fresnel lens capable to significantly reduce chromatic aberration in solar applications. The optical performance of this achromatic lens has been analyzed through ray-tracing simulations, showing a concentration factor three times higher than that attained by a classic Silicone On Glass (SOG) Fresnel lens while maintaining the same acceptance angle. This should avoid the need for a secondary optical element, reducing the cost associated with its manufacturing and assembly and increasing the module reliability. The achromatic lens is made of inexpensive plastic and elastomer which allows a highly scalable and cost-competitive manufacturing process similar to the one currently used for the fabrication of SOG Fresnel lenses. (C)2016 Optical Society of Americ

Measuring primary lens efficiency: A proposal for standardization

This article describes the procedure proposed by IES-UPM to measure the optical efficiency and the irradiance of the focused spot of a primary optic for concentrator PV (CPV). The method using a broadband source (solar simulator) with a solar cell as the sensor and analysis of the focused spot recorded by a camera is described in detail here to convey the details of the optical characterization in the emerging IEC 62989 technical specification. Special emphasis is placed in noting the main sources of error and the accuracy of the measurement method. As an example, the main outcomes attained in the characterization of a set of Fresnel lenses are reported

PENGUKURAN NILAI BULLWHIP EFFECT PADA ELEMEN ESELON SUPPLY CHAIN YANG DIPENGARUHI PERMINTAAN DAN PENJUALAN FLUKTUATIF DENGAN SIMULASI ARENA

Abstrak : Bullwhip Effect atau disebut juga Whiplash Effect adalah suatu fenomena amatan di dalam saluran distribusi yang terpicu peramalan permintaan. Semakin besar nilai bullwhip effect yang terjadi di elemen eselon supply chain menunjukan bahwa variabilitas permintaan meningkat. Selain elemen eselon supply chain distribusi waktu proses juga berpengaruh terhadap naiknya nilai bullwhip effect hal ini terjadi pada Distribusi weibull yang mempunyai rata-rata sebesar 7.09. Semakin kecil nilai bullwhip effect yang terjadi di elemen eselon supply chain menunjukan bahwa terjadi penghalusan pola pesanan pada variabilitas permintaan dari arah hilir menuju arah hulu supply chain. Kata kunci : supply chain, bullwhip effect, persediaan, variabilitas