1,087 research outputs found
Travel cost and time measurement in travel cost models.
Cost; Measurement; Model; Models; Time; Working;
In vitro modeling of dysfunctional glial cells in neurodegenerative diseases using human pluripotent stem cells
Most neurodegenerative diseases are characterized by a complex and mostly still unresolved pathology. This
fact, together with the lack of reliable models, have precluded the development of effective therapies counteracting the disease progression. In the past few years, several studies have evidenced that lack of proper functionality of glial cells (astrocytes, microglia and oligodendrocytes) has a key role in the pathology of several neurodegenerative conditions including Alzheimer´s disease, amyotrophic lateral sclerosis and multiple sclerosis among others. However, this glial dysfunction is poorly modelled by available animal models, and we hypothesize that patientderived cells can serve as a better platform where to study this glial dysfunction. In this sense, human pluripotent stem cells (hPSCs) has revolutionized the field allowing the generation of disease-relevant neural cell types that can be used for disease modelling, drug screening and, possibly, cell transplantation purposes. In the case of the generation of oligodendrocytes (OLs) from hPSCs, we have developed a fast and robust protocol to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The generated cells resemble primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OLneuron co-cultures, effective myelination of neurons can also be demonstrated. This platform is being translated as well to the generation of the other glial cell types, allowing the derivation of patient-specific glial cells where to model disease-specific dysfunction.
This methodology can be used for elucidating pathogenic pathways associated with neurodegeneration and to identify therapeutic targets susceptible of drug modulation, contributing to the development of novel and effective drugs for these devastating disorders.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by PI18/01557 (to AG) and P18/1556 (to JV) grants from ISCiii of Spain co-financed by FEDER funds from European Union, and PI-0276-2018 grant (to JAGL) from Consejeria de Salud of Junta de Andalucia. JAGL held a postdoctoral contract from the I Research Plan Propio of the University of Malaga. CV and KE were supported by IWT-SBO-150031-iPSCAF and the Thierry Lathran Foundation grant – ALS-OL, and KN by
FWO1166518
Using a gamified monitoring app to change adolescents' snack intake : the development of the REWARD app and evaluation design
Background: As the snacking pattern of European adolescents is of great concern, effective interventions are necessary. Till now health promotion efforts in children and adolescents have had only limited success in changing adolescents' eating patterns and anthropometrics. Therefore, the present study proposes an innovative approach to influence dietary behaviors in youth based on new insights on effective behavior change strategies and attractive intervention channels to engage adolescents. This article describes the rationale, the development, and evaluation design of the 'Snack Track School' app. The aim of the app is to improve the snacking patterns of Flemish 14- to 16-year olds.
Methods: The development of the app was informed by the systematic, stepwise, iterative, and collaborative principles of the Intervention Mapping protocol. A four week mHealth intervention was developed based on the dual-system model with behavioral change strategies targeting both the reflective (i.e., active learning, advance organizers, mere exposure, goal-setting, monitoring, and feedback) and automatic processes (i.e., rewards and positive reinforcement). This intervention will be evaluated via a controlled pre-post design in Flemish schools among 1400 adolescents.
Discussion: When this intervention including strategies focused on both the reflective and automatic pathway proves to be effective, it will offer a new scientifically-based vision, guidelines and practical tools for public health and health promotion (i.e., incorporation of learning theories in intervention programs)
Naar een betere zorgrelatie tussen generatiearmen en gezondheidswerkers in de perinatale zorg : projectmatig wetenschappelijk onderzoek opleidingen Professionele Bachelor Verpleegkunde en Vroedkunde
Rat interleukin-2-activated natural killer (A-NK) cell-mediated lysis is determined by the presence of CD18 on A-NK cells and the absence of major histocompatibility complex class I on target cells
The precise mechanism by which target cells are recognized and subsequently lysed by interleukin-2-activated natural killer (A-NK) cells is poorly understood. In this study the role of major histocompatibility complex (MHC) class I and adhesion molecules in the recognition and lysis of tumor cells was investigated in a syngeneic Wag rat model. Preincubation of tumor cells with F(ab′)2 fragments of anti-MHC class I monoclonal antibody (mAb) OX18 strongly enhanced the A-NK cell-mediated lysis. Also normal syngeneic cells such as T cells and A-NK cells became highly sensitive for lysis by A-NK cells after preincubation with mAb OX18. Two other mAb against MHC class I had no effect on lysis of target cells. These data indicate that masking of MHC class I on syngeneic tumor and normal cells by mAb OX18 is sufficient for A-NK cells to recognize target cells as non-self, resulting in lysis. In addition, we found that the presence of mAb against the β2 (CD18)-integrins blocked the lysis of all tumor cell lines by A-NK cells in 51Cr-release assays, also when target cells were preincubated with mAb OX18. Because of the absence of CD18 on most tumor cells we concluded that a CD18-associated integrin on A-NK cells is essential for lysis of target cells. These results show that in this syngeneic rat model CD18 on A-NK cells together with MHC class I on tumor cells determine A-NK cell-mediated lysis. Furthermore, we hypothesize that the anti-MHC class I OX18 recognizes an epitope on rat MHC class I which is, or is very close to, the restriction element determining A-NK cell-mediated lysis
Independent Set Reconfiguration in Cographs
We study the following independent set reconfiguration problem, called
TAR-Reachability: given two independent sets and of a graph , both
of size at least , is it possible to transform into by adding and
removing vertices one-by-one, while maintaining an independent set of size at
least throughout? This problem is known to be PSPACE-hard in general. For
the case that is a cograph (i.e. -free graph) on vertices, we show
that it can be solved in time , and that the length of a shortest
reconfiguration sequence from to is bounded by , if such a
sequence exists.
More generally, we show that if is a graph class for which (i)
TAR-Reachability can be solved efficiently, (ii) maximum independent sets can
be computed efficiently, and which satisfies a certain additional property,
then the problem can be solved efficiently for any graph that can be obtained
from a collection of graphs in using disjoint union and complete join
operations. Chordal graphs are given as an example of such a class
Histamine, a vasoactive agent with vascular disrupting potential, improves tumour response by enhancing local drug delivery
Tumour necrosis factor (TNF)-based isolated limb perfusion (ILP) is an approved and registered treatment for sarcomas confined to the limbs in Europe since 1998, with limb salvage indexes of 76%. TNF improves drug distribution in solid tumours and secondarily destroys the tumour-associated vasculature (TAV). Here we explore the synergistic antitumour effect of another vasoactive agent, histamine (Hi), in doxorubicin (DXR)-based ILP and evaluate its antivascular effects on TAV. We used our well-established rat ILP model for in vivo studies looking at tumour response, drug distribution and effects on tumour vessels. In vitro studies explored drug interactions at cellular level on tumour cells (BN-175) and Human umbilical vein endothelial cells (HUVEC). There was a 17% partial response and a 50% arrest in tumour growth when Hi was combined to DXR, without important side effects, against 100% progressive disease with DXR alone and 29% arrest in tumour growth for Hi alone. Histology documented an increased DXR leakage in tumour tissue combined to a destruction of the TAV, when Hi was added to the ILP. In vitro no synergy between the drugs was observed. In conclusion, Hi is a vasoactive drug, targeting primarily the TAV and synergises with different chemotherapeutic agents
Semantic learning in autonomously active recurrent neural networks
The human brain is autonomously active, being characterized by a
self-sustained neural activity which would be present even in the absence of
external sensory stimuli. Here we study the interrelation between the
self-sustained activity in autonomously active recurrent neural nets and
external sensory stimuli.
There is no a priori semantical relation between the influx of external
stimuli and the patterns generated internally by the autonomous and ongoing
brain dynamics. The question then arises when and how are semantic correlations
between internal and external dynamical processes learned and built up?
We study this problem within the paradigm of transient state dynamics for the
neural activity in recurrent neural nets, i.e. for an autonomous neural
activity characterized by an infinite time-series of transiently stable
attractor states. We propose that external stimuli will be relevant during the
sensitive periods, {\it viz} the transition period between one transient state
and the subsequent semi-stable attractor. A diffusive learning signal is
generated unsupervised whenever the stimulus influences the internal dynamics
qualitatively.
For testing we have presented to the model system stimuli corresponding to
the bars and stripes problem. We found that the system performs a non-linear
independent component analysis on its own, being continuously and autonomously
active. This emergent cognitive capability results here from a general
principle for the neural dynamics, the competition between neural ensembles.Comment: Journal of Algorithms in Cognition, Informatics and Logic, special
issue on `Perspectives and Challenges for Recurrent Neural Networks', in
pres
A Case Study in the Future Challenges in Electricity Grid Infrastructure
The generation by renewables and the loading by electrical vehicle charging imposes severe challenges in the redesign of today’s power supply systems. Indeed, accommodating these emerging power sources and sinks requires traditional power systems to evolve from rigid centralized unidirectional architectures to intelligent decentralized entities allowing a bidirectional power flow. In the case study proposed by ENDINET, we investigate how the penetration of solar panels and of battery charging stations on large scale affects the voltage quality and loss level in a distribution network servicing a residential area in Eindhoven, NL. In our case study we take the average household load during summer and winter into account and consider both a radial and meshed topology of the network. Our study results for both topologies considered in a quantification of the levels of penetration and a strategy for electrical vehicle loading strategy that meet the voltage and loss requirements in the network
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