88 research outputs found
Computability and dynamical systems
In this paper we explore results that establish a link between dynamical
systems and computability theory (not numerical analysis). In the last few decades,
computers have increasingly been used as simulation tools for gaining insight into
dynamical behavior. However, due to the presence of errors inherent in such numerical
simulations, with few exceptions, computers have not been used for the
nobler task of proving mathematical results. Nevertheless, there have been some recent
developments in the latter direction. Here we introduce some of the ideas and
techniques used so far, and suggest some lines of research for further work on this
fascinating topic
Computability of ordinary differential equations
In this paper we provide a brief review of several results about the
computability of initial-value problems (IVPs) defined with ordinary differential
equations (ODEs). We will consider a variety of settings and analyze
how the computability of the IVP will be affected. Computational
complexity results will also be presented, as well as computable versions
of some classical theorems about the asymptotic behavior of ODEs.info:eu-repo/semantics/publishedVersio
Understanding within-session loss-chasing: an experimental investigation of the impact of stake size on cognitive control
Loss-chasing is a central feature of problematic gambling, yet it remains a
poorly conceived and understood concept. Loss-chasing is believed to stem from an ero-
sion of cognitive control when gambling. The opportunity to gamble at significantly dis-
parate stake sizes on a gambling activity is considered to be a risk factor for loss-chasing.
This study investigated the impact of gambling at disparate stake sizes on executive
processes integral to maintaining cognitive control when gambling, namely response
inhibition and reflection impulsivity. Frequent adult non-problem gamblers (n = 32)
participated in a repeated measures experiment; and gambled at three disparate stake sizes
(£20, £2 and no stake per bet) on a simulated gambling task. Participants’ response
inhibition performance and reflection impulsivity levels after gambling at various stake
sizes were compared via a go/no-go task and information sampling task, respectively.
Quality of decision-making i.e. the evaluation of available information to make probability
judgements was impaired after gambling at higher stakes in comparison to lower stakes,
indicating an increase in reflection impulsivity. No effect on response inhibition was
observed. Although exploratory, this suggests that the opportunity for participants to
substantially increase stake size on a gambling activity may be a risk factor for impaired
cognitive performance when gambling, and perhaps create vulnerability for within-session
loss-chasing in some players.
Keywords Problem gambling -
Cognitive control -
Loss-chasing -
Response inhibition -
Reflection impulsivit
Combining dispersion modelling with synoptic patterns to understand the wind-borne transport into the UK of the bluetongue disease vector
Bluetongue, an economically important animal disease, can be spread over long distances by carriage of insect vectors (Culicoides biting midges) on the wind. The weather conditions which influence the midge’s flight are controlled by synoptic scale atmospheric circulations. A method is proposed that links wind-borne dispersion of the insects to synoptic circulation through the use of a dispersion model in combination with principal component analysis (PCA) and cluster analysis. We illustrate how to identify the main synoptic situations present during times of midge incursions into the UK from the European continent. A PCA was conducted on high-pass-filtered mean sea-level pressure data for a domain centred over north-west Europe from 2005 to 2007. A clustering algorithm applied to the PCA scores indicated the data should be divided into five classes for which averages were calculated, providing a classification of the main synoptic types present. Midge incursion events were found to mainly occur in two synoptic categories; 64.8% were associated with a pattern displaying a pressure gradient over the North Atlantic leading to moderate south-westerly flow over the UK and 17.9% of the events occurred when high pressure dominated the region leading to south-easterly or easterly winds. The winds indicated by the pressure maps generally compared well against observations from a surface station and analysis charts. This technique could be used to assess frequency and timings of incursions of virus into new areas on seasonal and decadal timescales, currently not possible with other dispersion or biological modelling methods
Human predecidual stromal cells are mesenchymal stromal/stem cells and have a therapeutic effect in an immune-based mouse model of recurrent spontaneous abortion
Human decidual stromal cells (DSCs) are involved in the maintenance and development of
pregnancy, in which they play a key role in the induction of immunological maternal–fetal tolerance. Precursors of
DSCs (preDSCs) are located around the vessels, and based on their antigen phenotype, previous studies suggested
a relationship between preDSCs and mesenchymal stromal/stem cells (MSCs). This work aimed to further elucidate
the MSC characteristics of preDSCs. Under the effect of P4 and cAMP, the preDSC lines and clones decidualized in vitro: the cells became rounder
and secreted PRL, a marker of physiological decidualization. PreDSC lines and clones also exhibited MSC characteristics.
They differentiated into adipocytes, osteoblasts, and chondrocytes, and preDSC lines expressed stem cell markers OCT-
4, NANOG, and ABCG2; exhibited a cloning efficiency of 4 to 15%; significantly reduced the embryo resorption rate
(P < 0.001) in the mouse model of abortion; and survived for prolonged periods in immunocompetent mice. The fact
that 3 preDSC clones underwent both decidualization and mesenchymal differentiation shows that the same type of
cell exhibited both DSC and MSC characteristics. Together, our results confirm that preDSCs are decidual MSCs and suggest that these cells are involved
in the mechanisms of maternal–fetal immune toleranceThis work was supported by the Plan Estatal de Investigación CientÃfica y
Técnica y de Innovación 2013–2016, ISCIII-Subdirección General de Evaluación y
Fomento de la Investigación, the Ministerio de EconomÃa y Competitividad,
Spain (Grant PI16/01642) and European Regional Development Fund (ERDF/
FEDER funding), the European Community, and the Cátedra de Investigación
Anto nio Chamorro–Alejandro Otero, Universidad de Granada (CACH2017-1)
Capillary Regeneration in Scleroderma: Stem Cell Therapy Reverses Phenotype?
BACKGROUND. Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS. We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue), antiangiogenic interferon α (overexpressed in the scleroderma dermis) and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon α and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. CONCLUSION/SIGNIFICANCE. These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have implications for other diseases characterized by loss of capillaries including hypertension, congestive heart failure and scar formation.Scleroderma Research Foundatio
Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography
Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic) dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation
Genomic copy number variation in Mus musculus.
BACKGROUND: Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.
RESULTS: We found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).
CONCLUSION: The analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies
Autosomal recessive cerebellar ataxias
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia
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