The logic of identity and copy for computational artefacts

Defining identity for entities is a longstanding logical problem in philosophy, and it has resurfaced in current investigations within the philosophy of technology. The problem has not yet been explored for the philosophy of information, and of Computer Science in particular. This paper provides a logical analysis of identity and copy for computational artefacts. Identity is here understood as the relation holding between an instance of a computational artefact and itself. By contrast, the copy relation holds between two distinct computational artefacts. We distinguish among exact, inexact and approximate copies. We use process algebra to provide suitable formal definitions of these relations, using in particular the notion of bisimulation to define identity and exact copies, and simulation for inexact and approximate copies. Equivalence is unproblematic for identical computational artefacts at each individual time and for inexact copies; we will examine to which extent the formal constraints on identity criteria discussed in the literature are satisfied by our approach. As for inexact and approximate copy, they are intended as a weakening of the identity relation in that equivalence and other constraints on identity are violated. The proposed approach also suggests a computable treatment of identity and copy checking

Infringing software property rights : ontological, methodological, and ethical questions

This paper contributes to the computer ethics debate on software ownership protection by examining the ontological, methodological, and ethical problems related to property right infringement that should come prior to any legal discussion. The ontological problem consists in determining precisely what it is for a computer program to be a copy of another one, a largely neglected problem in computer ethics. The methodological problem is defined as the difficulty of deciding whether a given software system is a copy of another system. And the ethical problem corresponds to establishing when a copy constitutes, or does not constitute, a property right infringement. The ontological problem is solved on the logical analysis of abstract machines, and the latter are argued to be the appropriate level of abstraction for software at which the methodological and the ethical problems can be successfully addressed

Do Daily Activities Impact Gas Tamponade - Retina Contact after Pars Plana Vitrectomy? A Computational Fluid Dynamics Study

Purpose:To calculate the retinal surface alternatively in contact with gas and aqueous because of fluid sloshing during daily activities such as ocular saccade, turning the head, standing up, and being a passenger of a braking car.Methods:Fluid dynamics of aqueous and gas tamponade was reproduced using computational methods using the OpenFOAM open-source library. The double-fluid dynamics was simulated by the volume of fluid method and setting the contact angle at the aqueous-gas-retina interface.Results:Sloshing increased the retinal surface in contact with aqueous by 13% to 16% regardless of fill rate and standing up determined the largest area of wet retina, followed by car braking, head rotation, and ocular saccade (P < 0.001). All activities except the ocular saccade determined a significant increase in the surface of retina in contact with the aqueous (P < 0.005). Car braking induced the highest shear stress (6.06 Pa); standing up determined the highest specific impulse and saccade the lowest.Conclusion:Daily activities instantaneously reduce the amount of retina consistently in contact with gas tamponade and increase shear stress giving aqueous a potential access to the subretinal space regardless of patients' compliance

The ergogenic effects of transcranial direct current stimulation on exercise performance

The physical limits of the human performance have been the object of study for a considerable time. Most of the research has focused on the locomotor muscles, lungs and heart. As a consequence, much of the contemporary literature has ignored the importance of the brain in the regulation of exercise performance. With the introduction and development of new non-invasive devices, the knowledge regarding the behaviour of the central nervous system during exercise has advanced. A first step has been provided from studies involving neuroimaging techniques where the role of specific brain areas have been identified during isolated muscle or whole-body exercise. Furthermore, a new interesting approach has been provided by studies involving non-invasive techniques to manipulate specific brain areas. These techniques most commonly involve the use of an electrical or magnetic field crossing the brain. In this regard, there has been emerging literature demonstrating the possibility to influence exercise outcomes in healthy people following stimulation of specific brain areas. Specifically, transcranial direct current stimulation (tDCS) has been recently used prior to exercise in order to improve exercise performance under a wide range of exercise types. In this review article, we discuss the evidence provided from experimental studies involving tDCS. The aim of this review is to provide a critical analysis of the experimental studies investigating the application of tDCS prior to exercise and how it influences brain function and performance. Finally, we provide a critical opinion of the usage of tDCS for exercise enhancement. This will consequently progress the current knowledge base regarding the effect of tDCS on exercise and provides both a methodological and theoretical foundation on which future research can be based

BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT.

The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants - other than HLA class I and II - associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R2 =0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P<0.00001 for BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P=1.15 × 10-8; and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT

The effect of vascular changes on the photoplethysmographic signal at different hand elevations

In order to further understand the contribution of venous and arterial effects to the photoplethysmographic (PPG) signal, recordings were made from twenty healthy volunteer subjects during an exercise in which the right hand was raised and lowered with reference to heart level. Red (R) and infrared (IR) PPG signals were obtained from the right index finger using a custom-made PPG processing system. Laser Doppler flowmetry (LDF) signals were also recorded from an adjacent fingertip. The signals were compared with simultaneous PPG signals obtained from the left index finger. On lowering the hand to 50 cm below heart level, both ac and dc PPG amplitudes from the finger decreased (e.g. 18.70% and 63.15% decrease in infrared dc and ac signals respectively). The decrease in dc amplitude most likely corresponded to increased venous volume, while the decrease in ac PPG amplitude was due to regulatory adjustments on the arterial side in response to venous distension. Conversely, ac and dc PPG amplitudes increased on raising the arm above heart level. Morphological changes in the ac PPG signal are thought to be due to vascular resistance changes, predominately venous, as the hand position is changed

Ischemic preconditioning of the muscle reduces the metaboreflex response of the knee extensors

Purpose: This study investigated the effect of ischemic preconditioning (IP) on metaboreflex activation following dynamic leg extension exercise in a group of healthy participants. Method: Seventeen healthy participants were recruited. IP and SHAM treatments (3 × 5 min cuff occlusion at 220 mmHg or 20 mmHg, respectively) were administered in a randomized order to the upper part of exercising leg’s thigh only. Muscle pain intensity (MP) and pain pressure threshold (PPT) were monitored while administrating IP and SHAM treatments. After 3 min of leg extension exercise at 70% of the maximal workload, a post-exercise muscle ischemia (PEMI) was performed to monitor the discharge group III/IV muscle afferents via metaboreflex activation. Hemodynamics were continuously recorded. MP was monitored during exercise and PEMI. Results: IP significantly reduced mean arterial pressure compared to SHAM during metaboreflex activation (mean ± SD, 109.52 ± 7.25 vs. 102.36 ± 7.89 mmHg) which was probably the consequence of a reduced end diastolic volume (mean ± SD, 113.09 ± 14.25 vs. 102.42 ± 9.38 ml). MP was significantly higher during the IP compared to SHAM treatment, while no significant differences in PPT were found. MP did not change during exercise, but it was significantly lower during the PEMI following IP (5.10 ± 1.29 vs. 4.00 ± 1.54). Conclusion: Our study demonstrated that IP reduces hemodynamic response during metaboreflex activation, while no effect on MP and PPT were found. The reduction in hemodynamic response was likely the consequence of a blunted venous return

Epigenetics, stem cells, and autophagy: Exploring a path involving miRNA

MiRNAs, a small family of non-coding RNA, are now emerging as regulators of stem cell pluripotency, differentiation, and autophagy, thus controlling stem cell behavior. Stem cells are undifferentiated elements capable to acquire specific phenotype under different kind of stimuli, being a main tool for regenerative medicine. Within this context, we have previously shown that stem cells isolated from Wharton jelly multipotent stem cells (WJ-MSCs) exhibit gender differences in the expression of the stemness related gene OCT4 and the epigenetic modulator gene DNA-Methyltransferase (DNMT1). Here, we further analyze this gender difference, evaluating adipogenic and osteogenic differentiation potential, autophagic process, and expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived from males and females. These miRNAs were selected since they are involved in OCT4 and DNMT1 gene expression, and in stem cell differentiation. Our results indicate a difference in the regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in male WJ-MSCs as compared to female cells. Moreover, no difference was detected in the expression of the two-differentiation regulating miRNA (miR-145 and miR-185). Taken together, our results highlight a different behavior of WJ-MSCs from males and females, disclosing the chance to better understand cellular processes as autophagy and stemness, usable for future clinical applications

The value of some Corsican sub-populations for genetic association studies

<p>Abstract</p> <p>Background</p> <p>Genetic isolates with a history of a small founder population, long-lasting isolation and population bottlenecks represent exceptional resources in the identification of disease genes. In these populations the disease allele reveals Linkage Disequilibrium (LD) with markers over significant genetic intervals, therefore facilitating disease locus identification. In a previous study we examined the LD extension on the Xq13 region in three Corsican sub-populations from the inner mountainous region of the island. On the basis of those previous results we have proposed a multistep procedure to carry out studies aimed at the identification of genes involved in complex diseases in Corsica. A prerequisite to carry out the proposed multi-step procedure was the presence of different degrees of LD on the island and a common genetic derivation of the different Corsican sub-populations. In order to evaluate the existence of these conditions in the present paper we extended the analysis to the Corsican coastal populations.</p> <p>Methods</p> <p>Samples were analyzed using seven dinucleotide microsatellite markers on chromosome Xq13-21: DXS983, DXS986, DXS8092, DXS8082, DXS1225, DXS8037 and DXS995 spanning approximately 4.0 cM (13.3 Mb). We have also investigated the distribution of the DXS1225-DXS8082 haplotype which has been recently proposed as a good marker of population genetic history due to its low recombination rate.</p> <p>Results</p> <p>the results obtained indicate a decrease of LD on the island from the central mountainous toward the coastal sub-populations. In addition the analysis of the DXS1225-DXS8082 haplotype revealed: 1) the presence of a particular haplotype with high frequency; 2) the derivation from a common genetic pool of the sub-populations examined in the present study.</p> <p>Conclusion</p> <p>These results indicate the Corsican sub-populations useful for the fine mapping of genes contributing to complex diseases.</p

Immune responses to oligomeric α-synuclein in Parkinson’s disease peripheral blood mononuclear cells

Parkinson's disease displays clinical heterogeneity, presenting with motor and non-motor symptoms. Heterogeneous phenotypes, named brain-first and body-first, may reflect distinct alpha-synuclein pathology starting either in the central nervous system or in the periphery. The immune system plays a prominent role in the central and peripheral pathology, with misfolded alpha-synuclein being placed at the intersection between neurodegeneration and inflammation. Here, we characterized the inflammatory profile and immune-phenotype of peripheral blood mononuclear cells (PBMCs) from Parkinson's disease patients upon stimulation with alpha-synuclein monomer or oligomer, and investigated relationships of immune parameters with clinical scores of motor and non-motor symptoms. Freshly isolated PBMCs from 21 Parkinson's disease patients and 18 healthy subjects were exposed in vitro to alpha-synuclein species. Cytokine/chemokine release was measured in the culture supernatant by Multiplex Elisa. The immune-phenotype was studied by FACS-flow cytometry. Correlation analysis was computed between immune parameters and parkinsonian motor and non-motor scales. We found that Parkinson's disease patients exhibited a dysregulated PBMC-cytokine profile, which remained unaltered after exposure to alpha-synuclein species and correlated with both motor and non-motor severity, with a strong correlation observed with olfactory impairment. Exposure of PBMCs from healthy controls to alpha-synuclein monomer/oligomer increased the cytokine/chemokine release up to patient's values. Moreover, the PBMCs immune phenotype differed between patients and controls and revealed a prominent association of the Mos profile with olfactory impairment, and of NK profile with constipation. Results suggest that a deranged PBMC-immune profile may reflect distinct clinical subtypes and would fit with the recent classification of Parkinson's disease into peripheral-first versus brain-first phenotype