Parkinson's Disease Gene Screening in Familial Cases from Central and South America.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Geometric Analysis of Signals for Inference of Multiple Faults in Induction Motors.

Multiple fault identification in induction motors is essential in industrial processes due to the high costs that unexpected failures can cause. In real cases, the motor could present multiple faults, influencing systems that classify isolated failures. This paper presents a novel methodology for detecting multiple motor faults based on quaternion signal analysis (QSA). This method couples the measured signals from the motor current and the triaxial accelerometer mounted on the induction motor chassis to the quaternion coefficients. The QSA calculates the quaternion rotation and applies statistics such as mean, variance, kurtosis, skewness, standard deviation, root mean square, and shape factor to obtain their features. After that, four classification algorithms are applied to predict motor states. The results of the QSA method are validated for ten classes: four single classes (healthy condition, unbalanced pulley, bearing fault, and half-broken bar) and six combined classes. The proposed method achieves high accuracy and performance compared to similar works in the state of the art.

Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies.

Pre-mRNA splicing factors play a fundamental role in regulating transcript diversity both temporally and spatially. Genetic defects in several spliceosome components have been linked to a set of non-overlapping spliceosomopathy phenotypes in humans, among which skeletal developmental defects and non-syndromic retinitis pigmentosa (RP) are frequent findings. Here we report that defects in spliceosome-associated protein CWC27 are associated with a spectrum of disease phenotypes ranging from isolated RP to severe syndromic forms. By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurological defects. Remarkably, variable expressivity of the human phenotype can be recapitulated in Cwc27 mutant mouse models, with significant embryonic lethality and severe phenotypes in the complete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degeneration phenotype. Our study describes a retinal dystrophy-related phenotype spectrum as well as its genetic etiology and highlights the complexity of the spliceosomal gene network.

Intestinal Microbiota Analyses of Litopenaeus vannamei During a Case of Atypical Massive Mortality in Northwestern Mexico.

This study investigated the intestinal microbial community structure of Litopenaeus vannamei at six different stages during shrimp farming. Our goal was to elucidate the bacterial profile and the changes in the relative abundance of taxa during an atypical massive mortality event in Sonora, Mexico. High-throughput sequencing of the 16S rRNA gene and denaturing gradient gel electrophoresis showed that Vibrionaceae was persistent with high relative abundances in the intestine from cultivated shrimp during all the studied stages. The massive mortality observed at day 63 could be related to an overabundance of different Operational Taxonomic Units (OTUs) of Vibrio, Shewanella and Clostridium. Principal coordinate analysis (PCoA) showed variations in microbial structure at different culture times. These findings suggest that OTUs of different taxa contributed to the community switch from healthy to diseased individuals, questioning the hypothesis that single bacterial species is the cause of disease outbreaks. This study provided data to improve the understanding of disease outbreaks during shrimp farming.

Amino acid residues in HIV-2 reverse transcriptase that restrict the development of nucleoside analogue resistance through the excision pathway.

Nucleoside reverse transcriptase (RT) inhibitors (NRTIs) are the backbone of current antiretroviral treatments. However, the emergence of viral resistance against NRTIs is a major threat to their therapeutic effectiveness. In HIV-1, NRTI resistance-associated mutations either reduce RT-mediated incorporation of NRTI triphosphates (discrimination mechanism) or confer an ATP-mediated nucleotide excision activity that removes the inhibitor from the 3' terminus of DNA primers, enabling further primer elongation (excision mechanism). In HIV-2, resistance to zidovudine (3'-azido-3'-deoxythymidine (AZT)) and other NRTIs is conferred by mutations affecting nucleotide discrimination. Mutations of the excision pathway such as M41L, D67N, K70R, or S215Y (known as thymidine-analogue resistance mutations (TAMs)) are rare in the virus from HIV-2-infected individuals. Here, we demonstrate that mutant M41L/D67N/K70R/S215Y HIV-2 RT lacks ATP-dependent excision activity, and recombinant virus containing this RT remains susceptible to AZT inhibition. Mutant HIV-2 RTs were tested for their ability to unblock and extend DNA primers terminated with AZT and other NRTIs, when complexed with RNA or DNA templates. Our results show that Met73 and, to a lesser extent, Ile75 suppress excision activity when TAMs are present in the HIV-2 RT. Interestingly, recombinant HIV-2 carrying a mutant D67N/K70R/M73K RT showed 10-fold decreased AZT susceptibility and increased rescue efficiency on AZT- or tenofovir-terminated primers, as compared with the double-mutant D67N/K70R. Molecular dynamics simulations reveal that Met73influences ß3-ß4 hairpin loop conformation, whereas its substitution affects hydrogen bond interactions at position 70, required for NRTI excision. Our work highlights critical HIV-2 RT residues impeding the development of excision-mediated NRTI resistance.

Multifocus HDR VIS/NIR hyperspectral imaging and its application to works of art.

This paper presents a complete framework for capturing and processing hyperspectral reflectance images of artworks in situ, using a hyperspectral line scanner. These capturing systems are commonly used in laboratory conditions synchronized with scanning stages specifically designed for planar surfaces. However, when the intended application domain does not allow for image capture in these controlled conditions, achieving useful spectral reflectance image data can be a very challenging task (due to uncontrolled illumination, high-dynamic range (HDR) conditions in the scene, and the influence of chromatic aberration on the image quality, among other factors). We show, for the first time, all the necessary steps in the image capturing and post-processing in order to obtain high-quality HDR-based reflectance in the visible and near infrared, directly from the data captured by using a hyperspectral line scanner coupled to a rotating tripod. Our results show that the proposed method outperforms the normal capturing process in terms of dynamic range, color and spectral accuracy. To demonstrate the potential interest of this processing strategy for on-site analysis of artworks, we applied it to the study of a vintage copy of the famous painting "Transfiguration" by Raphael, as well as a facsimile of "The Golden Haggadah" from the British Library of London. The second piece has been studied for the identification of highly reflective gold-foil covered areas.

Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents.

Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target.

The Fruit Fly Lure CeraTrap: An Effective Tool for the Study of the Arboreal Ant Fauna (Hymenoptera: Formicidae).

Despite preliminary reports of ants trapped in food-baited fruit fly traps, little is known regarding the identity of the myrmecofauna that can be sampled using this technique. This study aimed to examine the inventory completeness, activity and species occurrence of canopy ant assemblages collected in baited traps used for monitoring fruit flies in different fruit orchards in central Veracruz, Mexico. The trap models used in the sampling were Multilure, McPhail glass, and 500 ml blue polyethylene bottles. Three commercial fruit fly food attractants (CeraTrap, Captor + Borax, and BioLure) and two grape juice products (Jumex grape juice and Tang) were used as baits for sampling. In total 3,626 ant workers belonging to 54 species, 19 genera, 10 tribes, and 5 subfamilies were collected. Among the five food attractants used in this study, CeraTrap recorded a markedly higher inventory completeness, ant activity and species occurrence per trap. This study reports for the first time the use of CeraTrap, as a promising and effective food attractant for collecting the foraging ants in the canopy of agroecosystems, which may be applicable to other habitats such as natural forests, mangroves, or agricultural settings such as coffee plantations.

A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples.

Unbiased next-generation sequencing (NGS) approaches enable comprehensive pathogen detection in the clinical microbiology laboratory and have numerous applications for public health surveillance, outbreak investigation, and the diagnosis of infectious diseases. However, practical deployment of the technology is hindered by the bioinformatics challenge of analyzing results accurately and in a clinically relevant timeframe. Here we describe SURPI ("sequence-based ultrarapid pathogen identification"), a computational pipeline for pathogen identification from complex metagenomic NGS data generated from clinical samples, and demonstrate use of the pipeline in the analysis of 237 clinical samples comprising more than 1.1 billion sequences. Deployable on both cloud-based and standalone servers, SURPI leverages two state-of-the-art aligners for accelerated analyses, SNAP and RAPSearch, which are as accurate as existing bioinformatics tools but orders of magnitude faster in performance. In fast mode, SURPI detects viruses and bacteria by scanning data sets of 7-500 million reads in 11 min to 5 h, while in comprehensive mode, all known microorganisms are identified, followed by de novo assembly and protein homology searches for divergent viruses in 50 min to 16 h. SURPI has also directly contributed to real-time microbial diagnosis in acutely ill patients, underscoring its potential key role in the development of unbiased NGS-based clinical assays in infectious diseases that demand rapid turnaround times.

Comparison of Prokaryotic Diversity in Cold, Oligotrophic Remote Lakes of Chilean Patagonia.

The prokaryotic abundance and diversity in three cold, oligotrophic Patagonian lakes (Témpanos, Las Torres and Mercedes) in the northern region Aysén (Chile) were compared in winter and summer using 16S rRNA fluorescence in situ hybridization and PCR-denaturing gradient gel electrophoresis technique. Prokaryotic abundances, numerically dominated by Bacteria, were quite similar in the three lakes, but higher in sediments than in waters, and they were also higher in summer than in winter. The relative contribution of Archaea was greater in waters than in sediments, and in winter rather than in summer. Despite the phylogenetic analysis indicated that most sequences were affiliated to a few taxonomic groups, mainly referred to Proteobacteria (consisting of Beta-, Alpha- and Gammaproteobacteria) and Euryarchaeota (mainly related to uncultured methanogens), their relative abundances differed in each sample, resulting in different bacterial and archaeal assemblages. In winter, the abundance of the dominant bacterial phylotypes were mainly regulated by the increasing levels of total organic carbon in waters. Archaeal abundance and richness appeared mostly influenced by pH in winter and total nitrogen content in summer. The prokaryotic community composition at Témpanos lake, located most northerly and closer to a glacier, greatly differed in respect to the other two lakes. In this lake was detected the highest bacterial diversity, being Betaproteobacteria the most abundant group, whereas Alphaproteobacteria were distinctive of Mercedes. Archaeal community associated with sediments was mainly represent by members related to the order of Methanosarcinales at Mercedes and Las Torres lakes, and by Crenarchaeota at Témpanos lake. Our results indicate that the proximity to the glacier and the seasonality shape the composition of the prokaryotic communities in these remote lakes. These results may be used as baseline information to follow the microbial community responses to potential global changes and to anthropogenic impacts.

Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis.

HIV-1 reverse transcriptase (RT) connection subdomain mutations at positions 348, 369 and 376 have been associated with resistance to non-nucleoside RT inhibitors (NNRTIs). N348I may interfere with the initiation of (+)-strand DNA synthesis by reducing polypurine tract (PPT) removal in the presence of nevirapine. The effect of NNRTIs on the RNase H-mediated cleavage of PPT-containing template-primers has been studied with wild-type HIV-1 RT and mutants N348I, T369I, T369V, T376S and N348I/T369I. In the presence of NNRTIs, all RTs were able to stimulate PPT cleavage after primer elongation. The enhancing effects of nevirapine and efavirenz were reduced in RTs carrying mutation N348I, and specially N348I/T369I. However, those mutations had no effect on rilpivirine-mediated cleavage. Prior to elongation, the PPT remains resilient to cleavage, although efavirenz and rilpivirine facilitate RNase H-mediated trimming of its 3'-end. The integrity of the 3'-end is essential for the initiation of (+)-strand DNA synthesis. In the presence of dNTPs, rilpivirine was the most effective inhibitor of (+)-strand DNA synthesis blocking nucleotide incorporation and preventing usage of available PPT primers. The N348I/T369I RT showed reduced ability to generate short RNA products revealing a cleavage window defect. Its lower RNase H activity could be attributed to enhanced rigidity compared to the wild-type enzyme.

DNA microarray for detection of gastrointestinal viruses.

Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 10(3) virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant virus. The microarray described in this work should help in understanding the etiology of gastroenteritis in humans and animals.

Restriction of HIV-1 replication in primary macrophages by IL-12 and IL-18 through the upregulation of SAMHD1.

Monocyte-derived macrophages (MDM) can polarize into different subsets depending on the environment and the activation signal to which they are submitted. Differentiation into macrophages allows HIV-1 strains to infect cells of the monocytic lineage. In this study, we show that culture of monocytes with a combination of IL-12 and IL-18 led to macrophage differentiation that was resistant to HIV-1 infection. In contrast, M-CSF-derived MDM were readily infected by HIV-1. When monocytes were differentiated in the presence of M-CSF and then further treated with IL-12/IL-18, cells became resistant to infection. The restriction on HIV-1 replication was not dependent on virus entry or coreceptor expression, as vesicular stomatitis virus-pseudotyped HIV-1 replication was also blocked by IL-12/IL-18. The HIV-1 restriction factor sterile α motif and HD domain-containing protein-1 (SAMHD1) was significantly overexpressed in IL-12/IL-18 MDM compared with M-CSF MDM, and degradation of SAMHD1 by RNA interference or viral-like particles carrying the lentiviral protein Vpx restored HIV-1 infectivity of IL-12/IL-18 MDM. SAMHD1 overexpression induced by IL-12/IL-18 was not dependent on IFN-γ. Thus, we conclude that IL-12 and IL-18 may contribute to the response against HIV-1 infection through the induction of restriction factors such as SAMHD1.

Adaptive exposure estimation for high dynamic range imaging applied to natural scenes and daylight skies.

Digital imaging of natural scenes and optical phenomena present on them (such as shadows, twilights, and crepuscular rays) can be a very challenging task because of the range spanned by the radiances impinging on the capture system. We propose a novel method for estimating the set of exposure times (bracketing set) needed to capture the full dynamic range of a scene with high dynamic range (HDR) content. The proposed method is adaptive to scene content and to any camera response and configuration, and it works on-line since the exposure times are estimated as the capturing process is ongoing. Besides, it requires no a priori information about scene content or radiance values. The resulting bracketing sets are minimal in the default method settings, but the user can set a tolerance for the maximum percentage of pixel population that is underexposed or saturated, which allows for a higher number of shots if a better signal-to-noise ratio (SNR) in the HDR scene is desired. This method is based on the use of the camera response function that is needed for building the HDR radiance map by stitching together several differently exposed low dynamic range images of the scene. The use of HDR imaging techniques converts our digital camera into a tool for measuring the relative radiance outgoing from each point of the scene, and for each color channel. This is important for accurate characterization of optical phenomena present in the atmosphere while not suffering any loss of information due to its HDR. We have compared our method with the most similar one developed so far [IEEE Trans. Image Process.17, 1864 (2008)]. Results of the experiments carried out for 30 natural scenes show that our proposed method equals or outperforms the previously developed best approach, with less shots and shorter exposure times, thereby asserting the advantage of being adaptive to scene content for exposure time estimation. As we can also tune the balance between capturing time and the SNR in our method, we have compared its SNR performance against that of Barakat's method as well as against a ground-truth HDR image of maximum SNR. Results confirm the success of the proposed method in exploiting its tunability to achieve the desired balance of total Δt and SNR.

Combining transverse field detectors and color filter arrays to improve multispectral imaging systems.

This work focuses on the improvement of a multispectral imaging sensor based on transverse field detectors (TFDs). We aimed to achieve a higher color and spectral accuracy in the estimation of spectral reflectances from sensor responses. Such an improvement was done by combining these recently developed silicon-based sensors with color filter arrays (CFAs). Consequently, we sacrificed the filter-less full spatial resolution property of TFDs to narrow down the spectrally broad sensitivities of these sensors. We designed and performed several experiments to test the influence of different design features on the estimation quality (type of sensor, tunability, interleaved polarization, use of CFAs, type of CFAs, number of shots), some of which are exclusive to TFDs. We compared systems that use a TFD with systems that use normal monochrome sensors, both combined with multispectral CFAs as well as common RGB filters present in commercial digital color cameras. Results showed that a system that combines TFDs and CFAs performs better than systems with the same type of multispectral CFA and other sensors, or even the same TFDs combined with different kinds of filters used in common imaging systems. We propose CFA+TFD-based systems with one or two shots, depending on the possibility of using longer capturing times or not. Improved TFD systems thus emerge as an interesting possibility for multispectral acquisition, which overcomes the limited accuracy found in previous studies.

Temperature measurement in PV facilities on a per-panel scale.

This paper presents the design, construction and testing of an instrumentation system for temperature measurement in PV facilities on a per-panel scale (i.e., one or more temperature measurements per panel). Its main characteristics are: precision, ease of connection, immunity to noise, remote operation, easy scaling; and all of this at a very low cost. The paper discusses the advantages of temperature measurements in PV facilities on a per-panel scale. The paper presents the whole development to implementation of a real system that is being tested in an actual facility. This has enabled the authors to provide the readers with practical guidelines, which would be very difficult to achieve if the developments were implemented by just simulation or in a theoretical way. The instrumentation system is fully developed, from the temperature sensing to its presentation in a virtual instrument. The developed instrumentation system is able to work both locally and remotely connected to both wired and wireless network.

[The PROPRESE trial: results of a new health care organizational model in primary care for patients with chronic coronary heart disease based on a multifactorial intervention]. / El estudio PROPRESE: resultados de un nuevo modelo organizativo en atención primaria para pacientes con cardiopatía isquémica crónica basado en una intervención multifactorial.

OBJECTIVE: Comparison of the results from the EUROASPIRE I to the EUROASPIRE III, in patients with coronary heart disease, shows that the prevalence of uncontrolled risk factors remains high. The aim of the study was to evaluate the effectiveness of a new multifactorial intervention in order to improve health care for chronic coronary heart disease patients in primary care. METHODS: In this randomized clinical trial with a 1-year follow-up period, we recruited patients with a diagnosis of coronary heart disease (145 for the intervention group and 1461 for the control group). An organizational intervention on the patient-professional relationship (centered on the Chronic Care Model, the Stanford Expert Patient Programme and the Kaiser Permanente model) and formative strategy for professionals were carried out. The main outcomes were smoking control, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). A multivariate analysis was performed. RESULTS: The characteristics of patients were: age (68.4±11.8 years), male (71.6%), having diabetes mellitus (51.3%), dyslipidemia (68.5%), arterial hypertension (76.7%), non-smokers (76.1%); LDL-C < 100mg/dL (46.9%); SBP < 140mmHg (64.5%); DBP < 90 (91.2%). The multivariable analysis showed the risk of good control for intervention group to be: smoking, adjusted relative risk (aRR): 15.70 (95% confidence interval [95%CI], 4.2-58.7); P < .001; LDL-C, aRR: 2.98 (95%CI, 1.48-6.02); P < .002; SPB, aRR: 1.97 (95%CI, 1.21-3.23); P < .007, and DBP: aRR: 1.51 (95%CI, 0.65-3.50); P < .342. CONCLUSIONS: An intervention based on models for chronic patients focused in primary care and involving patients in medical decision making improves cardiovascular risk factors control (smoking, LDL-C and SBP). Chronic care strategies may be an efficacy tool to help clinicians to involve the patients with a diagnosis of CHD to reach better outcomes.

Degradation of Mechanical Properties of Flax/PLA Composites in Hygrothermal Aging Conditions.

The main advantage of green composites is their biodegradability, but this biodegradability can also be considered a drawback if the degradation appears during the service life of the component. Therefore, the study of the mechanical behavior of green composites after hygrothermal aging tests is necessary to analyze their degradation process. This study aims to comprehensively analyze the hygrothermal aging behavior and aging mechanism of flax-fiber-reinforced polylactic acid (PLA) biocomposites. The fully biodegradable composites are manufactured by compression molding. In addition, the influence of atmospheric-pressure plasma treatment on the mechanical properties of the biocomposite is studied. Specimens are exposed to water vapor and 40 °C environmental conditions in a stove for up to 42 days. Several specimens of each type are taken out at regular intervals and tested to examine the water absorption, mechanical properties, and thermal characterization. The results show that the stiffness was significantly reduced after 24 h due to matrix degradation, while the strength was reduced only after three weeks.

Impact of geometric and hemodynamic changes on a mechanobiological model of atherosclerosis.

BACKGROUND AND OBJECTIVE: In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. METHODS: For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material. RESULTS: Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. CONCLUSIONS: The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.

Towards a GDPR-compliant cloud architecture with data privacy controlled through sticky policies.

Data privacy is one of the biggest challenges facing system architects at the system design stage. Especially when certain laws, such as the General Data Protection Regulation (GDPR), have to be complied with by cloud environments. In this article, we want to help cloud providers comply with the GDPR by proposing a GDPR-compliant cloud architecture. To do this, we use model-driven engineering techniques to design cloud architecture and analyze cloud interactions. In particular, we develop a complete framework, called MDCT, which includes a Unified Modeling Language profile that allows us to define specific cloud scenarios and profile validation to ensure that certain required properties are met. The validation process is implemented through the Object Constraint Language (OCL) rules, which allow us to describe the constraints in these models. To comply with many GDPR articles, the proposed cloud architecture considers data privacy and data tracking, enabling safe and secure data management and tracking in the context of the cloud. For this purpose, sticky policies associated with the data are incorporated to define permission for third parties to access the data and track instances of data access. As a result, a cloud architecture designed with MDCT contains a set of OCL rules to validate it as a GDPR-compliant cloud architecture. Our tool models key GDPR points such as user consent/withdrawal, the purpose of access, and data transparency and auditing, and considers data privacy and data tracking with the help of sticky policies.