Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.     

Embryonic Trophectoderm Secretomics Reveals Chemotactic Migration and Intercellular Communication of Endometrial and Circulating MSCs in Embryonic Implantation

Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial–mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures eight endometrial MSC (eMSC) and five peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: (i) their epithelial–mesenchymal phenotype; (ii) as a result of the uptake of eMSC- or pbMSC-EV previously stimulated or not with embryonic signals (IFN-τ); (iii) because of the stimulation with the endometrial cytokines present in the uterine fluid in the peri-implantation period.     

Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10⁻⁵, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10⁻⁵, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10⁻⁵, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10⁻⁵, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10⁻⁵, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10⁻², p = 5.1 × 10⁻³, p = 1.2 × 10⁻², respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.     

Optimal linear filter design for systems with correlation in the measurement matrices and noises: recursive algorithm and applications

This paper addresses the optimal least-squares linear estimation problem for a class of discrete-time stochastic systems with random parameter matrices and correlated additive noises. The system presents the following main features: (1) one-step correlated and cross-correlated random parameter matrices in the observation equation are assumed; (2) the process and measurement noises are one-step autocorrelated and two-step cross-correlated. Using an innovation approach and these correlation assumptions, a recursive algorithm with a simple computational procedure is derived for the optimal linear filter. As a significant application of the proposed results, the optimal recursive filtering problem in multi-sensor systems with missing measurements and random delays can be addressed. Numerical simulation examples are used to demonstrate the feasibility of the proposed filtering algorithm, which is also compared with other filters that have been proposed.     

A hybrid dynamic motion prediction method for multibody digital human models based on a motion database and motion knowledge

In this paper, we present a novel method to predict human motion, seeking to combine the advantages of both data-based and knowledge-based motion prediction methods. Our method relies on a database of captured motions for reference and introduces knowledge in the prediction in the form of a motion control law, which is followed while resembling the actually performed reference motion. The prediction is carried out by solving an optimization problem in which the following conditions are imposed to the motion: must fulfill the goals of the task; resemble the reference motion selected from the database; follow a knowledge-based dynamic motion control law; and ensure the dynamic equilibrium of the human model, considering its interactions with the environment. In this work, we apply the proposed method to a database of clutch pedal depression motions, and we present the results for three predictions. The method is validated by comparing the results of the prediction to motions actually performed in similar conditions. The predicted motions closely resemble the motions in the validation database and no significant differences have been noted either in the motion’s kinematics or in the motion’s dynamics.     

Beast methodology: An agile testing methodology for multi-agent systems based on behaviour driven development

This paper presents a testing methodology to apply Behaviour Driven Development (BDD) techniques while developing Multi-Agent Systems (MASs), termed BEhavioural Agent Simple Testing (BEAST) Methodology. This methodology is supported by the open source framework (BEAST Tool) which automatically generates test cases skeletons from BDD scenarios specifications. The developed framework allows the testing of MASs based on JADE or JADEX platforms. In addition, this framework offers a set of configurable Mock Agents with the aim of being able to execute tests while the MAS is under development. The BEAST Methodology presents transparent traceability from user requirements to test cases. Thus, the stakeholders can be aware of the project status. The methodology and the associated tool have been validated in the development of a MAS for fault diagnosis in FTTH (Fiber To The Home) networks. The results have been measured in quantifiable way obtaining a reduction of the tests implementation time.     

Morphology and thermomechanical properties of recycled PET–organoclay nanocomposites

Recycled PET/organoclay nanocomposites were prepared by melt intercalation process with several amounts (1, 3, and 5 wt %) of clay modified with quaternary ammonium salt (DELLITE 67G) dispersed in a recycled poly(ethylene terephthalate) (rPET) matrix. The resultant mechanical properties (modulus and yield strength) of the nanocomposites were found to be different from those of rPET. Wide angle X‐ray scattering (WAXS) and Transmission Electron Microscopy (TEM) measurements have shown that although complete exfoliation was not achieved, delaminated clay platelets could be observed. Thermal analysis did not show significant changes in the thermal properties from those of recycled PET. Mechanical testing showed that nanocomposite properties were superior to the recycled PET in terms of strength and elasticity modulus. This improvement was attributed to nanoscale effects and strong interaction between the rPET matrix and the clay interface, as revealed by WAXS and TEM. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1839–1844, 2007     

Protection of stainless steel by polyaniline films against corrosion in aqueous environments

Polyaniline (PANI) thin films were electrochemically deposited by cyclic voltammetry on stainless steel electrode previously covered by a thin film of polyvinyl acetate (PVAc). The corrosion resistance of PANI covered stainless steel substrates was estimated by using potentiodynamic polarization curves and its linear polarization resistance (LPR) was measured in 0.5 M H₂SO₄, 0.5 M NaCl and 0.5 M NaOH aqueous solutions at room temperature. The results indicate that the PANI-PVAc films did improve the corrosion resistance of the stainless steel in NaOH, behaving even worst, in the case of PANI film, than the uncoated substrate. In H₂SO₄ both PANI and PANI-PVAc coatings gave good protection for the stainless steel electrode, with a slightly better performance of PANI-PVAc than PANI. In NaCl solution both PANI and PANI-PVAc films provided a good protection against corrosion. The better performance of PANI-PVAc coatings for corrosion protection in basic media may be due to its major chemical stability compared to simple PANI films, which lose their conductivity in high pH solutions. The E _corr (free corrosion potential) value of the coated substrate was in the passive region of the uncoated substrate in acidic environment but in the active region in neutral or basic environment.     

Designing biomass supply chains within planetary boundaries

The design of sustainable supply chains, which recently emerged as an active area of research in process systems engineering, is vital to ensure sustainable development. Despite past and ongoing efforts, the available methods often overlook impacts beyond climate change or incorporate them via standard life cycle assessment metrics that are hard to interpret from an absolute sustainability viewpoint. We here address the design of biomass supply chains considering critical ecological limits of the Earth—planetary boundaries—which should never be surpassed by anthropogenic activities. Our method relies on a mixed-integer linear program that incorporates a planetary boundaries-based damage model to quantify absolute sustainability precisely. We apply this approach to the sugarcane-to-ethanol industry in Argentina, identifying the optimal combination of technologies and network layout that minimize the impact on these ecological boundaries. Our framework can find applications in a wide range of supply chain problems related to chemicals and fuels production, energy systems, and agriculture planning.