The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease,Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.     

Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.     

Resolution proof transformation for compression and interpolation

Verification methods based on SAT, SMT, and theorem proving often rely on proofs of unsatisfiability as a powerful tool to extract information in order to reduce the overall effort. For example a proof may be traversed to identify a minimal reason that led to unsatisfiability, for computing abstractions, or for deriving Craig interpolants. In this paper we focus on two important aspects that concern efficient handling of proofs of unsatisfiability: compression and manipulation. First of all, since the proof size can be very large in general (exponential in the size of the input problem), it is indeed beneficial to adopt techniques to compress it for further processing. Secondly, proofs can be manipulated as a flexible preprocessing step in preparation for interpolant computation. Both these techniques are implemented in a framework that makes use of local rewriting rules to transform the proofs. We show that a careful use of the rules, combined with existing algorithms, can result in an effective simplification of the original proofs. We have evaluated several heuristics on a wide range of unsatisfiable problems deriving from SAT and SMT test cases.     

Role of anionic and nonionic surfactants on the control of particle size and latex colloidal stability in the seeded emulsion polymerization of butyl methacrylate

The evolution of the main colloidal parameters in the seeded starved‐feed semi‐continuous emulsion polymerization of butyl methacrylate (BMA) was investigated, with the main purpose of assessing the effectiveness of the semi‐empirical relationship S = K · S_S · ΔA/A_S as a tool to define the surfactant/monomer feed ratio (∝ K) best suited to achieve a target particle size. In particular, the effect of the type and amount of surfactant [i.e., anionic, sodium dodecyl sulfate (SDS), or nonionic, Brij 58P] added during the semi‐continuous stage was considered. Coagulum formation was never observed under the adopted experimental conditions. To detect the occurrence of secondary nucleation or particle aggregation, or both, the particle size and number of particles, the surface tension and the particle surface coverage ratio were correlated. The best results were obtained with SDS and 0.8 ≤ K ≤ 3. In fact, under the selected experimental conditions, only with SDS did the number of particles remain nearly constant throughout the polymerization at the value defined by the seed latex; the particle size distribution was highly monodisperse, and the final particle diameter closely matched the calculated one (～ 120 nm). The above semi‐empirical relationship based on the adjustable parameter K was validated by running test polymerizations aimed at lattices with well‐defined particle size. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3083–3094, 2006     

With a little help from my friends

In this paper, we propose a content-based method the for semi-automatic organization of photo albums based on the analysis of how different users organize their own pictures. The goal is to help the user in dividing his pictures into groups characterized by a similar semantic content. The method is semi-automatic: the user starts to assign labels to the pictures and unlabeled pictures are tagged with proposed labels. The user can accept the recommendation or made a correction. To formulate the suggestions is exploited the knowledge encoded in how other users have partitioned their images. The method is conceptually articulated in two parts. First, we use a suitable feature representation of the images to model the different classes that the users have collected, second, we look for correspondences between the criteria used by the different users. Boosting is used to integrate the information provided by the analysis of multiple users. A quantitative evaluation of the proposed approach is obtained by simulating the amount of user interaction needed to annotate the albums of a set of members of the flickr^® photo-sharing community.     

Upcycling of polypropylene with various concentrations of peroxydicarbonate and dilauroyl peroxide and two processing steps

The influence of two peroxides (peroxydicarbonate/dilauroyl peroxide) with various concentrations (10–200 mmol/kg PP) and their effective opportunity to introduce long chain branched (LCB) were investigated. The dependence of a single and double extrusion step and the changes of the properties were studied. Experiments were carried out in a single screw extruder at 180°C for the first extrusion step (modification) and at 240°C for the second extrusion step (processing simulation). Melt flow rate and dynamic rheological properties were studied at a measuring temperature of 230°C. For the definitive determination of long chain branched polypropylene (LCB-PP) served the extensional rheology measurements. The mechanical properties were examined via tensile test and impact tensile test. Summarized, LCB (melt strength) could be observed via extensional rheology for all modified specimens and the mechanical properties were maintained or even improved for the modified samples. Particularly, samples containing dilauroyl peroxide display excellent mechanical properties in this study.     

When simulated environments make the difference: the effectiveness of different types of training of car service procedures

An empirical analysis was performed to compare the effectiveness of different approaches to training a set of procedural skills to a sample of novice trainees. Sixty-five participants were randomly assigned to one of the following three training groups: (1) learning-by-doing in a 3D desktop virtual environment, (2) learning-by-observing a video (show-and-tell) explanation of the procedures, and (3) trial-and-error. In each group, participants were trained on two car service procedures. Participants were recalled to perform a procedure either 2 or 4 weeks after the training. The results showed that: (1) participants trained through the virtual approach of learning-by-doing performed both procedures significantly better (i.e. p < .05 in terms of errors and time) than people of non-virtual groups, (2) the virtual training group, after a period of non-use, were more effective than non-virtual training (i.e. p < .05) in their ability to recover their skills, (3) after a (simulated) long period from the training—i.e. up to 12 weeks—people who experienced 3D environments consistently performed better than people who received other kinds of training. The results also suggested that independently from the training group, trainees’ visuospatial abilities were a predictor of performance, at least for the complex service procedure, adj R ² = .460, and that post-training performances of people trained through virtual learning-by-doing are not affected by learning styles. Finally, a strong relationship (p < .001, R ² = .441) was identified between usability and trust in the use of the virtual training tool—i.e. the more the system was perceived as usable, the more it was perceived as trustable to acquire the competences.     

A Review of Element-Based Galerkin Methods for Numerical Weather Prediction: Finite Elements,Spectral Elements,and Discontinuous Galerkin

Numerical weather prediction (NWP) is in a period of transition. As resolutions increase, global models are moving towards fully nonhydrostatic dynamical cores, with the local and global models using the same governing equations; therefore we have reached a point where it will be necessary to use a single model for both applications. The new dynamical cores at the heart of these unified models are designed to scale efficiently on clusters with hundreds of thousands or even millions of CPU cores and GPUs. Operational and research NWP codes currently use a wide range of numerical methods: finite differences, spectral transform, finite volumes and, increasingly, finite/spectral elements and discontinuous Galerkin, which constitute element-based Galerkin (EBG) methods. Due to their important role in this transition, will EBGs be the dominant power behind NWP in the next 10 years, or will they just be one of many methods to choose from? One decade after the review of numerical methods for atmospheric modeling by Steppeler et al. (Meteorol Atmos Phys 82:287–301, 2003), this review discusses EBG methods as a viable numerical approach for the next-generation NWP models. One well-known weakness of EBG methods is the generation of unphysical oscillations in advection-dominated flows; special attention is hence devoted to dissipation-based stabilization methods. Since EBGs are geometrically flexible and allow both conforming and non-conforming meshes, as well as grid adaptivity, this review is concluded with a short overview of how mesh generation and dynamic mesh refinement are becoming as important for atmospheric modeling as they have been for engineering applications for many years.     

On vector averaging over the unit hypersphere

Sample averaging is a commonly used way to smooth out irregularities of data and to get rid of random fluctuations in measurements analysis. In adaptive signal processing, where an adaptive system learns its own parameters in order to perform a predefined task, the learnt parameters-pattern may depend on the initial learning state and on the fluctuations of the statistical features of the input signals to the system. In adaptive system learning, averaging may be employed as a method to merge several learnt parameters-patterns in order to get a better representative pattern. Even in the case of scalar parameters, the concept of averaging is not uniquely defined as scalar parameters spaces may exhibit a rich structure to be dealt with. The case of multiple parameter patterns where single parameters are mutually constrained to each other may exhibit an even richer structure. In the present paper, we deal with the case of parameters-patterns belonging to the unit hypersphere and develop an averaging technique based on the differential geometrical structure of such a curved space. Numerical experiments illustrate the behavior of the developed averaging algorithm.     

Asymptotic switched composite adaptive control with application to robotic interaction tasks

This article proposes a new switched adaptive control design for uncertain switched systems with composite (time-driven and state-dependent) switching and shows its applicability in switched impedance control. A composite switched adaptive control design, consisting of the direct switched adaptive control and the indirect switched adaptive control counterpart, is developed to improve the control performance. Specifically, a new stability condition for composite switching is proposed by making use of differential matrix equations and Sylvester matrix equations, which are a generalization of Lyapunov matrix equations. The design results in a time-varying multiple Lyapunov function that is decreasing at the switching instants. From the theoretical point of view, the relevance of this work is the construction of the adaptive laws that guarantee asymptotic tracking error and asymptotic estimation for the direct and indirect switched adaptive control loops, respectively. From the practical point of view, the relevance of this work is validated in a new switched impedance control for the robot interaction with uncertain and discontinuous environments.