Parkinson's disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress.

Advanced age represents one of the major risk factors for Parkinson's Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson's Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson's Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson's Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson's Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson's Disease patients, and healthy siblings of Parkinson's Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson's Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson's Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson's Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson's Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson's Disease.

Inflammaging is a low-grade inflammatory state generated by the aging process that can contribute to frailty and age-related diseases in the elderly. However, it can have distinct effects in the elderly living in endemic areas for infectious diseases. An increased inflammatory response may confer protection against infectious agents in these areas, although this advantage can cause accelerating epigenetic aging. In this study, we evaluated the inflammatory profile and the epigenetic age of infected and noninfected individuals from an endemic area in Brazil. The profile of cytokines, chemokines and growth factors analyzed in the sera of the two groups of individuals showed similarities, although infected individuals had a higher concentration of these mediators. A significant increase in IL-1ra, CXCL8, CCL2, CCL3 and CCL4 production was associated with leprosy infection. Notably, elderly individuals displayed distinct immune responses associated with their infection status when compared to adults suggesting an adaptive remodelling of their immune responses. Epigenetic analysis also showed that there was no difference in epigenetic age between the two groups of individuals. However, individuals from the endemic area had a significant accelerated aging when compared to individuals from São Paulo, a non-endemic area in Brazil. Moreover, the latter cohort was also epigenetically aged in relation to an Italian cohort. Our data shows that living in endemic areas for chronic infectious diseases results in remodelling of inflammaging and acceleration of epigenetic aging in individuals regardless of their infectious status. It also highlights that geographical, genetic and environmental factors influence aging and immunosenescence in their pace and profile.

Usually, clinicians assess the correct hemodynamic behavior and fetal wellbeing during the gestational age thanks to their professional expertise, with the support of some indices defined for Doppler fetal waveforms. Although this approach has demonstrated to be satisfactory in the most of the cases, it can be largely improved with the aid of more advanced techniques, i.e. numerical analysis and simulation. Another key aspect limiting the analysis is that clinicians rely on a limited number of Doppler waveforms observed during the clinical examination. Moreover, the use of simple velocimetric indicators for deriving possible malfunctions of the fetal cardiovascular system can be misleading, being the fetal assessment based on a mere statistical analysis (comparison with physiological ranges), without any deep physiopathological interpretations of the observed hemodynamic changes. The use of a lumped mathematical model, properly describing the entire fetal cardiovascular system, would be absolutely helpful in this context: by targeting physiological model parameters on the clinical reliefs, we could gain deep insights of the full system. The calibration of model parameters may also help in formulating patient-specific early diagnosis of fetal pathologies. In the present work, we develop a robust parameter estimation algorithm based on two different optimization methods using synthetic data. In particular, we deal with the inverse problem of recognizing the most significant parameters of a lumped fetal circulation model by using time tracings of fetal blood flows and pressures obtained by the model. This represents a first methodological work for the assessment of the accuracy in the identification of model parameters of an algorithm based on closed-loop mathematical model of fetal circulation and opens the way to the application of the algorithm to clinical data.

Editorial

Questo documento riassume l'attività svolta nei vari WP, le azioni completate e lo stato di del progetto progetto per il periodo di attività dal 9 giugno 2021 (RA3) al 19 aprile 2022 (RA4)

o The first draft version of the Interface definition report has been delivered at PM2. The draft pointed out the various problems and solutions in defining the netCDF interface. At PM2 it was decided to concentrate the efforts on defining the output file interfaces, since these are the main files that will be used to analyze the result, both in the FORUM Scienza community, and in the general remote sensing community. o The second draft of the document was delivered at PM3. It contained the specification of the output interface. o This final version is delivered at PM4 and contains the revised specification for the output files. o Example fortran 95 routines that read and write a compliant output file are also delivered. These also include an extensive documentation on how to interface a proprietary code with the supplied routines.

We review some recent results on crystallization in two dimensions for pairwise interaction energies adopting a variational approach.We discuss the behavior of minimizers and quasi-minimizers of the Heitmann-Radin sticky disc model and we see how this model can be enriched in order to deal with collective behavior for systems of oriented particles.

Bandelt and Mulder’s structural characterization of bipartite distance hereditary graphs asserts that such graphs can be built inductively starting from a single vertex and by repeatedly adding either pendant vertices or twins (i.e., vertices with the same neighborhood as an existing one). Dirac and Duffin’s structural characterization of 2–connected series–parallel graphs asserts that such graphs can be built inductively starting from a single edge by adding either edges in series or in parallel. In this paper we give an elementary proof that the two constructions are the same construction when bipartite graphs are viewed as the fundamental graphs of a graphic matroid. We then apply the result to re-prove known results concerning bipartite distance hereditary graphs and series–parallel graphs and to provide a new class of polynomially-solvable instances for the integer multi-commodity flow of maximum value.

Individual tracking of museum visitors based on portable radio beacons, an asset for behavioural analyses and comfort/performance improvements, is seeing increasing diffusion. Conceptually, this approach enables room-level localisation based on a network of small antennas (thus, without invasive modification of the existent structures). The antennas measure the intensity (RSSi) of self-advertising signals broadcasted by beacons individually assigned to the visitors. The signal intensity provides a proxy for the distance to the antennas and thus indicative positioning. However, RSSi signals are well-known to be noisy, even in ideal conditions (high antenna density, absence of obstacles, absence of crowd, ...). In this contribution, we present a method to perform accurate RSSi-based visitor tracking when the density of antennas is relatively low, e.g. due to technical constraints imposed by historic buildings. We combine an ensemble of "simple" localisers, trained based on ground-truth, with an encoding of the museum topology in terms of a total-coloured graph. This turns the localisation problem into a cascade process, from large to small scales, in space and in time. Our use case is visitors tracking in Galleria Borghese, Rome (Italy), for which our method manages >96% localisation accuracy, significantly improving on our previous work (J. Comput. Sci. 101357, 2021).

An early research in solid modeling led by Herbert Voelcker at the University of Rochester and later at Cornell suggested that every solid representation scheme corresponds to an algebra, where the elements of the algebra are solid representations constructed and edited using operations in the algebra. For example, every CSG representation describes an element in a finite Boolean algebra of closed regular sets, whereas every boundary representation describes an element of a vector space of 2-chains in an algebraic topological chain complex. In this paper, we elucidate the precise relationships (functors) between all algebras used for CSG and boundary representations of solids. Based on these properties, we show that many solid modeling operations, including boundary evaluation, reduce to straightforward algebraic operations or application of identified functors that are efficiently implemented using point membership tests and sparse matrix operations. To fully exploit the efficacy of the new algebraic approach to solid modeling, all algorithms are fully implemented in Julia, the modern language of choice for numerical and scientific computing.

The development of Boolean algebra based algorithms lied the foundation for a wide variety of cryptanalysis techniques based on the reformulation of a cryptosystem as a polynomial function over F2. Widely used approaches to solve multivariate system of equations include Gröbner bases (see [11]) and linearisation techniques like XL [4] and XSL [5]). Performances of these methodologies were however completely unfeasible for real problems’ size, making it impossible to directly find useful relations between cryptographic schemes’ input and output. At Eurocrypt’09 a new methodology settled in this environment, providing a feasible family of attacks able to retrieve useful in- put/output relations within feasible time: Dinur and Shamir Cube Attack [7]. The attack relied on the new concept of tweakable poly- nomials, polynomials in variables the attacker can set at will during the attack through which a black-box representation of the cipher is analysed. The resonance of this approach was unexpected, making it the forefather of many other approaches ranging from generic finite fields [1, 15] and non-linear [14] approaches to Meet-in-the- Middle [2, 13] and side channels [8] attacks. The idea of tweakable polynomials was also exploited to provide property (cube) testers which generated Conditional [12] and Dynamic [9] cube attacks. All of these approaches come with their own nomenclature, often making it unclear about their real contribute to the state of the art. The aim of this work is to introduce a novel notation to provide a global representation of the cube attacks family.

We describe studies undertaken in support of the Far-infrared Outgoing Radiation Understanding and Monitoring mission, European Space Agency's ninth Earth Explorer, designed to investigate whether airborne observations of far-infrared radiances can provide beneficial information on mid and upper tropospheric water vapor concentrations. Initially we perform a joint temperature and water vapor retrieval and show that the water vapor retrieval exploiting far-infrared measurements from the Tropospheric Airborne Fourier Transform Spectrometer (TAFTS) shows improvement over the a-priori Unified Model global forecast when compared to in situ dropsonde measurements. For this case the improvement is particularly noticeable in the mid-upper troposphere. Equivalent retrievals using mid-infrared radiances measured by the Airborne Research Interferometer Evaluation System (ARIES) show much reduced performance, with the degrees of freedom for signal (DFS), reduced by a factor of almost 2. Further sensitivity studies show that this advantage is decreased, but still present when the spectral resolution of the TAFTS measurements is reduced to match that of ARIES. The beneficial role of the far infrared for this case is further confirmed by performing water vapor only retrievals using ARIES and TAFTS individually, and then in combination. We find that the combined retrieval has a DFS value of 6.7 for water vapor, marginally larger than that obtained for the TAFTS retrieval and almost twice as large as that obtained for ARIES. These results provide observational support of theoretical studies highlighting the potential improvement that far-infrared observations could bring for the retrieval of tropospheric water vapor.

Considering the concept of attainable sets for differential inclusions, we introduce the isochronous manifolds relative to a piecewise smooth dynamical systems in R2 and R3, and study how analytical and topological properties of such manifolds are related to sliding motion and to partially nodal attractivity conditions on the discontinuity manifolds. We also investigate what happens to isochronous manifolds at tangential exit points, where attractivity conditions cease to hold. In particular, we find that isochronous curves in R2, which are closed simple curves under attractivity regime, become open curves at such points.

Introduction. In high-contact sport athletes, repetitive head trauma might be linked to permanent brain damage. In particular, findings in professional American football players indicate that brain injury is often associated with long-term cognitive slowing. In this context, hemp extracts might have beneficial effects. Methods. Forty-two former professional American football players were recruited (age = 49.6 ± 9.8 years). Before or immediately after the oral administration of a THC-free hemp extract, the following measures were acquired: 1) the median theta/beta ratio and posterior peak alpha frequency (PAF) during resting state; 2) P200 and P300b latencies as well as reaction times (RT) during performance of a Go/NoGo task. Results. After treatment, a smaller median theta/beta ratio (p < .01) was detected. An onset latency reduction was also found for the P200 (p < .01) and P300b (p < .05) measures, which was accompanied by smaller RT variances (p < .05). Finally, a positive correlation between RT measures and P300b latencies was found only after treatment. Conclusion. The administration of THC-free hemp extracts in former professional high-impact athletes might have beneficial effects on both cognitive performance and emotion regulation. Also, recent technological advances in EEG detection and analysis could play an important role in the management of patients with sport-related brain injuries.

In this paper, we present TLBfind, a GPU code for simulating the hydrodynamics of droplets along with a dynamic temperature field. TLBfind hinges on a two-dimensional multi-component lattice Boltzmann (LB) model simulating a concentrated emulsion with finite-size droplets evolving in a thermal convective state, just above the transition from conduction to convection. The droplet concentration of the emulsion system is tunable and at the core of the code lies the possibility to measure a large number of physical observables characterising the flow and droplets. Furthermore, TLBfind includes a parallel implementation on GPU of the Delaunay triangulation useful for the detection of droplets' plastic rearrangements, and several types of boundary conditions, supporting simulations of channels with structured rough walls. Program summary: Program Title: TLBfind CPC Library link to program files: https://doi.org/10.17632/hbk45696nf.1 Developer's repository link: https://github.com/FrancescaPelusi/TLBfind Licensing provisions: MIT Programming language: CUDA-C Nature of problem: Hydrodynamics of concentrated emulsions with finite-size droplets in a thermal convective state. Solution method: Single relaxation time Lattice Boltzmann method to solve Navier-Stokes equations for fluids, coupled with the temperature field dynamics. The output describes the dynamics of finite-size droplets of concentrated emulsions in presence of a temperature field. The temperature field obeys the advection-diffusion equation. Additional comments including restrictions and unusual features: Plastic rearrangements of droplets are detected via the parallel implementation of the Delaunay triangulation, and boundary conditions are tunable.

Under the condition of partial surface wettability, thin liquid films can be destabilized by small perturbations and rupture into droplets. As successfully predicted by the thin film equation (TFE), the rupture dynamics are dictated by the liquid-solid interaction. The theory describes the latter using the disjoining pressure or, equivalently, the contact angle. The introduction of a secondary fluid can lead to a richer phenomenology, thanks to the presence of different fluid/surface interaction energies but has so far not been investigated. In this work, we study the rupture of liquid films with different heights immersed in a secondary fluid using a multi-component lattice Boltzmann (LB) approach. We investigate a wide range of surface interaction energies, equilibrium contact angles, and film thicknesses. We found that the rupture time can differ by about one order of magnitude for identical equilibrium contact angles but different surface free energies. Interestingly, the TFE describes the observed breakup dynamics qualitatively well, up to equilibrium contact angles as large as 130°. A small film thickness is a much stricter requirement for the validity of the TFE, and agreement with LB results is found only for ratios ε = h / L of the film height h and lateral system size L, such as ε≲ × 10 - 3.

The problem of choosing appropriate values for missing data is often encountered in the data science. We describe a novel method containing both traditional mathematics and machine learning elements for prediction (imputation) of missing data. This method is based on the notion of distance between shifted linear subspaces representing the existing data and candidate sets. The existing data set is represented by the subspace spanned by its first principal components. Solutions for the case of the Euclidean metric are given.

Let X = {X-1, X-2,..., X-m} be a system of smooth vector fields in R-n satisfying the Hormander's finite rank condition. We prove the following Sobolev inequality with reciprocal weights in Carnot-Caratheodory space G associated to system X(1/integral(BR) K(x) dx integral(BR) vertical bar u vertical bar(t) K (x) dx)(1/t) <= C R (1/integral(BR) 1/K(x) dx integral(BR) vertical bar Xu vertical bar(2)/K(x) dx)(1/2),where Xu denotes the horizontal gradient of u with respect to X. We assume that the weight K belongs to Muckenhoupt's class A(2) and Gehring's class G tau, where tau is a suitable exponent related to the homogeneous dimension.

Recent research shows reductions in the VLF signal noise amplitude that begin before particular earthquakes whose epicentres are more than 100 km away from the signal propagation path. In this paper, we extend this research to studying the noise amplitude during periods of intense seismic activity in a localized area. We analyse variations in the VLF signal noise amplitude over a period of 10 days (25 October-3 November 2016) when 981 earthquakes with the minimum magnitude of 2 occurred in Central Italy. Out of these events, 31 had the magnitude equal or greater than 4, while the strongest one had the magnitude of 6.5. We observe the VLF signal emitted by the ICV transmitter located in Sardinia (Italy) and recorded in Belgrade (Serbia). Bearing in mind that the trajectory of this signal crosses the area in which the observed earthquakes occurred, we extend the existing research to study of variations in the noise amplitude of the signal propagating at short distances from the epicentres of the considered earthquakes. In addition, we analyse the impact of a large number earthquakes on characteristics of the noise amplitude and its reductions before particular events. In order to examine the localization of the recorded changes, we additionally analysed the noise amplitude of two reference signals emitted in Germany and Norway. The obtained results show the existence of the noise amplitude reduction preceding individual strong or relatively strong earthquakes, and earthquakes followed by others that occurred in a shorter time interval. However, the additional noise amplitude reductions are either not pronounced or they do not exist before the considered events in periods of the reduced noise amplitude remain from previous earthquakes. Reductions in noise amplitudes for all observed signals indicate a larger perturbed area through which they spread or its closer location to the receiver. The analysis of daily values of parameters describing the noise amplitude reveals their variations start up to 2 weeks before the seismically active period occurs.