The protozoan parasite Trypanosoma cruz causes the Chagas disease, which final outcome can be morbidity or death. The complexity of this infection is due to the many kinds of players involved in the immune response and to the variety of host cells targeted by the parasite. We built an ordinary differential equation model which includes aspects of innate and adaptive immune response to study the T. cruzi infection. The model also includes cardiomyocytes to represent how the infection affects the heart. We used parasitemia experimental data of infected wild-type mice to estimate the model parameters. We investigated how the number of parasites and infected cardiomyocytes were affected by changes of parameters controlling the survival rates of the parasite. We thus introduce a 20% variation in either macrophages, CDS+T cells, or anti- parasite specific antibody activity. This resulted in a change of the parasitemia as expected, and produced a broader variation in the number of parasites around the peak of parasitemia. Moreover, the same three model modifications were enabled one at a time to simulate a knockout effect in the host. The results of the knockout effects were a faster parasite growth and death of the host in all three cases, in agreement with in vivo experimental data. The model also is corroborated by in vivo data from the literature where the inhibition of macrophages, antibody, or CTL is not compensated by the other parasite killing mechanisms, and as a result lead to death of the host. Altogether these results indicate that the immune system plays a crucial role in controlling T. cruzi infection and impairment of one modality of action greatly reduces its efficiency and results in a much larger extensionof the infection of cardiomyocytes.

Infection by Leishmania can cause diseases ranging from self-healing cutaneous to visceral dissemination that can lead to death if untreated. In order to explore the early phase of the infection and the role of macrophages, we implement a system of differential equations involving the major players in the innate immune response to leishmaniasis (i.e., parasites in the intracellular and free form, infected and uninfected macrophages, and NO/ROS). The model was adjusted and validated using data from C57BL/6, KO and SCID mice published in the literature. The key findings were the surprisingly more active macrophages in the mice knockouts for IL-12 and IFN-g. This result can be interpreted as an indication of an M2b polarization of the macrophages in these mice. Sensitivity Analysis shows that NO/ROS secretion rate is more important to Leishmania control then the mechanisms of killing intracellular parasites. This model is a useful tool for comprehending the infection and treatments. Index Terms-leishmaniasis, cutaneous, innate-immune-response, macrophages, ODE

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) is a limb-viewing infrared Fourier transform spectrometer that operated from 2002 to 2012 onboard the ENVISAT satellite. The maintenance and the upgrade of both L1 and L2 ESA processors are accomplished by the Quality Working Group, where a fruitful collaboration among Level 1, Level 2 and validation teams can be exploited. Recently both ESA L1 and L2 processors have been updated, as well as the spectroscopic database and some absorption cross-sections. In addition to the products already present in the current release (V7) of ESA MIPAS data (temperature and the VMR of H2O, O3, HNO3, CH4, N2O, NO2, CFC-11, CFC-12, N2O5, ClONO2, HCFC-22, COF2, CF4, HCN and CCl4), the VMR of six additional species (OCS, CH3Cl, HDO, C2H2, C2H6, COCl2) will be provided in V8 dataset. In preparation of V8 full mission reprocessing, three Diagnostic Datasets have been generated to check the performances of all L1, L2 processors and the new auxiliary data.The analysis of these Diagnostic Datasets and the comparison with previous full mission dataset V7 will be used to perform a first assessment of the quality of the new V8 products. In the paper special focus will be given to the new species.

New remote sensing satellite sensors for the measurements of atmospheric radiation offer the advantage of very high spectral resolution and spectral and/or spatial and temporal coverage. The analysis of these measurements often requires a forward model (FM) for the simulation of the radiation collected by the sensor. The FM should model all the processes affecting the radiance, such as absorption and scattering by molecules and particles. Despite the advancement in sensor technology, the radiative transfer solvers are almost the same since several decades. Among these, the DISORT solver is still one of the most widely used. The DISORT code was developed 30 years ago, and while the code is maintained and updated regularly, the improvements are more geared towards new features than to a revision of the original setup. While the implementation was the best possible at the time, the memory constrains and language limitations of the time are nowadays considerably changed. On the other hand there is still the need of NRT retrievals, and the computing time of the multiple scattering needed in cloudy sky conditions is still the bottleneck of the FM calculation. We modified the DISORT algorithm in three directions: 1) Language improvements. Making use of dynamical assignment and modularity of modern fortran reduces execution time. 2) Algorithm improvements. By approaching the delta-m transformation on a per-layer basis, many computations were saved, expecially when the cloud pattern does not cover all the atmospheric range. 3) Numerical analysis improvements. While these improvements do not shorten the computational time, they improve the precision of the solution of the eigenvalue sub-problems that arises in the multiple scattering calculations. The modifications in the DISORT solver produce an improvement in calculation performances of a factor 3 with respect to the original version. The new solver is named as fast-DISORT (fDISORT).

We consider a general statistical linear inverse problem, where the solution is represented via a known (possibly overcomplete) dictionary that allows its sparse representation. We propose two different approaches. A model selection estimator selects a single model by minimizing the penalized empirical risk over all possible models. By contrast with direct problems, the penalty depends on the model itself rather than on its size only as for complexity penalties. A Q-aggregate estimator averages over the entire collection of estimators with properly chosen weights. Under mild conditions on the dictionary, we establish oracle inequalities both with high probability and in expectation for the two estimators. Moreover, for the latter estimator these inequalities are sharp. The proposed procedures are implemented numerically and their performance is assessed by a simulation study.

This chapter presents the most common and useful tests of hypothesis for bioinformatics applications. The hypothesis tests divide essentially into two categories: parametric and nonparametric. At the first category belong those tests based on the assumption of knowing the distribution of the sampling population(s) and inference is drawn on one or more unknown parameter(s); at the second category belong those tests that are "distribution-free" which generally have much less assumptions. For each test, we will present the mathematical hypothesis under which it is applicable and the statistics used to apply it.

Viene studiata l'evoluzione nel tempo del degrado del rivestimento interno di un tubo metallico al cui interno scorre un fluido. Il degrado si manifesta in tagli longitudinali del rivestimento. Per questo motivo il problema puo' essere posto e risolto (per mezzo di Thin Plate Approximation) in due dimensioni. We deal with the mathematical model of the incremental degradation of the internal coating (e.g. a polymeric material) of a metallic pipe in which a fluid flows relatively fast. The fluid drags solid impurities so that longitudinal scratches, inaccessible to any direct inspection procedure, are produced on the coating. Time evolution of this kind of defects can be reconstructed from the knowledge of a sequence of temperature maps of the external surface. The time-varying orthogonal section of this damaged interface is determined as a function of time and polar angle through the identification of a suitable effective heat transfer coefficient by means of Thin Plate Approximation.

Traffic data, automatically collected en masse every day, can be mined to discover information or patterns to support police investigations. Leveraging on domain expertise, in this paper we show how unsupervised clustering techniques can be used to infer trending behaviors for road-users and thus classify both routes and vehicles. We describe a tool devised and implemented upon openly-available scientific libraries and we present a new set of experiments involving three years worth data. Our classification results show robustness to noise and have high potential for detecting anomalies possibly connected to criminal activity.

In this paper we propose two numerical algorithms to solve a coupled PDE-ODE system which models a slow vehicle (bottleneck) moving on a road together with other cars. The resulting system is fully coupled because the dynamics of the slow vehicle depends on the density of cars and, at the same time, it causes a capacity drop in the road, thus limiting the car flux. The first algorithm, based on the Wave Front Tracking method, is suitable for theoretical investigations and convergence results. The second one, based on the Godunov scheme, is used for numerical simulations. The case of multiple bottlenecks is also investigated.

In this paper we deal with the study of travel flows and patterns of people in large populated areas. Information about the movements of people is extracted from coarse-grained aggregated cellular network data without tracking mobile devices individually. Mobile phone data are provided by the Italian telecommunication company TIM and consist of density profiles (i.e. the spatial distribution) of people in a given area at various instants of time. By computing a suitable approximation of the Wasserstein distance between two consecutive density profiles, we are able to extract the main directions followed by people, i.e. to understand how the mass of people distribute in space and time. The main applications of the proposed technique are the monitoring of daily flows of commuters, the organization of large events, and, more in general, the traffic management and control.

Trajectory-based approaches to excited-state, nonadiabatic dynamics are promising simulation techniques to describe the response of complex molecular systems upon photo-excitation. They provide an approximate description of the coupled quantum dynamics of electrons and nuclei trying to access systems of growing complexity. The central question in the design of those approximations is a proper accounting of the coupling electron-nuclei and of the quantum features of the problem. In this paper, we approach the problem in the framework of the exact factorization of the electron-nuclear wavefunction, re-deriving and improving the coupled-trajectory mixed quantum-classical (CT-MQC) algorithm recently developed to solve the exact-factorization equations. In particular, a procedure to include quantum nuclear effects in CT-MQC is derived, and tested on a model system in different regimes.

In various cellular processes, bio-filaments like F-actin and F-tubulin are able to exploit chemical energy associated with polymerization to perform mechanicalwork against an obstacle loaded with an external force. The force-velocity relationship quantitatively summarizes the nature of this process. By a stochastic dynamical model, we give, together with the evolution of a staggered bundle of N-f rigid living filaments facing a loaded wall, the corresponding force-velocity relationship. We compute the evolution of the model in the infinite wall diffusion limit and in supercritical conditions (monomer density reduced by critical density (rho) over cap (1) > 1), and we show that this solution remains valid for moderate non-zero values of the ratio between the wall diffusion and the chemical time scales. We consider two classical protocols: the bundle is opposed either to a constant load or to an optical trap setup, characterized by a harmonic restoring force. The constant load case leads, for each F value, to a stationary velocity V-stat (F; N-f, (rho) over cap (1)) after a relaxation with characteristic time tau(micro)(F). When the bundle (initially taken as an assembly of filament seeds) is subjected to a harmonic restoring force (optical trap load), the bundle elongates and the load increases up to stalling over a characteristic time tau(OT). Extracted from this single experiment, the force-velocity V-OT (F; N-f, (rho) over cap (1)) curve is found to coincide with V-stat (F; N-f, (rho) over cap (1)), except at low loads. We show that this result follows from the adiabatic separation between tau(micro) and tau(OT), i. e., tau(micro) << tau(OT).

A dynamical system submitted to holonomic constraints is Hamiltonian only if considered in the reduced phase space of its generalized coordinates and momenta, which need to be defined ad hoc in each particular case. However, specially in molecular simulations, where the number of degrees of freedom is exceedingly high, the representation in generalized coordinates is completely unsuitable, although conceptually unavoidable, to provide a rigorous description of its evolution and statistical properties. In this paper, we first review the state of the art of the numerical approach that defines the way to conserve exactly the constraint conditions (by an algorithm universally known as SHAKE) and permits integrating the equations of motion directly in the phase space of the natural Cartesian coordinates and momenta of the system. We then discuss in detail SHAKE numerical implementations in the notable cases of Verlet and velocity-Verlet algorithms. After discussing in the same framework how constraints modify the properties of the equilibrium ensemble, we show how, at the price of moving to a dynamical system no more (directly) Hamiltonian, it is possible to provide a direct interpretation of the dynamical system and so derive its Statistical Mechanics both at equilibrium and in non-equilibrium conditions. To achieve that, we generalize the statistical treatment to systems no longer conserving the phase space volume (equivalently, we introduce a non-Euclidean invariant measure in phase space) and derive a generalized Liouville equation describing the ensemble even out of equilibrium. As a result, we can extend the response theory of Kubo (linear and nonlinear) to systems subjected to constraints.

The time reversal invariance of classical dynamics is reconsidered in this paper with specific focus on its consequences for time correlation functions and associated properties such as transport coefficients. We show that, under fairly common assumptions on the interparticle potential, an isolated Hamiltonian system obeys more than one time reversal symmetry and that this entails non trivial consequences. Under an isotropic and homogeneous potential, in particular, eight valid time reversal operations exist. The presence of external fields that reduce the symmetry of space decreases this number, but does not necessarily impair all time reversal symmetries. Thus, analytic predictions of symmetry properties of time correlation functions and, in some cases, even of their null value are still possible. The noteworthy case of a constant external magnetic field, usually assumed to destroy time reversal symmetry, is considered in some detail. We show that, in this case too, some of the new time reversal operations hold, and that this makes it possible to derive relevant properties of correlation functions without the uninteresting inversion of the direction of the magnetic field commonly enforced in the literature.

We present the most recent release of our parallel implementation of the BFS and BC algorithms for the study of large scale graphs. Although our reference platform is a high-end cluster of new generation NVIDIA GPUs and some of our optimizations are CUDA specific, most of our ideas can be applied to other platforms offering multiple levels of parallelism. We exploit multi level parallel processing through a hybrid programming paradigm that combines highly tuned CUDA kernels, for the computations performed by each node, and explicit data exchange through the Message Passing Interface (MPI), for the communications among nodes. The results of the numerical experiments show that the performance of our code is comparable or better with respect to other state-of-the-art solutions. For the BFS, for instance, we reach a peak performance of 200 Giga Teps on a single GPU and 5.5 Terateps on 1024 Pascal GPUs. We release our source codes both for reproducing the results and for facilitating their usage as a building block for the implementation of other algorithms.

We study the initial-boundary value problem [Formula presented]where [Formula presented] is an interval and [Formula presented] is a nonnegative Radon measure on [Formula presented]. The map [Formula presented] is increasing in [Formula presented] and decreasing in [Formula presented] for some [Formula presented], and satisfies [Formula presented]. The regularizing map [Formula presented] is increasing and bounded. We prove existence of suitably defined nonnegative Radon measure-valued solutions. The solution class is natural since smooth initial data may generate solutions which become measure-valued after finite time.

The paper traces the early stages of Berni Alder's scientific accomplishments, focusing on his contributions to the development of Computational Methods for the study of Statistical Mechanics. Following attempts in the early 50s to implement Monte Carlo methods to study equilibrium properties of many-body systems, Alder developed in collaboration with Tom Wainwright the Molecular Dynamics approach as an alternative tool to Monte Carlo, allowing to extend simulation techniques to non-equilibrium properties. This led to the confirmation of the existence of a phase transition in a system of hard spheres in the late 50s, and was followed by the discovery of the unexpected long-time tail in the correlation function about a decade later. In the late 70s Alder was among the pioneers of the extension of Computer Simulation techniques to Quantum problems. Centered around Alder's own pioneering contributions, the paper covers about thirty years of developments in Molecular Simulation, from the birth of the field to its coming of age as a self-sustained discipline.

During the seismic cycle, in nature and as well as in lab samples, the crack density of rocks varies substantially, as stressed rocks approach a critical state and eventually fail (Vasseur et al, 2017; Nur, 1972; Gupta, 1973) . At Earth scales, small periodical stress variations such as seasonal loading/unloading and tides (Johnson_etal_2017) are constantly being superimposed on the tectonic loading stress of crustal rocks, inducing periodic changes in crack porosity, pore-fluid pressure, and saturation, that should leave a signature on crustal attenuation. However, results from seismic techniques applied thus far have been too noisy, or lacked sufficient resolution, to yield meaningful measurements. Here we use a new technique that shows that seismic attenuation on the creeping section of the San Andreas Fault (SAF) at Parkfield is modulated by recognizable periodicities mostly due to tides, as well as to longer period fluctuations in creep rates (between 1.5 and 3-4 years) that have been previously observed (Nadeau sensitive to periodic stress perturbations well below 100 Pa, more than one order of magnitude smaller than the largest of all periodic stress fluctuations, due to water/snow loading/unloading (Johnson earthquake, we observe changes in anelastic attenuation on both sides of the SAF. and McEvilly, 2004; Turner et al., 2015) . Our analysis is et al., 2017) . Before and after the 2004 M6 Parkfield main Frequency-dependent precursors with opposite signs are seen on the two sides of the fault, reflecting the fact that prior to the earthquake, the Pacific side of the SAF was under decreasing compressional stress, whereas the North-American side of the fault was experiencing increasing compression. Coseismic and post-seismic stress relaxation cause anomalies of opposite signs on the two sides of the SAF at Parkfield, opposite to the pre-seismic ones. Due to rock damage, pre-2008 fluctuations show enhanced sensitivity to seasonal stresses and solid tides (Gao eta., 2000) , with amplitudes modulated by decreasing slip rate through healing. Post-2008 fluctuations indicate close-to-fault medium healing.

During the last 20 years, three seismic sequences affected the Apenninic belt (central Italy): Colfiorito (1997-98), L'Aquila (2009) and Amatrice Visso-Norcia Campotosto (2016-17). They lasted for a long time, with a series of moderate-to-large earthquakes distributed over 40-60 km long Apenninic-trending segments. Their closeness in space and time suggested to study their aftershock sequences to highlight similarities and differences. Aftershock space migration and the distribution of aftershock inter-arrival time were studied. Mathematical Morphology and nonparametric statistics were applied to reduce the effect of spatial noise. Parametric analysis in time domain and spectral analysis were performed. Two different types of aftershock sequences were found. The L'Aquila sequence presented a continuous and periodic temporal variation (period ? 120 days) of aftershock activity centre along the sequence axis, while the other two sequences showed a piecewise continuous pattern and a shorter duration. We also found two different types of temporal evolution of the mean radial distance between the aftershock ipocentres and the one of a reference event corresponding to the start of a large and fast increase of daily energy release. One type was well described by a simple exponential model, while a power-law model was more appropriate for the other one. Furthermore, in the first case, the aftershock inter-arrival time were very well fitted by an exponential model, while noticeable deviations were present in the other case. A possible explanation was provided in terms of the local geological and hydrogeological properties, which depend on the region location w.r.t. the Ancona-Anzio tectonic lineament.