Mechanistic Approaches To The Prevention Of Mutation And Cancer

Cancer and other mutation-related diseases can be prevented at three levels: primary prevention, which is addressed to healthy individuals in order to prevent occurrence of the disease; secondary prevention, which is addressed to early stage patients in order to prevent progression of the disease; and tertiary prevention, which is addressed to patients after therapy in order to prevent relapses of the disease. Although the most obvious approach to prevention is to minimize exposures to recognized risk factors, a complementary strategy is represented by chemoprevention, using dietary and pharmacological agents that reinforce the host defence machinery. Since 1988, I proposed detailed classifications of mechanisms of inhibitors of mutagenesis and carcinogenesis. They may apply not only to cancer but also to other degenerative diseases that have replaced infectious diseases as the leading causes of death in the population. In fact, certain mechanisms, such as damage to nuclear DNA and mtDNA, oxidative stress, chronic inflammation, signal transduction alterations and epigenetic changes may be involved in the pathogenesis of different diseases. Studies performed in our laboratory have shown that certain genomic alterations that are usually investigated in cancer research may also be detected in other chronic diseases, such as atherosclerosis, degenerative heart diseases, chronic obstructive pulmonary diseases, neurological disorders, eye diseases, skin ageing, and alopecia. Similar alterations were investigated in critical periods of life, such as birth and ageing. The nucleotide alterations occurring at birth in the lung render the newborn particularly vulnerable to the action of environmental agents. In fact, we demonstrated that cigarette smoke becomes a potent carcinogen in mice when exposure starts at birth and continues early in life. We investigated a number of chemopreventive agents by evaluating modulation of intermediate biomarkers and carcinogenicity. An optimal agent should not excessively alter the physiological patterns of gene expression, microRNA and proteome profiles, but at the same time it should be effective in inhibiting alterations induced by mutagens and carcinogens. It should be noted that most chemopreventive agents possess pleiotropic properties. The knowledge of mechanisms can be exploited to combine different agents working with complementary mechanisms. Like the therapy of important diseases, such as cancer, cardiovascular diseases, AIDS, etc., uses combinations of drugs, combined chemoprevention is a quite promising strategy. Although a large number of agents are potentially able to prevent cancer, we are in search of tools to predict, hopefully in the single individual, their efficacy and safety in humans

Local roughness exponent in the nonlinear molecular-beam-epitaxy universality class in one-dimension

We report local roughness exponents, $\alpha_{\text{loc}}$, for three interface growth models in one dimension which are believed to belong the non-linear molecular-beam-epitaxy (nMBE) universality class represented by the Villain-Lais-Das Sarma (VLDS) stochastic equation. We applied an optimum detrended fluctuation analysis (ODFA) [Luis et al., Phys. Rev. E 95, 042801 (2017)] and compared the outcomes with standard detrending methods. We observe in all investigated models that ODFA outperforms the standard methods providing exponents in the narrow interval $\alpha_{\text{loc}}\in[0.96,0.98]$ consistent with renormalization group predictions for the VLDS equation. In particular, these exponent values are calculated for the Clarke-Vvdensky and Das Sarma-Tamborenea models characterized by very strong corrections to the scaling, for which large deviations of these values had been reported. Our results strongly support the absence of anomalous scaling in the nMBE universality class and the existence of corrections in the form $\alpha_{\text{loc}}=1-\epsilon$ of the one-loop renormalization group analysis of the VLDS equation

Theory of controlled quantum dynamics

We introduce a general formalism, based on the stochastic formulation of quantum mechanics, to obtain localized quasi-classical wave packets as dynamically controlled systems, for arbitrary anharmonic potentials. The control is in general linear, and it amounts to introduce additional quadratic and linear time-dependent terms to the given potential. In this way one can construct for general systems either coherent packets moving with constant dispersion, or dynamically squeezed packets whose spreading remains bounded for all times. In the standard operatorial framework our scheme corresponds to a suitable generalization of the displacement and scaling operators that generate the coherent and squeezed states of the harmonic oscillator.Comment: LaTeX, A4wide, 28 pages, no figures. To appear in J. Phys. A: Math. Gen., April 199

Coupling radio propagation and weather forecast models to maximize Ka-band channel transmission rate for interplanetary missions

Deep space (DS) missions for interplanetary explorations are aimed at acquiring information about the solar system and its composition. To achieve this result a radio link is established between the space satellite and receiving stations on the Earth. Significant channel capacity must be guaranteed to such spacecraft-to-Earth link considering their large separation distance as well. Terrestrial atmospheric impairments on the space-to-Earth propagating signals are the major responsible for the signal degradation thus reducing the link’s channel temporal availability. Considering the saturation and the limited bandwidth of the conventional systems used working at X-band (around 8.4 GHz), frequencies above Ku-band (12-18 GHz) are being used and currently explored for next future DS missions. For example, the ESA mission EUCLID, planned to be launched in 2020 to reach Sun-Earth Lagrange point L2, will use the K-band (at 25.5-27 GHz). The BepiColombo (BC) ESA mission to Mercury, planned to be launched in 2016, will use Ka-band (at 32-34 GHz) with some modules operating at X-band too. The W-band is also being investigated for space communications (Lucente et al., IEEE Systems J., 2008) as well as near-infrared band for DS links (Luini at al., 3rd IWOW, 2014; Cesarone et al., ICSOS, 2011). If compared with X-band channels, K-band and Ka-band can provide an appealing data rate and signal-to-noise ratio in free space due to the squared-frequency law increase of antenna directivity within the downlink budget (for the same physical antenna size). However, atmospheric path attenuation can be significant for higher frequencies since the major source of transmission outage is not only caused by convective rainfall, as it happens for lower frequencies too, but even non-precipitating clouds and moderate precipitation produced by stratiform rain events are detrimental. This means that accurate channel models are necessary for DS mission data link design at K and Ka band. A physical approach can offer advanced radiopropagation models to take into account the effects due to atmospheric gases, clouds and precipitation. The objective of this work is to couple a weather forecast numerical model with a microphysically- oriented radiopropagation model, providing a description of the atmospheric state and of its effects on a DS downlink. This work is developed in the framework of the RadioMeteorological Operations Planner (RMOP) program, aimed at performing a feasibility study for the BC mission (Biscarini et al., EuCAP 2014). The RMOP chain for the link budget computation is composed by three modules: weather forecast (WFM), radio propagation (RPM) and downlink budget (DBM). WFM is aimed at providing an atmospheric state vector. Among the available weather forecast models, for RMOP purposes we have used the Mesoscale Model 5. The output of the WFM is the input of the RPM for the computation of the atmospheric attenuation and sky-noise temperature at the receiving ground station antenna. RPM makes use of radiative transfer solver based on the Eddington approximations well as accurate scattering models. Time series of attenuation and sky-noise temperature coming from the RPM are converted into probability density functions and then ingested by the DBM to compute the received data volume (DV). Using the BC mission as a reference test case for the Ka-band ground station at Cebreros (Spain), this work will show the advantages of using a coupled WFM-RPM approach with respect to climatological statistics in a link budget optimization procedure. The signal degradation due to atmospheric effects in DS links in terms of received DV will be also investigated not only at Ka band, but also at X, K and W for intercomparison. The quality of the DS downlink will be given in terms of received DV and the results at different frequencies compared showing the respective advantages and drawbacks

Complex phenotype in an Italian family with a novel mutation in SPG3A.

Mutations in the SPG3A gene represent a significant cause of autosomal dominant hereditary spastic paraplegia with early onset and pure phenotype. We describe an Italian family manifesting a complex phenotype, characterized by cerebellar involvement in the proband and amyotrophic lateral sclerosis-like syndrome in her father, in association with a new mutation in SPG3A. Our findings further widen the notion of clinical heterogeneity in SPG3A mutations

When do the symptoms of autonomic nervous system malfunction appear in patients with Parkinson’s disease?

Background/Aim. Dysautonomia appears in almost all patients with Parkinson’s disease (PD) in a certain stage of their condition. The aim of our study was to detect the development and type of autonomic disorders, find out the factors affecting their manifestation by analyzing the potential association with demographic variables related to clinical presentation, as well as the symptoms of the disease in a PD patient cohort. Methods. The patients with PD treated at the Clinic of Neurology in Belgrade during a 2-year period, divided into 3 groups were studied: 25 de novo patients, 25 patients already treated and had no long-term levodopa therapy-related complications and 22 patients treated with levodopa who manifested levodopa-induced motor complications. Simultaneously, 35 healthy control subjects, matched by age and sex, were also analyzed. Results. Autonomic nervous system malfunction was defined by Ewing diagnostic criteria. The tests, indicators of sympathetic and parasympathetic nervous systems, were significantly different in the PD patients as compared with the controls, suggesting the failure of both systems. However, it was shown, in the selected groups of patients, that the malfunction of both systems was present in two treated groups of PD patients, while de novo group manifested only sympathetic dysfunction. For this reason, the complete autonomic neuropathy was diagnosed only in the treated PD patients, while de novo patients were defined as those with the isolated sympathetic dysfunction. The patients with the complete autonomic neuropathy differed from the subjects without such neuropathy in higher cumulative and motor unified Parkinson’s disease rating score (UPDRS) (p < 0.01), activities of daily living scores (p < 0.05), Schwab-England scale (p < 0.001) and Hoehn-Yahr scale. There was no difference between the patients in other clinical-demographic characteristics (sex, age at the time of diagnosis, actual age, duration of disease, involved side of the body, pain and freezing), but mini mental status (MMS) score and Hamilton depression and anxiety rating scale were significantly lower (p < 0.05). Conclusion. Our results confirm a high prevalence of autonomic nervous system disturbances among PD patients from the near onset of disease, with a predominant sympathetic nervous system involvement. The patients who developed complete autonomic neuropathy (both sympathetic and parasympathetic) were individuals with considerable level of functional failure, more severe clinical presentation and the existing anxiety and depression. [Projekat Ministarstva nauke Republike Srbije, br. 175090

BRST invariant formulation of the Bell-CHSH inequality in gauge field theories

A study of the Bell-CHSH inequality in gauge field theories is presented. By using the Kugo-Ojima analysis of the BRST charge cohomology in Fock space, the Bell-CHSH inequality is formulated in a manifestly BRST invariant way. The examples of the free four-dimensional Maxwell theory and the Abelian Higgs model are scrutinized. The inequality is probed by using BRST invariant squeezed states, allowing for large Bell-CHSH inequality violations, close to Tsirelson's bound. An illustrative comparison with the entangled state of two $1/2$ spin particles in Quantum Mechanics is provided.Comment: 12 pages. Revised version. Accepted for publication in SciPost Physic

DYNAMICAL CONTROL OF THE HALO IN PARTICLE BEAMS: A STOCHASTIC–HYDRODYNAMIC APPROACH

In this paper we describe the beam distribution in particle accelerators in the framework of a stochastic–hydrodynamic scheme. In this scheme the possible reproduction of the halo after its elimination is a consequence of the stationarity of the transverse distribution which plays the role of an attractor for every other distribution. The relaxation time toward the halo is estimated, and a few examples of controlled transitions toward a permanent halo elimination are discussed

Annealed Ising model on hierarchical structures: a transfer matrix approach.

Spin systems in the presence of disorder are described by two sets of degrees of freedom, associated with orientational (spin) and disorder variables, which may be characterized by two distinct relaxation times. Disordered spin models have been mostly investigated in the quenched regime, which is the usual situation in solid state physics, and in which the relaxation time of the disorder variables is much larger than the typical measurement times. In this quenched regime, disorder variables are fixed, and only the orientational variables are duly thermalized. Recent studies in the context of lattice statistical models for the phase diagrams of nematic liquid-crystalline systems have stimulated the interest of going beyond the quenched regime. The phase diagrams predicted by these calculations for a simple Maier-Saupe model turn out to be qualitative different from the quenched case if the two sets of degrees of freedom are allowed to reach thermal equilibrium during the experimental time, which is known as the fully annealed regime. In this work, we develop a transfer matrix formalism to investigate annealed disordered Ising models on two hierarchical structures, the diamond hierarchical lattice (DHL) and the Apollonian network (AN). The calculations follow the same steps used for the analysis of simple uniform systems, which amounts to deriving proper recurrence maps for the thermodynamic and magnetic variables in terms of the generations of the construction of the hierarchical structures. In this context, we may consider different kinds of disorder, and different types of ferromagnetic and anti-ferromagnetic interactions. In the present work, we analyze the effects of dilution, which are produced by the removal of some magnetic ions. The system is treated in a “grand canonical" ensemble. The introduction of two extra fields, related to the concentration of two different types of particles, leads to higher-rank transfer matrices as compared with the formalism for the usual uniform models. Preliminary calculations on a DHL indicate that there is a phase transition for a wide range of dilution concentrations. Ising spin systems on the AN are known to be ferromagnetically ordered at all temperatures; in the presence of dilution, however, there are indications of a disordered (paramagnetic) phase at low concentrations of magnetic ions