Estimation of Weighted Extropy with Focus on Its Use in Reliability Modeling.

In the literature, estimation of weighted extropy is infrequently considered. In this paper, some non-parametric estimators of weighted extropy are given. The validation and comparison of the estimators are implemented with the help of simulation study and data illustration. The usefulness of the estimators is demonstrated using real data sets.

Jensen-Inaccuracy Information Measure.

The purpose of the paper is to introduce the Jensen-inaccuracy measure and examine its properties. Furthermore, some results on the connections between the inaccuracy and Jensen-inaccuracy measures and some other well-known information measures are provided. Moreover, in three different optimization problems, the arithmetic mixture distribution provides optimal information based on the inaccuracy information measure. Finally, two real examples from image processing are studied and some numerical results in terms of the inaccuracy and Jensen-inaccuracy information measures are obtained.

Weighted Cumulative Past Extropy and Its Inference.

This paper introduces and studies a new generalization of cumulative past extropy called weighted cumulative past extropy (WCPJ) for continuous random variables. We explore the following: if the WCPJs of the last order statistic are equal for two distributions, then these two distributions will be equal. We examine some properties of the WCPJ, and a number of inequalities involving bounds for WCPJ are obtained. Studies related to reliability theory are discussed. Finally, the empirical version of the WCPJ is considered, and a test statistic is proposed. The critical cutoff points of the test statistic are computed numerically. Then, the power of this test is compared to a number of alternative approaches. In some situations, its power is superior to the rest, and in some other settings, it is somewhat weaker than the others. The simulation study shows that the use of this test statistic can be satisfactory with due attention to its simple form and the rich information content behind it.

Fractional Deng Entropy and Extropy and Some Applications.

Deng entropy and extropy are two measures useful in the Dempster-Shafer evidence theory (DST) to study uncertainty, following the idea that extropy is the dual concept of entropy. In this paper, we present their fractional versions named fractional Deng entropy and extropy and compare them to other measures in the framework of DST. Here, we study the maximum for both of them and give several examples. Finally, we analyze a problem of classification in pattern recognition in order to highlight the importance of these new measures.

Kernel Estimation of Cumulative Residual Tsallis Entropy and Its Dynamic Version under ρ-Mixing Dependent Data.

Tsallis introduced a non-logarithmic generalization of Shannon entropy, namely Tsallis entropy, which is non-extensive. Sati and Gupta proposed cumulative residual information based on this non-extensive entropy measure, namely cumulative residual Tsallis entropy (CRTE), and its dynamic version, namely dynamic cumulative residual Tsallis entropy (DCRTE). In the present paper, we propose non-parametric kernel type estimators for CRTE and DCRTE where the considered observations exhibit an ρ-mixing dependence condition. Asymptotic properties of the estimators were established under suitable regularity conditions. A numerical evaluation of the proposed estimator is exhibited and a Monte Carlo simulation study was carried out.

A Dual Measure of Uncertainty: The Deng Extropy.

The extropy has recently been introduced as the dual concept of entropy. Moreover, in the context of the Dempster-Shafer evidence theory, Deng studied a new measure of discrimination, named the Deng entropy. In this paper, we define the Deng extropy and study its relation with Deng entropy, and examples are proposed in order to compare them. The behaviour of Deng extropy is studied under changes of focal elements. A characterization result is given for the maximum Deng extropy and, finally, a numerical example in pattern recognition is discussed in order to highlight the relevance of the new measure.

Transgenerational inheritance of enhanced susceptibility to radiation-induced medulloblastoma in newborn Ptch1⁺/⁻ mice after paternal irradiation.

The hypothesis of transgenerational induction of increased cancer susceptibility after paternal radiation exposure has long been controversial because of inconsistent results and the lack of a mechanistic interpretation. Here, exploiting Ptch1 heterozygous knockout mice, susceptible to spontaneous and radiation-induced medulloblastoma, we show that exposure of paternal germ cells to 1 Gy X-rays, at the spermatogonial stage, increased by a considerable 1.4-fold the offspring susceptibility to medulloblastoma induced by neonatal irradiation. This effect gained further biological significance thanks to a number of supporting data on the immunohistochemical characterization of the target tissue and preneoplastic lesions (PNLs). These results altogether pointed to increased proliferation of cerebellar granule cell precursors and PNLs cells, which favoured the development of frank tumours. The LOH analysis of tumor DNA showed Ptch1 biallelic loss in all tumor samples, suggesting that mechanisms other than interstitial deletions, typical of radiation-induced medulloblastoma, did not account for the observed increased cancer risk. This data was supported by comet analysis showing no differences in DNA damage induction and repair in cerebellar cells as a function of paternal irradiation. Finally, we provide biological plausibility to our results offering evidence of a possible epigenetic mechanism of inheritance based on radiation-induced changes of the microRNA profile of paternal sperm.

Molecular Damage in Glaucoma: from Anterior to Posterior Eye Segment. The MicroRNA Role.

Glaucoma targets a variety of different tissues located in both anterior (e.g., trabecular meshwork) and posterior (e.g., optic nerve head) ocular segments. The transmission of damage between these structures cannot be simply ascribed to intraocular pressure increase. Recent experimental findings provide evidence for the involvement of molecular mediators including proteins and microRNAs. Aqueous humor protein composition is characteristically altered during glaucoma progression. Immunohistochemistry analyses indicate that proteins characterizing glaucomatous aqueous humor are released by damaged trabecular meshwork. This feature incudes (a) Nestin, involved in stem cell recruitment and glial cell activation; (b) A Kinase anchor protein, released as consequence of mitochondrial damage and Rho activation establishing cell shape and motility; (c) Actin related protein 2/3 complex, involved in actin polymerization and cell shape maintenance. As established both in vitro and in glaucomatous aqueous humor, trabecular meshwork cells damaged by oxidative stress release extracellular microRNAs inducing glial cell activation, an established pathogenic mechanism in neurodegenerative diseases. Released microRNAs include miR-21 (apoptosis), miR-450 (cell aging, maintenance of contractile tone), miR-107 (Nestin expression, apoptosis), miR-149 (endothelia and extracellular matrix homeostasis). Experimental evidences indicate that the uveoscleral pathway, via suprachoroidal space, can provide a potential route of access from the anterior region to the posterior segment of the eye and could represent the path followed by biologic mediators to reach the inner layer of the peripapillary retina and transmit damage signals from the anterior to posterior segment during glaucoma course.

Genomic and post-genomic effects of anti-glaucoma drugs preservatives in trabecular meshwork.

Oxidative stress plays an important role in glaucoma. Some preservatives of anti-glaucoma drugs, commonly used in glaucoma therapy, can prevent or induce oxidative stress in the trabecular meshwork. The aim of this study is to evaluate cellular and molecular damage induced in trabecular meshwork by preservatives contained in anti-glaucoma drugs. Cell viability (MTT test), DNA fragmentation (Comet test), oxidative DNA damage (8-oxo-dG), and gene expression (cDNA microarray) have been evaluated in trabecular meshwork specimens and in human trabecular meshwork cells treated with benzalkonium chloride, polyQuad, purite, and sofzia-like mixture. Moreover, antimicrobial effectiveness and safety of preservative contents in drugs was tested. In ex vivo experiments, benzalkonium chloride and polyQuad induced high level of DNA damage in trabecular meshwork specimens, while the effect of purite and sofzia were more attenuated. The level of DNA fragmentation induced by benzalkonium chloride was 2.4-fold higher in subjects older than 50 years than in younger subjects. Benzalkonium chloride, and polyQuad significantly increased oxidative DNA damage as compared to sham-treated specimens. Gene expression was altered by benzalkonium chloride, polyQuad, and purite but not by sofzia. In in vitro experiments, benzalkonium chloride and polyQuad dramatically decreased trabecular meshwork cell viability, increased DNA fragmentation, and altered gene expression. A lesser effect was also exerted by purite and sofzia. Genes targeted by these alterations included Fas and effector caspase-3. The efficacy of the preservatives in inhibiting bacterial growth increased the adverse effects in trabecular meshwork in terms of DNA damage and alteration of gene expression. Presented data indicates the delicate balance between efficacy and safety of drug preservatives as not yet optimized.

On a spike train probability model with interacting neural units.

We investigate an extension of the spike train stochastic model based on the conditional intensity, in which the recovery function includes an interaction between several excitatory neural units. Such function is proposed as depending both on the time elapsed since the last spike and on the last spiking unit. Our approach, being somewhat related to the competing risks model, allows to obtain the general form of the interspike distribution and of the probability of consecutive spikes from the same unit. Various results are finally presented in the two cases when the free firing rate function (i) is constant, and (ii) has a sinusoidal form.

Quantitative analysis of scanning tunneling microscopy images of mixed-ligand-functionalized nanoparticles.

Ligand-protected gold nanoparticles exhibit large local curvatures, features rapidly varying over small scales, and chemical heterogeneity. Their imaging by scanning tunneling microscopy (STM) can, in principle, provide direct information on the architecture of their ligand shell, yet STM images require laborious analysis and are challenging to interpret. Here, we report a straightforward, robust, and rigorous method for the quantitative analysis of the multiscale features contained in STM images of samples consisting of functionalized Au nanoparticles deposited onto Au/mica. The method relies on the analysis of the topographical power spectral density (PSD) and allows us to extract the characteristic length scales of the features exhibited by nanoparticles in STM images. For the mixed-ligand-protected Au nanoparticles analyzed here, the characteristic length scale is 1.2 ± 0.1 nm, whereas for the homoligand Au NPs this scale is 0.75 ± 0.05 nm. These length scales represent spatial correlations independent of scanning parameters, and hence the features in the PSD can be ascribed to a fingerprint of the STM contrast of ligand-protected nanoparticles. PSD spectra from images recorded at different laboratories using different microscopes and operators can be overlapped across most of the frequency range, proving that the features in the STM images of nanoparticles can be compared and reproduced.

High-resolution scanning tunneling microscopy characterization of mixed monolayer protected gold nanoparticles.

Gold nanoparticles protected by a binary mixture of thiolate molecules have a ligand shell that can spontaneously separate into nanoscale domains. Complex morphologies arise in such ligand shells, including striped, patchy, and Janus domains. Characterization of these morphologies remains a challenge. Scanning tunneling microscopy (STM) imaging has been one of the key approaches to determine these structures, yet the imaging of nanoparticles' surfaces faces difficulty stemming from steep surface curvature, complex molecular structures, and the possibility of imaging artifacts in the same size range. Images obtained to date have lacked molecular resolution, and only domains have been resolved. There is a clear need for images that resolve the molecular arrangement that leads to domain formation on the ligand shell of these particles. Herein we report an advance in the STM imaging of gold nanoparticles, revealing some of the molecules that constitute the domains in striped and Janus gold nanoparticles. We analyze the images to determine molecular arrangements on parts of the particles, highlight molecular "defects" present in the ligand shell, show persistence of the features across subsequent images, and observe the transition from quasi-molecular to domain resolution. The ability to resolve single molecules in the ligand shell of nanoparticles could lead to a more comprehensive understanding of the role of the ligand structure in determining the properties of mixed-monolayer-protected gold nanoparticles.

Scalable patterning of one-dimensional dangling bond rows on hydrogenated Si(001).

Silicon dangling bonds exposed on the monohydride silicon (001) (Si(001):H) surface are highly reactive, thus enabling site-selective absorption of atoms and single molecules into custom patterns designed through the controlled removal of hydrogen atoms. Current implementations of high-resolution hydrogen lithography on the Si(001):H surface rely on sequential removal of hydrogen atoms using the tip of a scanning probe microscope. Here, we present a scalable thermal process that yields very long rows of single dimer wide silicon dangling bonds suitable for self-assembly of atoms and molecules into one-dimensional structures of unprecedented length on Si(001):H. The row consists of the standard buckled Si dimer and an unexpected flat dimer configuration.

Interferon-related transcriptome alterations in the cerebrospinal fluid cells of Aicardi-Goutières patients.

Aicardi-Goutières syndrome (AGS) is a rare interferon (IFN)-related encephalopathy with onset during the first year of life. AGS, is clinically characterized by progressive microcephaly, bilateral basal ganglia calcification, cerebral atrophy, cerebrospinal fluid (CSF), lymphocytosis, delayed development of psychomotor abilities with pyramidal-extrapyramidal syndrome and mimics congenital viral infections. Microarray analysis examining the expression of 18 880 human genes has been applied to the CSF lymphocytes of 20 AGS cases (age 4.5 +/- 4.4 years, mean +/- standard deviation) characterized by high IFN-alpha levels in CSF and 20 matched controls (age 4.4 +/- 4.3 years, mean +/- standard deviation). Gene-expression data reveal significant differences between AGS cases and controls for all controls and 18 AGS cases. The two AGS cases unclassified as compared with controls were both older than 7 years. AGS cases presented upregulation of genes involved in IFN-dependent pathways and lymphocyte functions, paralleled by the downregulation of genes encoding for angiopoietic activities. The cystatin F and DNAJ genes, having a negative feedback on IFN pathways, underwent a progressive age-related increase in their expression. These gene-expression signature parallels a progressive attenuation of clinical symptoms with age. Obtained results provide evidence that exposure to IFN-alpha is harmful for developing brain.

Modulation of cigarette smoke-related end-points in mutagenesis and carcinogenesis.

The epidemic of lung cancer and the increase of other tumours and chronic degenerative diseases associated with tobacco smoking have represented one of the most dramatic catastrophes of the 20th century. The control of this plague is one of the major challenges of preventive medicine for the next decades. The imperative goal is to refrain from smoking. However, chemoprevention by dietary and/or pharmacological agents provides a complementary strategy, which can be targeted not only to current smokers but also to former smokers and passive smokers. This article summarises the results of studies performed in our laboratories during the last 10 years, and provides new data generated in vitro, in experimental animals and in humans. We compared the ability of 63 putative chemopreventive agents to inhibit the bacterial mutagenicity of mainstream cigarette smoke. Modulation by ethanol and the mechanisms involved were also investigated both in vitro and in vivo. Several studies evaluated the effects of dietary chemopreventive agents towards smoke-related intermediate biomarkers in various cells, tissues and organs of rodents. The investigated end-points included metabolic parameters, adducts to haemoglobin, bulky adducts to nuclear DNA, oxidative DNA damage, adducts to mitochondrial DNA, apoptosis, cytogenetic damage in alveolar macrophages, bone marrow and peripheral blood erytrocytes, proliferation markers, and histopathological alterations. The agents tested in vivo included N-acetyl-L-cysteine, 1,2-dithiole-3-thione, oltipraz, phenethyl isothiocyanate, 5,6-benzoflavone, and sulindac. We started applying multigene expression analysis to chemoprevention research, and postulated that an optimal agent should not excessively alter per se the physiological background of gene expression but should be able to attenuate the alterations produced by cigarette smoke or other carcinogens. We are working to develop an animal model for the induction of lung tumours following exposure to cigarette smoke. The most encouraging results were so far obtained in models using A/J mice and Swiss albino mice. The same smoke-related biomarkers used in animal studies can conveniently be applied to human chemoprevention studies. We participated in trials evaluating the effects of N-acetyl-L-cysteine and oltipraz in smokers from Italy, The Netherlands, and the People's Republic of China. We are trying to develop a pharmacogenomic approach, e.g. based on genetic metabolic polymorphisms, aimed at predicting not only the risk of developing cancer but also the individual responsiveness to chemopreventive agents.