Stochastic Analysis and Regeneration of Rough Surfaces

We investigate Markov property of rough surfaces. Using stochastic analysis we characterize the complexity of the surface roughness by means of a Fokker-Planck or Langevin equation. The obtained Langevin equation enables us to regenerate surfaces with similar statistical properties compared with the observed morphology by atomic force microscopy.Comment: 4 pages, 7 figure

Functionalized Mesoporous Silica Nanoparticles as a Novel Antioxidant Delivery System

Abstract Antioxidants have an important role in control and prevention of dangerous diseases like cancers, but instabilit

Height Fluctuations and Intermittency of V2O5V_2 O_5 Films by Atomic Force Microscopy

The spatial scaling law and intermittency of the $V_2 O_5$ surface roughness by atomic force microscopy has been investigated. The intermittency of the height fluctuations has been checked by two different methods, first, by measuring scaling exponent of q-th moment of height-difference fluctuations i.e. $C_q =$ and the second, by defining generating function $Z(q,N)$ and generalized multi-fractal dimension $D_q$. These methods predict that there is no intermittency in the height fluctuations. The observed roughness and dynamical exponents can be explained by the numerical simulation on the basis of forced Kuramoto-Sivashinsky equation.Comment: 6 pages (two columns), 11 eps. figures, late

Enhanced dynamic functional connectivity (whole-brain chronnectome) in chess experts

Multidisciplinary approaches have demonstrated that the brain is potentially modulated by the long-term acquisition and practice of specific skills. Chess playing can be considered a paradigm for shaping brain function, with complex interactions among brain networks possibly enhancing cognitive processing. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) can be useful to explore the effect of chess playing on whole-brain fluidity/dynamism (the chronnectome). Dynamic connectivity parameters of 18 professional chess players and 20 beginner chess players were evaluated applying spatial independent component analysis (sICA), sliding-time window correlation, and meta-state approaches to rs-fMRI data. Four indexes of meta-state dynamic fluidity were studied: i) the number of distinct meta-states a subject pass through, ii) the number of switches from one meta-state to another, iii) the span of the realized meta-states (the largest distance between two meta-states that subjects occupied), and iv) the total distance travelled in the state space. Professional chess players exhibited an increased dynamic fluidity, expressed as a higher number of occupied meta-states (meta-state numbers, 75.8 ± 7.9 vs 68.8 ± 12.0, p = 0.043 FDR-corrected) and changes from one meta-state to another (meta-state changes, 77.1 ± 7.3 vs 71.2 ± 11.0, p = 0.043 FDR-corrected) than beginner chess players. Furthermore, professional chess players exhibited an increased dynamic range, with increased traveling between successive meta-states (meta-state total distance, 131.7 ± 17.8 vs 108.7 ± 19.7, p = 0.0004 FDR-corrected). Chess playing may induce changes in brain activity through the modulation of the chronnectome. Future studies are warranted to evaluate if these potential effects lead to enhanced cognitive processing and if "gaming" might be used as a treatment in clinical practice

Two-Scale Kirchhoff Theory: Comparison of Experimental Observations With Theoretical Prediction

We introduce a non-perturbative two scale Kirchhoff theory, in the context of light scattering by a rough surface. This is a two scale theory which considers the roughness both in the wavelength scale (small scale) and in the scales much larger than the wavelength of the incident light (large scale). The theory can precisely explain the small peaks which appear at certain scattering angles. These peaks can not be explained by one scale theories. The theory was assessed by calculating the light scattering profiles using the Atomic Force Microscope (AFM) images, as well as surface profilometer scans of a rough surface, and comparing the results with experiments. The theory is in good agreement with the experimental results.Comment: 6 pages, 8 figure

Dissemination in time and space in presymptomatic granulin mutation carriers: a GENFI spatial chronnectome study

The presymptomatic brain changes of granulin (GRN) disease, preceding by years frontotemporal dementia, has not been fully characterized. New approaches focus on the spatial chronnectome can capture both spatial network configurations and their dynamic changes over time. To investigate the spatial dynamics in 141 presymptomatic GRN mutation carriers and 282 noncarriers from the Genetic Frontotemporal dementia research Initiative cohort. We considered time-varying patterns of the default mode network, the language network, and the salience network, each summarized into 4 distinct recurring spatial configurations. Dwell time (DT) (the time each individual spends in each spatial state of each network), fractional occupacy (FO) (the total percentage of time spent by each individual in a state of a specific network) and total transition number (the total number of transitions performed by each individual in a specifict state) were considered. Correlations between DT, FO, and transition number and estimated years from expected symptom onset (EYO) and clinical performances were assessed. Presymptomatic GRN mutation carriers spent significantly more time in those spatial states characterised by greater activation of the insula and the parietal cortices, as compared to noncarriers (p < 0.05, FDR-corrected). A significant correlation between DT and FO of these spatial states and EYO was found, the longer the time spent in the spatial states, the closer the EYO. DT and FO significantly correlated with performances at tests tapping processing speed, with worse scores associated with increased spatial states’ DT. Our results demonstrated that presymptomatic GRN disease presents a complex dynamic reorganization of brain connectivity. Change in both the spatial and temporal aspects of brain network connectivity could provide a unique glimpse into brain function and potentially allowing a more sophisticated evaluation of the earliest disease changes and the understanding of possible mechanisms in GRN disease

Optimization of Topical Therapy for Leishmania major Localized Cutaneous Leishmaniasis Using a Reliable C57BL/6 Model

When initiating the cutaneous disease named cutaneous leishmaniasis (CL), Leishmania parasites develop within the parasitophorous vacuoles of phagocytes residing in and/or recruited to the dermis, a process leading to more or less chronic dermis and epidermis-damaging inflammatory processes. Topical treatment of CL could be a mainstay in its management. Any improvements of topicals, such as new vehicles and shorter optimal contact regimes, could facilitate their use as an ambulatory treatment. Recently, WR279396, a third-generation aminoglycoside ointment, was designed with the aim to provide stability and optimal bioavailability for the molecules expected to target intracellular Leishmania. Two endpoints were expected to be reached: i) accelerated clearance of the maximal number of parasites, and ii) accelerated and stable repair processes without scars. A mouse model of CL was designed: it relies on the intradermal inoculation of luciferase-expressing Leishmania, allowing for in vivo bioluminescence imaging of the parasite load fluctuation, which can then be quantified simultaneously with the onset and resolution of clinical signs. These quantitative readout assays, deployed in real time, provide robust methods to rapidly assess efficacy of drugs/compounds i) to screen treatment modalities and ii) allow standardized comparison of different therapeutic agents

WR279,396, a Third Generation Aminoglycoside Ointment for the Treatment of Leishmania major Cutaneous Leishmaniasis: A Phase 2, Randomized, Double Blind, Placebo Controlled Study

Cutaneous leishmaniasis is due to a small parasite (Leishmania) that creates disfiguring sores, and affects more than one million persons (mainly children) each year. Treating lesions with a cream—instead of with injections as currently done—would greatly improve the well-being of affected patients. No cream formulation that would be efficient and would not create important skin irritation has been identified yet. Here, we tested a new cream formulation (WR279,396) containing paromomycin and gentamicin, two members of a well-known family of antibacterial antibiotics (aminoglycosides). Injectable paromomycin is efficient in other forms of the disease (visceral leishmaniasis). This was a carefully monitored study (phase 2) involving mainly children in Tunisia and France. The cream was applied twice a day for 20 days. The proportion of patients treated with the paromomycin-containing cream (active formulation) that cured (94%) was higher than that observed (71%) in patients treated with a cream that did not contain the active product (placebo formulation). Local irritation affected less than one-third of the patients and was usually mild. This new cream formulation was safe and effective in treating cutaneous leishmaniasis, thereby providing a new, simple, easily applicable, and inexpensive treatment for this neglected disease

Is Paromomycin an Effective and Safe Treatment against Cutaneous Leishmaniasis? A Meta-Analysis of 14 Randomized Controlled Trials

Millions of people worldwide are suffering from cutaneous leishmaniasis that is caused by parasites of the genus Leishmania. Although pentavalent antimony compounds are the treatment of choice, their use is limited by high cost, poor compliance, and systemic toxicity. Paromomycin was developed to overcome such limitations. However, there is no consensus on its efficacy. This meta-analysis assessed the efficacy and safety of paromomycin compared with placebo and pentavalent antimony compounds. Fourteen randomized controlled trials, including 1,221 patients, met our selection criteria. Topical paromomycin appeared to have therapeutic activity against the old world and new world cutaneous leishmaniasis, with increased local reactions, when combined with methylbenzethonium chloride. Topical paromomycin was not significantly different from intralesional pentavalent antimony compounds in treating the old world form, whereas it was inferior to parenteral pentavalent antimony compounds in treating the new world form. However, a similar efficacy was found between parenteral paromomycin and pentavalent antimony compounds in treating the new world form. Fewer systemic side effects were observed with topical and parenteral paromomycin than pentavalent antimony compounds. These results suggest that topical paromomycin with methylbenzethonium chloride could be a therapeutic alternative to pentavalent antimony compounds for selected cases of the old world cutaneous leishmaniasis

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients