Role of traditional and new biomarkers in breast carcinogenesis

In recent decades, several biomarkers have been investigated as predictors of breast cancer risk, development, prognosis and treatment efficacy

Anharmonic calculations of vibrational spectra for molecular adsorbates: A divide-and-conquer semiclassical molecular dynamics approach

The vibrational spectroscopy of adsorbates is becoming an important investigation tool for catalysis and material science. This paper presents a semiclassical molecular dynamics method able to reproduce the vibrational energy levels of systems composed by molecules adsorbed on solid surfaces. Specifically, we extend our divide-and-conquer semiclassical method for power spectra calculations to gas-surface systems and interface it with plane-wave electronic structure codes. The Born-Oppenheimer classical dynamics underlying the semiclassical calculation is full dimensional, and our method includes not only the motion of the adsorbate but also those of the surface and the bulk. The vibrational spectroscopic peaks related to the adsorbate are accounted together with the most coupled phonon modes to obtain spectra amenable to physical interpretations. We apply the method to the adsorption of CO, NO, and H2O on the anatase-TiO2 (101) surface. We compare our semiclassical results with the single-point harmonic estimates and the classical power spectra obtained from the same trajectory employed in the semiclassical calculation. We find that CO and NO anharmonic effects of fundamental vibrations are similarly reproduced by the classical and semiclassical dynamics and that H2O adsorption is fully and properly described in its overtone and combination band relevant components only by the semiclassical approach

Shaping and Dilating the Fitness Landscape for Parameter Estimation in Stochastic Biochemical Models

The parameter estimation (PE) of biochemical reactions is one of the most challenging tasks in systems biology given the pivotal role of these kinetic constants in driving the behavior of biochemical systems. PE is a non-convex, multi-modal, and non-separable optimization problem with an unknown fitness landscape; moreover, the quantities of the biochemical species appearing in the system can be low, making biological noise a non-negligible phenomenon and mandating the use of stochastic simulation. Finally, the values of the kinetic parameters typically follow a log-uniform distribution; thus, the optimal solutions are situated in the lowest orders of magnitude of the search space. In this work, we further elaborate on a novel approach to address the PE problem based on a combination of adaptive swarm intelligence and dilation functions (DFs). DFs require prior knowledge of the characteristics of the fitness landscape; therefore, we leverage an alternative solution to evolve optimal DFs. On top of this approach, we introduce surrogate Fourier modeling to simplify the PE, by producing a smoother version of the fitness landscape that excludes the high frequency components of the fitness function. Our results show that the PE exploiting evolved DFs has a performance comparable with that of the PE run with a custom DF. Moreover, surrogate Fourier modeling allows for improving the convergence speed. Finally, we discuss some open problems related to the scalability of our methodology

Substituted nano-hydroxyapatite toothpastes reduce biofilm formation on enamel and resin-based composite surfaces

Background: Toothpastes containing nano-hydroxyapatite (n-HAp) substituted with metal ions provide calcium and phosphate ions to dental hard tissues, reducing demineralization, and promoting remineralization. Few data are available about the effect of these bioactive compounds on oral microbiota. Methods: This in vitro study evaluated the influence of two commercially-available substituted n-HAp-based toothpastes (\u3b1: Zn-carbonate substituted n-HAp; \u3b2: F, Mg, Sr-carbonate substituted n-HAp) on early colonization (EC, 12 h) and biofilm formation (BF, 24 h) by oral microbiota. Controls were brushed with distilled water. Artificial oral microcosm and Streptococcus mutans biofilms were developed using human enamel and a resin-based composite (RBC) as adherence surfaces. Two test setups, a shaking multiwell plate and a modified drip-flow reactor (MDFR), were used to simulate clinical conditions during the night (low salivary flow and clearance) and daytime, respectively. Energy-dispersive X-ray spectrometry (EDS) was used to evaluate specimens\u2019 surfaces after toothpaste treatment. Fluoride release from \u3b2 toothpaste was evaluated. Viable adherent biomass was quantified by MTT assay, and biofilms\u2019 morphology was highlighted using confocal microscopy. Results: EDS showed the presence of remnants from the tested toothpastes on both adherence surfaces. \u3b2 toothpaste showed significantly lower EC and BF compared to control using the artificial oral microcosm model, while \u3b1 toothpaste showed lower EC and BF compared to control, but higher EC and BF compared to \u3b2 toothpaste. The effect shown by \u3b2 toothpaste was, to a minimal extent, due to fluoride release. Interestingly, this result was seen on both adherence surfaces, meaning that the tested toothpastes significantly influenced EC and BF even on RBC surfaces. Furthermore, the effect of toothpaste treatments was higher after 12 h than 24 h, suggesting that toothbrushing twice a day is more effective than brushing once. Conclusions: The efficacy of these treatments in reducing microbial colonization of RBC surfaces may represent a promising possibility in the prevention of secondary caries

Elective surgery for colorectal cancer in the aged: a clinical-economical evaluation.

A series of 56 consecutive patients, referred for surgery to a specialized institute, had elective laparotomies with various surgical procedures aimed at curing locoregional colorectal cancer. Data defining patient and tumour-related preoperative, operative and postoperative variables, including costs, were collected. The study group was divided into two age groups (< 65 vs > or = 65 years), which were similar in terms of patient- and tumour-related variables. Differences were not statistically significant (Pounds 440; 95% exact CI; Pounds -50; 1800). There is no evidence to suggest that there are any total charge differences in treating the two age groups, as confirmed by the cost analysis

MAGNETO: cell type marker panel generator from single-cell transcriptomic data

Single-cell RNA sequencing experiments produce data useful to identify different cell types, including uncharacterized and rare ones. This enables us to study the specific functional roles of these cells in different microenvironments and contexts. After identifying a (novel) cell type of interest, it is essential to build succinct marker panels, composed of a few genes referring to cell surface proteins and clusters of differentiation molecules, able to discriminate the desired cells from the other cell populations. In this work, we propose a fully-automatic framework called MAGNETO, which can help construct optimal marker panels starting from a single-cell gene expression matrix and a cell type identity for each cell. MAGNETO builds effective marker panels solving a tailored bi-objective optimization problem, where the first objective regards the identification of the genes able to isolate a specific cell type, while the second conflicting objective concerns the minimization of the total number of genes included in the panel. Our results on three public datasets show that MAGNETO can identify marker panels that identify the cell populations of interest better than state-of-the-art approaches. Finally, by fine-tuning MAGNETO, our results demonstrate that it is possible to obtain marker panels with different specificity levels

Molecular basis of autotrophic vs mixotrophic growth in Chlorella sorokiniana

In this work, we investigated the molecular basis of autotrophic vs. mixotrophic growth of Chlorella sorokiniana, one of the most productive microalgae species with high potential to produce biofuels, food and high value compounds. To increase biomass accumulation, photosynthetic microalgae are commonly cultivated in mixotrophic conditions, adding reduced carbon sources to the growth media. In the case of C. sorokiniana, the presence of acetate enhanced biomass, proteins, lipids and starch productivity when compared to autotrophic conditions. Despite decreased chlorophyll content, photosynthetic properties were essentially unaffected while differential gene expression profile revealed transcriptional regulation of several genes mainly involved in control of carbon flux. Interestingly, acetate assimilation caused upregulation of phosphoenolpyruvate carboxylase enzyme, enabling potential recovery of carbon atoms lost by acetate oxidation. The obtained results allowed to associate the increased productivity observed in mixotrophy in C. sorokiniana with a different gene regulation leading to a fine regulation of cell metabolism

Fast ion energy distribution from third harmonic radio frequency heating measured with a single crystal diamond detector at the Joint European Torus

Neutron spectroscopy measurements with a single crystal diamond detector have been carried out at JET, for the first time in an experiment aimed at accelerating deuterons to MeV energies with radio frequency heating at the third harmonic. Data are interpreted by means of the expected response function of the detector and are used to extract parameters of the highly non-Maxwellian distribution function generated in this scenario. A comparison with observations using a time of flight and liquid scintillator neutron spectrometers is also presented. The results demonstrate the capability of diamond detectors to contribute to fast ion physics studies at JET and are of more general relevance in view of the application of such detectors for spectroscopy measurements in the neutron camera of next step tokamak devices.EURATOM 63305