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The effects of the phenolic compounds of extra virgin olive oil (EVOO) on AGS cells have never been studied so far, which is the aim of this study. The profiles of the main phenolic components in EVOOs, mainly secoiridoid compounds derived from the transformation of oleuropein during the olive milling process, were evaluated and compared. Oils of different origins were evaluated aiming at verifying whether chemical differences in the phenolic composition of the dry extracts played a role in the metabolism and in maintaining the cellular redox state of AGS cells. The following key enzymes of some metabolic pathways were studied: lactate dehydrogenase, enolase, pyruvate kinase, glucose 6-phosphate dehydrogenase, citrate synthase, 3-Hydroxyacyl-CoA dehydrogenase and hexokinase. As confirmed through PCA analysis, pretreatments with the dry extracts of EVOOs at different concentrations appeared to be able to counteract the enzymatic activity alterations due to oxidative stress induced by H2O2 1 mM and 2 mM. The studied phytocomplexes showed the ability to protect AGS cells from oxidative damage and the secoiridoid derivatives from both oleuropein and ligstroside contributed to the observed effects. The results suggested that EVOOs with medium to high concentrations of phenols can exert this protection.

Pâté is a by-product of olive oil production which represents an abundant source of phenolic compounds and can be used for food formulation, reducing its environmental impact and promoting a circular economy. In this context, the effects of a hydroalcoholic extract of pâté were evaluated for the first time in an AGS human cell line commonly used as model of gastric mucosa. Pâté was obtained from Tuscan olives; the total phenolic content was 16.6 mg/g dried extract, with verbascoside and secoiridoid derivatives as the most abundant phenols. The phenolic pâté extract did not alter viability, distribution of cell cycle phases or proliferation and migration of AGS cells at the tested concentrations. Seven enzymes were chosen to investigate the metabolic effect of the pâté extract in the context of oxidative stress. Pâté produced a statistically significant increase in the activity of key enzymes of some metabolic pathways: Lactate dehydrogenase, Enolase, Pyruvate kinase, Glucose 6-phosphate dehydrogenase, Citrate synthase, 3-Hydroxyacyl-CoA dehydrogenase and Hexokinase. Pre-treatments with the extract of pâté at 100 µg/mL or 200 µg/mL, as observed through PCA analysis, appeared able to counteract the enzymatic activity alterations due to oxidative stress induced by H2O2 1 mM and 2 mM. The results indicate that dried pâté, due to its phenolic components, can be proposed as a new functional food ingredient.

To compare two left breast cancer patient cohorts (tangential vs. locoregional deep-inspiration breath-hold - DIBH treatment) with different predefined beam gating thresholds and to evaluate their impact on motion management and DIBH stability.An SGRT-based clinical workflow was adopted for the DIBH treatment. Intrafractional monitoring was performed by tracking both the respiratory signal and the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift"). Beam gating tolerances were 5 mm/4 mm for the SGRT shifts and 5 mm/3 mm for the gating window amplitude for breast tangential and breast + lymph nodes locoregional treatments, respectively. A total of 24 patients, 12 treated with a tangential technique and 12 with a locoregional technique, were evaluated for a total number of 684 fractions. Statistical distributions of SGRT shift and respiratory signal for each treatment fraction, for each patient treatment, and for the two population samples were generated.Lateral cumulative distributions of SGRT shifts for both locoregional and tangential samples were consistent with a null shift, whereas longitudinal and vertical ones were slightly negative (mean values 1 mm). The distribution of the percentage of beam on time with SGRT shift 3 mm, 4 mm, or 5 mm was extended toward higher values for the tangential sample than for the locoregional sample. The variability in the DIBH respiration signal was significantly greater for the tangential sample.Different beam gating thresholds for surface-guided DIBH treatment of left breast cancer can impact motion management and DIBH stability by reducing the frequency of the maximum SGRT shift and increasing respiration signal stability when tighter thresholds are adopted.

Pâté is a by-product of olive oil production which represents an abundant source of phenolic compounds and can be used for food formulation, reducing its environmental impact and promoting a circular economy. In this context, the effects of a hydroalcoholic extract of pâté were evaluated for the first time in an AGS human cell line commonly used as model of gastric mucosa. Pâté was obtained from Tuscan olives; the total phenolic content was 16.6 mg/g dried extract, with verbascoside and secoiridoid derivatives as the most abundant phenols. The phenolic pâté extract did not alter viability, distribution of cell cycle phases or proliferation and migration of AGS cells at the tested concentrations. Seven enzymes were chosen to investigate the metabolic effect of the pâté extract in the context of oxidative stress. Pâté produced a statistically significant increase in the activity of key enzymes of some metabolic pathways: Lactate dehydrogenase, Enolase, Pyruvate kinase, Glucose 6-phosphate dehydrogenase, Citrate synthase, 3-Hydroxyacyl-CoA dehydrogenase and Hexokinase. Pre-treatments with the extract of pâté at 100 µg/mL or 200 µg/mL, as observed through PCA analysis, appeared able to counteract the enzymatic activity alterations due to oxidative stress induced by H2O2 1 mM and 2 mM. The results indicate that dried pâté, due to its phenolic components, can be proposed as a new functional food ingredient.

In the field of photodynamic therapy (PDT), optimization of the in vivo therapeutic efficacy needs a comprehensive study of the photo-killing action spectrum that depends on both the photosensitizer (PS) absorption and the tissue optical properties. This is especially true in the case of gastric infections by Helicobacter pylori: PS absorption has been largely investigated in vitro, while the contribution of tissue optical properties and illumination geometry has been poorly studied, despite being parameters that reflect the specific in vivo conditions. To investigate their influence, we focussed on the case of a point-like light source positioned in the antrum. This models a therapeutic device developed by our team which consists of a LED-based ingestible pill. By a simple 3D illumination model, our approach mediates light-tissue interaction over the illuminated stomach wall surface, then calculates its average transmittance T by means of a 1D model representative of the mean gastric mucosa structure. Finally, by merging T(λ) with the photosensitizers' absorption we obtained the in vivo action spectrum. This shows two peaks at about 500 and 630 nm, indicating a noticeable influence of the tissue with respect to in vitro studies, where the action spectrum reflects PS absorption only. Our approach defines one average action spectrum for this specific therapeutic context, which reflects the need to choose one emission spectrum for the light source used. The proposed methodology could be applied to any other illumination geometry of cave organs, provided appropriate model modifications for the light source and tissue characteristics are made.

Helicobacter pylori gastric infections are among the most diffused worldwide, suffering from a rising rate of antibiotic resistance. In this context, some of the authors have previously designed an ingestible device in the form of a luminous capsule to perform antibacterial photodynamic inactivation in the stomach. In this study, the light-emitting capsules were tested to verify the safety of use prior to perform clinical efficacy studies. First, laboratory tests measured the capsule temperature while in function and verified its chemical resistance in conditions mimicking the gastric and gut environments. Second, safety tests in a healthy minipig model were designed and completed, to verify both the capsule integrity and the absence of side effects, associated with its illumination and transit throughout the gastrointestinal tract. To this aim, a capsule administration protocol was defined considering a total of 6 animals with n = 2 treated with 8 capsules, n = 2 treated with 16 capsules and n = 2 controls with no capsule administration. Endoscopies were performed in sedated conditions before–after every capsule administration. Biopsies were taken from the corpus and antrum regions, while the gastric cavity temperature was monitored during illumination. The bench tests confirmed a very good chemical resistance and a moderate (about 3 °C) heating of the capsules. The animal trials showed no significant effects on the gastric wall tissues, both visually and histologically, accompanied with overall good animal tolerance to the treatment. The integrity of the administered capsules was verified as well. These encouraging results pose the basis for the definition of successive trials at the clinical level. Graphical abstract

Aim: The objective of this study was to investigate the possible synergy between doxycycline and photodynamic therapy against Helicobacter pylori and to evaluate the possible side effects on adenocarcinoma gastric cells with and without protoporphyrin IX. Materials & methods: Three H. pylori strains (ATCC 700392, 43504 and 49503) were grown on solid medium either with, or without, doxycycline at subinhibitory concentrations, and irradiated for 10, 20 and 30 minutes with a 400 nm-peaked light source. The phototoxicity tests on AGS cells were evaluated by MTT assay. Results: The photodynamic therapy and doxycycline combination showed an antibacterial synergistic effect with no significant toxicities. Conclusion: The synergistic treatment could be considered as an interesting therapeutic option.

This work inserts in the research field regarding the effects of altered gravity conditions on biological plant processes. Pinus pinea seeds germination was studied in simulated microgravity (2x10−3g) and hypergravity (20g) conditions. The effects of simulated gravity were evaluated monitoring the levels of the key enzymes, involved in the main metabolic pathway during germination process of lipid–rich seeds (oilseeds): isocitrate lyase and malate synthase for glyoxylate cycle, 3-hydroxyacyl-CoA dehydrogenase for beta-oxidation, isocitrate dehydrogenase for Krebs cycle, pyruvate kinase for glycolysis and glucose 6 phosphate dehydrogenase for pentose phosphate shunt. The simulated micro and hypergravity conditions were obtained by a Random Position Machine and a Hyperfuge, respectively. Results show that the levels of some tested enzymes, at different lag times of the germination process, have the same trend of controls (g = 1), but with significant differences from quantitative point of view. They are higher in microgravity conditions and lower in hypergravity ones, suggesting that, from a biochemical point of view, the germination process results accelerated in microgravity conditions and delayed in hypergravity ones. These biochemical results show a good correlation with morphological ones, obtained with the measurement of the length of the seeds sprouting radicle. These results give promising indications regarding the possibility to grow plant with lipid-rich seeds in spatial environment, to obtain food sources for astronauts during long term space missions and to reconstitute new atmosphere.

Cell staining techniques are well established in cell biology and associated with a broad range of dedicated dyes; however, they are accompanied by non-negligible costs, preparation time and unavoidable alterations of the sample with foreign molecules. In this context, we point out and propose the use of darkfield microscopy (DM) combined with different fixation protocols (to be used anyway) to enhance the different cell structures and districts as a timesaving and inexpensive support to the techniques that need staining or immuno-staining protocols and products. In a first step, we have analysed the effect of different fixation protocols on DM images for various human cellular lines. The presented imaging study shows that cell morphology actually changes with the fixation protocols that enhance, through contrast and luminosity variations, different shapes and patterns and thus structures of the cells. The different chemical action of various fixations, in fact, modifies the local scattering coefficient, thus affecting in a different way the morphology shown by DM images. As a second step we have compared the observed DM morphologies to those of selective fluorescent staining being therefore able to associate them to specific cell districts (e.g. nucleus, membrane or cytoskeleton). The obtained results indicate that this common microscopy technique can give images with particular cellular structures or districts enhanced more than others depending on the choice of fixation protocol. Therefore Darkfield Microscopy can be considered as a simpler, cheaper and faster method to provide morphological indications, respect to staining techniques, even at low and medium magnifications.

Spartium junceum L. is a typical species of Mediterranean shrubland areas, also grown in gardens and parks as an ornamental. In recent years in Europe, S. junceum has been recurrently found to be infected by different subspecies and genotypes of the quarantine regulated bacterium Xylella fastidiosa (Xf). This work presents for the first time the anatomy of S. junceum plants that we found, by means of genetic and immunochemistry analysis, to be naturally infected by Xf subsp. multiplex ST87 (XfmST87) in Monte Argentario (Grosseto, Tuscany, Italy), a new outbreak area within the EU. Our anatomical observations showed that bacteria colonized exclusively the xylem conductive elements and moved horizontally to adjacent vessels through pits. Interestingly, a pink/violet matrix was observed with Toluidine blue staining in infected conduits indicating a high content of acidic polysaccharides. In particular, when this pink-staining matrix was observed, bacterial cells were either absent or degenerated, suggesting that the matrix was produced by the host plant as a defense response against bacterial spread. In addition, a blue-staining phenolic material was found in the vessels and, at high concentration, in the pits and inter-vessels. SEM micrographs confirmed that polysaccharide and phenolic components showed different structures, which appear to be related to two different morphologies: fibrillary and granular, respectively. Moreover, our LM observations revealed bacterial infection in xylem conductive elements of green shoots and leaves only, and not in those of other plant organs such as roots and flowers.

Purpose We investigate, by an extensive quality evaluation approach, performances and potential side effects introduced in Computed Tomography (CT) images by Deep Learning (DL) processing. Method We selected two relevant processing steps, denoise and segmentation, implemented by two Convolutional Neural Networks (CNNs) models based on autoencoder architecture (encoder-decoder and UNet) and trained for the two tasks. In order to limit the number of uncontrolled variables, we designed a phantom containing cylindrical inserts of different sizes, filled with iodinated contrast media. A large CT image dataset was collected at different acquisition settings and two reconstruction algorithms. We characterized the CNNs behavior using metrics from the signal detection theory, radiological and conventional image quality parameters, and finally unconventional radiomic features analysis. Results The UNet, due to the deeper architecture complexity, outperformed the shallower encoder-decoder in terms of conventional quality parameters and preserved spatial resolution. We also studied how the CNNs modify the noise texture by using radiomic analysis, identifying sensitive and insensitive features to the denoise processing. Conclusions The proposed evaluation approach proved effective to accurately analyze and quantify the differences in CNNs behavior, in particular with regard to the alterations introduced in the processed images. Our results suggest that even a deeper and more complex network, which achieves good performances, is not necessarily a better network because it can modify texture features in an unwanted way.

Since many years it has been acknowledged that some bacterial species, among which H. pylori, P. aeruginosa, P. acnes accumulate endogenous photosensitizers (PS) in the form of porphyrins. This makes antibacterial photodynamic therapy (PDT) easier to perform due to the possible avoidance of external PS. In this study, we focus on gastric infections associated with the presence of Helicobacter pylori (H. pylori), known to accumulate and release both protoporphyrin IX (PPIX) and coproporphyrins. PDT versus H. pylori can be carried out by modified endoscopes or by new ingestible luminous devices under development. In both cases of in vitro and in vivo applications, either for therapy (PDT) or diagnosis, scientific literature lacks studies on the possible side-effects of light treatments on the surrounding tissues. To this aim we evaluated in vitro side-effects due to a possible intrinsic photosensitivity of gastric mucosa or to a photosensitization by the PS released from the bacterium itself. Photo-toxicity studies were conducted on the AGS cell line (ATCC® CRL-1739™), commonly used as a model for the stomach mucosa tissue, considering PPIX as the photosensitizing agent. After first evaluations of PPIX dark toxicity, its uptake and accumulation sites, photo-toxicity tests were conducted using a LED light source peaked at 400 nm, by varying both PPIX concentration (50 nM – 2 μM) and light dose in the range 0.6–13 J/cm2, representing different treatment procedures found in literature. The oxidative stress consequent to irradiation was investigated both in terms of ROS production and assessment of the activity of enzymes involved in ROS-related biological mechanisms. A significant phototoxic effect was found only for PPIX concentration > 100 nM for all tested light doses. This indicates that the evaluated photo-treatments do not cause side effects even with the sensitization due to PPIX released by the bacteria.

Scratch assay is an easy and widely used "in vitro" technique to study cell migration and proliferation. In this work we focus on its modelling and on the capability to distinguish between these two phenomena that the simpler and common models are not able to disentangle. We adapted a model based on reaction-diffusion equation for being used with common microscopy instruments/data and therefore taking place in the gap between simpler modelling approaches and complex ones. An optimized image analysis pipeline and numerical least-squares fit provide estimates of the scratch proliferation and diffusion coefficients l and D. This work is intended as a first of a series in which the model is tested and its robustness and reproducibility are evaluated. Test samples were NIH3T3 cells scratch assays with proliferation and migration stimulated by varying the foetal bovine serum amount in the culture medium (10%, 7.5%, 5% and 2.5%). Results demonstrate, notwithstanding an expected l-D anticorrelation, the model capability to disentangle them. The 7.5% serum treatment can be identified as the model sensitivity limit. Treat-control l and D variations showed an intra-experiment reproducibility (∼±0.05∕h and ∼±200μm2∕h respectively) consistent with single fit typical uncertainties (∼±0.02∕h and ∼±300μm2∕h respectively).

We present a darkfield optical microspectroscopy technique devoted to the disentangled measurement of the absorption and scattering cross sections of nanoparticle (NP) samples with variable concentration. The robustness of the method, including the needed instrumental calibrations, is examined in detail by analyzing and quantifying the major sources of statistic and systematic errors. As an exemplary case, results are presented on a gold NP colloid. The technique takes advantage of a simple inverted microscope, coupled with a spectrograph and equipped with a darkfield condenser and a variable numerical aperture objective to obtain spectra either in darkfield or brightfield optical configurations. By adopting the Lambert-Beer (LB) equation modeling, we were able to disentangle and measure with a single setup the absorption, scattering, and extinction coefficients of the same sample by combining three spectra, obtained by opportunely varying the objective numerical aperture. Typical plasmonic resonances were recognized at approximately 520 and 750 nm. Optical coefficients were measured as a function of particle number density (0.04-3.94 µm(-3), corresponding to 40 µM-4 mM nominal Au concentration) and good linearity was verified up to ∼1.5 µm(-3) (∼1 mM Au). Moreover, extinction and scattering cross sections were quantified and the validity of the LB approximation was reviewed. Besides its applications to plasmonic NPs, this method may be appropriate for any colloid, provided there exists a characteristic spectral feature in the ultraviolet-visible-near infrared range. This technique may be exploited to localize NPs in biological samples.

We present a SINFONI integral field kinematical study of 33 galaxies at z~3 from the AMAZE and LSD projects which are aimed at studying metallicity and dynamics of high-redshift galaxies. The number of galaxies analyzed in this paper constitutes a significant improvement compared to existing data in the literature and this is the first time that a dynamical analysis is obtained for a relatively large sample of galaxies at z~3. 11 galaxies show ordered rotational motions (~30% of the sample), in these cases we estimate dynamical masses by modeling the gas kinematics with rotating disks and exponential mass distributions. We find dynamical masses in the range 2 \times 10^9 M\odot - 2 \times 10^11 M\odot with a mean value of ~ 2 \times 10^10 M\odot. By comparing observed gas velocity dispersion with that expected from models, we find that most rotating objects are dynamically "hot", with intrinsic velocity dispersions of the order of ~90 km s-1. The median value of the ratio between the maximum disk rotational velocity and the intrinsic velocity dispersion for the rotating objects is 1.6, much lower than observed in local galaxies value (~10) and slightly lower than the z~2 value (2 - 4). Finally we use the maximum rotational velocity from our modeling to build a baryonic Tully-Fisher relation at z~3. Our measurements indicate that z~3 galaxies have lower stellar masses (by a factor of ten on average) compared to local galaxies with the same dynamical mass. However, the large observed scatter suggests that the Tully-Fisher relation is not yet "in place" at these early cosmic ages, possibly due to the young age of galaxies. A smaller dispersion of the Tuly-Fisher relation is obtained by taking into account the velocity dispersion with the use of the S_0.5 indicator, suggesting that turbulent motions might have an important dynamical role., A&A accepted

In the framework of the increasing phenomenon of antibiotic-resistant infections, those caused by Helicobacter pylori (Hp) have a particular significance, being worldwide diffused and associated with severe pathologies, among which gastric cancer. To overcome antibiotic-resistance, we propose the use of photodynamic therapy (PDT), based upon cytotoxic species production following bacteria illumination with visible light. In the case of Hp infection, this is due to the presence of endogenous light absorbers (porphyrins). To perform intra-gastric PDT, we have recently designed an illuminating ingestible device equipped with LED sources, where a crucial parameter is the choice of the emission wavelengths optimizing Hp photo-killing. For this purpose, both porphyrin absorption peaks and optical penetration in tissues have to be carefully accounted. By merging data on Hp porphyrin absorption spectrum with those coming by a Monte-Carlo optical modelling for illumination of the stomach wall surface, we have calculated the relative Hp photo-killing efficacy in three representative tissue models in the 400-650nm range. Results indicate that in thicker models, the red wavelengths are ultimately more effective than the blue-shifted ones, due to the greater penetration length in tissues despite a minor porphyrin absorption.

In the fields of nanomedicine, biophotonics and radiation therapy, nanoparticle (NP) detection in cell models often represents a fundamental step for many in vivo studies. One common question is whether NPs have or have not interacted with cells. In this context, we propose an imaging based technique to detect the presence of NPs in eukaryotic cells. Darkfield images of cell cultures at low magnification (10x) are acquired in different spectral ranges and recombined so as to enhance the contrast due to the presence of NPs. Image analysis is applied to extract cell-based parameters (i.e. mean intensity), which are further analyzed by statistical tests (Student's t-test, permutation test) in order to obtain a robust detection method. By means of a statistical sample size analysis, the sensitivity of the whole methodology is quantified in terms of the minimum cell number that is needed to identify the presence of NPs. The method is presented in the case of HeLa cells incubated with gold nanorods labeled with anti-CA125 antibodies, which exploits the overexpression of CA125 in ovarian cancers. Control cases are considered as well, including PEG-coated NPs and HeLa cells without NPs. (C) 2016 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica.

We show that the mass-metallicity relation observed in the local universe is due to a more general relation between stellar mass M*, gas-phase metallicity and SFR. Local galaxies define a tight surface in this 3D space, the Fundamental Metallicity Relation (FMR), with a small residual dispersion of ~0.05 dex in metallicity, i.e, ~12%. At low stellar mass, metallicity decreases sharply with increasing SFR, while at high stellar mass, metallicity does not depend on SFR. High redshift galaxies, up to z~2.5 are found to follow the same FMR defined by local SDSS galaxies, with no indication of evolution. The evolution of the mass-metallicity relation observed up to z=2.5 is due to the fact that galaxies with progressively higher SFRs, and therefore lower metallicities, are selected at increasing redshifts, sampling different parts of the same FMR. By introducing the new quantity mu_alpha=log(M*)-alpha log(SFR), with alpha=0.32, we define a projection of the FMR that minimizes the metallicity scatter of local galaxies. The same quantity also cancels out any redshift evolution up to z~2.5, i.e, all galaxies have the same range of values of mu_0.32. At z>2.5, evolution of about 0.6 dex off the FMR is observed, with high-redshift galaxies showing lower metallicities. The existence of the FMR can be explained by the interplay of infall of pristine gas and outflow of enriched material. The former effect is responsible for the dependence of metallicity with SFR and is the dominant effect at high-redshift, while the latter introduces the dependence on stellar mass and dominates at low redshift. The combination of these two effects, together with the Schmidt-Kennicutt law, explains the shape of the FMR and the role of mu_0.32. The small metallicity scatter around the FMR supports the smooth infall scenario of gas accretion in the local universe.

The metal content in galaxies provides important information on the physical processes responsible for galaxy formation, but little was known for galaxies at z > 3, when the Universe was less than 15% of its current age. We report on our metallicity survey of galaxies at z > 3 using SINFONI at the VLT. We find that at z > 3, low-mass galaxies obey the same fundamental relation between metallicity, mass and star formation rate as at 0 < z < 2.5; however, at z > 3 massive galaxies deviate from this relation, being more metal-poor. In some of these massive galaxies we can even map the gas metallicity. We find that galaxies at z > 3.3 have regular rotation, though highly turbulent, and inverted abundance gradients relative to local galaxies, with lower abundances near the centre, close to the most active regions of star formation. Overall the results suggest that prominent inflow of pristine gas is responsible for the strong chemical evolution observed in galaxies at z > 3.

We present a darkfield optical microspectroscopy technique devoted to the disentangled measurement of the absorption and scattering cross sections of nanoparticle (NP) samples with variable concentration. The robustness of the method, including the needed instrumental calibrations, is examined in detail by analyzing and quantifying the major sources of statistic and systematic errors. As an exemplary case, results are presented on a gold NP colloid. The technique takes advantage of a simple inverted microscope, coupled with a spectrograph and equipped with a darkfield condenser and a variable numerical aperture objective to obtain spectra either in darkfield or brightfield optical configurations. By adopting the Lambert-Beer (LB) equation modeling, we were able to disentangle and measure with a single setup the absorption, scattering, and extinction coefficients of the same sample by combining three spectra, obtained by opportunely varying the objective numerical aperture. Typical plasmonic resonances were recognized at approximately 520 and 750 nm. Optical coefficients were measured as a function of particle number density (0.04-3.94 µm(-3), corresponding to 40 µM-4 mM nominal Au concentration) and good linearity was verified up to ∼1.5 µm(-3) (∼1 mM Au). Moreover, extinction and scattering cross sections were quantified and the validity of the LB approximation was reviewed. Besides its applications to plasmonic NPs, this method may be appropriate for any colloid, provided there exists a characteristic spectral feature in the ultraviolet-visible-near infrared range. This technique may be exploited to localize NPs in biological samples.

Background The interest for gold nanorods in biomedical optics is driven by their intense absorbance of near infrared light, their biocompatibility and their potential to reach tumors after systemic administration. Examples of applications include the photoacoustic imaging and the photothermal ablation of cancer. In spite of great current efforts, the selective delivery of gold nanorods to tumors through the bloodstream remains a formidable challenge. Their bio-conjugation with targeting units, and in particular with antibodies, is perceived as a hopeful solution, but the complexity of living organisms complicates the identification of possible obstacles along the way to tumors. Results Here, we present a new model of gold nanorods conjugated with anti-cancer antigen 125 (CA125) antibodies, which exhibit high specificity for ovarian cancer cells. We implement a battery of tests in vitro, in order to simulate major nuisances and predict the feasibility of these particles for intravenous injections. We show that parameters like the competition of free CA125 in the bloodstream, which could saturate the probe before arriving at the tumors, the matrix effect and the interference with erythrocytes and phagocytes are uncritical. Conclusions Although some deterioration is detectable, anti-CA125-conjugated gold nanorods retain their functional features after interaction with blood tissue and so represent a powerful candidate to hit ovarian cancer cells. Electronic supplementary material The online version of this article (doi:10.1186/s12951-014-0055-3) contains supplementary material, which is available to authorized users.

We present a darkfield optical microspectroscopy technique devoted to the disentangled measurement of the absorption and scattering cross sections of nanoparticle (NP) samples with variable concentration. The robustness of the method, including the needed instrumental calibrations, is examined in detail by analyzing and quantifying the major sources of statistic and systematic errors. As an exemplary case, results are presented on a gold NP colloid. The technique takes advantage of a simple inverted microscope, coupled with a spectrograph and equipped with a darkfield condenser and a variable numerical aperture objective to obtain spectra either in darkfield or brightfield optical configurations. By adopting the Lambert-Beer (LB) equation modeling, we were able to disentangle and measure with a single setup the absorption, scattering, and extinction coefficients of the same sample by combining three spectra, obtained by opportunely varying the objective numerical aperture. Typical plasmonic resonances were recognized at approximately 520 and 750 nm. Optical coefficients were measured as a function of particle number density (0.04-3.94 mu m(-3), corresponding to 40 mu M-4 mM nominal Au concentration) and good linearity was verified up to approximate to 1.5 mu m(-3) (approximate to 1 mM Au). Moreover, extinction and scattering cross sections were quantified and the validity of the LB approximation was reviewed. Besides its applications to plasmonic NPs, this method may be appropriate for any colloid, provided there exists a characteristic spectral feature in the ultraviolet-visible-near infrared range. This technique may be exploited to localize NPs in biological samples. Microsc. Res. Tech. 77:886-895, 2014. (c) 2014 Wiley Periodicals, Inc.

It has recently been suggested that galaxies in the early Universe can grow through the accretion of cold gas, and that this may have been the main driver of star formation and stellar mass growth. Because the cold gas is essentially primordial, it has a very low abundance of elements heavier than helium (metallicity). As it is funneled to the centre of a galaxy, it will lead the central gas having an overall lower metallicity than gas further from the centre, because the gas further out has been enriched by supernovae and stellar winds, and not diluted by the primordial gas. Here we report chemical abundances across three rotationally-supported star-forming galaxies at z~3, only 2 Gyr after the Big Bang. We find an 'inverse' gradient, with the central, star forming regions having a lower metallicity than less active ones, opposite to what is seen in local galaxies. We conclude that the central gas has been diluted by the accretion of primordial gas, as predicted by 'cold flow' models., To Appear in Nature Oct 14, 2010; Supplementary Information included here

Introduction In the framework of the growing rate of antibiotic-resistance, new therapeutic solutions are being considered against bacterial infections, among which photodynamic therapy (PDT) is a very attractive perspective. In recent years, innovative solutions for endoscopic illumination have been studied, e.g. for catheter infections, pancreas tumours and stomach infections by Helicobacter pylori (Hp) . Hp colonizes the human stomach with a worldwide infection prevalence exceeding 50%, besides being a class 1 carcinogen agent (World Health Organization). Currently, Hp infection is treated with pharmacologic therapies, showing high failure rates mainly due to antibiotic resistance. To overcome this limitation, endoscopic PDT devices have been tested. However, they exhibit clear disadvantages, namely great invasivity and adverse effects. Purpose To design and characterize a non-invasive light-emitting device to perform Hp phototherapy: an ingestible “LED antibiotic”, exploiting the presence of endogenous Hp photosensitizers. Materials and methods Merging experimental and simulation methods we obtain the light action spectrum for Hp phototherapy in the gastric environment. We have designed and assembled the pill containing LED sources, a battery and electronic board. Capsule emission parameters are measured by an integrating sphere and in vitro Hp irradiation performed. Results The action spectrum for Hp phototherapy is peaked in the violet and red spectrum regions. Capsule prototypes show emission parameters compatible with in vitro Hp eradication (>99% killing). Conclusion Our device has shown emission spectrum, intensity and duration compatible with an effective phototherapy of Hp , considering also the treatment repeatability (5–10 capsules in 2–3 weeks). Future clinical trials are envisaged. Disclosure GR, GT, BO and FF disclose being also Probiomedica srl ( www.probiomedica.com ).

We measure the black hole mass in the nearby active galaxy Centaurus A (NGC 5128) using a new method based on spectroastrometry of a rotating gas disk. The spectroastrometric approach consists in measuring the photocenter position of emission lines for different velocity channels. In a previous paper we focused on the basic methodology and the advantages of the spectroastrometric approach with a detailed set of simulations demonstrating the possibilities for black hole mass measurements going below the conventional spatial resolution. In this paper we apply the spectroastrometric method to multiple longslit and integral field near infrared spectroscopic observations of Centaurus A. We find that the application of the spectroastrometric method provides results perfectly consistent with the more complex classical method based on rotation curves: the measured BH mass is nearly independent of the observational setup and spatial resolution and the spectroastrometric method allows the gas dynamics to be probed down to spatial scales of ~0.02", i.e. 1/10 of the spatial resolution and ~1/50 of BH sphere of influence radius. The best estimate for the BH mass based on kinematics of the ionized gas is then log(MBH (sin i)^2/M\odot)=7.5 \pm 0.1 which corresponds to MBH = 9.6(+2.5-1.8) \times 10^7 M\odot for an assumed disk inclination of i = 35deg. The complementarity of this method with the classic rotation curve method will allow us to put constraints on the disk inclination which cannot be otherwise derived from spectroastrometry. With the application to Centaurus A, we have shown that spectroastrometry opens up the possibility of probing spatial scales smaller than the spatial resolution, extending the measured MBH range to new domains which are currently not accessible: smaller BHs in the local universe and similar BHs in more distant galaxies.

Galaxy dynamical masses are important physical quantities to constrain galaxy evolutionary models, especially at high redshifts. However, at z~2 the limited signal to noise ratio and spatial resolution of the data usually do not allow spatially resolved kinematical modeling and very often only virial masses can be estimated from line widths. But even such estimates require a good knowledge of galaxy size, which may be smaller than the spatial resolution. Spectroastrometry is a technique which combines spatial and spectral resolution to probe spatial scales significantly smaller than the spatial resolution of the observations. Here we apply it to the case of high-z galaxies and present a method based on spectroastrometry to estimate dynamical masses of high z galaxies, which overcomes the problem of size determination with poor spatial resolution. We construct and calibrate a "spectroastrometric" virial mass estimator, modifying the "classical" virial mass formula. We apply our method to the [O III] or H{\alpha} emission line detected in z~2-3 galaxies from AMAZE, LSD and SINS samples and we compare the spectroastrometric estimator with dynamical mass values resulting from full spatially resolved kinematical modeling. The spectroastrometric estimator is found to be a good approximation of dynamical masses, presenting a linear relation with a residual dispersion of only 0.15 dex. This is a big improvement compared to the "classical" virial mass estimator which has a non linear relation and much larger dispersion (0.47 dex) compared to dynamical masses. By applying our calibrated estimator to 16 galaxies from the AMAZE and LSD samples, we obtain masses in the ~10^7-10^10 M\odot range extending the mass range attainable with dynamical modeling.

We show that the mass-metallicity relation observed in the local universe is due to a more general relation between stellar mass M*, gas-phase metallicity and SFR. Local galaxies define a tight surface in this 3D space, the Fundamental Metallicity Relation (FMR), with a small residual dispersion of ~0.05 dex in metallicity, i.e, ~12%. At low stellar mass, metallicity decreases sharply with increasing SFR, while at high stellar mass, metallicity does not depend on SFR. High redshift galaxies, up to z~2.5 are found to follow the same FMR defined by local SDSS galaxies, with no indication of evolution. The evolution of the mass-metallicity relation observed up to z=2.5 is due to the fact that galaxies with progressively higher SFRs, and therefore lower metallicities, are selected at increasing redshifts, sampling different parts of the same FMR. By introducing the new quantity mu_alpha=log(M*)-alpha log(SFR), with alpha=0.32, we define a projection of the FMR that minimizes the metallicity scatter of local galaxies. The same quantity also cancels out any redshift evolution up to z~2.5, i.e, all galaxies have the same range of values of mu_0.32. At z>2.5, evolution of about 0.6 dex off the FMR is observed, with high-redshift galaxies showing lower metallicities. The existence of the FMR can be explained by the interplay of infall of pristine gas and outflow of enriched material. The former effect is responsible for the dependence of metallicity with SFR and is the dominant effect at high-redshift, while the latter introduces the dependence on stellar mass and dominates at low redshift. The combination of these two effects, together with the Schmidt-Kennicutt law, explains the shape of the FMR and the role of mu_0.32. The small metallicity scatter around the FMR supports the smooth infall scenario of gas accretion in the local universe., 14 pages, new version accepted by MNRAS

This is the first in a series of papers in which we study the application of spectroastrometry in the context of gas kinematical studies aimed at measuring the mass of supermassive black holes. The spectroastrometrical method consists in measuring the photocenter of light emission in different wavelength or velocity channels. In particular we explore the potential of spectroastrometry of gas emission lines in galaxy nuclei to constrain the kinematics of rotating gas disks and to measure the mass of putative supermassive black holes. By means of detailed simulations and test cases, we show that the fundamental advantage of spectroastrometry is that it can provide information on the gravitational potential of a galaxy on scales significantly smaller (~ 1/10) than the limit imposed by the spatial resolution of the observations. We then describe a simple method to infer detailed kinematical informations from spectroastrometry in longslit spectra and to measure the mass of nuclear mass concentrations. Such method can be applied straightforwardly to integral field spectra, which do not have the complexities due to a partial spatial covering of the source in the case of longslit spectra., Comment: Accepted for publication in A&A

We present the first results of a project, LSD, aimed at obtaining spatially-resolved, near-infrared spectroscopy of a complete sample of Lyman-Break Galaxies at z~3. Deep observations with adaptive optics resulted in the detection of the main optical lines, such as [OII], Hbeta and [OIII], which are used to study sizes, SFRs, morphologies, gas-phase metallicities, gas fractions and effective yields. Optical, near-IR and Spitzer/IRAC photometry is used to measure stellar mass. We obtain that morphologies are usually complex, with the presence of several peaks of emissions and companions that are not detected in broad-band images. Typical metallicities are 10-50% solar, with a strong evolution of the mass-metallicity relation from lower redshifts. Stellar masses, gas fraction, and evolutionary stages vary significantly among the galaxies, with less massive galaxies showing larger fractions of gas. In contrast with observations in the local universe, effective yields decrease with stellar mass and reach solar values at the low-mass end of the sample. This effect can be reproduced by gas infall with rates of the order of the SFRs. Outflows are present but are not needed to explain the mass-metallicity relation. We conclude that a large fraction of these galaxies are actively creating stars after major episodes of gas infall or merging., MNRAS, in press

We present new CRIRES spectroscopic observations of BrGamma in the nuclear region of the Circinus galaxy, obtained with the aim of measuring the black hole (BH) mass with the spectroastrometric technique. The Circinus galaxy is an ideal benchmark for the spectroastrometric technique given its proximity and secure BH measurement obtained with the observation of its nuclear H2O maser disk. The kinematical data have been analyzed both with the classical method based on the analysis of the rotation curves and with the new method developed by us and based on spectroastrometry. The classical method indicates that the gas disk rotates in the gravitational potential of an extended stellar mass distribution and a spatially unresolved mass of (1.7 +- 0.2) 10^7 Msun, concentrated within r < 7 pc. The new method is capable of probing gas rotation at scales which are a factor ~3.5 smaller than those probed by the rotation curve analysis. The dynamical mass spatially unresolved with the spectroastrometric method is a factor ~2 smaller, 7.9 (+1.4 -1.1) 10^6 Msun indicating that spectroastrometry has been able to spatially resolve the nuclear mass distribution down to 2 pc scales. This unresolved mass is still a factor ~4.5 larger than the BH mass measurement obtained with the H2O maser emission indicating that it has not been possible to resolve the sphere of influence of the BH. Based on literature data, this spatially unresolved dynamical mass distribution is likely dominated by molecular gas and it has been tentatively identified with the circum-nuclear torus which prevents a direct view of the central BH in Circinus. This mass distribution, with a size of ~2pc, is similar in shape to that of the star cluster of the Milky Way suggesting that a molecular torus, forming stars at a high rate, might be the earlier evolutionary stage of the nuclear star clusters which are common in late type spirals., A&A in press. We wish to honor the memory of our great friend and colleague David Axon. He will be greatly missed by all of us. arXiv admin note: text overlap with arXiv:1110.0936