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Summary: This study analyses the difference in 25OH-vitamin D values between two groups of patients both affected by severe osteoporosis with fragility fractures, but one group has vertebral fractures and the other one has hip fractures. Patients with hip fractures have vitamin D values lower than patients with vertebral fractures.Introduction: The purpose of this study was to evaluate 25OHD levels in patients with fragility vertebral fractures (VF) and hip fractures (HF) and make a comparison between the groups.Methods: In the first group were enrolled ambulatory patients with 3 or more moderate to severe VF; in the second group were enrolled patients hospitalized in the Department of Orthogeriatrics undergoing surgery for HF. For all patients, we collected values of 25OHD and PTH. The group of patients with VF was further subdivided into pre-existing VF or recent VF treated within 30 days with vertebroplasty.Results: The sample consists of 180 subjects divided into two groups: 90 with VF and 90 with HF. The average value of 25OHD in the total sample was 13.2 ± 9.6 ng/ml, Vitamin D was significantly lower in the HF group than the VF group (p < 0.001)(VF 18.6 ± 9.7 ng/ml, HF 7.9 ± 5.7 ng/ml). The mean PTH value in the total sample was 67.5 ± 54.9 pg/ml and PTH was significantly higher in the HF group compared to the group with VF (p < 0.001) (VF 55.6 ± 27.2 pg/ml, HF 78.7 ± 70.2 pg/ml). The mean 25OHD value in the recent VF group is 16.0 ± 6.6 ng/ml while in the pre-existing VF group is 19.5 ± 10.4 ng/ml with a statistically significant difference (p < 0.001).Conclusions: Patients of the same age with severe osteoporosis have a lower 25OHD value when the fracture occur at the hip and is recent, probably this is due to the inflammation caused by fracture and/or surgical intervention. [ABSTRACT FROM AUTHOR]

Results are presented from an experimental study of the equilibrium distribution of magnetization and processes of magnetization reversal of magnetoelastic nanostructures in the form of strips with constant or variable width. It is shown that the symmetry of the stable magnetization states in the nanostrip can be broken by a static magnetic field applied perpendicular to the ferromagnet's easy axis. A further change in the states of magnetization allows their manipulation (e.g., moving the domain wall) using the homogeneous mechanical effects induced by applying an electric field to the piezoelectric substrate. [ABSTRACT FROM AUTHOR]

Mosses and lichens are widely used to detect changes in the environmental concentrations of potential contaminants. Several studies have shown the usefulness of transplanted mosses and/or lichens to monitor air depositions of inorganic and organic pollutants at different scales. Here, we present the results of a biomonitoring study carried out in two cities, London (United Kingdom) and Naples (Italy), using four biomonitors (two lichens and two mosses). The lichens, Pseudevernia furfuracea (L.) Zopf var. furfuracea and Parmelia sulcata Taylor, and mosses, Sphagnum capillifolium (Ehrh.) Hedw. and Hypnum cupressiforme Hedw., were exposed in bags in urban streets of Naples and London and in semi-rural and rural areas. Samples were analysed for Cd, Cr, Cu, Fe, Ni, Pb, V and Zn by atomic absorption spectrometry after acid digestion and for 16 EPA polycyclic aromatic hydrocarbons (PAHs) by gas chromatography coupled to mass spectrometry after matrix solid-phase dispersion. For heavy metals, the comparison between the selected mosses indicated that, in all exposure sites, S. capillifolium had a better accumulation performance than H. cupressiforme, whereas for the lichens, it was P. furfuracea which accumulated higher concentrations of metals. Also for total PAHs, S. capillifolium showed a good accumulation capability compared to the other biomonitors investigated, especially compared to H. cupressiforme. It was observed an increasing heavy metal and PAH uptake by biomonitors from rural to urban sites, in both cities. [ABSTRACT FROM AUTHOR]

The paper proposes a Markovian approach to the performance evaluation of the ESSE (early slow start exit) modification of the TCP congestion control mechanism. ESSE takes advantage of estimating the optimal pipesize at the sender side to properly select initial slow start threshold. Previous simulative experiments have shown that ESSE allows one to speed-up TCP connections and significantly reduces the packet drop rate at the bottleneck. This work takes a step further in understanding the ESSE behavior by developing a model of TCP source to evaluate the influence of different settings of slow start threshold on a TCP performance. As confirmed by comparison with simulations, the model provides, significantly faster than simulations, accurate estimates of typical performance indicators such as the average completion time and average drop rate of short-lived TCP connections. [ABSTRACT FROM AUTHOR]

The Sun is a non-equilibrium, dissipative system subject to an energy flow that originates in its core. Convective overshooting motions create temperature and velocity structures that show a temporal and spatial multiscale evolution. As a result, photospheric structures are generally considered to be a direct manifestation of convective plasma motions. The plasma flows in the photosphere govern the motion of single magnetic elements. These elements are arranged in typical patterns, which are observed as a variety of multiscale magnetic patterns. High-resolution magnetograms of the quiet solar surface revealed the presence of multiscale magnetic underdense regions in the solar photosphere, commonly called voids, which may be considered to be a signature of the underlying convective structure. The analysis of such patterns paves the way for the investigation of all turbulent convective scales, from granular to global. In order to address the question of magnetic structures driven by turbulent convection at granular and mesogranular scales, we used a voids-detection method. The computed distribution of void length scales shows an exponential behavior at scales between 2 and 10 Mm and the absence of features at mesogranular scales. The absence of preferred scales of organization in the 2 - 10 Mm range supports the multiscale nature of flows on the solar surface and the absence of a mesogranular convective scale. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have an important role in a wide range of physiological and pathological processes, and their dysregulation has been reported to affect the development and progression of cancers, including hepatocellular carcinoma (HCC). However, in the plethora of dysregulated miRNAs, it is largely unknown which of them have a causative role in the hepatocarcinogenic process. In the present study, we first aimed to determine changes in the expression profile of miRNAs in human HCCs and to compare them with liver tumors generated in a rat model of chemically induced HCC. We found that members of the miR-100 family (miR-100, miR-99a) were downregulated in human HCCs; a similar downregulation was also observed in rat HCCs. Their reduction was paralleled by an increased expression of polo like kinase 1 (PLK1), a target of these miRNAs. The introduction of miR-100 in HCC cells impaired their growth ability and their capability to form colonies in soft agar. Next, we aimed at investigating, in the same animal model, if dysregulation of miR-100 and PLK1 is an early or late event along the multistep process of hepatocarcinogenesis. The obtained results showed that miR-100 downregulation (i) is already evident in very early preneoplastic lesions generated 9 weeks after carcinogenic treatment; (ii) is also observed in adenomas and early HCCs; and (iii) is not simply a marker of proliferating hepatocytes. To our knowledge, this is the first work unveiling the role of a miRNA family along HCC progression. [ABSTRACT FROM AUTHOR]

Coronal plumes, which extend from solar coronal holes (CH) into the high corona and-possibly-into the solar wind (SW), can now continuously be studied with modern telescopes and spectrometers on spacecraft, in addition to investigations from the ground, in particular, during total eclipses. Despite the large amount of data available on these prominent features and related phenomena, many questions remained unanswered as to their generation and relative contributions to the high-speed streams emanating from CHs. An understanding of the processes of plume formation and evolution requires a better knowledge of the physical conditions at the base of CHs, in plumes and in the surrounding inter-plume regions. More specifically, information is needed on the magnetic field configuration, the electron densities and temperatures, effective ion temperatures, non-thermal motions, plume cross sections relative to the size of a CH, the plasma bulk speeds, as well as any plume signatures in the SW. In spring 2007, the authors proposed a study on 'Structure and dynamics of coronal plumes and inter-plume regions in solar coronal holes' to the International Space Science Institute (ISSI) in Bern to clarify some of these aspects by considering relevant observations and the extensive literature. This review summarizes the results and conclusions of the study. Stereoscopic observations allowed us to include three-dimensional reconstructions of plumes. Multi-instrument investigations carried out during several campaigns led to progress in some areas, such as plasma densities, temperatures, plume structure and the relation to other solar phenomena, but not all questions could be answered concerning the details of plume generation process(es) and interaction with the SW. [ABSTRACT FROM AUTHOR]

The problem of predicting the effective elastic properties of multi-cracked and/or composite materials is both fundamental in materials mechanics and of large technological impact. In this paper we develop a continuum elasticity model, based on the Eshelby theory and on the differential homogenization technique, for the effective elastic moduli of a fibro-reinforced system and we address it to elaborate an estimation of the average failure condition of such composites. [ABSTRACT FROM AUTHOR]

We investigate the elastic properties of model composites, consisting in a dispersion of nonlinear (spherical or cylindrical) inhomogeneities into a linear solid matrix. Both phases are considered isotropic. Under the simplifying hypotheses of small deformation for the material body and of small volume fraction of the embedded phase, we develop a homogenization procedure based on the Eshelby theory, aimed at describing nonlinear features. We obtain the bulk and shear moduli and Landau coefficients of the overall material in terms of the elastic behavior of the constituents and of their volume fractions. The mixing laws for the nonlinear properties describe a complex scenario where possible strong amplifications of the nonlinearities may arise in some given conditions. [ABSTRACT FROM AUTHOR]

We prove a generic theorem stating the equivalence between a graded dielectric ellipsoid (with gradation along a family of internal confocal ellipsoids) and an anisotropic homogeneous ellipsoid. We then describe a procedure to obtain the three principal permittivities of the effective ellipsoid for any given dielectric gradation profile. Finally, we apply a multiscale approach to homogenize dispersions of ellipsoidal graded particles. [ABSTRACT FROM AUTHOR]

An analogy between celebrated Kendall equation for busy periods in the system M| GI|1 and analytical results for busy periods in the priority systems M r | GI r |1 is drawn. These results can be viewed as generalizations of the functional Kendall equation. The methodology and algorithms of numerical solution of recurrent functional equations which appear in the analysis of such queueing systems are developed. The efficiency of the algorithms is achieved by acceleration of the numerical procedure of solving the classical Kendall equation. An algorithm of calculation of the system workload coefficient calculation is given. [ABSTRACT FROM AUTHOR]

In spite of the established knowledge of the genetic alterations responsible for cancer onset, the genes promoting and maintaining the invasive/metastatic phenotype are still elusive. The MET proto-oncogene, encoding the tyrosine kinase receptor for hepatocyte growth factor (HGF), senses unfavorable micro-environmental conditions and drives cell invasion and metastasis. MET overexpression, often induced by tumor hypoxia, leads to constitutive activation of the receptor and correlates with poor prognosis. To establish the role of MET in different phases of tumor progression, we developed an inducible lentiviral delivery system of RNA interference. Silencing the endogenous MET gene, overexpressed in tumor cells, resulted in (i) impairment of the execution of the full invasive growth program in vitro, (ii) lack of tumor growth and (iii) decreased generation of experimental metastases in vivo. Notably, silencing MET in already established metastases led to their almost complete regression. This indicates that persistent expression of the MET oncogene is mandatory until the advanced phases of cancer progression.Oncogene (2008) 27, 684–693; doi:10.1038/sj.onc.1210697; published online 6 August 2007 [ABSTRACT FROM AUTHOR]

Several distinct mutations within the kinase domain of the epidermal growth factor receptor (EGFR) are associated with non-small cell lung cancer, but mechanisms underlying their oncogenic potential are incompletely understood. Although normally ligand-induced kinase activation targets EGFR to Cbl-mediated receptor ubiquitinylation and subsequent degradation in lysosomes, we report that certain EGFR mutants escape this regulation. Defective endocytosis characterizes a deletion mutant of EGFR, as well as a point mutant (L858R-EGFR), whose association with c-Cbl and ubiquitinylation are impaired. Our data raise the possibility that refractoriness of L858R-EGFR to downregulation is due to enhanced heterodimerization with the oncogene product HER2, which leads to persistent stimulation.Oncogene (2007) 26, 6968–6978; doi:10.1038/sj.onc.1210503; published online 7 May 2007 [ABSTRACT FROM AUTHOR]

Overexpression of the c-Met/hepatocyte growth factor receptor(HGF-R) proto-oncogene and abnormal generation of intracellular oxygen species (reactive oxygen species (ROS)) have been linked, by independent lines of evidence, to cell transformation and to malignant growth. By comparing two subpopulations of the B16 mouse melanoma (B16-F0 and B16-F10) endowed with different lung metastasis capacities (low and high, respectively) we found that both the expression/phosphorylation of c-Met and the steady-state levels of ROS positively correlated with metastatic growth. shRNA-mediated downregulation of c-Met in F10 cells led to a parallel decrease in the generation of oxygen species and in metastatic capacity, suggesting that oxidants may mediate the pro-metastatic activity of the HGF receptor. c-Met activation by a ligand elicits the formation of oxidant species through the oxidase-coupled small GTPase Rac-1, a relevant downstream target of the HGF-R. Moreover, cell treatment with the catalytic ROS scavengers EUK-134 and EUK-189 attenuates Met signaling to ERKs and inhibits the anchorage-independent growth of F10 cells, consistent with a critical role for oxygen species in HGF signaling and in aggressive cell behavior. Finally, genetic manipulation of the Rac-ROS cascade at different levels demonstrated its crucial role in the pro-metastatic activity of c-Met in vivo. Thus, we have outlined a novel cascade triggered by c-Met and mediated by ROS, linked to metastasis and potentially targetable by new antimetastatic, redox-based therapies.Oncogene (2006) 25, 3689–3698. doi:10.1038/sj.onc.1209409; published online 6 February 2006 [ABSTRACT FROM AUTHOR]

In this paper we investigated how the increase of human estrogen receptor alfa (ERα) gene expression may affect breast, osteoblast and osteoclast cells. Increase of ERα expression was obtained by interfering with the activity of a negative transcription factor and by removing it with a short and powerful decoy oligonucleotide (RA4-3′) mimicking a region of distal promoter C of ERα gene. We provide evidence that this decoy was able to induce apoptosis in osteoclasts, but not in osteoblasts and in breast cancer cells, in an estrogen dependent manner. This effect was associated with increase of the levels of Caspase 3 and Fas receptor. Since ERα is important in the transcription of different genes and is involved in several pathological processes, including neoplastic and osteopenic diseases, our findings may be of relevance for a possible new therapeutical approach of such diseases. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common malignant bone neoplasia occurring in young patients in the first two decades of life, and represents 20% of all primitive malignant bone tumours. At present, treatment of metastatic osteosarcoma is unsatisfactory. High-dose chemotherapy followed by CD34+ leukapheresis rescue may improve these poor results. Neoplastic cells contaminating the apheresis may, however, contribute to relapse. To identify markers suitable for detecting osteosarcoma cells in aphereses we analysed the expression of bone-specific genes (Bone Sialoprotein (BSP) and Osteocalcin) and oncogenes (Met and ErbB2) in 22 patients with metastatic osteosarcoma and six healthy stem cell donors. The expression of these genes in aphereses of patients affected by metastatic osteosarcoma was assessed by RT-PCR and Southern blot analysis. Met and Osteocalcin proved to be not useful markers since they are positive in aphereses of both patients with metastatic osteosarcoma and healthy stem cell donors. On the contrary, BSP was expressed at significant levels in 85% of patients. Moreover, 18% of patients showed a strong and significantly positive (seven to 16 times higher than healthy stem cell donors) ErbB2 expression. In all positive cases, neoplastic tissue also expressed ErbB2. Our data show that ErbB2 can be a useful marker for tumour contamination in aphereses of patients affected by ErbB2-expressing osteosarcomas and that analysis of Bone Sialoprotein expression can be an alternative useful marker. [ABSTRACT FROM AUTHOR]

Signal transduction by HGF receptor, the tyrosine kinase encoded by the MET oncogene, switches on a genetic program called ‘invasive growth’ inducing epithelial cell dissociation, migration, growth, and ultimately leading to differentiation into branched tubular structures. Sustained tyrosine phosphorylation of the downstream adaptor protein Gab1 is required for the HGF response. Here we show that serine/threonine phosphorylation of Gab1 provides a control mechanism for negative regulation. Treatment with okadaic acid, a potent inhibitor of the serine/threonine protein phosphatases PP1 and PP2A, was followed by activation of a number of serine/threonine kinases, hyper-phosphorylation in serine and threonine of Gab1 and severe inhibition of the HGF-induced biological responses. Under these conditions, Gab1 was found to be concomitantly hypo-phosphorylated in tyrosine, and thus endowed with reduced ability to recruit SH2 containing signal transducers such as PI3 kinase. Among the serine-threonine kinases activated by PP1 and PP2A inhibition, we found that PKC-α and PKC-β1 are required for negative regulation of Gab1. These data provide a novel negative mechanism for the HGF receptor signaling pathways and highlight a potentially useful target for inhibitors of invasive growth. Oncogene (2001) 20, 156–166. [ABSTRACT FROM AUTHOR]

A metastatic cancer develops by accumulation of mutations in genes that control growth, survival and spreading. The latter genes have not yet been identified. In lymph node metastases of head and neck squamous cell carcinomas (HNSCC), we found mutations in the MET oncogene, which encodes the tyrosine kinase receptor for Scatter Factor, a cytokine that stimulates epithelial cell motility and invasiveness during embryogenesis and tissue remodeling. We identified two somatic mutations: the Y1230C, known as a MET germline mutation which predisposes to hereditary renal cell carcinoma, and the Y1235D that is novel and changes a critical tyrosine, known to regulate MET kinase activity. The mutated MET receptors are constitutively active and confer an invasive phenotype to transfected cells. Interestingly, cells carrying the MET mutations are selected during metastatic spread: transcripts of the mutant alleles are highly represented in metastases, but barely detectable in primary tumors. These data indicate that cells expressing mutant MET undergo clonal expansion during HNSCC progression and suggest that MET might be one of the long sought oncogenes controlling progression of primary cancers to metastasis. Oncogene (2000) 19, 1547–1555. [ABSTRACT FROM AUTHOR]

Funaria hygrometrica gametophytes were grown in in vitro controlled systems in the presence and absence of lead. Their nuclear genomes were then analyzed directly in situ with A+T and G+C specific fluorochromes, image analysis and statistical data elaboration by specific software, in order to characterize the different fractions of repetitive DNA. The results reveal qualitative and quantitative differences between the nuclear genomes of lead-stressed and unstressed individuals. These differences seem to consist of a significant increase in G+C rich repetitive DNA sequences in nuclei of the stressed individuals. These sequences form well defined agglomerates, generally situated adjacent to the nucleolar region, which increase in both size and number in the presence of lead. Some hypotheses are discussed. [ABSTRACT FROM AUTHOR]

The plasma levels of tumor necrosis factor-α and interferon-γ were measured in 53 consecutive children with serologically confirmed Mediterranean spotted fever and were found to be increased during the acute phase compared with the convalescent phase (tumor necrosis factor-a mean 32.17 vs. 4.12 pg/ml, P<0.0001; interferon-γ mean 84.17 vs. 2.65 pg/ml, P = 0.0006). Plasma levels of both cytokines were higher in patients with a typical exanthema rather than those with a very mild or no exanthema; tumor necrosis factor-α levels were significantly lower in the latter (tumor necrosis factor-α 32.17 vs. 9.85 pg/ml, P<0.0001; interferon-γ 84.17 vs. 38.14 pg/ml, P = 0.35). Tumor necrosis factor-α and interferon-γ may be harmful or beneficial to the infected host, depending upon the amounts produced and whether they are circulating or confined locally to the site of inflammation. [ABSTRACT FROM AUTHOR]

Doppler dimming of the O vi resonance lines (λ1032 Å, λ1037 Å) in an expanding corona is calculated including the pumping effect on the O vi λ1037.61 Å of both C ii lines at λ1036.34 Å and λ1037.02 Å, and the effect of the width of the absorption profiles of the coronal oxygen ions along the incident radiation. The pumping effect of the C ii line at λ1036.34 Å allows us to extend to approximately 450 km s−1 the measurement of solar wind velocities with the O vi line ratio technique. Since the emissivity ratio of the O vi doublet depends on the width of the oxygen coronal absorbing profiles, this ratio can provide an accurate measurement of the solar wind velocity in the case that the width of the absorbing profile along the direction of the incident radiation is independently determined. However, if on the one hand the ratio of the emissivities of the O vi doublet has limitations in probing the wind velocity, on the other hand it can be used as a diagnostics for inferring the velocity distribution of the coronal O vi ions along the radial, and detecting possible velocity anisotropies. This diagnostics, applied to recent observational results, allows us to infer that the velocity distribution of the oxygen ions is much broader in the direction perpendicular to the magnetic field direction, and that the acceleration of the fast solar wind in the first 2 solar radii is high. [ABSTRACT FROM AUTHOR]

The SOHO Ultraviolet Coronagraph Spectrometer (UVCS/SOHO) is being used to observe the extended solar corona from 1.25 to 10 R⊙ from Sun center. Initial observations of polar coronal holes and equatorial streamers are described. The observations include measurements of spectral line profiles for HI Lα and Lβ, Ovi 1032 Å and 1037 Å, Mgx 625 Å, Fexii 1242 Å and several others. Intensities for Mgx 610 Å, Sixii 499 Å, and 520 Å, Sx 1196 Å, and 22 others have been observed. Preliminary results for derived H0, O5+, Mg9+, and Fe11+ velocity distributions and initial indications of outflow velocities for O5+ are described. In streamers, the H0 velocity distribution along the line of sight (specified by the value at e-1, along the line of sight) decreases from a maximum value of about 180 km s-1 at 2 R⊙ to about 140 km s-1 at 8 R⊙. The value for O5+ increases with height reaching a value of 150 km s-1 at 4.7 R⊙. In polar coronal holes, the O5+ velocity at e-1 is about equal to that of H0 at 1.7 R⊙ and significantly larger at 2.1 R⊙. The O5+ in both streamers and coronal holes were found to have anisotropic velocity distributions with the smaller values in the radial direction. [ABSTRACT FROM AUTHOR]

The Ultraviolet Coronagraph Spectrometer on the SOHO satellite covers the 940–1350 Å range as well as the 470–630 Å range in second order. It has detected coronal emission lines of H, N, O, Mg, Al, Si, S, Ar, Ca, Fe, and Ni, particularly in coronal streamers. Resonance scattering of emission lines from the solar disk dominates the intensities of a few lines, but electron collisional excitation produces most of the lines observed. Resonance, intercombination and forbidden lines are seen, and their relative line intensities are diagnostics for the ionization state and elemental abundances of the coronal gas. The elemental composition of the solar corona and solar wind vary, with the abundance of each element related to the ionization potential of its neutral atom (First Ionization Potential–FIP). It is often difficult to obtain absolute abundances, rather than abundances relative to O or Si. In this paper, we study the ionization state of the gas in two coronal streamers, and we determine the absolute abundances of oxygen and other elements in the streamers. The ionization state is close to that of a log T = 6.2 plasma. The abundances vary among, and even within, streamers. The helium abundance is lower than photospheric, and the FIP effect is present. In the core of a quiescent equatorial streamer, oxygen and other high-FIP elements are depleted by an order of magnitude compared with photospheric abundances, while they are depleted by only a factor of 3 along the edges of the streamer. The abundances along the edges of the streamer (‘legs’) resemble elemental abundances measured in the slow solar wind, supporting the identification of streamers as the source of that wind component. [ABSTRACT FROM AUTHOR]

In recent years much effort has been devoted to constructing systems for sharing resources within the solar physics community. Several advanced archives and data analysis systems do exist, but there is low availability of data visualization tools for displaying simultaneous multi instruments/wavelengths solar data. Meanwhile map server technology has received great attention by the IT researcher and geophysical community. In this paper we discuss a possible use of an open source environment for building spatially enabled Internet applications for the visualization and analysis of solar physics data sets. We present the preliminary status of the MINVIT (Multi Instrumental Visualization Tool) project, which shall be able to merge images and information produced by different instruments in a single/synoptic image available on-line. Moreover, the tool is designed in order to allow the visualization of the temporal evolution of data. We further discuss the possible integration into the grid framework, focusing on a middleware able to query EGSO resources such us UOC and SEC in order to include data from several space and ground-based solar observatories. [ABSTRACT FROM AUTHOR]

Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the similarity of tyrosine kinase receptor with the c-met proto-oncogene.