Biomedical radiation detecting probe Patent

Silicon radiation detecting probe design for in vivo biomedical us

Silica-magnesium-titanium Ziegler-Natta catalysts. Part 1: Structure of the pre-catalyst at a molecular level

In this paper, which is the first part of a more extended work, we elucidate the molecular level structure of a highly active SiO2-supported Ziegler-Natta precatalyst obtained by reacting a dehydroxylated silica and a solution of an organomagnesium compound with TiCl4. The synergetic combination of Ti K-edge and Ti L3-edge X-ray Absorption spectroscopy (XAS) and diffuse reflectance UV–Vis spectroscopies, complemented by Density Functional Theory (DFT) simulations, indicate that small TiCl3 clusters similar to β-TiCl3 coexist with isolated monomeric Ti(IV) species. Ti K-edge Extended X-ray Absorption Fine Structure (EXAFS) Spectroscopy allows the quantification of these two phases and demonstrates that the Ti(IV) sites are 6-fold coordinated (either by six chlorine ligands or by five chlorine and one oxygen ligands), but highly distorted, similar to what is modelled for TiCl4-capped MgCl2 nanoplatelets. Finally, IR spectroscopy suggests that the MgCl2 phase has a molecular character (Far-IR) and that the only accessible Mg2+ sites are uncoordinated cations acting as Lewis acid sites (IR of CO adsorbed at 100 K). Based on these experimental findings, we propose the co-existence in the precatalyst of small TiCl3 clusters and of mixed oxo-chloride magnesium-titanium structures deposited at the silica surface. The evolution of the precatalyst in the presence of the activator and of the monomer is discussed in the second part of this work

Numerical convergence of the block-maxima approach to the Generalized Extreme Value distribution

In this paper we perform an analytical and numerical study of Extreme Value distributions in discrete dynamical systems. In this setting, recent works have shown how to get a statistics of extremes in agreement with the classical Extreme Value Theory. We pursue these investigations by giving analytical expressions of Extreme Value distribution parameters for maps that have an absolutely continuous invariant measure. We compare these analytical results with numerical experiments in which we study the convergence to limiting distributions using the so called block-maxima approach, pointing out in which cases we obtain robust estimation of parameters. In regular maps for which mixing properties do not hold, we show that the fitting procedure to the classical Extreme Value Distribution fails, as expected. However, we obtain an empirical distribution that can be explained starting from a different observable function for which Nicolis et al. [2006] have found analytical results.Comment: 34 pages, 7 figures; Journal of Statistical Physics 201

Wind gust estimation for Mid-European winter storms: towards a probabilistic view

Three wind gust estimation (WGE) methods implemented in the numerical weather prediction (NWP) model COSMO-CLM are evaluated with respect to their forecast quality using skill scores. Two methods estimate gusts locally from mean wind speed and the turbulence state of the atmosphere, while the third one considers the mixing-down of high momentum within the planetary boundary layer (WGE Brasseur). One hundred and fifty-eight windstorms from the last four decades are simulated and results are compared with gust observations at 37 stations in Germany. Skill scores reveal that the local WGE methods show an overall better behaviour, whilst WGE Brasseur performs less well except for mountain regions. The here introduced WGE turbulent kinetic energy (TKE) permits a probabilistic interpretation using statistical characteristics of gusts at observational sites for an assessment of uncertainty. The WGE TKE formulation has the advantage of a ‘native’ interpretation of wind gusts as result of local appearance of TKE. The inclusion of a probabilistic WGE TKE approach in NWP models has, thus, several advantages over other methods, as it has the potential for an estimation of uncertainties of gusts at observational sites

Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer

The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P<0.05), leading to shorter disease-free survival in both cohorts. This finding was not a result of methodological bias as we verified the well-established association between breast cancer malignancy and increased proliferation, by applying our GPS to public breast cancer data. In this study, we show that reduced proliferation is a biological feature characterizing the majority of aggressive colon cancers. This contrasts with many other carcinomas such as breast cancer. Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options

The Prometastatic Microenvironment of the Liver

The liver is a major metastasis-susceptible site and majority of patients with hepatic metastasis die from the disease in the absence of efficient treatments. The intrahepatic circulation and microvascular arrest of cancer cells trigger a local inflammatory reaction leading to cancer cell apoptosis and cytotoxicity via oxidative stress mediators (mainly nitric oxide and hydrogen peroxide) and hepatic natural killer cells. However, certain cancer cells that resist or even deactivate these anti-tumoral defense mechanisms still can adhere to endothelial cells of the hepatic microvasculature through proinflammatory cytokine-mediated mechanisms. During their temporary residence, some of these cancer cells ignore growth-inhibitory factors while respond to proliferation-stimulating factors released from tumor-activated hepatocytes and sinusoidal cells. This leads to avascular micrometastasis generation in periportal areas of hepatic lobules. Hepatocytes and myofibroblasts derived from portal tracts and activated hepatic stellate cells are next recruited into some of these avascular micrometastases. These create a private microenvironment that supports their development through the specific release of both proangiogenic factors and cancer cell invasion- and proliferation-stimulating factors. Moreover, both soluble factors from tumor-activated hepatocytes and myofibroblasts also contribute to the regulation of metastatic cancer cell genes. Therefore, the liver offers a prometastatic microenvironment to circulating cancer cells that supports metastasis development. The ability to resist anti-tumor hepatic defense and to take advantage of hepatic cell-derived factors are key phenotypic properties of liver-metastasizing cancer cells. Knowledge on hepatic metastasis regulation by microenvironment opens multiple opportunities for metastasis inhibition at both subclinical and advanced stages. In addition, together with metastasis-related gene profiles revealing the existence of liver metastasis potential in primary tumors, new biomarkers on the prometastatic microenvironment of the liver may be helpful for the individual assessment of hepatic metastasis risk in cancer patients

An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types

Wiskott–Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis

CD24 Expression is an Independent Prognostic Marker in Cholangiocarcinoma

CD24 has been described as an adverse prognostic marker in several malignancies. This study evaluates CD24 expression in cholangiocarcinoma and correlates the findings with clinicopathologic data and patient survival. Between 1996 and 2002, 22 consecutive patients with cholangiocarcinoma were treated at our institution. Demographic data, SEER stage, pathologic data, treatment, expression of CD24, mitogen-activated protein kinase (MAPK), phosphorylated MAPK, and survival were analyzed. The majority of the tumors demonstrated CD24 (81.8%) and p-MAPK (87%) expression. A negative association was noted between the expression of CD24 and p-MAPK. Median survival for patients with low expression of CD24 was 36 months and high expression was 8 months. Median survival for patients who received chemotherapy with low CD24 expression was 163 months, and for seven patients with high CD24 expression, it was 17 months (p = 0.04). With the addition of radiation therapy, median survival for patients with low expression of CD24 was 52 months and high expression was 17 months (p = 0.08). On multivariate analysis, the use of chemotherapy (p = 0.0014, hazard ratio 0.069) and the CD24 overexpression (p = 0.02, hazard ratio 7.528) were predictive of survival. CD24 is commonly expressed in cholangiocarcinoma, and overexpression is predictive of poor survival and possibly of lack of response to chemotherapy and radiation therapy. These findings may improve selection of patients for the appropriate treatment modality and the development of CD24-targeted therapy