Evolving therapeutic concepts in prostate cancer based on genome-wide analyses (review).

Treatment of castration resistant prostate cancer (CRPC) continues to represent a major urooncological challenge due to tumor heterogeneity and the inevitable development of therapy resistance. Although androgen deprivation therapy retains an important role in the management of CRPC, recent evidence suggests that a broader spectrum of therapeutic targets may improve patient response and delay development of advanced disease. Genome-wide analyses have identified four major signaling nodes that are most frequently altered in prostate cancer: i) the androgen receptor (AR); ii) the PI3K pathway; iii) the Ras/Raf/MEK/ERK pathway; and iv) the retinoblastoma protein (pRB) signaling pathway.

Peer assessment of aviation performance: inconsistent for good reasons.

Research into expertise is relatively common in cognitive science concerning expertise existing across many domains. However, much less research has examined how experts within the same domain assess the performance of their peer experts. We report the results of a modified think-aloud study conducted with 18 pilots (6 first officers, 6 captains, and 6 flight examiners).

The Gβ5 protein regulates sensitivity to TRAIL-induced cell death in colon carcinoma.

Aberrant signaling via G protein-coupled receptors (GPCRs) is implicated in numerous diseases including colon cancer. The heterotrimeric G proteins transduce signals from GPCRs to various effectors. So far, the G protein subunit Gβ5 has not been studied in the context of cancer.

Trocar-sharpened needles for image-guided prostate biopsy improve sample quality and performance: first clinical results.

Objective: To show the benefit of trocar-sharpened needles for image-guided prostate biopsy compared with standard bevelled needles in patients.

Materials And Methods: Twenty-four men underwent magnetic resonance imaging-targeted fusion-guided transperineal saturation prostate biopsy, each with half standard bevelled and half trocar-sharpened needles. All taken biopsies were scored (1=worse to 5=best) by one urologist for the following criteria.

Phenotypic drug screening and target validation for improved personalized therapy reveal the complexity of phenotype-genotype correlations in clear cell renal cell carcinoma.

Objectives: Novel personalized therapeutic approaches are urgently needed for patients with metastatic clear cell renal cell carcinoma (ccRCC).

Methods And Materials: We combined the development of a primary patient-derived ccRCC cell line with a phenotypic drug screen consisting of 101 approved anticancer compounds.

Results: We identified the MNNG HOS transforming gene (MET)-anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of our drug screen, whereas compounds targeting the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only minor in vitro activity.

Application of quasi-equilibrated thermodesorption of linear and di-branched paraffin molecules for detailed porosity characterization of the mono-layered zeolite MCM-56, in comparison with MCM-22 and ZSM-5.

The pore characteristics of zeolite samples including two kinds of ZSM-5 crystals as a base case and the unique mono-layered MCM-56 in different structural forms have been studied by the new method QE-TPDA (quasi-equilibrated temperature-programmed desorption and adsorption) in comparison with the standard nitrogen adsorption. Both approaches produce consistent results in terms of micro- and meso-porous features as well as quantitative pore volume values. The benefits of QE-TPDA include fast data acquisition (hours) and small sample size (milligrams).

Swelling and pillaring of the layered precursor IPC-1P: tiny details determine everything.

The influence of swelling (i.e. the size of tetraalkylammonium surfactant molecule, the presence of tetrapropylammonium hydroxide (TPAOH), pH) and pillaring (i.

Functional characterization of the tumor-suppressor MARCKS in colorectal cancer and its association with survival.

The myristoylated alanine-rich C-kinase substrate (MARCKS) acts as a tumor suppressor in a variety of human neoplasms. In colorectal cancers (CRCs), MARCKS has been shown to be a preferential target of mutational inactivation in tumors following the microsatellite instability (MSI-H) pathway but little is known about its impact on intestinal carcinogenesis. To investigate the relevance of MARCKS inactivation in more detail, we analyzed 926 MSI-typed CRCs for MARCKS expression by immunohistochemistry and studied the functional consequences of MARCKS depletion in colorectal cancer cell lines.

High acidity unilamellar zeolite MCM-56 and its pillared and delaminated derivatives.

The unilamellar form of zeolite MWW, MCM-56, which is obtained by direct hydrothermal synthesis has been studied with regard to acidity and porosity in its original and post-synthesis modified pillared and delaminated forms. The acidity measured by FTIR was found to be only slightly lower than the highly active 3-D MWW forms, MCM-22 and MCM-49. Pivalonitrile adsorption, which is a measure of spatial openness, showed 50% accessibility vs.

Psychiatry on trial: the Norway 2011 massacre.

On July 22, 2011, Anders Breivik, a Norwegian citizen, detonated a fertilizer bomb near government buildings in Oslo, killing eight people, and then proceeded to a nearby island where the Labor Party was holding a youth camp. There, he killed 69 people before being arrested. Just before these events, he posted a "compendium" on the Web explaining his actions and encouraging others to do likewise.

Working out the interstitial and syncopic nature of the human psyche: on the analysis of verbal data.

Psychology studies the human mind and its development. Although it is often recognized that the human mind needs to be understood as a temporal (developmental) phenomenon between past and future and at the interstices between the idealities of pure Self and Other, the analytic methods interpretive researchers use tend to reify ahistorical and solipsist conceptions of the human being. In this article, I provide examples of an approach to the analysis of verbal data that immediately gets us to the interstitial and syncopic nature of the human psyche.

Nacherzeugung, Nachverstehen: A phenomenological perspective on how public understanding of science changes by engaging with online media.

It is widely acknowledged in science education that everyday understandings and evidence are generally inconsistent with the scientific view of the matter: "heartache" has little to do with matters cardiopulmonary, and a rising or setting sun actually reflects the movements of the earth. How then does a member of the general public, which in many areas of science is characterized as "illiterate" and "non-scientific," come to regard something scientifically? Moreover, how do traditional unscientific (e.g.

Notch1-dependent regulation of p27 determines cell fate in colorectal cancer.

Enhanced Notch signaling contributes to uncontrolled cell growth and cell death resistance in cancer. Here, we demonstrate that in colorectal carcinoma cells the Notch1-dependent activation of cell cycle and proliferation is mediated by repression of the cyclin-dependent kinase inhibitor (CDKI) p27. The half-life of p27 significantly increased after siRNA‑mediated knockdown of Notch1.

Body mass index and microsatellite instability in colorectal cancer: a population-based study.

Background: Previous studies reported a positive association of body mass index (BMI) with microsatellite-stable (MSS) but not with microsatellite-instable (MSI-high) colorectal cancer. However, information from population-based studies conducted in representative age groups is so far limited.

Methods: We conducted a population-based case-control study (DACHS) in Southern Germany, including 1,215 patients with incident colorectal cancer and 1,891 matched controls with no upper age limit.

Development of miliary tuberculosis under infliximab in a patient with spondyloarthritis and suspected Crohn's disease.

Tuberculosis (TB) infection is a major concern in patients with chronic autoimmune conditions under immunosuppressive therapy. Gastrointestinal tuberculosis can be misdiagnosed as Crohn's disease with detrimental consequences for the patient. We report on a 40-year old ethnic Turkish patient with HLA-B27 positive spondyloarthritis who developed gastrointestinal symptoms under immunosuppressive treatment with infliximab.

Skin fragility and impaired desmosomal adhesion in mice lacking all keratins.

Keratins perform major structural and regulatory functions in epithelia. Owing to redundancy, their respective contribution to epidermal integrity, adhesion, and cell junction formation has not been addressed in full. Unexpectedly, the constitutive deletion of type II keratins in mice was embryonic lethal ∼ E9.

The soluble Decoy Receptor 3 is regulated by a PI3K-dependent mechanism and promotes migration and invasion in renal cell carcinoma.

Background: Overexpression of Decoy Receptor 3 (DcR3), a soluble member of the tumor necrosis factor receptor superfamily, is a common event in several types of cancer. In renal cell carcinoma (RCC), DcR3 overexpression is associated with lymph node and distant metastasis as well as a poor prognosis. However, the functional role and regulation of DcR3 expression in RCC is so far unknown.

A new family of two-dimensional zeolites prepared from the intermediate layered precursor IPC-3P obtained during the synthesis of TUN zeolite.

The crystallization of zeolite TUN with 1,4-bis(N-methylpyrrolidinium)butane as template proceeds through an intermediate, designated IPC-3P, following the Ostwald rule of successive transformations. This apparently layered transient product has been thoroughly investigated and found to consist of MWW monolayers stacked without alignment in register, that is, disordered compared with MCM-22P. The structure was confirmed based on X-ray diffraction and high-resolution (HR)TEM analysis.

Situated cognition.

Unlabelled: Following the cognitive revolution, when knowing and learning have come to be theorized in terms of representations stored and processed in the mind, empirical and theoretical developments in very different scholarly disciplines have led to the emergence of the situated cognition hypothesis, which consists of a set of interlocking theses: cognition is embodied, fundamentally social, distributed, enacted, and often works without representations. We trace the historical origins of this hypothesis and discuss the evidential support this hypothesis receives from empirical and modeling studies. We distinguish the question of where cognition is located from the question of what cognition is, because the confounding of the two questions leads to misunderstandings in the sometimes-ardent debates concerning the situated cognition hypothesis.

Senescence-associated protein p400 is a prognostic marker in renal cell carcinoma.

Mutations of the von Hippel-Lindau (VHL) tumor suppressor gene cause hereditary and sporadic renal cell carcinomas (RCCs). The best characterized function of VHL protein is suppression of the α subunit of hypoxia inducible factor (HIF). Additional VHL functions have been reported, including induction of senescence upon loss of VHL mediated by downregulation of the chromatin remodeling factor p400.

Histology core-specific evaluation of the European Society of Urogenital Radiology (ESUR) standardised scoring system of multiparametric magnetic resonance imaging (mpMRI) of the prostate.

Objectives: To evaluate the Prostate Imaging Reporting and Data System (PIRADS) in multiparametric magnetic resonance imaging (mpMRI) based on single cores and single-core histology. To calculate positive (PPV) and negative predictive values (NPV) of different modalities of mpMRI.

Patients And Methods: We performed MRI-targeted transrectal ultrasound-guided perineal prostate biopsies on 50 patients (mean age 66 years, mean PSA level of 9.

Peptide-based identification of functional motifs and their binding partners.

Specific short peptides derived from motifs found in full-length proteins, in our case HIV-1 Nef, not only retain their biological function, but can also competitively inhibit the function of the full-length protein. A set of 20 Nef scanning peptides, 20 amino acids in length with each overlapping 10 amino acids of its neighbor, were used to identify motifs in Nef responsible for its induction of apoptosis. Peptides containing these apoptotic motifs induced apoptosis at levels comparable to the full-length Nef protein.