An improved return-mapping scheme for nonsmooth yield surfaces: PART I - the Haigh-Westergaard coordinates

The paper is devoted to the numerical solution of elastoplastic constitutive initial value problems. An improved form of the implicit return-mapping scheme for nonsmooth yield surfaces is proposed that systematically builds on a subdifferential formulation of the flow rule. The main advantage of this approach is that the treatment of singular points, such as apices or edges at which the flow direction is multivalued involves only a uniquely defined set of non-linear equations, similarly to smooth yield surfaces. This paper (PART I) is focused on isotropic models containing: $a)$ yield surfaces with one or two apices (singular points) laying on the hydrostatic axis; $b)$ plastic pseudo-potentials that are independent of the Lode angle; $c)$ nonlinear isotropic hardening (optionally). It is shown that for some models the improved integration scheme also enables to a priori decide about a type of the return and investigate existence, uniqueness and semismoothness of discretized constitutive operators in implicit form. Further, the semismooth Newton method is introduced to solve incremental boundary-value problems. The paper also contains numerical examples related to slope stability with available Matlab implementation.Comment: 25 pages, 10 figure

Two simple derivations of universal bounds for the C.B.S. inequality constant

summary:Universal bounds for the constant in the strengthened Cauchy-Bunyakowski-Schwarz inequality for piecewise linear-linear and piecewise quadratic-linear finite element spaces in 2 space dimensions are derived. The bounds hold for arbitrary shaped triangles, or equivalently, arbitrary matrix coefficients for both the scalar diffusion problems and the elasticity theory equations

Publication of original research in urologic journals - a neglected orphan?

The pathophysiologic mechanisms behind urologic disease are increasingly being elucidated. The object of this investigation was to evaluate the publication policies of urologic journals during a period of progressively better understanding and management of urologic disease. Based on the ISI Web of Knowledge Journal Citation Reports and the PubMed database, the number and percentage of original experimental, original clinical, review or commentarial articles published between 2002–2010 in six leading urologic journals were analyzed. “British Journal of Urology International”, “European Urology”, “Urologic Oncology-Seminars and Original Investigations” (“Urologic Oncology”), “Urology”, “The Journal of Urology”, and “World Journal of Urology” were chosen, because these journals publish articles in all four categories. The publication policies of the six journals were very heterogeneous during the time period from 2002 to 2010. The percentage of original experimental and original clinical articles, related to all categories, remained the same in “British Journal of Urology International”, “Urologic Oncology”, “Urology” and “The Journal of Urology”. The percentage of experimental reports in “World Journal of Urology” between 2002–2010 significantly increased from 10 to 20%. A distinct elevation in the percentage of commentarial articles accompanied by a reduction of clinical articles became evident in “European Urology” which significantly correlated with a large increase in the journal’s impact factor. No clearly superior policy could be identified with regard to a general increase in the impact factors from all the journals. The publication policy of urologic journals does not expressly reflect the increase in scientific knowledge, which has occurred over the period 2002–2010. One way of increasing the exposure of urologists to research and expand the interface between experimental and clinical research, would be to enlarge the percentage of experimental articles published. There is no indication that such policy would be detrimental to a journal’s impact factor

The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo

Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-α (IFN-α) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA–IFN-α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC

Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo

Targeted drugs have significantly improved the therapeutic options for advanced renal cell carcinoma (RCC). However, resistance often develops, negating the benefit of these agents. In the present study, the molecular mechanisms of acquired resistance towards the histone deacetylase (HDAC) inhibitor valproic acid (VPA) in a RCC in vivo model were investigated. NMRI:nu/nu mice were transplanted with Caki-1 RCC cells and then treated with VPA (200 mg/kg/day). Controls remained untreated. Based on tumor growth dynamics, the mice were divided into “responders” and “non-responders” to VPA. Histone H3 and H4 acetylation and expression of cell signaling and cell cycle regulating proteins in the RCC mouse tumors were evaluated by Western blotting. Tumor growth of VPA responders was significantly diminished, whereas that of VPA non-responders even exceeded control values. Cdk1, 2 and 4 proteins were strongly enhanced in the non-responders. Importantly, Akt expression and activity were massively up-regulated in the tumors of the VPA non-responders. Chronic application (12 weeks) of VPA to Caki-1 cells in vitro evoked a distinct elevation of Akt activity and cancer cells no longer responded with cell growth reduction, compared to the short 2 week treatment. We assume that chronic use of an HDAC-inhibitor is associated with (re)-activation of Akt, which may be involved in resistance development. Consequently, combined blockade of both HDAC and Akt may delay or prevent drug resistance in RCC

Monitoring and Analysis of Web Page Changes

Obsahem diplomové práce je řešení problematiky sledování a analýzy změn na webových stránkách. Práce nabízí přehled nástrojů a aplikací, které se dnes pro sledování používají a zabývá se jejich funkčností a implementací. Nejdůležitější část práce je věnována tvorbě informačního systému pro sledování změn. Přináší teoretický úvod, návrh a realizaci aplikace, která má za cíl sledování změn na základě uživatelsky definovaných filtrů. Aplikace tak podává uživateli informace jen o těch částech webu, které ho opravdu zajímají. Výsledky jsou poté prezentovány ve formě RSS kanálů. V práci je popsán kompletní návrh a implementace včetně možných budoucích rozšíření.The content of this thesis is the issue of monitoring and analysis of web page changes. Work offers an overview of tools and applications that are used today to monitoring and deals with their functionality and implementation. The most important part is devoted to creating an information system for detecting and monitoring changes. Provides a theoretical introduction, design and implementation of an application, that aims to detect changes based on user defined filters. So application gives users only the information, which really interested him. Results are presented in the form of RSS channels. The paper describes a complete design and implementation, including possible future expansion.

New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma

The anti-epileptic drug valproic acid is also under trial as an anti-cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti-neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA-derivatives (ACS2, ACS33) on pre-clinical prostate cancer models. PC3 and DU-145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up-regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU-145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti-tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer

HPC in Computational Micromechanics of Composite Materials

Proceedings of: Second International Workshop on Sustainable Ultrascale Computing Systems (NESUS 2015). Krakow (Poland), September 10-11, 2015.This work was supported by the European Regional Development Fund in the IT4Innovations Centre of Excellence project (CZ.1.05/1.1.00/02.0070) and the COST NESUS project with an additional CZ MEYS LD15105 support