The role of cytochromes P450 and aldo-keto reductases in prognosis of breast carcinoma patients

Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients.Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients. Eleven candidate genes were then evaluated in an independent series of 50 pretreatment patients. Protein expression of the most significant genes was confirmed by immunoblotting.AKR1A1 was significantly overexpressed and AKR1C1-4, KCNAB1, CYP2C19, CYP3A4, and CYP3A5 downregulated in tumors compared with control nonneoplastic tissues after correction for multiple testing. Significant association of CYP2B6 transcript levels in tumors with expression of hormonal receptors was found in the posttreatment set and replicated in the pretreatment set of patients. Significantly higher intratumoral levels of AKR1C1, AKR1C2, or CYP2W1 were found in responders to neoadjuvant chemotherapy compared with nonresponders. Patients with high AKR7A3 or CYP2B6 levels in the pretreatment set had significantly longer disease-free survival than patients with low levels. Protein products of AKR1C1, AKR1C2, AKR7A3, CYP3A4, and carbonyl reductase (CBR1) were found in tumors and those of AKR1C1, AKR7A3, and CBR1 correlated with their transcript levels. Small interfering RNA-directed knockdown of AKR1C2 or vector-mediated upregulation of CYP3A4 in MDA-MB-231 model cell line had no effect on cell proliferation after paclitaxel treatment in vitro.Prognostic and predictive roles of drug-metabolizing enzymes strikingly differ between posttreatment and pretreatment breast carcinoma patients. Mechanisms of action of AKR1C2, AKR7A3, CYP2B6, CYP3A4, and CBR1 should continue to be further followed in breast carcinoma patients and models.13-25222J, GACR, Czech Science FoundationCzech Science Foundation [13-25222J]; Internal Grant Agency of the Czech Ministry of Health [NT/14055-3

Realization of an automated production line workplace

Práce se věnuje problematice automatizování výrobního procesu pracoviště pro kování kovových dílů za tepla pro konkrétního zákazníka ve specifickém prostředí. V úvodu je proveden rozbor problematiky průmyslu čtvrté průmyslové revoluce. V další části se práce věnuje virtuálnímu zprovoznění pracoviště v programu Process Simulate. Následně se zabývá technickou částí návrhu a detailní specifikací jednotlivých komponent pracoviště a prostředí, do kterého bude nová linka integrována. Závěrem je zhodnoceno obchodní stanovisko a úspěšnost projektu po realizaci.The thesis deals with the automation of the production process of the workplace for forging of metal parts for a specific customer in a specific environment. In the introduction, there is an analysis of the industrial revolution. In the next part, the thesis is devoted to the virtual commissioning in Process Simulate. It then deals with the technical part of the design and detailed specifications of the individual components. Finally, the success of the project after the implementation is evaluated.

Indikator position behind the wall

The work sums up the basic measurement principles for different kinds of searching devises. It deals with measurement using resonance. The feature of resonance and measurement techniques are described to set the location of the radiating circuite. The work contains the design of a locator of position behind a wall itself as well as the concrete switch connection, schema and description of receiver and emitter in the circuit

Indikator position behind the wall

Práce shrnuje základní principy měření pro různé typy vyhledávacích přístrojů. Zabývá se měřením pomocí rezonance. Objasňuje jev rezonance a měřicí techniky, jimiž lze tohoto jevu využít, a to zejména k řešení problému určování polohy vyzařovacího obvodu. Práce obsahuje návrh vlastního indikátoru polohy místa za zdí s konkrétním zapojením, schématy a popisem přijímací i vyzařovací části obvodu.The work sums up the basic measurement principles for different kinds of searching devises. It deals with measurement using resonance. The feature of resonance and measurement techniques are described to set the location of the radiating circuite. The work contains the design of a locator of position behind a wall itself as well as the concrete switch connection, schema and description of receiver and emitter in the circuit.

Advanced approach of material region detections on fibre-reinforced concrete CT-scans

Detections of material regions on CT-scans of solids are commonly treated manually by an expert. Although such manual detections have many advantages, some amount of human error is also incorporated. Moreover, expert opinions may vary significantly. We present an application of the k-means++ clustering as an alternative option to manual way of material area detections. k-means++ clustering is derived from k-means (the method of vector quantization, originally from signal processing), popular for cluster analysis in data mining and image processing communities. The algorithm s main advantages are its simple implementation and fast convergence to a local optimum of an objective function. We benchmark the suggested approach on transverse CT-scans of a fibre-reinforced concrete solid. Moreover, we introduce a technique for processing air distribution, such that the appropriate pixels detected as the pixels of air are converted into pixels representing concrete. The technique is based on the connected component algorithm. Benchmark and results of proposed method conclude the paper

Steps to increase practical applicability of PragTic software

This paper describes various methods for increasing the computational speed of an existing fatigue solver called PragTic. The paper describes the basic workflow of computational fatigue analysis, including multiaxial fatigue analysis as well. It documents some of the inefficiencies of the original PragTic version, and parallelization and scalability testing of the parallelized PragTic in three different case studies. These studies include a simple model example (hundreds of nodes) and a real world example (millions of nodes). The implemented parallelization techniques are tested using numerical experiments to demonstrate their parallel scalability. As an output of a unique analysis, the number of necessary and feasible evaluated planes in multiaxial analyses is monitored, and the outcome favoring integral methods for the multiaxial fatigue analysis is commented.Web of Science129685

Parallel strategies for solving the FETI coarse problem in the PERMON toolbox

summary:PERMON (Parallel, Efficient, Robust, Modular, Object-oriented, Numerical) is a newly emerging collection of software libraries, uniquely combining Quadratic Programming (QP) algorithms and Domain Decomposition Methods (DDM). Among the main applications are contact problems of mechanics. This paper gives an overview of PERMON and selected ingredients improving scalability, demonstrated by numerical experiments

A Note on massively parallel implementation of FETI for the solution of contact problems

The paper deals with the solution of large multibody contact problems using massively parallel computers and domain decomposition methods. These methods can solve the problems discretized by billions of nodal variables at the cost nearly proportional to the number of variables using up to thousands cores before the communication costs start to dominate the computational costs. The paper describes the ingredients essential for efficient massively parallel implementation that increases the parallel scalability beyond the limit mentioned above. The improvements were enhanced into a new software package PERMON which is based on PETSc. The performance of the algorithm is demonstrated on the solution of an academic benchmark discretized by nearlybillion of nodal variables