Uninterruptible Power Supply

V této práci jsem se seznámil s hardwarovou realizací CLINICOM. Po popisu tohoto nemocničního systému jsem se zabýval důležitými vlastnostmi serveru. Dále bylo popsáno zařízení UPS, jeho druhy a parametry. Následně jsem se seznamoval se způsoby měření spotřeby počítačů a popisem měřicího přístroje Energy Logger. Dále jsem se zabýval měřením zatížení serveru NIS CLINICOM UBMI pomocí přístroje Energy Logger 3500 s následným výpočtem teoretické doby zálohování. Následně jsem všechna měření a odhady doby zálohování srovnal s reálným měřením doby zálohování. Nakonec jsem se zabýval možnostmi realizace automatického zasílání varovné zprávy správci a všem přihlášeným uživatelům nemocničního informačního systému o elektrickém výpadku v napájení sítě.In this work I have been briefed by hardware realization of CLINICOM. After description of this hospital information system I concerned with important attributes of the server. Next the UPS has been described with its kinds and parameters. Consequently I was getting acquainted with methods of measuring of power consumption of computers and description of instrument Energy Logger. At next I concerned with load measuring of the server NIS CLINICOM UBMI with instrument Energy Logger 3500 and in the next section of this part I have calculated theoretic backup time. Sequentially all gauging have been compared with real gauging of backup time. At the end I concerned with methods realization of automated sending of warning message about electric feed problems to administrator and every logged users of the hospital information system.

Molecular genetic investigations of histone deacetylase inhibitors as potential neurotherapeutics for autosomal recessive proximal spinal muscular atrophy (SMA)

Proximal spinal muscular atrophy (SMA) is a common neuromuscular disorder causing infant death in 50 percent of all patients. Homozygous absence of the survival motor neuron gene (SMN1) is the primary cause of SMA, while SMA severity is mainly determined by the number of SMN2 copies. One SMN2 copy produces only about 10 percent of full-length (FL) protein identical to SMN1, whereas the majority of SMN2 transcripts are aberrantly spliced due to a silent mutation within an exonic splicing enhancer in exon 7. However, correct splicing can be restored by over-expression of the SR-like splicing factor Htra2-beta1. In the present work, it is demonstrated that in fibroblast cultures derived from SMA patients treated with therapeutic doses (0.5-50 microM) of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) the level of SMN protein increased about 3fold. Augmented SMN protein levels could be attributed to elevated FL-SMN2 transcript levels which were triggered by two different mechanisms: a transcriptional activation of the SMN2 gene, and a preferred exon 7 inclusion in SMN2 transcripts. The latter observation was most likely due to increased levels of the splicing factor Htra2-beta1. In addition to Htra2-beta1, VPA increased the expression of further SR proteins which may have important implications for other disorders affected by alternative splicing. Importantly, the drug was able to elevate rSmn transcript and protein levels ex vivo through transcriptional activation in organotypic hippocampal brain slices from rats. This demonstrated that VPA also exerts an effect on neuronal tissue, the target for a potential SMA therapy. Since VPA is a drug highly successfully used in long-time epilepsy therapy, these findings opened the exciting perspective for a first causal therapy of an inherited disease by elevating the SMN2 transcription level and restoring its correct splicing. The evaluation of two second-generation HDAC inhibitors in SMA fibroblasts in vitro revealed that SAHA, a drug that belongs to the hydroxamic acids, also efficiently elevated SMN protein levels 2.4fold to 3fold. Therefore, SAHA was identified as another attractive candidate for SMA therapy. In contrast, the data obtained for MS-275, an HDAC inhibitor of the benzamide class, demonstrated that the drug does not possess enough potency to substantially elevate SMN protein levels in vitro. Thus, MS-275 will not have a chance to move forward to SMA clinical trials. Based on the promising data for VPA in vitro and ex vivo and given that VPA is already approved for application to humans, a first pilot trial with VPA was carried out in ten SMA carriers (parents of patients with SMA) aiming to evaluate drug potency to increase SMN transcript and protein levels in vivo. In order to further validate the outcome of the study, SMN2 gene expression was analyzed in peripheral whole blood derived from 20 patients with SMA (5x type I, 11x type II, 4x type III) treated with VPA in individual experimental curative approaches all over Germany according to section 41 of the German Drug Act (AMG). Moreover, the value of these screenings was determined for the development of a clinical biomarker to monitor the response to VPA and other HDAC inhibitors in treated individuals. Such a biomarker would be highly useful for clinical trials and future therapies in SMA patients. Drug treatment revealed elevated full-length SMN RNA and protein levels in blood from 7/10 SMA carriers. Importantly, SMN protein levels increased far more substantially (up to 13.8fold) than the levels of the intermediate product, FL-SMN RNA, that showed an increase of up to 3.4fold. These observations provided first proof of the in vivo activation of a therapeutic target gene by VPA in an inherited disease. Among the investigated SMA patients, FL-SMN2 RNA levels were increased 1.5fold to 1.9fold in seven subjects, whereas 13 patients presented unchanged or even decreased transcript levels. This data suggested that some individuals are responders to VPA, while others are most likely nonresponders or even negative-responders. However, so far it is unknown whether SMN expression in blood reflects SMN expression in alpha-motor neurons and correlates with muscle strength. Therefore, systematic long-term clinical trials in SMA patients that correlate SMN expression in blood with individual motor function tests are required in the future to address the question whether SMN transcript and protein levels in blood may serve as biomarker, and to study the effect of VPA on motor function

‘Love it or loath it’: a cross-national comparison of tabloid reading experiences in the UK and Germany

This thesis comprises a cross-national comparison of readership responses to the British tabloid The Sun and the German red-top Bild. The study is of qualitative nature: it draws on extensive material derived from a total of 18 focus groups conducted in both countries, in which 104 diverse adults participated. The first study to compare tabloid reading experience cross-nationally, the research sets out to explore how readers of The Sun and readers of Bild make sense of the papers, and how they evaluate them. The results are analysed with regards to emerging similarities and differences, which are pointed out and discussed in relation to the specific social and cultural contexts in the UK and Germany. While many academic approaches to genre consider popular newspapers hazardous to the workings of democratic society; this study takes a different approach. Drawing on a range of academic ideas that can largely be associated to the intellectual tradition of ‘cultural studies’, the research foregrounds the social and cultural functions of the popular press from the readers’ point of view; focussing in particular on notions of belonging and community as expressed in the construction of citizenship, social participation and collective identity formations. Among the key results of the study, cross-nationally shared modes of engagement with tabloids are highlighted, which contribute to an often tension-filled character of the reading experience. Moreover, the papers’ highly stimulating potential is stressed. I develop my idea of the ‘negotiative space’ generated by tabloids; arguing that this greatly contributes to readers’ development of their ‘vision of the good and bad’. Moreover, the thesis emphasises the significance of the popular press to various kinds of readers’ social and cultural identity formations; particularly with regards to notions of nationhood and national identity

Deformation Response of the Realization of the Exploration Work PAD4A within the Framework of the Construction of Metro I.D in Prague

V předložené práci bude zkoumána deformační odezva ražeb průzkumného díla PAD4A. Toto průzkumné dílo je jedním ze 4 ražených průzkumných děl prováděných v rámci stavby trasy I.D metra v Praze, provozního úseku Pankrác – Depo Písnice. První část práce seznámí s projektem průzkumných děl na trase I.D metra. V další části práce budou popsány geologické a hydrogeologické poměry zájmového území. Následně bude zkoumána samotná deformační odezva ražeb průzkumného díla PAD4A na okolní horninové prostředí a povrch, s přihlédnutím k použité technologii ražeb a skutečnému postupu prací. Analyzován bude rovněž vliv prováděných injektáží na zlepšení geotechnických vlastností horninového prostředí na tuto deformační odezvu. Výstupem práce bude shrnutí získaných poznatků a formulace doporučení pro realizace vlastní stanice metra Pankrác I.D.This thesis deals with deformation response of excavations of exploration work PAD4A. The exploration work is one of 4 excavated exploration works which are made within constructing metro line I.D in Prague, operating section Pankrác – Depo Písnice. The first part of this thesis will introduce you project of exploration works on operating section Prague metro I.D. In the second part of this thesis there are going to be described geological and hydrogeological conditions of the interest area. Then the deformation response itself will be investigated. Specifically, the deformation response of exploration work PAD4A on surrounded rock and surface, with assume to the used excavation technology and real work process. The influence of performed grouting will be also analyzed because of improvement geotechnical properties of rock on this deformation response. The output of the work will be a summary of the findings and the formulation of recommendations for the implementation of its own metro station Pankrác I.D.541 - Katedra geologického inženýrstvívelmi dobř

Shadowing property of numerical methods for partial differential equations

This thesis is focused on the shadowing property of numerical methods for partial differential equations. The goals of this thesis are the application of shadowing theory to the case of linear maps, modification of standard techniques for the purpose of this application and the application of the adapted theory to multistep schemes. In the in- troductory overview, we first focus on a study of the standard shadowing theory, then we formulate basic statements and prove a relationship between a conctractivity and shadowing. Afterwards we find the characterization of the shadowing property for linear maps. In the next sections, we adapt definitions of the shadowing theory to requirements of multistep methods. As an example, we apply the adapted theory to the Dufort-Frankel scheme in the third chapter. At the end of this thesis, remarks on shadowing in general multistep methods and remarks on a relationship between the shadowing property and stability are presented. 1Předkládaná práce se zabývá stínováním v numerických metodách pro parciální di- ferenciální rovnice. Cíle této práce jsou prostudovat problematiku stínování v případě lineárního zobrazení, vhodně upravit standardní metody pro účely zmíněné aplikace a aplikovat vybudovanou teorii na vícekrokové metody. V úvodní přehledové části se nejprve zaměříme na studium standardní teorie stínování, formulujeme základní tvrzení a uká- žeme vztah kontraktivity a stínování. Dále nalezneme charakterizaci stínovací vlastnosti pro lineární zobrazení. Následně vhodně adaptujeme stínovací teorii, aby byla umožněna aplikace ve vícekrokových numerických metodách. Příslušnou aplikaci potom vysvětlu- jeme na příkladu Dufortova-Frankelova schématu. V závěru práce uvádíme poznámky k vyšetřování stínování v obecných vícekrokových metodách a poznámky o vztahu stínování a stability. 1Department of Numerical MathematicsKatedra numerické matematikyMatematicko-fyzikální fakultaFaculty of Mathematics and Physic

Construction of a Pseudomonas aeruginosa Dihydroorotase Mutant and the Discovery of a Novel Link between Pyrimidine Biosynthetic Intermediates and the Ability to Produce Virulence Factors

The ability to synthesize pyrimidine nucleotides is essential for most organisms. Pyrimidines are required for RNA and DNA synthesis, as well as cell wall synthesis and the metabolism of certain carbohydrates. Recent findings, however, indicate that the pyrimidine biosynthetic pathway and its intermediates maybe more important for bacterial metabolism than originally thought. Maksimova et al., 1994, reported that a P. putida M, pyrimidine auxotroph in the third step of the pathway, dihydroorotase (DHOase), failed to produce the siderophore pyoverdin. We created a PAO1 DHOase pyrimidine auxotroph to determine if this was also true for P. aeruginosa. Creation of this mutant was a two-step process, as P. aeruginosa has two pyrC genes (pyrC and pyrC2), both of which encode active DHOase enzymes. The pyrC gene was inactivated by gene replacement with a truncated form of the gene. Next, the pyrC2 gene was insertionally inactivated with the aacC1 gentamicin resistance gene, isolated from pCGMW. The resulting pyrimidine auxotroph produced significantly less pyoverdin than did the wild type. In addition, the mutant produced 40% less of the phenazine antibiotic, pyocyanin, than did the wild type. As both of these compounds have been reported to be vital to the virulence response of P. aeruginosa, we decided to test the ability of the DHOase mutant strain to produce other virulence factors as well. Here we report that a block in the conversion of carbamoyl aspartate (CAA) to dihydroorotate significantly impairs the ability of P. aeruginosa to affect virulence. We believe that the accumulation of CAA in the cell is the root cause of this observed defect. This research demonstrates a potential role for pyrimidine intermediates in the virulence response of P. aeruginosa and may lead to novel targets for chemotherapy against P. aeruginosa infections

VLSI implementation of the SIFT algorithm for pitch detection

Speech voicing classification and pitch detection are fundamental techniques in speech analysis. Voicing information provides valuable insights into the nature of the excitation source used in speech production, and the pitch information is useful to many speech processing applications. In 1972 John Markel developed a technique which combines the benefits of inverse linear predictive (LPC) analysis and simple short-time autocorrelation to extract essential speech parameters. The research resulted in the simplified inverse filter tracking (SIFT) algorithm to make voiced/unvoiced classification of speech signals and determine the pitch period. Up until now this algorithm was used in various software algorithms only. However, this paper describes a real-time CMOS hardware implementation of this algorithm small enough to be implemented into various mobile communications equipment

Pioneers in CNS inhibition: 2. Charles Sherrington and John Eccles on inhibition in spinal and supraspinal structures

This article reviews the contributions of the English neurophysiologist, Charles Scott Sherrington [1857–1952], and his Australian PhD trainee and collaborator, John Carew Eccles [1903–1997], to the concept of central inhibition in the spinal cord and brain. Both were awarded Nobel Prizes; Sherrington in 1932 for “discoveries regarding the function of neurons,” and Eccles in 1963 for “discoveries concerning the ionic mechanisms involved in excitation and inhibition in central portions of the nerve cell membrane.” Both spoke about central inhibition at their Nobel Prize Award Ceremonies. The subsequent publications of their talks were entitled “Inhibition as a coordinative factor” and “The ionic mechanism of postsynaptic inhibition”, respectively. Sherrington's work on central inhibition spanned 41 years (1893–1934), and for Eccles 49 years (1928–1977). Sherrington first studied central inhibition by observing hind limb muscle responses to electrical (peripheral nerve) and mechanical (muscle) stimulation. He used muscle length and force measurements until the early 1900s and electromyography in the late 1920s. Eccles used these techniques while working with Sherrington, but later employed extracellular microelectrode recording in the spinal cord followed in 1951 by intracellular recording from spinal motoneurons. This considerably advanced our understanding of central inhibition. Sherrington's health was poor during his retirement years but he nonetheless made a small number of largely humanities contributions up to 1951, one year before his death at the age of 94. In contrast, Eccles retained his health and vigor until 3 years before his death and published prolifically on many subjects during his 22 years of official retirement. His last neuroscience article appeared in 1994 when he was 91. Despite poor health he continued thinking about his life-long interest, the mind-brain problem, and was attempting to complete his autobiography in the last years of his life

Laser-initiated Coulomb explosion imaging of small molecules

Momentum vectors of fragment ions produced by the Coulomb explosion of CO2z+ (z = 3 - 6) and CS2z+ (z = 3 - 13) in an intense laser field (~50 fs, 1 x 1015 W/cm2) are determined by the triple coincidence imaging technique. The molecular structure from symmetric and asymmetric explosion channels is reconstructed from the measured momentum vectors using a novel simplex algorithm that can be extended to study larger molecules. Physical parameters such as bend angle and bond lengths are extracted from the data and are qualitatively described using an enhanced ionization model that predicts the laser intensity required for ionization as a function of bond length using classical, over the barrier arguments. As a way of going beyond the classical model, molecular ionization is examined using a quantum-mechanical, wave function modified ADK method. The ADK model is used to calculate the ionization rates of H2, N2, and CO2 as a function of initial vibrational level of the molecules. A strong increase in the ionization rate, with vibrational level, is found for H2, while N2 and CO2 show a lesser increase. The prospects for using ionization rates as a diagnostic for vibrational level population are assessed