Time series analysis and modeling of the statistical properties of heart beat dynamics during atrial fibrillation

The present work makes a contribution to the statistical analysis of medical time series. In particular, the work discusses the possibility of detecting the rate of fibrillation – observed in the atrium during atrial fibrillation - based solely on the statistical properties of ventricular interbeat-intervals. First the work concentrates on the statistical analysis of ECG-recordings and of ventricular tachograms. It presents a new method – the generation of so-called morphograms – which enables one to analyse the entire information carried by an ECG-recording without complicated pattern recognition. It is shown that this method is suitable for determining different states of health. Second the work concentrates on the analysis of the statistical properties of ventricular interbeat-intervals, observed during atrial fibrillation. It presents a new characteristic, statistical feature – an exponential decay in the distribution of those intervals - which has not been published before. Furthermore it is shown, that different statistical features of ventricular interbeat-intervals during atrial fibrillation are interrelated. In the following the work concentrates on the mathematical modelling of the physiological process during the conduction of atrial impulses through the AV node. In particular the work concentrates on the conduction model originally proposed by Jorgensen et al.. It is shown that this model can be fully analytical described. Based on a detailed discussion of the original model and mathematical solutions for modified ones, two methods for determining the fibrillation rate are presented. The performance of these methods are demonstrated based on medical data. The present work demonstrates that during atrial fibrillation the rate of fibrillation can be determined solely based on the statistical properties of ventricular interbeat-intervals

Influence of mirtazapine on salivary cortisol in depressed patients

Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic alpha(2)-receptors, at postsynaptic 5-HT2 and 5-HT3 receptors, and at histaminergic H1 receptors. Furthermore, mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on salivary cortisol secretion was investigated in 12 patients (4 men, 8 women) suffering from major depression according to DSM-IV criteria. Patients were treated with mirtazapine for 3 weeks, receiving 15 mg mirtazapine on day 0, 30 mg on day 1 and 45 mg per day from day 2 up to the end of the study (day 21). Response to mirtazapine treatment was defined by a reduction of at least 50% in the Hamilton Rating Scale for Depression after 3 weeks of therapy. Salivary cortisol concentrations were measured before treatment (day -1), at the beginning of treatment (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Saliva samples were collected hourly from 08.00 until 20.00 h. The area under the curve values served as parameter for the salivary cortisol secretion. Following analysis of variance with a repeated measures design, tests with contrasts revealed a significant reduction of cortisol concentrations already after 1 day of mirtazapine treatment that was comparable in responders and nonresponders. In addition to new pharmacological approaches such as CRH1 receptor antagonists, mirtazapine therefore appears to be an effective strategy to decrease hypercortisolism and restore HPA system dysregulation in depression. However, the importance of the acute inhibitory effects of mirtazapine on cortisol secretion for its antidepressant efficacy has to be further clarified. Copyright (C) 2003 S. Karger AG, Basel

Shot Peening Method for Aerofoil Treatment of Blisk Assemblies

AbstractAdvanced compressor designs today often include blade integrated disc (blisk) rotors, with high demands on aerodynamic performance, resistance againsthigh load levels and foreign object damage (FOD).To increasethe highcycle fatigue (HCF) strength, compressive residual stresses are introduced into the surface and subsurface layer of aerofoil, fillet (transient area between aerofoil and disk) and annulus (intermediate area between aerofoils). For generatingcompressive residual stresses several different industrial production processes are used, beside ultrasonic shot peening, laser shock peening, deep rolling and shot peening wet and dry with glass or ceramic media is shot peening with steel media the mostly used technology. However, depending on the size of the componentaccessibility for tools might be limited and the set-up of economical production techniques challenging for blisk shot peening.This paper gives an introduction into blisk shot peening, a sophisticated mechanical surface technology for treating aerofoil surfaces of blisk rotors using special designed calliper nozzles assolution for introducing uniform residual compressive stress states, as well as consistentshot peening coverage levels

Function and transport of a herpesvirus encoded Ubiquitin-specific protease in virus entry and assembly

Herpes simplex virus type I (HSV-1), the prototype α-herpesvirus (HV), is a double stranded DNA virus that replicates in the nucleus of infected cells. The nuclear pore represents a gateway that must be engaged and navigated immediately after cell entry for successful infection by many classes of human viruses. For herpesviruses, capsid-tegument assemblies must be targeted to the pore where the viral genome exits and transport into the nucleus occurs. We currently have little mechanistic knowledge of this fundamental step of infection. A swath of evidence indicates that the conserved tegument protein VP1-2 is essential for early capsid transport and pore binding, and that it contains a conserved nuclear localisation signal (NLS) required for pore docking. In this thesis I undertook a detailed analysis to dissect functional determinants within the NLS from herpes simplex virus, to examine putative NLSs in VP1-2 homologues from representatives of all sub-families, to characterise protein interactions with VP1-2 and finally to construct a GFP expressing entry defective recombinant virus to study the consequences of infection. I show that the HSV NLS can function as a mono-or bipartite motif and has a particular organisation conserved in the a-herpesvirus homologues but distinct from those in the \beta- and \gamma-herpesviruses. The representatives of all 3 classes contain a functional NLS at approximately the same position. All bi-partite motifs were able to rescue the HSV VP1-2ΔNLS virus defect albeit to varying extent whereas the mono-partite HHV-8 motif did not. I constructed and purified chimeric recombinant viruses for the VZV, HCMV and EBV motifs and show distinct differences in their ability to replicate in non-complementing cells. In HSV, NLS function in the context of protein nuclear import or of viable virus replication, was dependent on lysine 428 and the integrity of the full bi-partite motif. Mutations which reduced NLS activity generally caused reduced fitness of recombinant viruses. For the analysis of interaction partners of VP1-2 and the NLS, I developed a one-step approach to analyse the capsid interactome during entry. Additionally, I constructed mammalian GST-VP1-2.NLS fusion proteins and cell lines which inducibly express the N-terminal region of VP1-2 for analysis of NLS interacting proteins. Using mass spectrometry (MS) I identified a number of VP1-2-interacting, cellular proteins including DTX3L, an important regulator of the DNA damage response.Open Acces

Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer

The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1) our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and progression; and (2) the potential of using cyclooxygenase and lipoxygenase inhibitors for pancreatic cancer treatment and prevention

How to Improve Accessibility of Natural Areas: About the Relevance of Providing Information on Accessible Services and Facilities in Natural Areas

Accessibility is a topic of increasing importance concerning all fields of life. This is underlined by current legislation as well as social meaning and economic benefits related to accessibility. Due to recent demographic changes in society characterised by steadily growing numbers of the elderly (with age-related physical deficits), enabling people with disabilities to manage their everyday independently gets even more important. However, in order to fully participate in life self-determined, the disabled demand for barrier free infrastructure in many ways. This is particularly true in terms of tourist and recreational activities in natural areas. At that, positive effects of being in nature (e.g. on people’s physical health and mental well-being as well as integration and family solidarity) are even more relevant for disabled people than for others. While many efforts exist on offering and improving barrier free services and facilities on-site, it seems that there is a lack of off-site material informing persons with disabilities of accessible services and facilities available in natural areas. That is surprising, since today, rapid advances in information and communication technologies offer many ways to provide digital, i.e. web-based solution suitable to impart all kinds of information and to meet the needs of disabled people. Concerning the spatial reference of nature-based recreation, i.e. in order to communicate location and spatial relationship of services and facilities, web-based maps are a central means of communication. But, which information regarding tourist and recreational visits of natural areas is required by disabled visitors? How to present this information to the target group in an accessible and useful way? How to design and integrate web-based maps as powerful tool to impart spatial information? Based on research conducted within the project “senTOUR”, this paper aims to offer suggestions for proving accessible digital information in order to support recreational and tourist activities in natural areas for disabled visitors, i.e. for the elderly who often suffer from age-related physical deficits