GENCOM - A Generalized Communication Model Concept

The paper describes the capabilities of a General Purpose Communication Network Simulation Program called GENCOM and traces the background leading up to its development. GENCOM, as a versatile, flexible, relatively simple program was conceived by the analysis of a complex, special purpose program written for the evaluation of the Minuteman Communication Network. The simulation of the Minuteman Communication network was written in Simscript and modelled in detail the complex procedures for the flow of messages through the system. Unexpectedly, the simulation showed that certain second order effects could cause the system to ring in such a manner as to seriously interfere with successful message transmissions. This phenomena would not have occurred in the system as originally designed and could be traced to a minor system modification. In addition to uncovering this problem, the simulation provided the means of investigating possible solutions and identifying the most efficient one. The success of this study spotlighted the desirability of using a simulation during the development of a system rather than after the design is frozen. The special purpose Minuteman program was analyzed to identify general techniques which might be applicable in a wide variety of communication networks. The results of this analysis led to the development of a completely General Purpose Communication Network Simulation program called GENCOM

Proteomic, circulating and functional biomarkers of cardiovascular disease

Cardiovascular disease is the leading cause of morbidity and mortality in the Western world, mainly through cerebrovascular and coronary artery related events. Cardiovascular disease is a chronic progressive disease with different stages. These stages can be assessed by a variety of biomarkers. Biomarker quantification can be used for different purposes: screening, prediction of disease recurrence, therapeutic monitoring, diagnosis and prognostication. Noninvasive, inexpensive diagnostic tests currently applied in clinical practice have a relative high rate of false positive and false negative results. Therefore further refinement of the diagnostic process could improve clinical care. Regarding prognostication the need for improvement also remains as current risk models only predict a small quantity of occurring cardiovascular events. The concept of the cardiovascular continuum postulates that cardiovascular disease consists of a chain of events, is initiated by numerous cardiovascular risk factors and subsequently progresses through pathophysiological processes, ultimately leading to end-stage heart failure. For that reason cardiovascular diseases are chronic progressive conditions and can be divided into different stages, such as early tissue dysfunction or subclinical atherosclerosis prior to development of clinically overt disease. Biomarkers suitable for prognostication and diagnosis can differ at each stage. The general aim of this thesis was therefore the investigation of a variety of biomarkers in diagnosis and prediction of cardiovascular disease at different stages of the cardiovascular continuum, as covered by three different study cohorts contributing to this thesis. This included several approaches: the comparison of central and peripheral pulse pressure in middle aged hypertensive patients in regards of their prognostic potential; the application of established circulating, functional and structural biomarkers to the diagnostic process of coronary artery disease in stable angina patients; the development/refinement of a urinary proteomic biomarker for coronary artery disease and the examination of its diagnostic potential in stable angina patients. Biomarkers successful in the diagnosis of coronary artery disease were included in multiple biomarker models. Aside from biomarker development for the general population, investigations of specific cohorts, such as patients with certain diseases and belonging to certain age groups or sharing specific biochemical features provided advances in the past. To estimate the potential of a biomarker in risk prediction association studies with surrogate biomarkers are applicable. We collected a cohort of middle-aged hypertensive patients to assess if central pulse pressure, derived from non-invasive assessment of arterial stiffness, could improve risk prediction. Central pulse pressure has been previously shown to have prognostic value in populations with end-stage renal failure, coronary artery disease and high prevalence of diabetes mellitus. Considering the prognostic information of peripheral pulse pressure in the elderly, the hypothesis that central pulse pressure could improve risk prediction is comprehensive and was investigated as part of this thesis. This was accomplished by comparing the strength of correlation between central or peripheral pulse pressure and these surrogate biomarkers. When compared to peripheral pulse pressure, central pulse pressure had stronger associations with aortic pulse wave velocity, carotid intima-media thickness, and left ventricular mass index, but equal association with the albumin:creatinine ratio. In contrast, after adjustment for age, mean arterial pressure, heart rate and hypertension status there was no significant difference between central and peripheral pulse pressure for prediction of listed surrogate biomarkers in multivariate analysis. These results suggested that central pulse pressure is unlikely to provide more prognostic information than peripheral pulse pressure in middle-aged hypertensive patients. The diagnosis of coronary artery disease is clinically relevant in symptomatic patients, either acute or stable. The diagnosis of stable flow limiting coronary artery disease is especially challenging as non-cardiac as well as other cardiac conditions can mimic symptoms. Non-invasive diagnostic tools have either moderate sensitivities or specificities, or are not widely available. Therefore new biomarkers for the diagnosis of flow limiting coronary artery disease have the potential to improve current diagnostic strategies. This could be accomplished adjacent to existing biomarkers or by replacement of such, due to cost effectiveness, better discriminatory etc. As part of this thesis, a biomarker identification and validation study was conducted into urinary proteomics of coronary artery disease. First we tried to replicate a study conducted by our research group in the past. Therein, an established coronary artery disease specific polypeptide pattern was unable to differentiate between patients with severe coronary artery disease and healthy controls despite strong cohort similarities to the original study. We therefore recalibrated the urinary polypeptide pattern using an enlarged biomarker discovery cohort and adjusted the pattern for lipid lowering and angiotensin converting enzyme inhibitor treatment effects. We calculated a score from the resulting polypeptide pattern, which identified coronary artery disease patients with a sensitivity of 79% and a specificity of 88% in a biomarker validation cohort. As the next step of biomarker development we performed a diagnostic validation study. The investigated clinical cohort consisted of stable angina patients with or without coronary artery disease. The new polypeptide pattern score was unable to differentiate between these two groups. The score however correlated strongly with coronary artery disease extent as measured by the Gensini score, implying that urinary proteomics in the diagnosis of coronary artery disease is promising, yet requires further effort before clinical employment. In addition to the urinary proteomic biomarker development second diagnostic approach was selected. As coronary artery disease is a complex chronic disease, the combination of different biomarkers should result in a better discrimination between stable angina patients with or without coronary artery disease. This approach attempts to position the individual as precisely as possible on the cardiovascular continuum including serologic, functional vascular and imaging biomarkers of subclinical atherosclerosis. Serologic markers thereby present a plasma proteomic approach covering pathophysiological processes with known correlation or causative for coronary artery disease. Functional and structural changes of the peripheral vasculature resemble the coronary artery system. We investigated circulating biomarkers and vascular biomarkers separately. A variety of circulating biomarkers differentiated patients with severe coronary artery disease from healthy control subjects. When patients with stable angina and with or without coronary artery disease as diagnosed by coronary angiography were investigated no statistically significant differences could be detected for circulating biomarkers. In the same study a microvascular biomarker, the reactive hyperaemia index, and a macrovascular biomarker, the carotide plaque score, were able to differentiated between cases and controls. Both markers either added separately or together improved the risk classification of exercise treadmill test results. This suggests that a multiple biomarker approach in the diagnosis of coronary artery disease in stable angina patients could be successful. Different aspects of the cardiovascular continuum can be applied to diagnosis and prognostication of cardiovascular disease. In this regard we were able to show, that early processes such as endothelial dysfunction or later processes such as plaque formation can support the diagnostic process. However, randomly collected circulating biomarkers might be unable to do this. Our finding that central pulse pressure is unlikely to have more prognostic value in middle aged hypertensive patients underlines that biomarkers can be useful in specific patient collectives but not necessarily in all cohorts. Instead of applying established biomarkers, also new biomarkers can be developed. Urine proteomics showed great promise in this regard, as specific polypeptide patterns reflect coronary artery disease and are strongly correlated to its extent

Dynamic control of Nanog expression in embryonic stem cells

Embryonic stem cells are defined by two key characteristics; apparently symmetrical self-renewing cell division and the ability to differentiate into cells of all three germ layers. Self-renewal depends on several extrinsic and intrinsic cues including a gene regulatory network centered around Oct4, Sox2 and Nanog that has been hypothesized to be reinforced by positive reciprocal interactions. Studies measuring Nanog expression by fluorescent reporters and immunoflourescence have shown that some undifferentiated Oct4 positive cells do not express Nanog (Chambers et al., 2007). However, the mechanisms responsible for generating this heterogeneity in Nanog expression are unknown. Here I show that Oct4 heterozygote ES cells lack Nanog-negative cells. Consistent with a model in which ES cell differentiation proceeds effectively through Nanog-negative cells, these Oct4 heterozygotes are retarded in their differentiation kinetics. Importantly, restoring Oct4 levels towards wild type reestablished both heterogenous Nanog expression and rapid differentiation. Analysis of ES cells carrying a mutation in the Oct4 binding site in the proximal Nanog promoter showed that Oct4 acts as a positive activator on the endogenous Nanog. Finally, comparison of gene expression in Nanog expressing and Nanog non-expressing ES cells has identified candidate genes that may be responsible for the switch in Nanog expression

Structural dichroism in the antiferromagnetic insulating phase of V_2O_3

We performed near-edge x-ray absorption spectroscopy (XANES) at V K edge in the antiferromagnetic insulating (AFI) phase of a 2.8% Cr-doped V_2O_3 single crystal. Linear dichroism of several percent is measured in the hexagonal plane and found to be in good agreement with ab-initio calculations based on multiple scattering theory. This experiment definitively proves the structural origin of the signal and therefore solves a controversy raised by previous interpretations of the same dichroism as non-reciprocal. It also calls for a further investigation of the role of the magnetoelectric annealing procedure in cooling to the AFI phase.Comment: 4 pages 3 figures. To be published in Phys. Rev. B (2005

Energy-dispersive EXAFS to study chemical reactions: the case of electron transfer reaction of hydroquinone

3 páginas, 3 figurasMost of the chemical processes that occur in nature take place in liquid media. For this reason, chemical reactions in solution have been widely studied for many years. Such studies have focused mainly on the mechanism of the reactions, whilst the structures of the species involved have received considerably less attention. This is mainly due to the difficulties of determining experimentally the structures of chemical species in liquid media. To date, this important question has largely been addressed by the standard techniques of UV-Vis and infrared spectroscopies. Unfortunately these techniques are seldom structurally specific, so the determination of the detailed chemical form of the majority of reactants has awaited the arrival of a fast and more structurally-focused method. Energy dispersive X-ray absorption spectroscopy (EDXAS), is ideal for this new class of experiments.Peer reviewe

Tuning the optical properties of 2D monolayer silver-bismuth bromide double perovskite by halide substitution

: Silver-bismuth double perovskites are promising replacement materials for lead-based ones in photovoltaic (PV) devices due to the lower toxicity and enhanced stability to environmental factors. In addition, they might even be more suitable for indoor PV, due to the size of their bandgap better matching white LEDs emission. Unfortunately, their optoelectronic performance does not reach that of the lead-based counterparts, because of the indirect nature of the band gap and the high exciton binding energy. One strategy to improve the electronic properties is the dimensional reduction from the 3D to the 2D perovskite structure, which features a direct band gap, as it has been reported for 2D monolayer derivates of Cs2AgBiBr6obtained by substituting Cs+cations with bulky alkylammonium cations. However, a similar dimensional reduction also brings to a band gap opening, limiting light absorption in the visible. In this work, we report on the achievement of a bathochromic shift in the absorption features of a butylammonium-based silver-bismuth bromide monolayer double perovskite through doping with iodide and study the optical properties and stability of the resulting thin films in environmental conditions. These species might constitute the starting point to design future sustainable materials to implement as active components in indoor photovoltaic devices used to power the IoT

Designing nanoparticles during the drawing step

International audienceNanoparticles in the core of optical fibres are widely studied due to the opportunity they give to tailor spectroscopic properties. Such fibres are usually obtained by drawing at high temperature a preform containing nanoparticles. This study focuses on the effect of the fibre drawing on nanoparticles. We fabricated an MCVD optical preform by doping the porous layer with nanoparticles. The optical fibre was studied by a FIB/SEM tomography.Figure 1 is the volume reconstruction of the core of the optical fibre. The yellow phase represents nanoparticles inside the core of the optical fibre. This reconstruction shows evidences of break-up, elongation and coalescence of particles. These features will be discussed according to phenomena well known from the rheology of emulsions and polymers. It comes from a competition between viscous stresses of the flow and surface tension.Observation of these size-controlling phenomena occuring during fibre drawing offer new perspectives to tailor the size of nanoparticles and are therefore of great interest for light scattering issues

Improving the lens design and performance of a contemporary electromagnetic shock wave lithotripter.

The efficiency of shock wave lithotripsy (SWL), a noninvasive first-line therapy for millions of nephrolithiasis patients, has not improved substantially in the past two decades, especially in regard to stone clearance. Here, we report a new acoustic lens design for a contemporary electromagnetic (EM) shock wave lithotripter, based on recently acquired knowledge of the key lithotripter field characteristics that correlate with efficient and safe SWL. The new lens design addresses concomitantly three fundamental drawbacks in EM lithotripters, namely, narrow focal width, nonidealized pulse profile, and significant misalignment in acoustic focus and cavitation activities with the target stone at high output settings. Key design features and performance of the new lens were evaluated using model calculations and experimental measurements against the original lens under comparable acoustic pulse energy (E+) of 40 mJ. The -6-dB focal width of the new lens was enhanced from 7.4 to 11 mm at this energy level, and peak pressure (41 MPa) and maximum cavitation activity were both realigned to be within 5 mm of the lithotripter focus. Stone comminution produced by the new lens was either statistically improved or similar to that of the original lens under various in vitro test conditions and was significantly improved in vivo in a swine model (89% vs. 54%, P = 0.01), and tissue injury was minimal using a clinical treatment protocol. The general principle and associated techniques described in this work can be applied to design improvement of all EM lithotripters