Test Results of DIA: A Real-Time Adaptive Integrity Monitoring Procedure, Used in an Integrated Naviation System

A practical method for real-time kinematic position determination and Quality Control (QC) in (integrated) navigation systems is presented as a combination of an extended iterated Kalm an Filter (KF) and the Detection, Identification and Adaptation (DIA) testing procedure for integrity monitoring as developed by the Delft University of Technology. DIA is a real-time recursive QC tool which can be used on multi-sensor integration. There will be no degradation in the number of sensors used by the navigation system, when applying the DIA theory to possible arising errors. Test results are presented of the KF&DIA procedure, which was implemented in the software of the survey vessel HNIMS BUYSKES of the Royal Netherlands Navy. The results of DIA are evaluated by comparing the position quality (precision and reliability) of the KF&DIA procedure with the solution of a standard integrated Least Squares (LS) position with F-test and w-test (DataSnooping, DS) as QC-tools. This analysis shows that the use of a Ka lm a n Filter in combination with DIA gives more precise results (factor = 1½) when compared to the Least Squares method with F-test and w-test. The reliability also increases, especially in cases where multiple errors in observations at one epoch occur. In general the quality of the KF&DIA solution is less influenced by errors than the LS&DS solution

Schatting van in situ fluxen van organische microverontreinigingen uit waterbodems

Dit rapport beschrijft de resultaten van een onderzoek naar naleveringsfluxen van organische microverontreinigingen, ten behoeve van het Deltares koploperproject “Biobeschikbaarheid en gedrag van stoffen”, deelproject A “Nalevering van stoffen uit waterbodems”. Hierin wordt het belang van nalevering voor de kwaliteit van het oppervlaktewater onderzocht. Dit project moet leiden tot inzicht in de situaties waarin nalevering van stoffen uit de waterbodem naar het oppervlaktewater een significante (secundaire) verontreinigingbron vormt. Dit met het oog op normoverschrijding in het oppervlaktewater (chemische doelstelling KRW), of het niet bereiken van een goede ecologische toestand (ecologische doelstelling KRW). In het voorliggende rapport worden de resultaten van kolom flux-experimenten besproken. Aan de orde komen: (a) opzet meetprogramma voor zover afwijkend van het meetplan, (b) informatie met betrekking tot kwaliteitscontrole, (c) specificatie van gebruikte analysevoorschriften (d) analyseresultaten met korte toelichtin

Area Computation of Polygons

Area computation has always been an important task for land surveyors. Until recently the hydrographic surveyor could utilize approximative methods, as results up to 0.1 km2 were sufficient for many purposes. Investigations resulted in computation algorithms, usable on the ellipsoid, with accuracies of the square metre magnitude

Towards better prognostic and diagnostic strategies for major obstetric haemorrhage

Postpartum haemorrhage, in this thesis defined as blood loss above 1000mL within the first 24 hours after birth, remains a major cause of maternal morbidity and mortality with an incidence that seems to be increasing over the last decade. In this thesis we focussed on improvement of prognostic and diagnostic strategies for major obstetric haemorrhage, which may subsequently lead to a reduction of severe maternal morbidity, mortality and need for surgical interventions. In pursuit of this aim, research questions were posed corresponding to all three phases leading up to adverse outcome due to postpartum haemorrhage: pregnancy (prior to childbirth), early postpartum haemorrhage and persistent postpartum haemorrhage. In the first part of this thesis we focused on prediction of postpartum haemorrhage.Bleeding assessment tools were found to have no predictive value for postpartum haemorrhage. The change of coagulation parameters during the course of postpartum haemorrhage was described, and fibrinogen was found to be an early predictor of a worse outcome of postpartum haemorrhage. The association between fibrinogen measured by the Clauss method and ROTEM Fibtem was described in this thesis.Leiden University, the department of gynaecology and obstetrics of the Leiden University Medical Center; Sanquin; Raad van Bestuur Groene Hart Ziekenhuis; CSL BehringLUMC / Geneeskunde Repositoriu

Опорно-анкерне кріплення гірничих виробок вугільних шахт України

В статье анализируется опыт применения анкерной крепи горных выработок в горно- геологических условиях угольных шахт Украины. Представлены результаты практического применения.In the article experience of applications of roof bolting of mine workings in geological conditions of Ukrainian coal mines is analyzed. Results of a practical intrusion are presented

Taylor-Couette instability in disk suspensions: Experimental observation and theory

Using the well-known hydrodynamic theory for dilute suspensions of spheroids, we have previously predicted the destabilization of Taylor-Couette flow due to anisotropic viscous stresses induced by suspended disk-shaped particles [Gillissen and Wilson, Phys. Rev. Fluids 3, 113903 (2018)]. Here we provide experimental evidence for the destabilization mechanism using suspensions of mica flakes. There is good qualitative agreement between the experiment and theory in the mica concentration dependence of the critical speed for instability onset and of the axial wavelength of the corresponding Taylor vortices. Quantitative differences are attributed to hydrodynamic interactions between the disks, which we account for in the theory in an ad hoc fashion using rotary diffusion

Bax/Bak-independent mitochondrial depolarization and reactive oxygen species induction by sorafenib overcome resistance to apoptosis in renal cell carcinoma

Renal cell carcinoma (RCC) is polyresistant to chemo- and radiotherapy or biologicals including TNF-related apoptosis inducing ligand (TRAIL). Sorafenib, a multikinase inhibitor approved for the treatment of RCC, has been shown to sensitize cancer cells toward TRAIL-induced apoptosis, in particular by downregulation of the Bak-inhibitory Bcl 2 family protein Mcl 1. Here, we demonstrate that sorafenib overcomes TRAIL resistance in RCC by a mechanism that does not rely on Mcl 1 downregulation. Instead, sorafenib induces a rapid dissipation of the mitochondrial membrane potential (ΔΨ(m)) that is accompanied by the accumulation of reactive oxygen species (ROS). Loss of ΔΨ(m) and ROS production induced by sorafenib are independent of caspase activities and do not depend on the presence of the pro-apoptotic Bcl 2 family proteins Bax or Bak indicating that both events are functionally up-stream of the mitochondrial apoptosis signaling cascade. More intriguingly, we find that it is sorafenib-induced ROS accumulation that enables TRAIL to activate caspase 8 in RCC. This leads to apoptosis that involves activation of an amplification loop via the mitochondrial apoptosis pathway. Thus, our mechanistic data indicate that sorafenib bypasses central resistance mechanisms through a direct induction of ΔΨ(m) breakdown and ROS production. Activation of this pathway might represent a useful strategy to overcome the cell-inherent resistance to cancer therapeutics including TRAIL in multiresistant cancers such as RCC

Targeted therapy of the XIAP/proteasome pathway overcomes TRAIL-resistance in carcinoma by switching apoptosis signaling to a Bax/Bak-independent 'type I' mode

TRAIL is a promising anticancer agent, capable of inducing apoptosis in a wide range of treatment-resistant tumor cells. In 'type II' cells, the death signal triggered by TRAIL requires amplification via the mitochondrial apoptosis pathway. Consequently, deregulation of the intrinsic apoptosis-signaling pathway, for example, by loss of Bax and Bak, confers TRAIL-resistance and limits its application. Here, we show that despite resistance of Bax/Bak double-deficient cells, TRAIL-treatment resulted in caspase-8 activation and complete processing of the caspase-3 proenzymes. However, active caspase-3 was degraded by the proteasome and not detectable unless the XIAP/proteasome pathway was inhibited. Direct or indirect inhibition of XIAP by RNAi, Mithramycin A or by the SMAC mimetic LBW-242 as well as inhibition of the proteasome by Bortezomib overcomes TRAIL-resistance of Bax/Bak double-deficient tumor cells. Moreover, activation and stabilization of caspase-3 becomes independent of mitochondrial death signaling, demonstrating that inhibition of the XIAP/proteasome pathway overcomes resistance by converting 'type II' to 'type I' cells. Our results further demonstrate that the E3 ubiquitin ligase XIAP is a gatekeeper critical for the 'type II' phenotype. Pharmacological manipulation of XIAP therefore is a promising strategy to sensitize cells for TRAIL and to overcome TRAIL-resistance in case of central defects in the intrinsic apoptosis-signaling pathway

Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin

BACKGROUND: Photodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointestinal carcinomas leading to an accumulation of protoporphyrin-IX within the tumor cells. Recent studies showed that a novel anti-cancer drug, Alectinib, an orally available, highly selective, potent second-generation inhibitor of anaplastic lymphoma tyrosinkinase binds to ferrochelatase. Therefore, we were interested to see whether Alectinib treatment might lead to an accumulation of protoporphyrin IX. METHODS: Tumor cells of different origin were cultured, treated with LED-light and Alectinib. Results were gained by flow cytometry, immunohistochemistry and western blotting. Apoptosis was determined by flow cytometric analysis of Annexin V-FITC stained cells. In addition, cells were counterstained with propidium iodide to distinguish early apoptotic cells and late apoptotic/necrotic cells. RESULTS: Here, we report that photodynamic treatment of tumor cell lines of different origin in combination with Alectinib increased protoporphyrin-IX specific fluorescence and concomitantly cell death. CONCLUSIONS: The usage of Alectinib could be another step for enhancing the effectiveness of photodynamic therapy. Further experiments will show whether photodynamic therapy in combination with Alectinib could be a new strategy for the treatment of e.g. peritoneal disseminated carcinomas