We present an electrooptic (EO) terahertz imaging technique providing a demodulating detector array for phase-sensitive multipixel terahertz detection. The terahertz radiation from a ...quartz-stabilized microelectronic emitter is mixed with the synchronized laser beat signal of a continuous-wave distributed-feedback diode laser pair. A fast laser current control loop provides stable phase locking between the terahertz emitter and the laser difference frequency, whereby a demodulating near-infrared photonic-mixer-device camera is used for depth-resolving EO terahertz imaging. Alternatively, a femtosecond laser is used for the EO read-out.
Dengue virus (DENV) infection causes viral haemorrhagic fever that is characterized by extensive activation of the immune system. The aim of this study is to investigate the kinetics of the ...transcriptome signature changes during the course of disease and the association of genes in these signatures with clinical parameters.
Sequential whole blood samples from DENV infected patients in Jakarta were profiled using affymetrix microarrays, which were analysed using principal component analysis, limma, gene set analysis, and weighted gene co-expression network analysis. We show that time since onset of disease, but not diagnosis, has a large impact on the blood transcriptome of patients with non-severe dengue. Clinical diagnosis (according to the WHO classification) does not associate with differential gene expression. Network analysis however, indicated that the clinical markers platelet count, fibrinogen, albumin, IV fluid distributed per day and liver enzymes SGOT and SGPT strongly correlate with gene modules that are enriched for genes involved in the immune response. Overall, we see a shift in the transcriptome from immunity and inflammation to repair and recovery during the course of a DENV infection.
Time since onset of disease associates with the shift in transcriptome signatures from immunity and inflammation to cell cycle and repair mechanisms in patients with non-severe dengue. The strong association of time with blood transcriptome changes hampers both the discovery as well as the potential application of biomarkers in dengue. However, we identified gene expression modules that associate with key clinical parameters of dengue that reflect the systemic activity of disease during the course of infection. The expression level of these gene modules may support earlier detection of disease progression as well as clinical management of dengue.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Endothelial cells are important in the development of plasma leakage during dengue. • Markers produced by endothelial cells in relation to plasma leakage were investigated. • Levels of ...angiopoietin-2 were increased in dengue patients with plasma leakage. • Levels of sVEGFR-2 were decreased in dengue patients with plasma leakage. • Angiopoietin-2 and sVEGFR-2 can serve as surrogate markers for plasma leakage.
Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent ...study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor (TF) expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVEC and subsequently specifically to PUUV virus particles. Infection of HUVEC with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased TF expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.
During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia ...is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances.
Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile.
Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A hybrid system for THz reflectometric imaging at 0.6 THz synchronizes a multiplied Gunn source with a femtosecond lasers for electro-optic detection and reaches 60 db dynamic range and 25 ms ...measurement time per pixel.
Fast active THz-camera with global illumination Weg, C.a.; Spiegel, W.v.; Senzel, F. ...
2009 34th International Conference on Infrared, Millimeter, and Terahertz Waves,
2009-Sept.
Conference Proceeding
We present a fast-scanning active THz-camera with two different illumination techniques. The first uses local illumination and offers high dynamic range while the second uses global illumination and ...allows to expand the range of angles over which specular reflections are detected. Furthermore, the second approach holds the promise that the object topography can be resolved with larger uniqueness.
We report on the simulation of a terahertz optics setup with the commercial, optic-design software package Zemax. We show that the analysis of both diffraction and abberation effects are well ...corroborated by the experimental results.
We report on the realization of an active fully electronic THz camera operating at 645 GHz and room temperature. It currently acquires images with about 9000 pixels in 10 seconds. Each pixel contains ...the amplitude as well as the phase information of the reflected THz signal. Frequency modulation allows to select a specific working distance and to suppress spurious reflections. The typical image size is in the order of hundreds of cm 2 .
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