Generation of short-pulse VUV and XUV radiation

Starting from intense short-pulse KrF (248 nm, 25 mJ, 400 fs), ArF (193 nm, 10 mJ, sim1 ps), and Ti:sapphire (810 nm, 100 mJ, 150 fs) laser systems, schemes for the generation of fixed-frequency and tunable VUV and XUV radiation by nonlinear optical techniques are investigated. With the KrF system, a four-wave mixing process in xenon yields tunable radiation in the range of 130–200 nm with output energies of, so far, 100 mgrJ in less than 1 ps. For the XUV spectral range below 100 nm, nonperturbative high-order harmonic generation and frequency mixing processes in noble gas jets are considered. To achieve tunability, the intense fixed-frequency pump laser radiation is mixed with less intense but broadly tunable radiation from short-pulse dye lasers or optical parametric generator-amplifier systems. In this way, tunability down to wavelengths of less than 40 nm has been demonstrated

Role of P-selectin in platelet sequestration in pulmonary capillaries during endotoxemia

Background: There is growing evidence that platelets accumulate in the lung and contribute to the pathogenesis of acute lung injury during endotoxemia. The aims of the present study were to localize platelet sequestration in the pulmonary microcirculation and to investigate the role of P-selectin as a molecular mechanism of platelet endothelial cell interaction. Methods: We used in vivo fluorescence microscopy to quantify the kinetics of fluorescently labeled erythrocytes and platelets in alveolar capillary networks in rabbit lungs. Results: Six hours after onset of endotoxin infusion we observed a massive rolling along and firm adherence of platelets to lung capillary endothelial cells whereas under control conditions no platelet sequestration was detected. P-selectin was expressed on the surface of separated platelets which were incubated with endotoxin and in lung tissue. Pretreatment of platelets with fucoidin, a P-selectin antagonist, significantly attenuated the endotoxin-induced platelet rolling and adherence. In contrast, intravenous infusion of fucoidin in endotoxin-treated rabbits did not inhibit platelet sequestration in pulmonary capillaries. Conclusion: We conclude that platelets accumulate in alveolar capillaries following endotoxemia. P-selectin expressed on the surface of platelets seems to play an important role in mediating this platelet-endothelial cell interaction. Copyright (c) 2006 S. Karger AG, Basel

Graph-based description of tertiary lymphoid organs at single-cell level

Our aim is to complement observer-dependent approaches of immune cell evaluation in microscopy images with reproducible measures for spatial composition of lymphocytic infiltrates. Analyzing such patterns of inflammation is becoming increasingly important for therapeutic decisions, for example in transplantation medicine or cancer immunology. We developed a graph-based assessment of lymphocyte clustering in full whole slide images. Based on cell coordinates detected in the full image, a Delaunay triangulation and distance criteria are used to build neighborhood graphs. The composition of nodes and edges are used for classification, e.g. using a support vector machine. We describe the variability of these infiltrates on CD3/CD20 duplex staining in renal biopsies of long-term functioning allografts, in breast cancer cases, and in lung tissue of cystic fibrosis patients. The assessment includes automated cell detection, identification of regions of interest, and classification of lymphocytic clusters according to their degree of organization. We propose a neighborhood feature which considers the occurrence of edges with a certain type in the graph to distinguish between phenotypically different immune infiltrates. Our work addresses a medical need and provides a scalable framework that can be easily adjusted to the requirements of different research questions

Impact analysis of accidents on the traffic flow based on massive floating car data

The wide usage of GPS-equipped devices enables the mass recording of vehicle movement trajectories describing the movement behavior of the traffic participants. An important aspect of the road traffic is the impact of anomalies, like accidents, on traffic flow. Accidents are especially important as they contribute to the the aspects of safety and also influence travel time estimations. In this paper, the impact of accidents is determined based on a massive GPS trajectory and accident dataset. Due to the missing precise date of the accidents in the data set used, first, the date of the accident is estimated based on the speed profile at the accident time. Further, the temporal impact of the accident is estimated using the speed profile of the whole day. The approach is applied in an experiment on a one month subset of the datasets. The results show that more than 72% of the accident dates are identified and the impact on the temporal dimension is approximated. Moreover, it can be seen that accidents during the rush hours and on high frequency road types (e.g. motorways, trunks or primaries) have an increasing effect on the impact duration on the traffic flow

Izloženost genotoksičnim agensima iz životnog okoliša tijekom prenatalnog razvoja i djetinjstva

Health disorders and diseases related to environmental exposure in children such as cancer and immunologic disturbances (asthma, allergies) are on the rise. However, complex transplacental and prepubertal genotoxicology is given very limited consideration, even though intrauterine development and early childhood may be critical for elucidating the cancer aetiology. The foetus is transplacentally exposed to contaminants in food and environment such as various chemicals, drugs, radiochemically contaminated water and air. Target organs of xenobiotic action may differ between the mother and the foetus due to specific stage of developmental physiology and enzyme distribution. This in turn may lead to different levels of clastogenic and aneugenic metabolites of the same xenobiotic in the mother and the foetus. Adult’s protective behaviour is not sufficient to isolate children from radioisotopes, pesticides, toxic metals and metalloids, environmental tobacco smoke, endocrine disrupting chemicals, and various food contaminants, which are just a part of the stressors present in a polluted environment. In order to improve legislation related to foetus and child exposure to genotoxic and possibly carcinogenic agents, oncologists, paediatricians, environmental health specialists, and genotoxicologists should work together much more closely to make a more effective use of accumulated scientific data, with the final aim to lower cancer incidence and mortality.Unatoč velikim naporima da se smanji okolišna izloženost u djece se dalje bilježi trend porasta pojavnosti karcinoma i imunosnih poremećaja (astma, alergije). Premda su intrauterini razvoj i rano djetinjstvo kritično razdoblje za tumačenje etiologije nastanka karcinoma, transplacentalna i prepubertetna genotoksikologija do danas su slabo istražene. Fetus je transplacentalno izložen brojnim fizikalnim i kemijskim čimbenicima: kontaminantima iz hrane i okoliša, radiokemijski kontaminiranoj vodi, zraku te lijekovima. Ciljna tkiva za djelovanje ksenobiotika mogu biti različita u majke i fetusa zbog različitosti u razvojnoj fiziologiji i distribuciji enzima. Zbog toga u organizmu majke i fetusa mogu nastati različite razine klastogenih i aneugenih metabolita istog ksenobiotika. Zaštitna uloga odraslih u namjeri da spriječe negativne utjecaje onečišćenog okoliša na djetetovo zdravlje često je ograničena jer su radioizotopi, olovo, PCB, pasivno pušenje, živa, endokrino aktivne tvari, pesticidi i kontaminanti prisutni u svim životnim područjima tijekom razvoja i rasta djeteta. Kako bi se poboljšalo zakonodavstvo vezano uz izloženost djece genotoksičnim i vjerojatno kancerogenim tvarima, tijekom razvoja potrebna je bolja suradnja onkologa, pedijatara, stručnjaka zdravstvene ekologije i genotoksikologa. Na taj način ostvarilo bi se uspješnije iskorištavanje postojećih znanstvenih podataka u cilju smanjenja incidencije karcinoma i mortaliteta

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in three infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALKrearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (seven and twelve from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated-ERK, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, while CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, ten with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis, and provides guidance for the clinical management of this emerging histiocytic entity.Molecular tumour pathology - and tumour genetic