Particulate matter (PM) 2.5 levels in ETS emissions of a Marlboro Red cigarette in comparison to the 3R4F reference cigarette under open- and closed-door condition

Introduction: Potential health damage by environmental emission of tobacco smoke (environmental tobacco smoke, ETS) has been demonstrated convincingly in numerous studies. People, especially children, are still exposed to ETS in the small space of private cars. Although major amounts of toxic compounds from ETS are likely transported into the distal lung via particulate matter (PM), few studies have quantified the amount of PM in ETS. Study aim The aim of this study was to determine the ETS-dependent concentration of PM from both a 3R4F reference cigarette (RC) as well as a Marlboro Red brand cigarette (MRC) in a small enclosed space under different conditions of ventilation to model car exposure. Method: In order to create ETS reproducibly, an emitter (ETSE) was constructed and mounted on to an outdoor telephone booth with an inner volume of 1.75 m3. Cigarettes were smoked under open- and closed-door condition to imitate different ventilation scenarios. PM2.5 concentration was quantified by a laser aerosol spectrometer (Grimm; Model 1.109), and data were adjusted for baseline values. Simultaneously indoor and outdoor climate parameters were recorded. The time of smoking was divided into the ETS generation phase (subset "emission") and a declining phase of PM concentration (subset "elimination"); measurement was terminated after 10 min. For all three time periods the average concentration of PM2.5 (Cmean-PM2.5) and the area under the PM2.5 concentration curve (AUC-PM2.5) was calculated. The maximum concentration (Cmax-PM2.5) was taken from the total interval. Results: For both cigarette types open-door ventilation reduced the AUC-PM2.5 (RC: from 59 400 +/- 14 600 to 5 550 +/- 3 900 mug*sec/m3; MRC: from 86 500 +/- 32 000 to 7 300 +/- 2 400 mug*sec/m3; p < 0.001) and Cmean-PM2.5 (RC: from 600 +/- 150 to 56 +/- 40 mug/m3, MRC from 870 +/- 320 to 75 +/- 25 mug/m3; p < 0.001) by about 90%. Cmax-PM2.5 was reduced by about 80% (RC: from 1 050 +/- 230 to 185 +/- 125 mug/m3; MRC: from 1 560 +/-500 mug/m3 to 250 +/- 85 mug/m3; p < 0.001). In the subset "emission" we identified a 78% decrease in AUC-PM2.5 (RC: from 18 600 +/- 4 600 to 4 000 +/- 2 600 mug*sec/m3; MRC: from 26 600 +/- 7 200 to 5 800 +/- 1 700 mug*sec/m3; p < 0.001) and Cmean-PM2.5 (RC: from 430 +/- 108 to 93 +/- 60 mug/m3; MRC: from 620 +/- 170 to 134 +/- 40 mug/m3; p < 0.001). In the subset "elimination" we found a reduction of about 96-98% for AUC-PM2.5 (RC: from 40 800 +/- 11 100 to 1 500 +/- 1 700 mug*sec/m3; MRC: from 58 500 +/- 25 200 to 1 400 +/- 800 mug*sec/m3; p < 0.001) and Cmean-PM2.5 (RC: from 730 +/- 200 to 27 +/- 29 mug/m3; MRC: from 1 000 +/- 450 to 26 +/- 15 mug/m3; p < 0.001). Throughout the total interval Cmax-PM2.5 of MRC was about 50% higher (1 550 +/- 500 mug/m3) compared to RC (1 050 +/- 230 mug/m3; p < 0.05). For the subset "emission" - but not for the other periods - AUC-PM2.5 for MRC was 43% higher (MRC: 26 600 +/- 7 200 mug*sec/m3; RC: 18 600 +/- 4 600 mug*sec/m3; p < 0.05) and 44% higher for Cmean-PM2.5 (MRC: 620 +/- 170 mug/m3; RC: 430 +/- 108 mug/m3; p < 0.05). Conclusion: This method allows reliable quantification of PM2.5-ETS exposure under various conditions, and may be useful for ETS risk assessment in realistic exposure situations. The findings demonstrate that open-door condition does not completely remove ETS from a defined indoor space of 1.75 m3. Because there is no safe level of ETS exposure ventilation is not adequate enough to prevent ETS exposure in confined spaces, e.g. private cars. Additionally, differences in the characteristics of cigarettes affect the amount of ETS particle emission and need to be clarified by ongoing investigations

Analysis of Agglomerative Clustering

The diameter k-clustering problem is the problem of partitioning a finite subset of R^d into k subsets called clusters such that the maximum diameter of the clusters is minimized. One early clustering algorithm that computes a hierarchy of approximate solutions to this problem for all values of k is the agglomerative clustering algorithm with the complete linkage strategy. For decades this algorithm has been widely used by practitioners. However, it is not well studied theoretically. In this paper we analyze the agglomerative complete linkage clustering algorithm. Assuming that the dimension dis a constant, we show that for any k the solution computed by this algorithm is an O(log k)-approximation to the diameter k-clustering problem. Moreover, our analysis does not only hold for the Euclidean distance but for any metric that is based on a norm

Siglec-16 : Ein Rezeptor des angeborenen Immunsystems auf Mikroglia

Mikroglia sind die ortsständigen Immunzellen des zentralen Nervensystems und somit wesentlich an der Überwachung und Erhaltung der Homöostase im empfindlichen neuralen Gewebe beteiligt. Sie treten als Teil des angeborenen Immunsystems über ihre Oberflächenrezeptoren mit ihrer Umgebung in Kontakt. Ein potentieller Rezeptor auf Mikroglia ist der erst kürzlich entdeckte humanspezifische Siglec-16-Rezeptor, der aufgrund einer Mutation nur in einer Subpopulation der Bevölkerung gebildet wird. Ziel dieser Arbeit war die Untersuchung von Vorkommen, Funktion und Wirkung von Siglec-16 auf Mikroglia. Dazu dienten humane Gewebeanalysen, Zellkulturmodelle von humaner und muriner Mikroglia und die Erzeugung eines Siglec-16 transgenen Mausmodells. In der vorliegenden Arbeit konnte erstmals der Nachweis einer Expression von Siglec-16 in adultem Hirngewebe sowie auf humanen aus induzierten pluripotenten Stammzellen generierten Mikroglia erbracht werden. Um eine bessere Aussage über den Genotyp und die Allelfrequenz von Siglec-16 treffen zu können, wurde ein auf PCR und Sequenzierung basierende Methode entwickelt, welche eine valide Genotypisierung ermöglicht. Die Etablierung einer Expression von Siglec-16 auf murinen aus embryonalen Stammzellen generierten Mikroglia war ebenso erfolgreich, wie die Erzeugung eines Siglec-16 transgenen Mausmodells mit einer selektiven Expression von Siglec-16 auf Mikroglia. Im murinen System konnte sowohl in Zellkultur als auch im Tiermodell ein hemmender Einfluss von Siglec-16 auf die Genexpression der Entzündungsmediatoren TNF-α und IL-1β gezeigt werden. In Funktionsanalysen von humanen Mikroglia in Zellkultur konnte eine durch LPS induzierte Steigerung der Siglec-16-Expression gezeigt werden. Interessanterweise zeigte sich ein abschwächender Effekt von Siglec-16 auf die durch LPS vermittelte Entzündungsreaktion im Siglec-16 transgenen Mausmodell. Im Weiteren zeigte sich ein positiver Einfluss von Siglec-16 auf die Phagozytoserate von Mikroglia. Weitere Untersuchungen könnten die Bedingungen analysieren, unter welchen Siglec-16 trotz seiner Assoziation mit dem ITAM tragenden DAP12 eine inhibierende Wirkung auf die Immunreaktion hat und welche Stimuli nötig sind sein aktivierendes Potential hervorzurufen. Darüber hinaus könnten weitere Analysen eine mögliche Beteiligung von Siglec-16 an pathologischen Zuständen des ZNS klären.Siglec-16 - A receptor of the innate immune system on microglia Microglia are the resident macrophages of the central nervous system. As a part of the innate immune system they survey the surrounding tissue with a variety of receptors on their cell surface. One potential receptor on microglia is Siglec-16. Siglec-16 is a DAP12-associated human specific receptor that binds to sialic acids on the glycocalyx of the cell surface. As a result of a deletion of 4 base pairs only a subpopulation of the human population is able to express the functional gene of Siglec-16. The aim of this thesis was to investigate the presence and the function of the Siglec-16 receptor on microglia. This included genomic studies, cell culture models and the establishment of a transgenic mouse model. In this thesis the detection of an expression of Siglec-16 in human brain tissue and on human-induced stem cell-derived microglia was successful. The development of a method for a PCR and sequencing based testing of the genotype of Siglec-16 led to new insights of the allele frequency of Siglec-16 in human population. It could be shown in cell culture models with human-induced stem cell-derived microglia that the expression of Siglec-16 depends on the influence of LPS. The establishment of a robust expression of Siglec-16 on murine embryonic-derived microglia and in a transgenic mouse model could be performed successfully. With these models it was possible to investigate the influence of Siglec-16 on the expression of inflammatory cytokines and the phagocytosis. We could show that the expression of Siglec-16 led to a down regulation of pro inflammatory molecules, such as TNF-α und IL-1β, and an up regulation of the phagocytosis rate. This influence seems to be modulated by the presence of LPS. Further studies should investigate how the DAP12-associated Siglec-16 is able to affect its anti inflammatory influence on the immune reaction of microglia. Moreover, the examination of the influence of Siglec-16 on neurological disorders, such as multiple sclerosis, stroke or infection, could be of interest for the understanding of the pathogenesis and the development of new therapy concepts

Konstruktion und Validierung einer Guttmann-Skala zur Messung des gegenwärtigen Institutionalisierungsgrades einer Partnerschaft: Ergebnisse eines Pretests und der TIP-Haupterhebung

Die Autoren stellen die Ergebnisse des TIP-Projektes dar, welche zeigen, dass der Institutionalisierungsprozess in Partnerschaften durch verschiedene objektive Ereignisse abgebildet werden kann, die sich nach dem Kriterium ihrer Schwierigkeit ordnen lassen und insgesamt die Konstruktion einer Guttmann-Skala erlauben, die eine befriedigende Reproduzierbarkeit und eine hinreichende Varianz aufweist. Für die Kriteriumsvalidität der Skala sprechen zudem systematische positive Korrelationen mit Merkmalen wie der Partnerschaftsdauer, den Investitionen in die Partnerschaft oder der Paaridentität. Die im vorliegenden Bericht dargestellte Skalenvariante kann zwischen vier Institutionalisierungs-Levels unterscheiden, die durch signifikante Ereignisse, wie z. B. das Tauschen der Wohnungsschlüssel, gekennzeichnet sind. Gegenüber einer einfachen Unterscheidung zwischen den Lebensformen "living apart together" (LAT) und "nichteheliche Lebensgemeinschaft" (NEL) kann somit die Varianz immerhin verdoppelt werden, indem bestimmte Zwischenschritte Berücksichtigung finden. (ICI2

Sodium retention in rats with liver cirrhosis is associated with increased renal abundance of NaCl cotransporter (NCC)

Background. Liver cirrhosis is associated with enhanced renal tubular sodium retention, the mechanism of which is still debated. We hypothesized that liver cirrhosis is associated with increased expression of renal epithelial sodium transporter(s). Methods. Liver cirrhosis was induced by bile duct ligation (BDL) in rats. Steady state mRNA of ENaC subunits α, β, γ serum and glucocorticoid inducible kinase (Sgk1) were measured by TaqMan PCR in kidney homogenates at week 1, 2, 3 and 4 after BDL. Renal protein content of ENaC subunits, ubiquitin-protein-ligase Nedd4-2 and NaCl cotransporter (NCC) were assessed by western blot. Subcellular localization of ENaC subunits and NCC were analysed by immunohistochemistry. Results. Steady state mRNA of ENaC α, β and γ were unchanged during the 4 weeks investigated, while ENaC protein decreased most prominently at week 2 (control vs BDL; α, −46%; β, −81%; and γ, −63%; n = 6). Subcellular localization of ENaC subunits was not altered at week 2. Sgk1 mRNA did not change, whereas Nedd4-2 protein was reduced by >50% 2-4 weeks after BDL. NCC protein significantly increased at week 1 (control vs BDL: +66%, n = 6, P<0.05) and decreased at week 3 (control vs BDL: −85%, n = 6, P<0.0005). Conclusions. Enhanced abundance of NCC was observed in the initial stage after BDL, followed by a marked decrease. ENaC transcription, translation or cell surface abundance was not increased after BD

Video Feedback and Video Modeling in Teaching Laparoscopic Surgery: A Visionary Concept from Kiel

Learning curves for endoscopic surgery are long and flat. Various techniques and methods are now available for surgical endoscopic training, such as pelvitrainers, virtual trainers, and body donor surgery. Video modeling and video feedback are commonly used in professional training. We report, for the first time, the application of video modeling and video feedback for endoscopic training in gynecology. The purpose is to present an innovative method of training. Attendees (residents and specialists) of minimally invasive surgery courses were asked to perform specific tasks, which were video recorded in a multimodular concept. Feedback was given later by an expert at a joint meeting. The attendees were asked to fill a questionnaire in order to assess video feedback given by the expert. The advantages of video feedback and video modeling for the development of surgical skills were given a high rating (median 84%, interquartile ranges (IQR) 72.5-97.5%, n = 37). The question as to whether the attendees would recommend such training was also answered very positively (median 100%, IQR 89.5-100%, n = 37). We noted a clear difference between subjective perception and objective feedback (58%, IQR 40.5-76%, n = 37). Video feedback and video modeling are easy to implement in surgical training setups, and help trainees at all levels of education

Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization

In most rodents and some other mammals, the removal of one lung results in compensatory growth associated with dramatic angiogenesis and complete restoration of lung capacity. One pivotal mechanism in neoalveolarization is neovascularization, because without angiogenesis new alveoli can not be formed. The aim of this study is to image and analyze three-dimensionally the different patterns of neovascularization seen following pneumonectomy in mice on a sub-micron-scale. C57/BL6 mice underwent a left-sided pneumonectomy. Lungs were harvested at various timepoints after pneumonectomy. Volume analysis by microCT revealed a striking increase of 143 percent in the cardiac lobe 14 days after pneumonectomy. Analysis of microvascular corrosion casting demonstrated spatially heterogenous vascular densitities which were in line with the perivascular and subpleural compensatory growth pattern observed in anti-PCNA-stained lung sections. Within these regions an expansion of the vascular plexus with increased pillar formations and sprouting angiogenesis, originating both from pre-existing bronchial and pulmonary vessels was observed. Also, type II pneumocytes and alveolar macrophages were seen to participate actively in alveolar neo-angiogenesis after pneumonectomy. 3D-visualizations obtained by high-resolution synchrotron radiation X-ray tomographic microscopy showed the appearance of double-layered vessels and bud-like alveolar baskets as have already been described in normal lung development. Scanning electron microscopy data of microvascular architecture also revealed a replication of perialveolar vessel networks through septum formation as already seen in developmental alveolarization. In addition, the appearance of pillar formations and duplications on alveolar entrance ring vessels in mature alveoli are indicative of vascular remodeling. These findings indicate that sprouting and intussusceptive angiogenesis are pivotal mechanisms in adult lung alveolarization after pneumonectomy. Various forms of developmental neoalveolarization may also be considered to contribute in compensatory lung regeneration. Electronic supplementary material The online version of this article (doi:10.1007/s10456-013-9399-9) contains supplementary material, which is available to authorized users

Light-Induced Mechanistic Divergence in Gold(I) Catalysis:Revisiting the Reactivity of Diazonium Salts

In a systematic study of the Au-catalyzed reaction of o-alkynylphenols with aryldiazonium salts, we find that essentially the same reaction conditions lead to a change in mechanism when a light source is applied. If the reaction is carried out at room temperature using a AuI catalyst, the diazonium salt undergoes electrophilic deauration of a vinyl AuI intermediate and provides access to substituted azobenzofurans. If the reaction mixture is irradiated with blue LED light, C−C bond formation due to N2-extrusion from the diazonium salt is realized selectively, using the same starting materials without the need for an additional photo(redox) catalyst under aerobic conditions. We report a series of experiments demonstrating that the same vinyl AuI intermediate is capable of producing the observed products under photolytic and thermal conditions. The finding that a vinyl AuI complex can directly, without the need for an additional photo(redox) catalyst, result in C−C bond formation under photolytic conditions is contrary to the proposed mechanistic pathways suggested in the literature till date and highlights that the role of oxidation state changes in photoredox catalysis involving Au is thus far only poorly understood and may hold surprises for the future. Computational results indicate that photochemical activation can occur directly from a donor–acceptor complex formed between the vinyl AuI intermediate and the diazonium salt

Analysis of meteorology-chemistry interactions during air pollution episodes using online coupled models within AQMEII Phase-2

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).This study reviews the top ranked meteorology and chemistry interactions in online coupled models recommended by an experts’ survey conducted in COST Action EuMetChem and examines the sensitivity of those interactions during two pollution episodes: the Russian forest fires 25 Jul -15 Aug 2010 and a Saharan dust transport event from 1 Oct -31 Oct 2010 as a part of the AQMEII phase-2 exercise. Three WRF-Chem model simulations were performed for the forest fire case for a baseline without any aerosol feedback on meteorology, a simulation with aerosol direct effects only and a simulation including both direct and indirect effects. For the dust case study, eight WRF-Chem and one WRF-CMAQ simulations were selected from the set of simulations conducted in the framework of AQMEII. Of these two simulations considered no feedbacks, two included direct effects only and five simulations included both direct and indirect effects. The results from both episodes demonstrate that it is important to include the meteorology and chemistry interactions in online-coupled models. Model evaluations using routine observations collected in AQMEII phase-2 and observations from a station in Moscow show that for the fire case the simulation including only aerosol direct effects has better performance than the simulations with no aerosol feedbacks or including both direct and indirect effects. The normalized mean biases are significantly reduced by 10-20% for PM10 when including aerosol direct effects. The analysis for the dust case confirms that models perform better when including aerosol direct effects, but worse when including both aerosol direct and indirect effects, which suggests that the representation of aerosol indirect effects needs to be improved in the model.Peer reviewedFinal Published versio