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Die Ibbenbürener Aa oberhalb des Aasees sowie drei Nebengewässer wurden über einen Zeitraum von 12 Monaten (April 1981-April 1982) hydrochemisch untersucht. Im Herbst 1981 und im Frühjahr 1982 wurde anhand einer auf den Makrozoobenthos beschränkten Saprobienanalyse von 9 Probestellen der Aa sowie von 2 Probestellen eines durch Fabrikabwässer beeinflußten Vorfluters die Gewässergüte bestimmt. Im Winter 1981/82 beobachtete Mikroorganismenkolonien (vornehmlich Abwasserpilz und Schwefelbakterien) wurden kartographiert und stichprobenartig mikroskopiert. Im Gegensatz zur Aussage der Gewässergütekarte von NRW (Stand 1980) weisen die erhobenen hydrochemischen und hydrobiologischen Kenndaten der Ibbenbürener Aa oberhalb des Aasees auf eine Verschlechterung der Gewässergüte nach Güteklasse 11-111 ("kritisch belastet") hin. Der durch Fabrikabwässer beeinflußte Vorfluter mußte in die Güteklasse 11I ("stark verschmutzt") eingeordnet werden. Durch das im Winter beobachtete z. T. extrem starke Pilztreiben des Abwasserpilzes Leptomitus lacteus ist diese Güteklasse auch für einen Teil der Nebengewässer angezeigt. Mögliche Ursachen der ermittelten Güteklasse(n) werden diskutiert.
Measurements of OH, the sum of peroxy radicals (ROx), non-methane hydrocarbons (NMHCs) and various other trace gases were made at the Meteorological Observatory Hohenpeissenberg in June 2000. The data from an intensive measurement period characterised by high solar insolation (18-21 June) are analysed. The maximum midday OH concentration ranged between 4.5 x 106 molecules cm-3 and 7.4 x 106 molecules cm-3. The maximum total ROx mixing ratio increased from about 55 pptv on 18 June to nearly 70 pptv on 20 and 21 June. A total of 64 NMHCs, including isoprene and monoterpenes, were measured every 1 to 6 hours. The oxidation rate of the NMHCs by OH was calculated and reached a total of over 14 x 106 molecules cm-3 s-1 on two days. A simple photostationary state balance model was used to simulate the ambient OH and ROx concentrations with the measured data as input. The model was able to reproduce the main features of the diurnal profiles of both OH and ROx. The model results proved to be most sensitive to assumptions about the mixing ratio of formaldehyde (HCHO), which was included as a proxy for carbonyl compounds, and about the partitioning between HO2 and RO2. The measured OH concentration and ROx mixing ratios were reproduced well by assuming the presence of 3 ppbv HCHO and a ratio HO2/RO2 between 1:1 and 1:2. The most important source of OH, and conversely the greatest sink for ROx, was the recycling of HO2 radicals to OH. This reaction was responsible for the recycling of more than 45 x 106 molecules cm-3 s-1 on two days. The most important sink for OH, and the largest source of ROx, was the oxidation of NMHCs, in particular, of isoprene and the monoterpenes.
Measurements of OH, total peroxy radicals, non-methane hydrocarbons (NMHCs) and various other trace gases were made at the Meteorological Observatory Hohenpeissenberg in June 2000. The data from an intensive measurement period characterised by high solar insolation (18-21 June) are analysed. The maximum midday OH concentration ranged between 4.5x106 molecules cm-3 and 7.4x106 molecules cm-3. The maximum total ROx (ROx =OH+RO+HO2+RO2) mixing ratio increased from about 55 pptv on 18 June to nearly 70 pptv on 20 and 21 June. A total of 64 NMHCs, including isoprene and monoterpenes, were measured every 1 to 6 hours. The oxidation rate of the NMHCs by OH was calculated and reached a total of over 14x106 molecules cm-3 s-1 on two days. A simple photostationary state balance model was used to simulate the ambient OH and peroxy radical concentrations with the measured data as input. This approach was able to reproduce the main features of the diurnal profiles of both OH and peroxy radicals. The balance equations were used to test the effect of the assumptions made in this model. The results proved to be most sensitive to assumptions about the impact of unmeasured volatile organic compounds (VOC), e.g. formaldehyde (HCHO), and about the partitioning between HO2 and RO2. The measured OH concentration and peroxy radical mixing ratios were reproduced well by assuming the presence of 3 ppbv HCHO as a proxy for oxygenated hydrocarbons, and a HO2/ RO2 ratio between 1:1 and 1:2. The most important source of OH, and conversely the greatest sink for peroxy radicals, was the recycling of HO2 radicals to OH. This reaction was responsible for the recycling of more than 45x106 molecules cm-3 s-1 on two days. The most important sink for OH, and the largest source of peroxy radicals, was the oxidation of NMHCs, in particular, of isoprene and the monoterpenes.
The blue pine wood borer (Phaenops cyanea) and the black pine sawyer beetle (Monochamus galloprovincialis) (Fig. 1) both are pests of the white pine (Pinus silvestris) and other Pinus species. Both insects have nearly the same demands regarding their breeding site. Larval development requires a fresh, unwilted inner bark. An infestation occurs on freshly cut trees or on trees suffering from stress (e.g. after dry seasons, loss of needles caused by feeding caterpillars or damage by forest fires). Phaenops cyanea detects susceptible pines by their volatile emissions (SCHÜTZ et al. 2004) and is able to infest the trees already at a low stress level. During feeding the larvae avoid the resin ducts of the tree and thus evade the oleoresin defence. The beetle is endemic in Europe and – under favourable climatic conditions – can cause substantial damage to pine forests. It is the most significant bark-breeding beetle of white pine in the lowlands of north-eastern Germany. Monochamus galloprovincialis is found in Europe and northern Africa. The larvae tend to a more copious feeding which makes them more susceptible to the oleoresin defence of the tree. Thus, M. galloprovincialis prefers trees that are weakened by a higher degree of stress. The economic damage caused by feeding of thebeetle is low. However, the beetle has gained a special attention of forest scientists because of its association with the nematode Bursaphelenchus xylophilus which is causing the pine wilt disease (PWD) in Pinus. The only outbreak of the PWD within Europe is limited to an area of 258.000 ha in Portugal. (MOTA et al. 1999).
Der Mangel von Faktor VIII (FVIII) führt zur häufigsten Gerinnungsstörung, der Hämophilie A. Die rekombinante Expression von FVIII für gentherapeutische Ansätze oder zur Herstellung von FVIII ist zwei bis drei Größenordnungen niedriger verglichen mit anderen Proteinen vergleichbarer Größe. Die Ursachen für die geringe Expression liegen zum großen Teil an der ineffizienten Transkription und dem ineffizientem intrazellulären Transport. (1) Im Rahmen der Untersuchung der FVIII-Sekretion, konnte durch Verwendung von FVIII-GFP Fusionsproteinen zum ersten Mal gezeigt werden, wie FVIII in lebenden Zellen transportiert wird. Außerdem wurde anhand von vergleichenden Immunfluoreszensfärbungen, FVIII-Messungen und Westernblotanalysen demonstriert, dass weder bei der B-Domäne deletierten noch bei der Volllängenvariante signifikante Unterschiede zwischen den GFP-fusionierten und Wildtyp-FVIII-Varianten messbar waren. Offensichtlich wird die Funktionalität von FVIII durch die C-terminal fusionierte GFP-Domäne nicht eingeschränkt. In ersten Lebendzellanalysen konnte gezeigt werden, dass sich FVIII in primären Zellen und Zelllinien hauptsächlich im ER befindet und eine für lumenale ER-Proteine charakteristischen Mobilität aufweist. Beim frühen sekretorischen Transport zeigte sich bei Temperaturblock-Experimenten eine verlängerte Dauer der Akkumulation in ER-Exit-Sites und eine vergleichsweise niedrige Frequenz von ER-Golgi-Bewegungen. Es konnte zum ersten Mal der Nachweis von FVIII-Transport durch vesikuläre tubuläre Cluster erbracht werden. Die Ergebnisse deuten darauf hin, dass der möglicherweise durch Faltungsprobleme blockierte Austritt aus dem ER das Hauptproblem des ineffizienten FVIII-Transports zu sein scheint und weniger der intrazelluläre Transport an sich. Mittels siRNA-Silencing wurde außerdem die überwiegende Beteiligung von COPI am intrazellulären Transport von FVIII deutlich, dessen Herunterregulierung zu einer 78 prozentigen Reduktion der FVIII-Sekretion im Gegensatz zu 32 Prozent bei COPII führte. Dagegen konnte durch Herunterregulierung der Expression der p24-Cargo-Rezeptor Familienmitglieder p24 und p26 und der Clathrin Adapterproteine µ- und -Adaptin bzw. durch physiologischen Knock-out im Falle von ER-Exit-Rezeptor MCFD2 kein Einfluß auf die FVIII-Sekretion festgestellt werden. (2) Als Alternative zu dem ineffizienten FVIII-Expressionsystem in unphysiologischen Zelllinien, bieten primäre Endothelzellen den Vorteil einer hocheffizienten FVIII-Sekretion. Zur Verwendung bei der rekombinanten Produktion benötigt man allerdings eine kontinuierlich wachsende gut charakterisierte Zelllinie. Zur Immortalisierung wurden aus Nabelschnurblut gewonnene Endothelprogenitorzellen mit der aktiven Untereinheit der humanen Telomerase (hTERT) transduziert. Trotz erfolgreicher Transduktion und langfristiger Expression von hTERT, welche im TRAP-Assay normale Aktivität zeigte, gingen die Zellen nach der natürlichen Teilungsspanne in die Seneszenz über. Möglicherweise wird noch ein weiteres Immortalisierungsgen benötigt oder hTERT ist durch die ektopischen Expression in diesen Endothelzellen nicht funktionell. (3) Der Einsatz hämatopoetischer Stammzellen für gentherapeutische Ansätze zur Expression von humanen FVIII ist bislang aufgrund niedriger Expressionseffizienz der Vektoren limitiert. Es wurden daher die Kombinationen verschiedener transkriptioneller und posttranskriptioneller Elemente in FVIII-Expressionsvektoren ausgetestet. Hierbei zeigte sich, dass die Verwendung einer 5’ untranslatierten Region (5’UTR) des hämatopoetisch exprimierten FXIIIA-Gens die FVIII-Sekretion in verschiedenen Zelllinien und primären Zellen deutlich steigerte. Am stärksten war die Wirkung in primären Monozyten, in denen die FVIII-Expression den 6fachen Wert im Vergleich zum Ursprungsvektor ohne 5’UTR erreichte. Leberzellen stellen weitere attraktive Zielzellen für gentherapeutische Ansätze dar, da Sie den primären physiologischen Ort der FVIII-Synthese darstellen. Die häufig für Gentherapievektoren verwendeten ubiquitär exprimierenden viralen Promotoren bewirken zwar hohe Expression in den transduzierten Zellen, haben allerdings den Nachteil durch ektopische Expression vermehrt Immunantworten auszulösen und durch starke Interaktion mit benachbarten Promotoren der Integrationsstelle im Genom möglicherweise tumorgene Effekte zu verursachen. Bei der Untersuchung verschiedener physiologischer Promotoren im Vergleich zum viralen CMV Promotor in Leberzellen konnte mit dem zum ersten mal getesteten minimalen FVIII-Promoter in einem lentiviralen Vektor der dritten Generation in Leberzelllinien eine vergleichsweise hohe Expression von 0,5 IU/ml FVIII /106 Zellen erzielt werden. Der FVIII-Promoter ist daher geeignet für eine lebergerichtete Expression und minimiert dabei das potentielle Risiko der häufig verwendeten ubiquitären viralen Promotoren.
Der Nordische Augentrost (Euphrasia frigida) ist eine boreal-montane Art, die einige vom Hauptareal abgesetzte Vorposten in deutschen Mittelgebirgen besitzt, wo sie extensiv genutztes, in der Regel ungedüngtes Grünland besiedelt. Aus den hessischen Mittelgebirgen lagen neuere Nachweise nur aus dem nördlichen Spessart vor (vier Populationen). Im Rahmen des Artenhilfsprogramms (und außerdem bei zwei FFH-Grunddatenerfassungen) konnten sechs weitere Spessart-Vorkommen festgestellt werden. Hinweise auf ein kleines Vorkommen im Hochtaunus (Neufund für den Naturraum) konnten bestätigt werden. Die Nachsuche an ehemaligen Wuchsorten im Vogelsberg, wo die Art bis in die 1970er Jahre vorkam, verlief hingegen durchweg erfolglos; allerdings gelang auch hier der Neufund einer kleinen Population. Auch im hessischen Teil der Hohen Rhön gelang inzwischen ein Erstnachweis (siehe Barth 2008). Insgesamt liegt mehr als die Hälfte aller bekannten deutschen Fundorte in Hessen. Dem Land kommt daher eine besondere Verantwortung für die Erhaltung der Art zu. Hauptgefährdungsursachen für die Art sind Nutzungsintensivierung (Düngung, zu früher Mahdtermin) und Nutzungsaufgabe sowie die Aufforstung von Grenzertragsgrünland. Die Erhaltung der Art ist am besten durch vertraglich vereinbarte extensive Grünlandnutzung (Verzicht auf Düngung, Mahd nicht vor Anfang Juli) zu gewährleisten.
In dieser Arbeit wurde deutlich, dass die Multilevel Monte Carlo Methode eine signifikante Verbesserung gegenüber der Monte Carlo Methode darstellt. Sie schafft es den Rechenaufwand zu verringern und in fast allen Fällen die gewollte Genauigkeit zu erreichen. Die Erweiterung durch Richardson Extrapolation brachte immer eine Verringerung des Rechenaufwands oder zumindest keine Verschlechterung, auch wenn nicht in allen Fällen die schwache Konvergenzordnung verdoppelt wurde.
Im Falle der Optionssensitivitäten ist eine Anwendung des MLMC-Algorithmus problematisch. Das Funktional, das auf den Aktienkurs angewendet wird, darf keine Unstetigkeitsstelle besitzen, bzw. im Falle des Gammas muss es stetig differenzierbar sein. Die Anwendung der MLMC Methode macht dann vor allem Sinn, wenn sich die Sensitivität als Funktion des Aktienkurses umformen lässt, so dass nur der Pfad der Aktie simuliert werden muss. Nur wenn dies nicht möglich ist, wäre es sinnvoll, die in Kapitel 6.5 am Beispiel des Deltas vorgestellte Methode zu benutzen, in der man einen zweiten Pfad für das Delta simuliert.
Weitere Verbesserungsmöglichkeiten könnten in der Wahl von anderen varianzreduzierenden Methoden liegen oder durch Verwendung von Diskretisierungsverfahren mit höherer starker Ordnung als das Euler-Verfahren (vgl. [7], Verwendung des Milstein-Verfahrens). In diesem Fall ist theoretisch ein Rechenaufwand der Größenordnung O(ϵexp-2) möglich, da die Anzahl der zu erstellenden Samples nicht mehr mit steigendem L erhöht wird. Somit könnte das L so groß gewählt werden, dass der Bias verschwindet und der MSE ausschließlich von der Varianz des Schätzers abhängt. Um diese auf eine Größenordnung von O(ϵexp2) zu bringen, ist es nötig, O(ϵexp2) Pfade zu erstellen (siehe Gleichung (3.6)), was den Rechenaufwand begründet.
The first measurement of two-pion Bose–Einstein correlations in central Pb–Pb collisions at √sNN=2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.
Inclusive transverse momentum spectra of primary charged particles in Pb–Pb collisions at √sNN=2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0–5% and 70–80% of the hadronic Pb–Pb cross section. The measured charged particle spectra in |η|<0.8 and 0.3<pT<20 GeV/c are compared to the expectation in pp collisions at the same sNN, scaled by the number of underlying nucleon–nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAA. The result indicates only weak medium effects (RAA≈0.7) in peripheral collisions. In central collisions, RAA reaches a minimum of about 0.14 at pT=6–7 GeV/c and increases significantly at larger pT. The measured suppression of high-pT particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb–Pb collisions at the LHC.
The inclusive charged particle transverse momentum distribution is measured in proton–proton collisions at s=900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (|η|<0.8) over the transverse momentum range 0.15<pT<10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for |η|<0.8 is 〈pT〉INEL=0.483±0.001 (stat.)±0.007 (syst.) GeV/c and 〈pT〉NSD=0.489±0.001 (stat.)±0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger 〈pT〉 than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.
Rapidity and transverse momentum dependence of inclusive J/ψ production in pp collisions at √s=7 TeV
(2011)
The ALICE experiment at the LHC has studied inclusive J/ψ production at central and forward rapidities in pp collisions at √s=7 TeV. In this Letter, we report on the first results obtained detecting the J/ψ through the dilepton decay into e+e− and μ+μ− pairs in the rapidity ranges |y|<0.9 and 2.5<y<4, respectively, and with acceptance down to zero pT. In the dielectron channel the analysis was carried out on a data sample corresponding to an integrated luminosity Lint=5.6 nb−1 and the number of signal events is NJ/ψ=352±32(stat.)±28(syst.); the corresponding figures in the dimuon channel are Lint=15.6 nb−1 and NJ/ψ=1924±77(stat.)±144(syst.). The measured production cross sections are σJ/ψ(|y|<0.9)=10.7±1.0(stat.)±1.6(syst.)−2.3+1.6(syst.pol.)μb and σJ/ψ(2.5<y<4)=6.31±0.25(stat.)±0.76(syst.)−1.96+0.95(syst.pol.)μb. The differential cross sections, in transverse momentum and rapidity, of the J/ψ were also measured.
Unmasking a temperature-dependent effect of the P. anserina i-AAA protease on aging and development
(2011)
Different molecular pathways involved in maintaining mitochondrial function are of fundamental importance to control cellular homeostasis. Mitochondrial i-AAA protease is part of such a surveillance system, and PaIAP is the putative ortholog in the fungal aging model Podospora anserina. Here, we investigate the role of PaIAP in aging and development. Deletion of the gene encoding PaIAP resulted in a specific phenotype. When incubated at 27°C, spore germination and fruiting body formation are not different from that of the corresponding wild-type strain. Unexpectedly, the lifespan of the deletion strain is strongly increased. In contrast, cultivation at an elevated temperature of 37°C leads to impairments in spore germination and fruiting body formation and to a reduced lifespan. The higher PaIAP abundance in wild-type strains of the fungus grown at elevated temperature and the phenotype of the deletion strain unmasks a temperature-related role of the protein. The protease appears to be part of a molecular system that has evolved to allow survival under changing temperatures, as they characteristically occur in nature.
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
Fragment mass distributions for fission after full momentum transfer were measured in the reactions of 30Si,34,36 S,31P,40Ar + 238U at bombarding energies around the Coulomb barrier. Mass distributions change significantly as a function of incident beam energy. The asymmetric fission probability increases at sub-barrier energy. The phenomenon is interpreted as an enhanced quasifission probability owing to orientation effects on fusion and/or quasifission. The evaporation residue (ER) cross sections were measured in the reactions of 30Si + 238U and 34S + 238U to obtain information on fusion. In the latter reaction, significant suppression of fusion was implied. This suggests that fission events different from compound nucleus are included in the masssymmetric fragments. The results are supported by a model calculation based on a dynamical calculation using Langevin equation, in which the mass distribution for fusion-fission and quasifission fragments are separately determined.
Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
(2012)
Lung ischaemia–reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2y/−) or the classical transient receptor potential channel 6 (TRPC6−/−) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca2+ influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2y/− cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE.
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
The link between atmospheric radicals and newly formed particles at a spruce forest site in Germany
(2013)
It has been claimed for more than a century that atmospheric new particle formation is primarily influenced by the presence of sulphuric acid. However, the activation process of sulphuric acid related clusters into detectable particles is still an unresolved topic. In this study we focus on the PARADE campaign measurements conducted during August/September 2011 at Mt. Kleiner Feldberg in central Germany. During this campaign a set of radicals, organic and inorganic compounds and oxidants and aerosol properties were measured or calculated. We compared a range of organic and inorganic nucleation theories, evaluating their ability to simulate measured particle formation rates at 3 nm in diameter (J3) for a variety of different conditions. Nucleation mechanisms involving only sulphuric acid tentatively captured the observed noon-time daily maximum in J3, but displayed an increasing difference to J3 measurements during the rest of the diurnal cycle. Including large organic radicals, i.e. organic peroxy radicals (RO2) deriving from monoterpenes and their oxidation products in the nucleation mechanism improved the correlation between observed and simulated J3. This supports a recently proposed empirical relationship for new particle formation that has been used in global models. However, the best match between theory and measurements for the site of interest was found for an activation process based on large organic peroxy radicals and stabilized Criegee intermediates (sCI). This novel laboratory derived algorithm simulated the daily pattern and intensity of J3 observed in the ambient data. In this algorithm organic derived radicals are involved in activation and growth and link the formation rate of smallest aerosol particles with OH during daytime and NO3 during nighttime. Because of the RO2s lifetime is controlled by HO2 and NO we conclude that peroxy radicals and NO seem to play an important role for ambient radical chemistry not only with respect to oxidation capacity but also for the activation process of new particle formation. This is supposed to have significant impact of atmospheric radical species on aerosol chemistry and should to be taken into account when studying the impact of new particles in climate feedback cycles.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
The link between atmospheric radicals and newly formed particles at a spruce forest site in Germany
(2014)
It has been claimed for more than a century that atmospheric new particle formation is primarily influenced by the presence of sulfuric acid. However, the activation process of sulfuric acid related clusters into detectable particles is still an unresolved topic. In this study we focus on the PARADE campaign measurements conducted during August/September 2011 at Mt Kleiner Feldberg in central Germany. During this campaign a set of radicals, organic and inorganic compounds and oxidants and aerosol properties were measured or calculated. We compared a range of organic and inorganic nucleation theories, evaluating their ability to simulate measured particle formation rates at 3 nm in diameter (J3) for a variety of different conditions. Nucleation mechanisms involving only sulfuric acid tentatively captured the observed noon-time daily maximum in J3, but displayed an increasing difference to J3 measurements during the rest of the diurnal cycle. Including large organic radicals, i.e. organic peroxy radicals (RO2) deriving from monoterpenes and their oxidation products, in the nucleation mechanism improved the correlation between observed and simulated J3. This supports a recently proposed empirical relationship for new particle formation that has been used in global models. However, the best match between theory and measurements for the site of interest was found for an activation process based on large organic peroxy radicals and stabilised Criegee intermediates (sCI). This novel laboratory-derived algorithm simulated the daily pattern and intensity of J3 observed in the ambient data. In this algorithm organic derived radicals are involved in activation and growth and link the formation rate of smallest aerosol particles with OH during daytime and NO3 during night-time. Because the RO2 lifetime is controlled by HO2 and NO we conclude that peroxy radicals and NO seem to play an important role for ambient radical chemistry not only with respect to oxidation capacity but also for the activation process of new particle formation. This is supposed to have significant impact of atmospheric radical species on aerosol chemistry and should be taken into account when studying the impact of new particles in climate feedback cycles.