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4-Nitrophenyl 1-naphthoate
(2010)
In the title compound, C17H11NO4, the dihedral angle between the two benzene rings is 8.66 (3)°. The nitro group is twisted by 4.51 (9)° out of the plane of the aromatic ring to which it is attached. The presence of intermolecular C—H ... O contacts in the crystal structure leads to the formation of chains along the c axis.
The two rings in the title compound, C11H12N2O4S, are roughly coplanar [dihedral angle = 6.77 (8)°]. Whereas the two outer methyl groups of the three methoxy groups are almost coplanar with the aromatic ring to which they are attached [C—C—O—C torsion angles = 8.5 (3) and -8.3 (3)°], the methyl group of the central methoxy substituent is not [C—C—C—C = -78.4 (3)°]. The crystal packing is stabilized by N—H ... O hydrogen bonding.
Leukotrienes constitute a group of bioactive lipids generated by the 5-lipoxygenase (5-LO) pathway. An increasing body of evidence supports an acute role for 5-LO products already during the earliest stages of pancreatic, prostate, and colorectal carcinogenesis. Several pieces of experimental data form the basis for this hypothesis and suggest a correlation between 5-LO expression and tumor cell viability. First, several independent studies documented an overexpression of 5-LO in primary tumor cells as well as in established cancer cell lines. Second, addition of 5-LO products to cultured tumor cells also led to increased cell proliferation and activation of anti-apoptotic signaling pathways. 5-LO antisense technology approaches demonstrated impaired tumor cell growth due to reduction of 5-LO expression. Lastly, pharmacological inhibition of 5-LO potently suppressed tumor cell growth by inducing cell cycle arrest and triggering cell death via the intrinsic apoptotic pathway. However, the documented strong cytotoxic off-target effects of 5-LO inhibitors, in combination with the relatively high concentrations of 5-LO products needed to achieve mitogenic effects in cell culture assays, raise concern over the assignment of the cause, and question the relationship between 5-LO products and tumorigenesis. Keywords: leukotriene, apoptosis, cell proliferation, mitogenic effects, cytotoxicity
65 Revisited
(2010)
Pennebaker hat doch zurückgeblickt. In weiteren fünfundsechzig Minuten zeigt er mit 65 REVISITED neue und ergänzende Facetten von Bob Dylan auf seiner 1965er Tournee durch England aus bisher unveröffentlichtem und digital aufgearbeitetem Material. Couchman (2002, 94) betont, dass Dylan über vierzig Jahre nach DON‘T LOOK BACK (1965) noch immer nichts von seiner enigmatischen Ausstrahlung verloren habe. Das gleiche gilt auch für den Film und für seine Ergänzung.
9-Bromo-9-borafluorene
(2010)
The title compound, C12H8BBr, crystallizes with three essentially planar molecules (r.m.s. deviations = 0.018, 0.020 and 0.021Å) in the asymmetric unit: since the title compound is rigid, there are no conformational differences between these three molecules. The crystal packing resembles a herringbone pattern.
Nach Erscheinen von Band 2: Sachsen-Anhalt des „Lexikon der Naturschutzbeauftragten“ im Jahre 2006 legt Hermann Behrens mit dem Band 3 „Naturschutzgeschichte und Naturschutzbeauftragte in Berlin und Brandenburg“ ein in Konzeption, Inhalt und Umfang beeindruckendes Werk vor. Allein schon der Umfang von 933 Seiten lässt die Erwartungen nach inhaltlicher Tiefe und Breite aufkommen. Und der Leser wird nicht enttäuscht! Das Werk hat die Qualität, zu einem Standard der deutschen Naturschutzgeschichte zu werden.
Der Artenschutz gehört zu den ältesten Instrumenten des Naturschutzes. Wo jedoch der Schutz innerhalb der natürlichen Lebensräume allein das Überleben gefährdeter Arten nicht mehr garantieren kann, dort sind weiterreichende Maßnahmen in Botanischen Gärten oder „Schutzgärten“ erforderlich. Die in dem Übersichtsbeitrag vorgestellten Verfahren gehen insofern auch über die reine Erhaltung von Sippen in „Genbanken“ hinaus, als die Wiederansiedlung am natürlichen Standort angestrebt wird.
Im Zusammenhang mit der Hutelandschaftspflege im Naturpark Soling-Vogler stellt das vorliegende Werk die Inhalte populärwissenschaftlich dar, um auf diese Art und Weise eine möglichst breite Öffentlichkeit zu informieren und von dem Sinn der Bemühungen zu überzeugen. Entstanden ist ein sehr sehenswertes, mit bestechend schönen Naturaufnahmen gefülltes Werk, das dem Laien ebenso wie dem Fachmann einen guten Überblick über das gesamte Vorhaben ermöglicht und die Begeisterung der an dem Projekt aktiv Beteiligten widerspiegelt.
Inhalt des vorliegenden Werkes sind die Ergebnisse des mehrjährigen Hutewaldprojektes des Naturpark Solling-Vogler. In dieser Form ist es das erste Projekt für einen Wald in der Bundesrepublik Deutschland. Es hat das Ziel, ein auf andere Regionen übertragbares Pflegekonzept, kombiniert mit Fragen der Natur- und Umweltbildung, der naturverträglichen Erholungsnutzung und Aspekten der Regionalplanung modellhaft zu entwickeln. Ein Hutewald ist ein als Weide genutzter Wald und der Vorteil der Waldweide wird im Zusammenhang mit Fragen zur Waldbewirtschaftung, zur Landschaftspflege und zum Naturschutz kontrovers diskutiert, sodass vorliegendes Buch zu einer Versachlichung der Diskussion beitragen könnte.
Im vorliegenden Heft 5 der Zeitschriftenreihe werden die Fachbeiträge der Mittelwaldtagung des Förder- und Landschaftspflegevereins Biosphärenreservat „Mittelelbe“ e. V. und der Kulturstiftung Dessau-Wörlitz, die am 29. September 2009 in Oranienbaum stattfand, publiziert. Die Tagung basiert auf einem Projekt des Fördervereins zur Wiedereinrichtung von Mittelwald. Beim Mittelwaldprojekt sollten ebenso kulturhistorische Aspekte berücksichtigt wie positive Wirkungen für den Naturschutz erzielt werden. Weiterhin galt es, das Wertholz- und Energieholzpotenzial des nachwachsenden Rohstoffes Holz optimal zu nutzen.
[Buchbesprechung:] Richarz, K. & M. Hormann (2008): Nisthilfen für Vögel und andere heimische Tiere.
(2010)
Wenn zwei Vollblutornithologen mit einem langjährigen beruflichen und publizistischen Erfahrungsschatz den Themenkomplex „Nisthilfen für Vögel“ auch noch auf Hilfsmittel für Wohnstätten anderer Tiergruppen ausdehnen, kann als Ergebnis der Bearbeitung wohl nur ein Handbuch entstehen. Doch selbst ein Handbuch vermochte dem Autorenduo offensichtlich nicht auszureichen, um die ihnen wichtigen Aspekte eines allumfassenden Vogel- und Artenschutzes darzustellen. Daher enthält die dem Buch beigefügte CD-ROM neben den 80 Quartier-Bauanleitungen für Vögel, Fledermäuse, Kleinsäuger und Insekten auch Hinweise zur sachgerechten Winterfütterung und sommerlichen Vogeltränke.
„Man kann nur schützen, was man kennt.“ Getreu diesem Grundsatz des Naturschutzes gibt das Buch „Naturschutzgebiete in Sachsen“ einen umfassenden Überblick, nicht nur über die 212 Naturschutzgebiete (NSG) und den Nationalpark des Bundeslandes, sondern einführend auch über wichtige Grundlagen der Landeskunde Sachsens mit Erläuterungen zur Geologie, zu den Böden, zum Klima und zu den Gewässern. Ein Kapitel widmet sich dem Schutz der Pflanzen- und Tierarten, gefolgt von einem Abschnitt mit Beschreibungen der Wälder, der Moore und des Grünlandes als wichtige Lebensräume in Sachsen. Zum Abschluss des Allgemeinen Teils wird die Geschichte der Naturschutzgebiete kurz vorgestellt und ein Überblick über die Systematik der Naturschutzgebiete gegeben.
Nunmehr im dritten Jahr in Folge legt Dr. Uwe Zuppke einen naturwissenschaftlich-heimatkundlichen Band über die Pflanzen- und Tierwelt seiner Heimatregion Lutherstadt Wittenberg vor. Nach einer Übersicht über die Lebensräume und Arten (2008) und die Vogelwelt (2009), stellt er zum Jahresende 2010 die Fischfauna und ihre Lebensräume einschließlich der Krebse, Muscheln und Hohltiere vor. Das Buch vermittelt Ergebnisse faunistischer Aufzeichnungen des Autors aus dem Gebiet für den zurückliegenden Zeitraum von 50 Jahren.
The focus of this contribution is on the mode of capitalism within the industrialized sectors of "emerging markets". Particularly in the context of the rise of the BRIC (Brazil, Russia, India and China) this question has gained considerable importance, also for the development of the world economy as a whole. The core question is whether the type of capitalism within these economies is similar to the capitalist variety of the triad, or diverges in more or less permanent ways. The article gives a preliminary answer to this question, by developing a rough sketch of a "BRIC" model of capitalism and illustrating this model with the case of Brazil. In terms of theory, the article extends the Comparative Capitalism (CC) perspective to the BRICs. On the one side, the focus is on the classical questions of CC, i.e. the determinants of economic development and the differences to other types of capitalism, on the other side the relationship between these varieties and social inequality. It argues that the "state-permeated market economies" of the BRICs rely on clans as a mode of social coordination. As demonstrated by the case of Brazil, this type of capitalism can be quite successful, but is based on a highly unequal distribution of economic and political resources.
O artigo resulta de pesquisa realizada entre os meses de abril e junho de 2010 no Instituto de Estudos Brasileiros (USP) e apresenta a listagem completa dos títulos pertencentes à biblioteca de João Guimarães Rosa que de algum modo se relacionam à língua e cultura alemãs. Descrevemos nosso procedimento e procuramos privilegiar alguns aspectos do material estudado, elaborando uma introdução ao levantamento, comentando as presenças mais significativas, os temas recorrentes e a marginália encontrada em volumes de autores como Nietzsche, Kafka e Erich Auerbach, bem como o contexto da relação de Guimarães Rosa com as leituras alemãs. Intentamos contribuir no estudo de fontes da obra do autor de "Grande sertão: veredas" e desejamos por fim divulgar um objeto de provável interesse no âmbito dos estudos germanísticos brasileiros.
O presente artigo discute as atuais transformações nos sistemas educacionais em todo o mundo. Tendo como foco a União Europeia (UE) e a Organização para a Cooperação e o Desenvolvimento Econômico (OCDE) como atores de políticas, seu argumento é que tais transformações implicam uma tripla "economização" da política educacional, que pode ser constatada em todos os níveis da área educacional. A importância cada vez maior dessas organizações nas questões educacionais configura uma transição para uma "constelação pós-nacional" também na área educacional, na medida em que a soberania educacional nacional está, no mínimo, passando por reajustes. No entanto, a "economização" das políticas educacionais não se limita a aproximar a educação das necessidades da economia e a transformar seus serviços em mercadorias comercializáveis. Ela também afeta o nível operacional da educação. Uma lógica de produção está sendo implementada na descrição realizada pelas próprias instituições do sistema educacional, que deixaram de ser estabelecimentos burocraticamente administrados para ser concebidos como uma atividade comercial gerencialmente controlada, uma atividade na qual uma ação empresarial se faz necessária. Esse novo tipo de administração faz surgir o problema da legitimação democrática das decisões políticas que, em termos ideais, combina três elementos: o democrático, o "expertocrático" e o ético-profissional. O artigo discute as consequências de uma mudança no equilíbrio desses três elementos no caso da Alemanha.
O presente artigo tem por objetivo investigar como se dá a questão da busca do conhecimento ilustrada pela figura da deusa Saïs no fragmento de romance de Novalis 'Die Lehrlinge zu Saïs', escrito em 1801. Em nossa investigação, traçamos um paralelo entre o uso alegórico do mito de Saïs em Novalis e no poema de Schiller 'Das verschleierte Bild zu Saïs', a fim de melhor caracterizar o conceito de verdade novalisiano. Por fim, procuramos analisar o conto de fadas 'Hyazinth und Rosenblüte', que se encontra no interior da narrativa em questão, uma vez que nele se dá o encontro ideal da Verdade almejado pelos poetas do primeiro-romantismo alemão, em especial, por Novalis.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Este artigo é formado por dois momentos distintos, porém articulados. Em primeiro lugar, pretende-se colocar algumas questões centrais para a discussão sobre a historiografia literária. Isso será feito tanto pelo questionamento de seu estatuto nos dias de hoje, bem como das dificuldades de se estabelecer uma história literária em língua alemã, quando se tem em vista autores austríacos contemporâneos. Num segundo segmento, a partir das considerações anteriores, iremos discorrer sobre a pertinência de uma perspectiva imanente. Para isso discutiremos alguns aspectos sobre a última peça do austríaco Thomas Bernhard, "Praça dos Heróis" ("Heldenplatz"), de 1988. Todo seu processo de escrita e encenação foi marcado por um escândalo programado pelo autor. Deste modo, a própria concepção da peça envolve a recepção em uma dialética entre arte e sociedade muito fecunda, resultando numa provocação elevada ao nível da forma, e não meramente acidental. Assim, questiona uma concepção de obra de arte orgânica e fechada, atualizando uma tradição épica decisiva.
In this Letter we study the radiation measured by an accelerated detector, coupled to a scalar field, in the presence of a fundamental minimal length. The latter is implemented by means of a modified momentum space Green's function. After calibrating the detector, we find that the net flux of field quanta is negligible, and that there is no Planckian spectrum. We discuss possible interpretations of this result, and we comment on experimental implications in heavy ion collisions and atomic systems.
Variants resistant to compounds specifically targeting HCV are observed in clinical trials. A multi-variant viral dynamic model was developed to quantify the evolution and in vivo fitness of variants in subjects dosed with monotherapy of an HCV protease inhibitor, telaprevir. Variant fitness was estimated using a model in which variants were selected by competition for shared limited replication space. Fitness was represented in the absence of telaprevir by different variant production rate constants and in the presence of telaprevir by additional antiviral blockage by telaprevir. Model parameters, including rate constants for viral production, clearance, and effective telaprevir concentration, were estimated from 1) plasma HCV RNA levels of subjects before, during, and after dosing, 2) post-dosing prevalence of plasma variants from subjects, and 3) sensitivity of variants to telaprevir in the HCV replicon. The model provided a good fit to plasma HCV RNA levels observed both during and after telaprevir dosing, as well as to variant prevalence observed after telaprevir dosing. After an initial sharp decline in HCV RNA levels during dosing with telaprevir, HCV RNA levels increased in some subjects. The model predicted this increase to be caused by pre-existing variants with sufficient fitness to expand once available replication space increased due to rapid clearance of wild-type (WT) virus. The average replicative fitness estimates in the absence of telaprevir ranged from 1% to 68% of WT fitness. Compared to the relative fitness method, the in vivo estimates from the viral dynamic model corresponded more closely to in vitro replicon data, as well as to qualitative behaviors observed in both on-dosing and long-term post-dosing clinical data. The modeling fitness estimates were robust in sensitivity analyses in which the restoration dynamics of replication space and assumptions of HCV mutation rates were varied.
A idéia central deste artigo é apontar o papel fundamental de alguns aspectos do pensamento romântico na compreensão da relação entre artista e sociedade, exposta criticamente por Thomas Mann em seu romance Doktor Faustus. Nessa perspectiva, considerase que uma exacerbação deformadora da tradição romântica - nos moldes em que ela é sugerida no romance e na trajetória do protagonista, o músico Adrian Leverkühn – é, enquanto ponto em comum da avaliação de Mann sobre o papel social do artista, sobre o caráter hermético da estética moderna e a decadência existencial e artística do protagonista do romance, um aspect decisivo para entendimento da problematização da relação entre arte e sociedade ali apresentada. A estrutura do artigo propõe o entendimento da relevância desta influência romântica nos rumos da arte moderna a partir de três ângulos distintos e complementares. Nomeadamente: as considerações estéticas e políticas do intelectual Thomas Mann; as relações entre o Romantismo e a dissolução do sistema tonal na música moderna e, por fim, o intelectualismo estéril e mudo da arte de Leverkühn. A idéia desta divisão é, pois, passando pela dimensão sócio-política da reflexão crítica (auto-avaliação do autor) e pela dimensão estética (as transformações dentro do sistema tonal da música erudita), contemplar os dois elementos fundamentais que estruturam o romance e vislumbrar mais nitidamente a proposição crítica da elaboração literária de tais questões.
In dyadic communication, both interlocutors adapt to each other linguistically, that is, they align interpersonally. In this article, we develop a framework for modeling interpersonal alignment in terms of the structural similarity of the interlocutors’ dialog lexica. This is done by means of so-called two-layer time-aligned network series, that is, a time-adjusted graph model. The graph model is partitioned into two layers, so that the interlocutors’ lexica are captured as subgraphs of an encompassing dialog graph. Each constituent network of the series is updated utterance-wise. Thus, both the inherent bipartition of dyadic conversations and their gradual development are modeled. The notion of alignment is then operationalized within a quantitative model of structure formation based on the mutual information of the subgraphs that represent the interlocutor’s dialog lexica. By adapting and further developing several models of complex network theory, we show that dialog lexica evolve as a novel class of graphs that have not been considered before in the area of complex (linguistic) networks. Additionally, we show that our framework allows for classifying dialogs according to their alignment status. To the best of our knowledge, this is the first approach to measuring alignment in communication that explores the similarities of graph-like cognitive representations. Keywords: alignment in communication; structural coupling; linguistic networks; graph distance measures; mutual information of graphs; quantitative network analysis
This paper presents an analysis of the recent tropospheric molecular hydrogen (H2) budget with a particular focus on soil uptake and surface emissions. A variational inversion scheme is combined with observations from the RAMCES and EUROHYDROS atmospheric networks, which include continuous measurements performed between mid-2006 and mid-2009. Net H2 surface flux, soil uptake distinct from surface emissions and finally, soil uptake, biomass burning, anthropogenic emissions and N2 fixation-related emissions separately were inverted in several scenarios. The various inversions generate an estimate for each term of the H2 budget. The net H2 flux per region (High Northern Hemisphere, Tropics and High Southern Hemisphere) varies between −8 and 8 Tg yr−1. The best inversion in terms of fit to the observations combines updated prior surface emissions and a soil deposition velocity map that is based on soil uptake measurements. Our estimate of global H2 soil uptake is −59 ± 4.0 Tg yr−1. Forty per cent of this uptake is located in the High Northern Hemisphere and 55% is located in the Tropics. In terms of surface emissions, seasonality is mainly driven by biomass burning emissions. The inferred European anthropogenic emissions are consistent with independent H2 emissions estimated using a H2/CO mass ratio of 0.034 and CO emissions considering their respective uncertainties. To constrain a more robust partition of H2 sources and sinks would need additional constraints, such as isotopic measurements.
Poster Presentation from Nineteenth Annual Computational Neuroscience Meeting: CNS*2010 San Antonio, TX, USA. 24-30 July 2010 In order to model extracellular potentials the Line-Source method provides [1] a very powerful and accurate approach. In this method transmembane fluxes are understood as sources for potential distributions which obey the Poission-equation with zero boundary conditions in the infinity. Its solutions reveal that the waveforms are proportional to local transmembrane net currents. The extracellular potentials are comparable small in amplitude and with the aid of their second special derivatives, it is possible to interpret them as additional fluxes to be included into the cable equation having an impact on the membrane potential of surrounding cells [2]. On this basis ephaptic interactions have been studied and have been considered to play a minor role in the network activity. This modeling study provides a new approach based on the first principle of the conservation of charges which leads to a generalized form of the cable equation taking into account the full three-dimensional detail of the cell’s geometry and the presence of the extracellular potential. So instead of coupling the compartment model and the model for extracellular potentials by means of the transmembrane currents, a non-linear system of partial differential equations is solved. Because the abstraction of deviding the cell’s geometry into compartments falls apart, it is possible to examine the contribution of the precise cell geometry to the signal processing while not neglecting the impact which could result from the extracellular potential. Some simulations of propagating action potentials on ramified geometries are going to be shown as well as the resulting distributions of extracellular action potentials.
We solved the crystal structure of a novel type of c-ring isolated from Bacillus pseudofirmus OF4 at 2.5 Å, revealing a cylinder with a tridecameric stoichiometry, a central pore, and an overall shape that is distinct from those reported thus far. Within the groove of two neighboring c-subunits, the conserved glutamate of the outer helix shares the proton with a bound water molecule which itself is coordinated by three other amino acids of outer helices. Although none of the inner helices contributes to ion binding and the glutamate has no other hydrogen bonding partner than the water oxygen, the site remains in a stable, ion-locked conformation that represents the functional state present at the c-ring/membrane interface during rotation. This structure reveals a new, third type of ion coordination in ATP synthases. It appears in the ion binding site of an alkaliphile in which it represents a finely tuned adaptation of the proton affinity during the reaction cycle. Formal Correction: This article has been formally corrected to address the following errors. 1. The images for Figures S2 and S3 were incorrectly switched. The image that appears as Figure S2 should be Figure S3, and the image that appears as Figure S3 should be Figure S2. The figure legends appear in the correct order. Please view the correct... (read formal correction) 2. The images for Figures S2 and S3 were incorrectly switched. The image that appears as Figure S2 should be Figure S3, and the image that appears as Figure S3 should be Figure S2. The figure legends appear in the correct order. Please view the correct... (read formal correction)
Als die amerikanische Rockband Matchbox Twenty im Jahr 2004 nach dem Start ihres Albums More Than You Think You Are auf Tour durch die Vereinigten Staaten gingen, beschlossen sie, der Tour einen Konzertfilm folgen zu lassen. Er wurde unter dem Titel SHOW: A NIGHT IN THE LIFE OF MATCHBOXTWENTY als Doppel-DVD veröffentlicht.
Background: Abnormalities of 11q23 involving the MLL gene are found in approximately 10% of human leukemias. To date, nearly 100 different chromosome bands have been described in rearrangements involving 11q23 and 64 fusion genes have been cloned and characterized at the molecular level. In this work we present the identification of a novel MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia. Methods: Cytogenetics, fluorescence in situ hybridization (FISH), molecular studies (RT-PCR and LDI-PCR), and bioinformatic sequence analysis were used to characterize the CT45A2 gene as novel MLL fusion partner in pediatric acute leukemia. Results: Fluorescence in situ hybridization of the patient G-banded metaphases demonstrated a cryptic insertion of 11q23 in Xq26.3 involving the MLL gene. Breakpoint fusion analysis revealed that a DNA fragment of 653 kb from 11q23, containing MLL exons 1-9 in addition to 16 other 11q23 genes, was inserted into the upstream region of the CT45A2 gene located at Xq26.3. In addition, a deletion at Xq26.3 encompassing the 3' region of the DDX26B gene (exons 9-16) and the entire CT45A1 gene was identified. RNA analysis revealed the presence of a novel MLL-CT45A2 fusion transcript in which the first 9 exons of the MLL gene were fused in-frame to exon 2 of the CT45A2 gene, resulting in a spliced MLL fusion transcript with an intact open reading frame. The resulting chimeric transcript predicts a fusion protein where the N-terminus of MLL is fused to the entire open reading frame of CT45A2. Finally, we demonstrate that all breakpoint regions are rich in long repetitive motifs, namely LINE/L1 and SINE/Alu sequences, but all breakpoints were exclusively identified outside these repetitive DNA sequences. Conclusion: We have identified CT45A2 as a novel spliced MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia, as a result of a cryptic insertion of 11q23 in Xq26.3. Since CT45A2 is the first Cancer/Testis antigen family gene found fused with MLL in acute leukemia, future studies addressing its biologic relevance for leukemogenesis are warranted.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
Passaram já mais de vinte anos sobre a apresentação no Centro Pompidou, em Paris, da exposição 'Vienne, 1880-1938, naissance d'un siècle'. Tratou-se, como alguns se recordarão, de um acontecimento de grande repercussão em toda a Europa. A definitiva consolidação do mito cultural da “Viena de 1900” está estreitamente associada a este acontecimento. A ressonância do evento, contudo, não poderá ser cabalmente entendida se não se tiver presente que, em meados dos anos oitenta a controvérsia sobre o pós-modernismo estava no auge. A verdade é que o comissário da exposição, Jean Clair, programou-a expressamente como uma espécie de manifesto pós-moderno, à luz de uma interpretação da modernidade vienense como um sítio arqueológico maior da pós-modernidade. […] É evidente que esta afirmação distintamente pós-histórica e pós-filosófica se baseia numa imagem da 'Wiener Moderne' como lugar de uma critica implícita à narrativa do progresso como perpétua inovação. A actualidade da Viena de 1900 reside, aos olhos de Jean Clair, justamente, numa específica noção de temporalidade que é hostil à ideia do novo como ruptura irreversível […]. É este, de facto, o núcleo da “hipótese vienense”, para usar a expressão proposta na época por Paolo Portoghesi, um dos mais influentes teóricos da arquitectura pós-modernista nos anos oitenta (Portoghesi 1984). Não vou ocupar-me aqui dos equívocos, por vezes grotescos, gerados em torno dessa hipótese no âmbito da teoria do pós-modernismo. Vou, simplesmente, concentrar-me no conceito de repetição e nas suas consequências para um entendimento mais lato do paradigma modernista, já que, na verdade, a “hipótese vienense”, as lições literalmente excêntricas da 'Wiener Moderne', representam, no fundamental, a percepção do carácter aberto e plural das respostas modernistas à condição moderna.
The paper presents a new classification and information about associations of the order Fagetalia sylvaticae on the territory of Ukraine. The order includes 9 alliances (Asperulo-Fagion, Cephalanthero- Fagion, Carpinion betuli, Tilio platyphylli-Acerion pseudoplatani, Dentario quinquefolii-Fagion, Paeonio dauricae-Quercion petraeae, Querco roboris-Tilion cordatae, Scillo sibericae-Quercion roboris, Alnion incanae) and 31 syntaxa of the level of association. The synoptic table contains data on constancy of species in all associations with constancy more than 10%. Maps of distribution of these associations in Ukraine are given.
Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5'-end) and complementary sequences in the 3'UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low.
This paper introduces a new methodology for the fabrication of strain-sensor elements for MEMS and NEMS applications based on the tunneling effect in nano-granular metals. The strain-sensor elements are prepared by the maskless lithography technique of focused electron-beam-induced deposition (FEBID) employing the precursor trimethylmethylcyclopentadienyl platinum [MeCpPt(Me)3]. We use a cantilever-based deflection technique to determine the sensitivity (gauge factor) of the sensor element. We find that its sensitivity depends on the electrical conductivity and can be continuously tuned, either by the thickness of the deposit or by electron-beam irradiation leading to a distinct maximum in the sensitivity. This maximum finds a theoretical rationale in recent advances in the understanding of electronic charge transport in nano-granular metals.
We have developed a versatile software package for the simulation of di-electron production in pp and dp collisions at moderate beam kinetic energies (1-2GeV). Particular attention has been paid to incorporate different descriptions of the Dalitz decay Δ rightarrow Ne + e - via a common interface. In addition, suitable parameterizations for the virtual bremsstrahlung process NN rightarrow NNe + e - based on one-boson exchange models have been implemented. Such simulation tools with high flexibility of the framework are important for the interpretation of the di-electron data taken with the HADES spectrometer and demonstrates the wide applicability within the field of nuclear and hadronic physics.
BACKGROUND: Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO) mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT) was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR) of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD) was absent in corticostriatal slices from old transgenic mice. CONCLUSIONS/SIGNIFICANCE: Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches.
Der Aufsatz untersucht die Frage, inwiefern die theatrale Konstruktion von christlichen Märtyrerfiguren eine Dynamik der Konversion zum bzw. des Abfalls vom Glauben voraussetzt, die in Figuralität und Ostentation zu begründen ist. Gegenstand der Untersuchung sind die Trauerspiele 'Catharina von Georgien', 'Papinian' und 'Carolus Stuardus'.
This article discusses the communicative and the intercultural approaches to language teaching and learning. Firstly, it describes the core theoretical principles, goals, and the roles of teachers and learners in both approaches, as well as the way they are treated in different German textbooks. Secondly, it discusses a set of core principles and concepts (‘activity’, ‘interaction’, ‘motivation’ and ‘communicative posture’), as well as the didactic-pedagogical implications of implementing a communicative approach to language teaching and learning. Finally, it includes a reflection about the necessity for the language teacher to develop an intercultural background, as well as the eclectic use of different linguistic theories and language teaching approaches to make the acquisition of communicative and intercultural competence viable.
Abrupt climate changes of the last deglaciation detected in a Western Mediterranean forest record
(2010)
Abrupt changes in Western Mediterranean climate during the last deglaciation (20 to 6 cal ka BP) are detected in marine core MD95-2043 (Alboran Sea) through the investigation of high-resolution pollen data and pollen-based climate reconstructions by the modern analogue technique (MAT) for annual precipitation (Pann) and mean temperatures of the coldest and warmest months (MTCO and MTWA). Changes in temperate Mediterranean forest development and composition and MAT reconstructions indicate major climatic shifts with parallel temperature and precipitation changes at the onsets of Heinrich stadial 1 (equivalent to the Oldest Dryas), the Bölling-Allerød (BA), and the Younger Dryas (YD). Multi-centennial-scale oscillations in forest development occurred throughout the BA, YD, and early Holocene. Shifts in vegetation composition and (Pann reconstructions indicate that forest declines occurred during dry, and generally cool, episodes centred at 14.0, 13.3, 12.9, 11.8, 10.7, 10.1, 9.2, 8.3 and 7.4 cal ka BP. The forest record also suggests multiple, low-amplitude Preboreal (PB) climate oscillations, and a marked increase in moisture availability for forest development at the end of the PB at 10.6 cal ka BP. Dry atmospheric conditions in the Western Mediterranean occurred in phase with Lateglacial events of high-latitude cooling including GI-1d (Older Dryas), GI-1b (Intra-Allerød Cold Period) and GS-1 (YD), and during Holocene events associated with high-latitude cooling, meltwater pulses and N. Atlantic ice-rafting. A possible climatic mechanism for the recurrence of dry intervals and an opposed regional precipitation pattern with respect to Western-central Europe relates to the dynamics of the westerlies and the prevalence of atmospheric blocking highs. Comparison of radiocarbon and ice-core ages for well-defined climatic transitions in the forest record suggests possible enhancement of marine reservoir ages in the Alboran Sea by 200 years (surface water age 600 years) during the Lateglacial.
We report the first measurements of 1,1,1,2,3,3,3-heptafluoropropane (HFC-227ea), a substitute for ozone depleting compounds, in air samples originating from remote regions of the atmosphere and present evidence for its accelerating growth. Observed mixing ratios ranged from below 0.01 ppt in deep firn air to 0.59 ppt in the current northern mid-latitudinal upper troposphere. Firn air samples collected in Greenland were used to reconstruct a history of atmospheric abundance. Year-on-year increases were deduced, with acceleration in the growth rate from 0.029 ppt per year in 2000 to 0.056 ppt per year in 2007. Upper tropospheric air samples provide evidence for a continuing growth until late 2009. Furthermore we calculated a stratospheric lifetime of 370 years from measurements of air samples collected on board high altitude aircraft and balloons. Emission estimates were determined from the reconstructed atmospheric trend and suggest that current "bottom-up" estimates of global emissions for 2005 are too high by a factor of three.
Background: Because Endomyocardial Biopsy has low sensitivity of about 20%, it can be performed near to myocardium that presented as Late Gadolinium Enhancement (LGE) in cardiovascular magnetic resonance (CMR). However the important issue of comparing topography of CMR and histological findings has not yet been investigated. Thus the current study was performed using an animal model of myocarditis. Results: In 10 male Lewis rats Experimental Autoimmune myocarditis was induced, 10 rats served as control. On day 21 animals were examined by CMR to compare topographic distribution of LGE to histological inflammation. Sensitivity, specificity, positive and negative predictive values for LGE in diagnosing myocarditis were determined for each segment of myocardium. Latter diagnostic values varied widely depending on topographic distribution of LGE and inflammation as well as on the used CMR sequence. Sensitivity of LGE was up to 76% (left lateral myocardium) and positive predictive values were up to 85% (left lateral myocardium), whereas sensitivity and positive predictive value dropped to 0 - 33% (left inferior myocardium). Conclusions: Topographic distribution of LGE and histological inflammation seem to influence sensitivity, specifity, positive and negative predictive values. Nevertheless, positive predictive value for LGE of up to 85% indicates that Endomyocardial Biopsy should be performed "MR-guided". LGE seems to have greater sensitivity than Endomyocardial Biopsy for the diagnosis of myocarditis.
Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens
(2010)
Background: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. Methodology/Principal Findings: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. Conclusions/Significance: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.
Background: The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex. Methods: By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue. Results: We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases. Conclusions: The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.
Hepatitis C virus (HCV) naturally infects only humans and chimpanzees. The determinants responsible for this narrow species tropism are not well defined. Virus cell entry involves human scavenger receptor class B type I (SR-BI), CD81, claudin-1 and occludin. Among these, at least CD81 and occludin are utilized in a highly species-specific fashion, thus contributing to the narrow host range of HCV. We adapted HCV to mouse CD81 and identified three envelope glycoprotein mutations which together enhance infection of cells with mouse or other rodent receptors approximately 100-fold. These mutations enhanced interaction with human CD81 and increased exposure of the binding site for CD81 on the surface of virus particles. These changes were accompanied by augmented susceptibility of adapted HCV to neutralization by E2-specific antibodies indicative of major conformational changes of virus-resident E1/E2-complexes. Neutralization with CD81, SR-BI- and claudin-1-specific antibodies and knock down of occludin expression by siRNAs indicate that the adapted virus remains dependent on these host factors but apparently utilizes CD81, SR-BI and occludin with increased efficiency. Importantly, adapted E1/E2 complexes mediate HCV cell entry into mouse cells in the absence of human entry factors. These results further our knowledge of HCV receptor interactions and indicate that three glycoprotein mutations are sufficient to overcome the species-specific restriction of HCV cell entry into mouse cells. Moreover, these findings should contribute to the development of an immunocompetent small animal model fully permissive to HCV.
Die folgende Übersicht an Addenda und Corrigenda entstand aus der Arbeit mit dem obengenannten Buch zwecks einer Rezension, die in Kürze in der Zeitschrift KLIO erscheinen wird. In der von Marco Traverso vorgelegten Inschriftensammlung finden sich eine Reihe von Einträgen, deren Darstellung und Interpretation teils aus formalen, teils aus inhaltlichen Gründen einiger Korrekturen und Anmerkungen bedürfen, die in einer Rezension für gewöhnlich nicht untergebracht werden können.
Processes occurring in the tropical upper troposphere (UT), the Tropical Transition Layer (TTL), and the lower stratosphere (LS) are of importance for the global climate, for stratospheric dynamics and air chemistry, and for their influence on the global distribution of water vapour, trace gases and aerosols. In this contribution we present aerosol and trace gas (in-situ) measurements from the tropical UT/LS over Southern Brazil, Northern Australia, and West Africa. The instruments were operated on board of the Russian high altitude research aircraft M-55 "Geophysica" and the DLR Falcon-20 during the campaigns TROCCINOX (Araçatuba, Brazil, February 2005), SCOUT-O3 (Darwin, Australia, December 2005), and SCOUT-AMMA (Ouagadougou, Burkina Faso, August 2006). The data cover submicron particle number densities and volatility from the COndensation PArticle counting System (COPAS), as well as relevant trace gases like N2O, ozone, and CO. We use these trace gas measurements to place the aerosol data into a broader atmospheric context. Also a juxtaposition of the submicron particle data with previous measurements over Costa Rica and other tropical locations between 1999 and 2007 (NASA DC-8 and NASA WB-57F) is provided. The submicron particle number densities, as a function of altitude, were found to be remarkably constant in the tropical UT/LS altitude band for the two decades after 1987. Thus, a parameterisation suitable for models can be extracted from these measurements. Compared to the average levels in the period between 1987 and 2007 a slight increase of particle abundances was found for 2005/2006 at altitudes with potential temperatures, theta, above 430 K. The origins of this increase are unknown except for increases measured during SCOUT-AMMA. Here the eruption of the Soufrière Hills volcano in the Caribbean caused elevated particle mixing ratios. The vertical profiles from Northern hemispheric mid-latitudes between 1999 and 2006 also are compact enough to derive a parameterisation. The tropical profiles all show a broad maximum of particle mixing ratios (between theta ~ 340 K and 390 K) which extends from below the TTL to above the thermal tropopause. Thus these particles are a "reservoir" for vertical transport into the stratosphere. The ratio of non-volatile particle number density to total particle number density was also measured by COPAS. The vertical profiles of this ratio have a maximum of 50% above 370 K over Australia and West Africa and a pronounced minimum directly below. Without detailed chemical composition measurements a reason for the increase of non-volatile particle fractions cannot yet be given. However, half of the particles from the tropical "reservoir" contain compounds other than sulphuric acid and water. Correlations of the measured aerosol mixing ratios with N2O and ozone exhibit compact relationships for the tropical data from SCOUT-AMMA, TROCCINOX, and SCOUT-O3. Correlations with CO are more scattered probably because of the connection to different pollution source regions. We provide additional data from the long distance transfer flights to the campaign sites in Brazil, Australia, and West-Africa. These were executed during a time window of 17 months within a period of relative volcanic quiescence. Thus the data represent a "snapshot picture" documenting the status of a significant part of the global UT/LS fine aerosol at low concentration levels 15 years after the last major (i.e., the 1991 Mount Pinatubo) eruption. The corresponding latitudinal distributions of the measured particle number densities are presented in this paper to provide data of the UT/LS background aerosol for modelling purposes.
New projects, services and collaborations have recently brought the infrastructural services for African Studies a big step forward. This report gives an account of new subject gateways and digitisation projects. It discusses recent European cooperation ventures in the field of librarianship. Additionally, new developments and services of the Africa Collection at Frankfurt University Library are presented, which help to address the changing needs of researchers and to handle information overload, while keeping up with the latest developments. Nevertheless, the fragmentation and compartmentalisation of the different services still hinder more integrated information services.
Ausgehend von zwei Punkten - die Gefühle als zentraler Inhalt dieser Werke und ihre spezifische aus dem Sujet hervorgehende Form - lassen sich Gemeinsamkeiten zwischen Ovid und Kluge beobachten, die die Substanz dieser Werke betreffen. Das bedeutet, wenn wir zunächst bei der Form bleiben, dass Ovids Werk keine Ganzheit ist, jedenfalls keine Ganzheit im traditionellen Sinn, und das bedeutet umgekehrt, dass Kluges Werk die 'disiecta membra' eines Ganzen entwirft, auf das es sich virtuell zubewegt. Die These ist, dass Kluges und Ovids Werk von derselben Formidee getragen ist und dass diese sich dieser Formidee lediglich von zwei verschiedenen Seiten nähern, Kluge von der Seite der modernen Kleinstform des Fragments, Ovid von der Seite der antiken Großform des Epos.