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The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors.
Gamma synchronization has generally been associated with grouping processes in the visual system. Here, we examine in monkey V1 whether gamma oscillations play a functional role in segmenting surfaces of plaid stimuli. Local field potentials (LFPs) and spiking activity were recorded simultaneously from multiple sites in the opercular and calcarine regions while the monkeys were presented with sequences of single and superimposed components of plaid stimuli. In accord with the previous studies, responses to the single components (gratings) exhibited strong and sustained gamma-band oscillations (30–65 Hz). The superposition of the second component, however, led to profound changes in the temporal structure of the responses, characterized by a drastic reduction of gamma oscillations in the spiking activity and systematic shifts to higher frequencies in the LFP (~10% increase). Comparisons between cerebral hemispheres and across monkeys revealed robust subject-specific spectral signatures. A possible interpretation of our results may be that single gratings induce strong cooperative interactions among populations of cells that share similar response properties, whereas plaids lead to competition. Overall, our results suggest that the functional architecture of the cortex is a major determinant of the neuronal synchronization dynamics in V1. Key words: attention , gamma , gratings , oscillation , visual cortex
Dynamical systems driven by Gaussian noises have been considered extensively in modeling, simulation, and theory. However, complex systems in engineering and science are often subject to non-Gaussian fluctuations or uncertainties. A coupled dynamical system under a class of Lévy noises is considered. After discussing cocycle property, stationary orbits, and random attractors, a synchronization phenomenon is shown to occur, when the drift terms of the coupled system satisfy certain dissipativity and integrability conditions. The synchronization result implies that coupled dynamical systems share a dynamical feature in some asymptotic sense.
L’esthétique a grandi dans les bras maternels de la philosophie. Mais la philosophie a toujours le droit de se porter vers l’esthétique sans perdre pour autant de son essence : le philosophe se tournant de tous les côtés pour trouver la signification et le fondement de ce qui est donné n’a pas besoin de détourner son regard des faits esthétiques. S’il veut appréhender en toute rigueur conceptuelle ce qui est et se manifeste en tant que beau, laid, sublime, etc., il doit pouvoir rapporter des constats empiriques (comme par exemple le caractère satisfaisant de certains couples de couleurs) à un concept plus général (par exemple celui d’harmonie), et rapporter ce dernier à son tour à une attitude intellectuelle plus large (disons, celle de la pure contemplation gratuite). C’est par cette réduction progressive aux principes les plus généraux que peuvent apparaître les relations [Zusammenhang] qu’entretiennent entre elles les connaissances singulières, ces dernières pouvant souvent prendre alors un nouveau sens. Grâce à cette méthode, on peut en particulier espérer saisir dans leur dernier fondement le caractère différent des grandes formes de culture que sont la religion, la science et l’art. Si des forces particulières sont à l’œuvre dans chacun de ces trois grands domaines, si des attitudes intellectuelles différentes constituent le préalable à ces formes de culture, il est sans doute aussi possible de définir la fonction rationnelle à travers laquelle l’esprit humain construit le champ de valeur esthétique. Si l’on pose que, dans le plaisir et la création artistiques, le donné est circonscrit et mis en forme par la fonction intellectuelle de la pure contemplation, non seulement l’attitude esthétique s’avère distincte des attitudes religieuse et scientifique mais, en outre, le trait fondamental qui traverse toute la vie esthétique se voit ainsi qualifié. ...
In dieser Betrachtung wird versucht, die Besonderheiten und Schwächen von Ehrensteins 'Pe-Lo-Thien' zu erläutern und aus einer chinesischen Perspektive zu bewerten, ob seine Nachdichtungen den ursprünglichen Stil und Wert von Pe Lo Thiens Gedichten beibehalten, ferner: durch die Analyse der Hauptthemen und des Sprachgebrauchs herauszufinden, ob seine Nachdichtungen expressionistische Elemente enthalten. Außerdem wird Pe Lo Thiens Gedicht 'In der Nacht einen Singenden hören. Übernachten in E Zhou' mit Ehrensteins Nachdichtung 'Ein Mensch weint in der Nacht' und mit Klabunds Nachdichtung 'Das nächtliche Lied und die fremde Frau' verglichen, um die Mehrdeutigkeit von Pe Lo Thiens Gedicht aufzuzeigen und einige Unterschiede zwischen der westlichen und der chinesischen Dichtung zu verdeutlichen.
For many services, consumers can choose among a range of optional tariffs that differ in their access and usage prices. Recent studies indicate that tariff-specific preferences may lead consumers to choose a tariff that does not minimize their expected billing rate. This study analyzes how tariff-specific preferences influence the responsiveness of consumers’ usage and tariff choice to changes in price. We show that consumer heterogeneity in tariff-specific preferences leads to heterogeneity in their sensitivity to price changes. Specifically, consumers with tariff-specific preferences are less sensitive to price increases of their preferred tariff than other consumers. Our results provide an additional reason why firms should offer multiple tariffs rather than a uniform nonlinear pricing plan to extract maximum consumer surplus.
'Übergang' ist eine Metapher für die Beschreibung ideengeschichtlicher Prozesse. Sicher ist ihr Bedeutungsfeld weiter. Kurt Röttgers (2007) nennt neben der anthropologischen Konstante: dem Übergang als Erfahrung von Tod und Geburt, den Übergang als Metamorphose, den Übergang als Transzendieren sowie dessen Negation: nämlich das Transzendieren als ein unstatthaftes, gar mit Tabu belegtes Übergehen von einer Sphäre in die andere. Hinüberzugehen kann, so Röttgers weiter, auch bedeuten, über eine Schwelle zu gehen, fortzuschreiten zu Neuem und in diesem Akt des Fortschreitens das Werden und die Geschichte, ja die Geschichtlichkeit selbst, auch in ihrer radikalen Verneinung alles Vorangegangenen, zu bejahen. Gerade im Zusammenhang mit letzteren Bedeutungszuschreibungen hat die Metapher des Übergangs im geschichtsphilosophischen beziehungsweise bewusstseinsphilosophischen Konzept des Deutschen Idealismus ihre Nobilitierung erfahren. Bewusstseinsphilosophisch ist dieses Konzept insofern, als es von den seit Descartes zentralen Prämissen der Orientierung an sich selbst sowie der Bildung von Allgemeinbegriffen ausschließlich auf der Grundlage von Erfahrung und damit auf der Grundlage von etwas zunächst in der Vorstellung Gegebenem ausgeht (vgl. Zeuch 2001). Die Frage, der ich im Folgenden nachgehe, ist, ob diesem Konzept, das seinen Kairos um 1800 hat, ein besonderes Potential zukommt, das der Ideengeschichte gegen ihre Kritiker auch in der Gegenwart eine 'raison d'etre' verleiht, wenn es um den Rekonstruktionsversuch komplexer gesellschaftlicher, politischer, philosophischer Zusammenhänge und Kontinuitäten über mehrere Epochen oder Zeitabschnitte hinweg geht.
Taxonomische Neukombinationen zur Flora Mittel- und Osteuropas, insbesondere Nordrhein-Westfalens
(2010)
Im Rahmen der Erarbeitung mehrerer umfassender floristischer Inventare von Regionen Mittel- und Osteuropas wurden umfangreiche phytotaxonomische Studien durchgeführt. Als ein Ergebnis dieser Untersuchungen werden Neu- und Umkombinationen bei Sippen verschiedener Familien in den Art- und Unterartstatus vorgenommen und kommentiert sowie einige Gattungen und infragenerische Taxa neu aufgestellt.
The title compound, [Tl4(C4H9O)4], featuring a (Tl—O)4 cube, crystallizes with a quarter-molecule (located on a special position of site symmetry An external file that holds a picture, illustration, etc. Object name is e-66-m1621-efi1.jpg..) and a half-molecule (located on a special position of site symmetry 23.) in the asymmetric unit. The Tl—O bond distances range from 2.463 (12) to 2.506 (12) Å. All O—Tl—O bond angles are smaller than 90° whereas the Tl—O—Tl angles are wider than a rectangular angle.
Ad fontes. Wir wissen, daß fast alle Werke Thomas Manns ihre langen Wurzeln haben, und kaum ein anderer Roman hat längere als die Geschichte des Doktor Faustus. Sie sind, wenn man so sagen darf, über vierzig Jahre lang, und es versteht sich von selbst, daß sich der Stoff über einen so großen Zeitraum wandelte. Wir kennen den berühmten Dreizeilenplan aus dem Jahre 1901 - so wurde er von Thomas Mann selbst am 17. März 1943 benannt. Aber es war - darauf hat Peter de Mendelssohn in seinem Nachwort zur Frankfurter Ausgabe des Romans hingewiesen - nicht ein Dreizeilenplan, sondern es gab derer zwei. Der erste lautete (in Thomas Manns Notizbuch 7 festgehalten): "Zum Roman. Der syphilitische Künstler nähert sich von Sehnsucht getrieben einem reinen, süßen jungen Mädchen, betreibt die Verlobung mit der Ahnungslosen und erschießt sich dicht vor der Hochzeit". Man kann diesen Plan durchaus als Variation der Verführungsgeschichte Fausts und Gretchens lesen, auch wenn von einem Teufelspakt nicht die Rede ist und nicht Gretchen umkommt, sondern der Künstler, der Opfer einer venerischen Erkrankung ist. Aber das "reine, süße junge Mädchen": unverkennbar eine Gretchen-Gestalt. Der zweite Plan, wohl auf Ende 1904 zu datieren, ist von Mendelssohn als Variante und Fortführung der ersten Niederschrift charakterisiert worden, aber bei genauerem Hinsehen zeigt sich, daß es eigentlich ein ganz anderer Plan ist, in den der erste zwar aufgenommen ist, aber darin ein Fremdkörper bleibt.
Ĉlánek je zasazen do kontextu vyuĉování němĉiny jako cizího jazyka. Zabývá se vztahem mezi deskriptivním, resp. narativním textem a textovou prací zaloţenou na naraci ţáka na straně jedné a emocemi ţáka na straně druhé. Výsledky dosavadních výzkumŧ tohoto vztahu, jeţ vycházejí z posledních konceptŧ narace jako základní existenciální struktury bytí, naznaĉují, ţe narativní text a receptivní i produktivní narativní pracovní postupy ve vyuĉování a uĉení se jazyku indukují specifický potenciál pozitivních emocí a postojŧ ţáka.
NEW TECHNOLOGIES LIKE GRID COMPUTING WHICH CAN CONNECT RESOURCES AT DIVERSE LOCATIONS ARE MORE AND MORE ADOPTED FROM ORGANIZATIONS. SUCH TECHNOLOGIES CAN BOTH TRIGGER LINKAGES BETWEEN ORGANIZATIONS AND DIFFERENT DEPARTMENTS IN ONE SINGLE ORGANIZATION. WE DEVELOP A MODEL WHICH ACCOUNTS BOTH FOR INTER- AND INTRA-ORGANIZATIONAL INFLUENCE FACTORS ON THE ADOPTION PROCESS AND EMPIRICALLY IDENTIFIES THE MOST SIGNIFICANT INFLUENCE FACTORS.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m3 and is operated in a 0.5 T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
Moderately elevated levels of plasma plant sterols have been suspected to be causally involved in atherosclerosis. The aim of this study was to investigate whether plant sterols and other markers of sterol metabolism predicted all-cause and cardiovascular mortality in participants of the Ludwigshafen Risk and Cardiovascular health (LURIC) study. A total of 1,257 individuals who did not use statins and at baseline had a mean (± SD) age of 62.8 (± 11.0) years were included in the present analysis. Lathosterol, cholestanol, campesterol, and sitosterol were measured to estimate cholesterol synthesis and absorption. The mean (± SD) time of the follow-up for all-cause and cardiovascular mortality was 7.32 (± 2.3) years. All-cause (P = 0.001) and cardiovascular (P = 0.006) mortality were decreased in the highest versus the lowest lathosterol to cholesterol tertile. In contrast, subjects in the third cholestanol to cholesterol tertile had increased all-cause (P < 0.001) and cardiovascular mortality (P = 0.010) compared with individuals in the first tertile. The third campesterol to cholesterol tertile was associated with increased all-cause mortality (P = 0.025). Sitosterol to cholesterol tertiles were not significantly related to all-cause or cardiovascular mortality. The data suggest that high absorption and low synthesis of cholesterol predict increased all-cause and cardiovascular mortality in LURIC participants.
From the 1980 Maitatsine uprising to the 2009 Boko Haram uprising, Nigeria was bedevilled by ethno-religious conflicts with devastating human and material losses. But the Boko Haram uprising of July 2009 was significant in that it not only set a precedent, but also reinforced the attempts by Islamic conservative elements at imposing a variant of Islamic religious ideology on a secular state. Whereas the religious sensitivity of Nigerians provided fertile ground for the breeding of the Boko Haram sect, the sect’s blossoming was also aided by the prevailing economic dislocation in Nigerian society, the advent of party politics (and the associated desperation of politicians for political power), and the ambivalence of some vocal Islamic leaders, who, though they did not actively embark on insurrection, either did nothing to stop it from fomenting, or only feebly condemned it. These internal factors coupled with growing Islamic fundamentalism around the world make a highly volatile Nigerian society prone to violence, as evidenced by the Boko Haram uprising. Given the approach of the Nigerian state to religious conflict, this violence may remain a recurring problem. This paper documents and analyses the Boko Haram uprising, as well as its links with the promotion of Islamic revivalism and the challenges it poses to the secularity of the Nigerian state.
Central elements of the Bologna declaration have been implemented in a huge variety of curricula in humanities, social sciences, natural sciences and engineering sciences at German universities. Overall the results have been nothing less than disastrous. Surprisingly, this seems to be the perfect time for German universities to talk about introducing a curriculum that is fully compatible with the Bologna declaration for medical education as well. However, German medical education does not have problems the Bologna declaration is intended to solve, such as quality, mobility, internationalization and employability. It is already in the Post-Bologna age.
The Nep1 (Emg1) SPOUT-class methyltransferase is an essential ribosome assembly factor and the human Bowen–Conradi syndrome (BCS) is caused by a specific Nep1D86G mutation. We recently showed in vitro that Methanocaldococcus jannaschii Nep1 is a sequence-specific pseudouridine-N1-methyltransferase. Here, we show that in yeast the in vivo target site for Nep1-catalyzed methylation is located within loop 35 of the 18S rRNA that contains the unique hypermodification of U1191 to 1-methyl-3-(3-amino-3-carboxypropyl)-pseudouri-dine (m1acp3Psi). Specific 14C-methionine labelling of 18S rRNA in yeast mutants showed that Nep1 is not required for acp-modification but suggested a function in Psi1191 methylation. ESI MS analysis of acp-modified Psi-nucleosides in a DeltaNep1-mutant showed that Nep1 catalyzes the Psi1191 methylation in vivo. Remarkably, the restored growth of a nep1-1ts mutant upon addition of S-adenosylmethionine was even observed after preventing U1191 methylation in a deltasnr35 mutant. This strongly suggests a dual Nep1 function, as Psi1191-methyltransferase and ribosome assembly factor. Interestingly, the Nep1 methyltransferase activity is not affected upon introduction of the BCS mutation. Instead, the mutated protein shows enhanced dimerization propensity and increased affinity for its RNA-target in vitro. Furthermore, the BCS mutation prevents nucleolar accumulation of Nep1, which could be the reason for reduced growth in yeast and the Bowen-Conradi syndrome.
The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation. We have carried out an extensive alanine scanning study to identify critical regions within the inhibitory domain. These experiments show that a stretch of ~13 amino acids is crucial for the binding function. Further, investigation of transcriptional activity and the intracellular level of mutants that cannot be sumoylated suggests that sumoylation reduces the concentration of p63. We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63. Keywords: p63, transcriptional regulation, auto-inhibition, sumoylation
The canopy spiders of the floodplain forest in Leipzig have become a focus of ecological studies in recent years. In 2006 we sampled 30 tree canopies in the ‘Burgaue’ nature reserve with pyrethrum knock-down fogging, recording 502 adult spiders belonging to 48 species and 11 families. Based on these data and the results of a previous fogging study, the studied spider community was dominated by forest and forest-edge species with a preference for the shrub and canopy strata as well as by spiders of the web spider feeding guild. The community structure was typical for arboreal spider communities from northern temperate forests but very different from communities in the tropics. Species richness and evenness were similar to the old growth near-primary Białowieża Forest in Poland. The checklist of 96 canopy spider species of the floodplain forest of Leipzig includes 54 additions to the spider fauna of Leipzig and vicinity by recent canopy studies and eight first canopy records for Leipzig from our field work. The theridiid Dipoena torva (Thorell, 1875) was recorded for the first time in Saxony. The floodplain forest of Leipzig sustains a large and species-rich arboreal spider community and is thus a valuable habitat for a large proportion of endangered species (12%).