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We use detailed data on exporters from Costa Rica, Ecuador and Uruguay as well as on their buyers to show that: aggregate exports are disproportionally driven by few multi-buyers exporters; and each multi-buyer exporter's foreign sales of any product are in turn accounted for by few dominant buyers. We propose an analytically solvable multi-country model of endogenous selection in which dominant exporters, dominant products and dominant buyers emerge in parallel as multi-product sellers with heterogeneous technologies compete for buyers with heterogeneous needs. The model not only provides an explanation of the existence of dominant buyers but also makes specific predictions on how the relative importance of dominant buyers should vary across export destinations depending on their market size and accessibility. We show that these predictions are borne out by our data and discuss their welfare implications in terms of gains from trade.
For the transport of high-intensity hadron beams in low-energy beam lines of linear accelerators, the compensation of space charge forces by the accumulation of particles of opposite charge is an important effect, reducing the required focusing strength and potentially the emittance growth due to space charge forces. In this thesis, space charge compensation was studied by including the secondary particles in particle-in-cell simulations.
For this purpose, a new electrostatic particle-in-cell code named bender was developed. The software was tested using known self-consistent solutions for an electron plasma confined in an external potential as well as for a KV distributed beam in a periodic focusing lattice. For the simulation of compensation, models for residual gas ionisation by proton and electron impact were implemented.
The compensation process was studied for a 120 keV, 100 mA proton beam transported through a short drift section. Various features in the particle distributions were identified, which can not explained by a uniform reduction in the electric field of the beam. These were tied to the presence of thermal electrons confined within the beam potential. Using the Poisson-Boltzmann equation, their distribution could be reproduced and their influence on the beam for a wider range of parameters studied. However, the observed temperatures show a significant numerical influence. The hypothesis was formed, that stochastical heating present in particle-in-cell simulations is the mechanism leading to the formation of the observed (partial) thermal equilibrium.
For the low-energy beam transport line of the Frankfurt neutron source FRANZ, bender was used to predict the pulse shaping in the novel ExB chopper system. The code was also used for the design and the study of an electron lens for the Integrable Optics Test Accelerator at Fermi National Accelerator Laboratory. Aberrations due to guiding center drifts and the strong electric field of the electron beam as well as the current limits in such a system were investigated.
This paper explores the impact of immigrants on the imports, exports and productivity of service- producing firms in the U.K. Immigrants may substitute for imported intermediate inputs (offshore production) and they may impact the productivity of the firm as well as its export behavior. The first effect can be understood as the re-assignment of offshore productive tasks to immigrant workers. The second can be seen as a productivity or cost cutting effect due to immigration, and the third as the effect of immigrants on specific bilateral trade costs. We test the predictions of our model using differences in immigrant inflows across U.K. labor markets, instrumented with an enclave-based instrument that distinguishes between aggregate and bilateral immigration, as well as immigrant diversity. We find that immigrants increase overall productivity in service-producing firms, revealing a cost cutting impact on these firms. Immigrants also reduce the extent of country-specific offshoring, consistent with a reallocation of tasks and, finally, they increase country-specific exports, implying an important role in reducing communication and trade costs for services.
In light of increasing division of labour in healthcare, the training and acquisition of both profession-specific and interprofessional competencies have been attributed growing significance, creating the need to test and establish specific teaching formats. Despite ever more complex and interconnected healthcare systems, an increase in patients’ active self-responsibility and innumerable pedagogical and technological innovations, educational systems have not reacted adequately to these new demands. Many authors, not lease the German Council of Science and Humanities, have therefore urged a rethinking of traditional medical education. Student-centred learning activities, such as problem-based and research-based learning, are becoming increasingly significant in view of the numbers of students achieving unsatisfactory levels of competence in critical thinking, communication and writing abilities and complex clinical decision making, for example. The Council of Science and Humanities arrived at a positive evaluation of the various model and reformed courses of study attempting to effectuate a comprehensive reorganisation of medical studies in content and structure as well as methods and didactics. The persistent pervasiveness of instructor-centred learning formats is not only to be found in medical education but in all of the health professions. Although alternative teaching and instruction formats have already been designed and their effectiveness deemed positive in empirical evaluation, the lecture remains the most practised means of transmitting knowledge. In its essence, however, learning is not a question of transmitting information but, moreover, a question of processing information. In traditional instruction units, referred to as “chalk and talk classes” by Becker and Watts, the teaching party presents material in the form of a lecture. As appropriate, questions may be permitted or short processing periods for the students may be integrated into the lecture. The knowledge-assimilating and most essential analysis of the lecture’s contents takes place in the subsequent self-instruction phase, in which the student works alone on concrete tasks. It is during the transfer of knowledge conveyed in the lectures, however, that most questions arise. Of further disadvantage in the traditional lecture is the low level of motivation among students to attend lectures as well as their often heterogeneous knowledge. The Inverted Classroom Model seems to be an eligible instrument for greater facilitation of student-centred and interprofessional learning.
Dieser Artikel beschreibt die Inverted-Classroom-Methode(ICM) im Sinne einer Einführung in die Thematik und soll als Praxisleitleitfaden für diejenigen dienen, die diese Methode in der medizinischen Aus-, Fort- und Weiterbildung einsetzen möchten. Es handelt sich bei der ICM um einen Blended-Learning-Methode, bei dem eine Selbstlernphase (individuelle Phase) vor die Präsenzunterrichtsphase gesetzt wird. In der Online-Phase wird Faktenwissen vermittelt, das als Grundlage für die Präsenzphase dient. Die Präsenzphase soll anschließend dafür genutzt werden, das erlernte Wissen zu vertiefen und anzuwenden. Dem gegenüber stehen die traditionellen Kurskonzepte, in denen das Faktenwissen beispielsweise in Vorlesungen oder in anderen Präsenzunterricht-Formaten vermittelt wird und die Vertiefung dieses Wissens durch die Studierenden im Anschluss daran im Selbststudium stattfinden soll. Das Ziel der ICM ist die Verschiebung des passiven Lernens hin zum aktivierenden Lernen, um das Lernen auf kognitiv anspruchvollen Ebenen wie Analyse, Synthese und Evaluation zu unterstützen. Dabei haben die gestiegene Produktion und Nutzung von Screencasts und Lernvideos, die „Bewegung“ der „Open Educational Resources“ und die verbreitete Nutzung von „Massive Open Online Courses“ (MOOCs) zu einer gestiegenen Verbreitung der Inverted-Classroom-Methode beigetragen. Der Artikel soll als Einführung in die Thematik dienen und dabei eine kurze Übersicht über wichtige Projekte und Forschungsergebnisse in der medizinischen Ausbildung und in weiteren Gesundheitsberufen geben. Außerdem werden die Vor- und Nachteile der Methode und ihr potentieller Nutzen für die zukünftige medizinische Aus- und Weiterbildung dargestellt.
Himaloaesalus gaoligongshanus Huang and Chen, new species (Coleoptera: Lucanidae: Aesalinae) is described from the Gaoligongshan Mts., Yunnan, China. It is the fi fth species of the genus Himaloaesalus Huang and Chen. This new species is similar to the Himalayan species Himaloaesalus himalayicus Kurosawa and H. saburoi Araya et al., from which it is distinguished. The male and female genitalia of all the known species of Himaloaesalus are illustrated. Dorcus yongreni Huang and Chen, new species (Coleoptera: Lucanidae: Lucaninae) is described from Ruili area, Yunnan, China. It belongs to the elegans group (Huang and Chen 2013). This new species is similar to the Indian species Dorcus apatani (Okuda and Maeda), new combination, originally described in Digonophorus Waterhouse. The male genitalia of both species are compared and illustrated.
El género Oogenius Solier, 1851, es revisado y ahora incluye siete especies: O. arrowi Gutiérrez (Argentina), O. castilloi Martínez y Peña (Chile), O. chilensis Ohaus (Chile), O. kuscheli Gutiérrez (Chile), O. lariosae Martínez (Argentina), O. penai Mondaca (Chile), y O. virens Solier (Chile). El género es redescrito, adultos macho y hembra de cada una de las especies son caracterizados, fotografi ados, y los caracteres morfológicos de valor diagnóstico ilustrados. Se incluye una clave de identifi cación, un mapa de distribución e información general sobre la biología de las especies. Basado en el estudio del material tipo, O. chilensis barrosi Gutiérrez, 1949, es considerado un nuevo sinónimo de O. chilensis Ohaus, 1905. Se designan lectotipos para Oogenius chilensis Ohaus, 1905 y Oogenius virens Solier, 1851.
Four species of the genus Enoclerus (Coleoptera: Cleridae) are reported to prey on chemically protected Coccinellidae in North America. The possibility that aposematically colored Enoclerus also mimic prey ladybird species is discussed, and the further possibility that clerid predators acquire chemical protection through sequestration of ladybird prey’s toxic alkaloids is suggested as an important avenue of investigation. The data presented are primarily based on photographs taken by non-specialists, discovered through Internet search. The crowdsourcing of natural history observations can reveal aspects of animal behavior heretofore unreported and even unsuspected.
Two new species of Eburiini (Coleoptera, Cerambycidae, Cerambycinae) are described from Mexico (Guerrero): Susuacanga boteroi; and Eburia (Eburia) girouxae. Both are included in previous keys.
The Republic of Panama currently has 300 recorded species of Trichoptera distributed among 14 families. Herein we add 42 new country records for Panama, including one new family (Anomalopsychidae) and three new genera (Anomalopsychidae: Contulma; Hydroptilidae: Byrsopteryx and Cerasmatrichia). The newly recorded caddisfly taxa increase Panama’s total known fauna to 342 species, distributed among 15 families and 50 genera. These results are part of an ongoing effort to characterize the caddisfly fauna of Panama, and to evaluate that country’s major watersheds (cuencas).
A new species of Neostenoptera (Diptera: Cecidomyiidae: Winnertziinae) from eastern North America
(2016)
A new species of paedogenetic gall midge, Neostenoptera appalachiensis sp. nov., (Diptera: Cecidomyiidae: Winnertziinae: Heteropezini) from the eastern United States is described and illustrated, and pertinent collection and biological data are also provided. It is compared to its congeners, N. kiefferi (Meunier), a subfossil described from African copal, and N. congoensis Gagné, from the Congo. This rare, exciting discovery is the first record of the genus Neostenoptera in the New World.
Parajulid milliped studies XI : Initial assessment of the tribe Gosiulini (Diplopoda: Julida)
(2016)
The parajulid milliped tribe Gosiulini (Diplopoda: Julida) comprises two genera – Gosiulus Chamberlin, with three projections on the posterior gonopod and two species in the southcentral/southwestern United States (US) [Arizona, Colorado, New Mexico, and Texas], and monotypic Minutissimiulus Shelley, n. gen., with two projections, in Nuevo León, Mexico. Gosiulus conformatus Chamberlin occupies the plains/fl atlands of Texas, while its congener inhabits high elevations to the west in all four US states. Both are anticipated in Mexico (Coahuila, Chihuahua, and Sonora), and G. conformatus is expected in southeastern Colorado, eastern New Mexico, and the Oklahoma panhandle. The eastern boundary of G. conformatus and the genus/tribe conforms to the western border of the Piney Woods biome in eastern Texas. As shown by the posterior gonopod drawing in the original description, Parajulus timpius Chamberlin, previously considered of “uncertain generic position or validity,” is unquestionably the oldest name for the western species. The anteriormost posterior gonopod projection, absent from Minutissimiulus, is considered the “prefemoral process,” while the “solenomere” and a third branch arise from a common base.
Because of positional homology with “process ‘C’” in Nesoressini, the last projection is accorded this name, which may also apply to the “prefemoral process” in Aniulini. Minutissimiulus biramus Shelley, n. sp., is proposed along with the following new subjective synonymies: Apacheiulus Loomis under Gosiulus; Ziniulus aethes and Z. medicolens, both by Chamberlin, and Z. ambiguus and Z. nati, both by Loomis, under G. conformatus; and A. pinalensis and A. guadelupensis, both by Loomis, under G. timpius, new combination. Ziniulus navajo Chamberlin becomes an objective synonym of P. timpius because its holotype is designated neotype of the latter. Minutissimiulus biramus Shelley is the fi rst Mexican gosiuline and “mainland” Mexican parajulid not in the tribe Parajulini.
Sandrart.net
(2014)
Sandrart.net describes itself as a ‘research platform for the history of art and culture of the 17th century’. It is a digital edition of Joachim von Sandrart’s magnum opus, the ‘Teutsche Academie’, published between 1675 and 1680 in a German and between 1680 and 1684 in a Latin version. Facsimiles and full texts for both publications are provided as well as a bibliography and additional texts. Browse and search functionalities allow for easy access. Particular emphasis lies on commenting the text and identifying entities such as places, works of art or persons, for which extensive dossiers are provided. These kind of information can also be downloaded as raw XML and as semantic data expressed in RDF. The project undoubtedly marks the state of the art in the critically digitizing and editing 17th century prints.
Es wird davon ausgegangen, dass das ehemalige Larven-Mikrohabitat der Asiatische Tigermücke Aedes albopictus (synonym: Stegomyia albopicta) die Phytotelmata in den Waldgebieten von Südostasien darstellte. In den letzten vier Jahrzehnten adaptierte sich die Art jedoch an urbanere Regionen und ihre Antrotelmata. Dank ihrer Eigenschaft, Eier mit einer gewissen Trocken- und Kältetoleranz zu produzieren, verbreitete sich die Art zusammen mit den international gehandelten Waren weltweit. Zudem ist Ae. albopictus ein theoretischer Vektor für mindestens 27 Viren sowie Parasiten und spielt eine Hauptrolle bei der Übertragung von Dengue-Viren und Chikungunya-Viren und Zika-Vieren. Daher wird die Art als große Gefahr für die öffentliche Gesundheit betrachtet.
Die vorliegende Arbeit thematisiert drei Untersuchungen zum Anpassungs- und Etablierungs-potential der invasiven Asiatischen Tigermücke.
In einem ersten Ansatz wurde das Problem behandelt, dass es lediglich zwei standardisierte toxikologische Testverfahren für Culicidae gab. Daher wurde ein Dosis-Wirkungs-Testsystem entwickelt, das den Weg für weitere biologische Endpunkte und ihre integrativen Parameter freimachte und dadurch ein besseres Verständnis für die Wirkweisen von Insektiziden ermöglicht. Hierdurch konnte nun der Frage nachgegangen werden, ob es Unterschiede in der ökotoxikologischen Reaktion zwischen der invasiven tropisch-subtropischen Asiatischen Tigermücke und der einheimischen nördlichen Hausstechmücke Culex pipiens auf das Insektizid λ-Cyhalothrin gibt. Weiter wurde der Einfluss von Temperatur und die Verfügbarkeit von Nahrung auf die Insektizidsensitivitäten der Arten getestet. Schließlich konnte in einer Risikobewertung festgestellt werden, dass bei falsch angewendeten Bekämpfungsmaßnahmen höhere Temperaturen sowie der Ausfall von aquatischen Top-Prädatoren zu Fitnessvorteilen für die Art führen können.
In einer zweiten Untersuchung wurde der Mechanismus der Kältetoleranz der Eier (Kälteakklimatisierung und Diapause) näher untersucht, da dieser für die erfolgreiche Invasion in gemäßigten Breitengraden verantwortlich gemacht wird. Nachdem eine lang vorherrschende Hypothese verworfen wurde, dass die Einlagerung von Polyolen die Frosttoleranz bewirken würde, war der aktuelle Stand der Wissenschaft, dass eine Verdickung der Wachsschicht des Chorions dafür verantwortlich sei. Jedoch lag keine detaillierte Evaluierung von Stechmücken-Eihüllen vor. Mittels einer transmissionselektronenmikroskopischen Studie konnte gezeigt werden, dass nicht nur die Wachsschicht nicht in der Serosa-Cuticula zu verorten ist, sondern im Endochorion und sie zudem im Zuge der Diapause in der Mächtigkeit schrumpft. Daher wird auf Basis der gewonnenen Erkenntnisse auf eine Kompaktierung der Schicht geschlossen.
Die dritte Untersuchung schließlich hatte das hohe Adaptationspotential in gemäßigten Breiten zum Gegenstand. Eine Adaptation auf genetischen Level gilt als unwahrscheinlich, da Gründerpopulationen in den neu besiedelten Gebieten eine niedrige genetische Diversität aufwiesen und ein regelmäßiger Neueintrag von Allelen unwahrscheinlich ist. Jedoch bietet das Konzept der epigenetischen Temperatur-Adaptation einen Erklärungsansatz für dieses Phänomen. Daher wurde die Frage gestellt, ob es möglich ist, eine vererbbare Diversifizierung dieses kältetoleranten Phänotyps nach einer randomisierten epigenetischen Behandlung der DNA zu detektieren. Es wurde eine transgenerationale Untersuchung der Effekte von zwei epigenetischen Agenzien (und einem Lösemittel) auf die Kältetoleranz der Eier durchgeführt. Die Ergebnisse zeigten ein Korrelationsmuster, das den durch die Agenzien veränderten Methylierungsgrad der DNA mit der Forsttoleranz verband, was die gestellte Hypothese unterstützte.
In Folge dieser drei Untersuchungen wurde festgestellt, dass Ae. albopictus ein hohes Potential hat, in weiteren Ländern – vor allem in gemäßigten Breiten – ein Gesundheitsrisiko darzustellen. Da die Art einerseits Fitnessvorteile durch falsche Bekämpfungsmaßnahmen und andererseits möglicherweise eine hohes epigenetisches Adaptationspotential besitzt, kann zusammenfassend empfohlen werden, dass der Fokus für weitere Forschung maßgeblich auf der Entwicklung von Impfstoffen für die übertragenen Viren und Pathogene liegen sollte. Dadurch kann die Bevölkerung geschützt werden, ohne Ökosysteme und ihre Dienstleistungen zu gefährden, und dies wäre zudem ökonomisch gesehen die effektivere Lösung.
When assessing global water resources with hydrological models, it is essential to know about methodological uncertainties. The values of simulated water balance components may vary due to different spatial and temporal aggregations, reference periods, and applied climate forcings, as well as due to the consideration of human water use, or the lack thereof. We analyzed these variations over the period 1901–2010 by forcing the global hydrological model WaterGAP 2.2 (ISIMIP2a) with five state-of-the-art climate data sets, including a homogenized version of the concatenated WFD/WFDEI data set. Absolute values and temporal variations of global water balance components are strongly affected by the uncertainty in the climate forcing, and no temporal trends of the global water balance components are detected for the four homogeneous climate forcings considered (except for human water abstractions). The calibration of WaterGAP against observed long-term average river discharge Q significantly reduces the impact of climate forcing uncertainty on estimated Q and renewable water resources. For the homogeneous forcings, Q of the calibrated and non-calibrated regions of the globe varies by 1.6 and 18.5 %, respectively, for 1971–2000. On the continental scale, most differences for long-term average precipitation P and Q estimates occur in Africa and, due to snow undercatch of rain gauges, also in the data-rich continents Europe and North America. Variations of Q at the grid-cell scale are large, except in a few grid cells upstream and downstream of calibration stations, with an average variation of 37 and 74 % among the four homogeneous forcings in calibrated and non-calibrated regions, respectively. Considering only the forcings GSWP3 and WFDEI_hom, i.e., excluding the forcing without undercatch correction (PGFv2.1) and the one with a much lower shortwave downward radiation SWD than the others (WFD), Q variations are reduced to 16 and 31 % in calibrated and non-calibrated regions, respectively. These simulation results support the need for extended Q measurements and data sharing for better constraining global water balance assessments. Over the 20th century, the human footprint on natural water resources has become larger. For 11–18% of the global land area, the change of Q between 1941–1970 and 1971–2000 was driven more strongly by change of human water use including dam construction than by change in precipitation, while this was true for only 9–13 % of the land area from 1911–1940 to 1941–1970.
Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to an acetylated domain in E2F-1, and PAD4 and BRD4 coexist with E2F-1 on cytokine gene promoters. Accordingly, the combined inhibition of PAD4 and BRD4 disrupts the chromatin-bound complex and suppresses cytokine gene expression. In the murine collagen-induced arthritis model, chromatin-bound E2F-1 in inflammatory cells and consequent cytokine expression are diminished upon small-molecule inhibition of PAD4 and BRD4, and the combined treatment is clinically efficacious in preventing disease progression. Our results shed light on a new transcription-based mechanism that mediates the inflammatory effect of PAD4 and establish the interplay between citrullination and acetylation in the control of E2F-1 as a regulatory interface for driving inflammatory gene expression.
A revised annotated checklist for the butterfly family Lycaenidae (Lepidoptera) of Trinidad is presented, updating nomenclature, and indicating synonyms from earlier lists and papers. The checklist includes 131 species of Lycaenidae, comprising 127 species of 49 genera of Eumaeini, Theclinae, and four species of three genera of Polyommatinae.
There are more than 30 new island records. No lycaenid species is endemic to Trinidad, and the fauna consists primarily of widespread species (71%) that occur from Central America to the Amazon Basin. However, the primary biogeographic affi nity is the Amazon Region, where 94% of the Trinidad lycaenid fauna also occurs.
Corrections are made to the literature cited in the first author’s earlier checklists on other Trinidad butterflies.
The genus Rhinolaemus Steel is revised. A new island and a new country record are presented for the type species, R. maculatus Steel. A new species, R. niueensis Thomas, new species, is described from Niue, and Rhinolaemus tuberculatus (Grouvelle), new combination, is transferred from Laemophloeus (sens. lat.). The members of the genus are illustrated and a key to their identification is presented.
Epimelitta Bates, 1870 (Coleoptera, Cerambycidae) is redescribed with two species: Epimelitta scoparia (Klug, 1825) and Epimelitta rufiventris Bates, 1870; Epimelitta meliponica Bates, 1870 syn. nov. and Epimelitta acutipennis Fisher, 1947 syn. nov. are considered junior synonyms of E. scoparia. Exepimelitta gen. nov. is described with five species: Exepimelitta mimica (Bates, 1873), Ex. nigerrima (Bates, 1892), Ex. consobrina (Melzer, 1931) (=Epimelitta nigerrima var. flavipubescens Fisher, 1947, syn. nov.), Ex. lestradei (Peñaherrera-Leiva and Tavakilian, 2003) and Ex. windsori sp. nov. Charisia Champion, 1892 is revalidated and redescribed with six species: Charisia euphrosyne (Newman, 1840), C. mneme (Newman, 1841), C. melanaria Gounelle, 1911, C. ornaticollis Zajciw, 1973, C. bleuzeni (Peñaherrera-Leiva and Tavakilian, 2003) and C. durantoni (Peñaherrera-Leiva and Tavakilian, 2003).
Erratamelitta gen. nov. is described with two species: Erratamelitta erato (Newman, 1840) (= Epimelitta bicolor (Bates, 1873), syn. nov.) and Er. eliasi sp. nov.. Adepimelitta gen. nov. is described with two species: Adepimelitta debilis (Gounelle, 1911) and Ad. eupheme (Lameere, 1884). A brief synopsis of the genus Acorethra Bates, 1873 is presented, with two species included: Acorethra chrysaspis Bates, 1873, revalidated, and Ac. aureofasciata Gounelle, 1911. All species are illustrated (including genitalia when available); and keys to the genera, and their species, are provided.
Seven specimens of Sybra alternans (Wiedemann) (Cerambycidae: Lamiinae: Apomecynini) were captured with a UV light trap and by beating branches of trees in the urban area of Easter Island (Chile) during 2011–2016, representing the fi rst record of the species in this Chilean insular territory, but not continental Chile.
Sybra alternans is native to Southeast Asia and has been introduced accidentally to Hawaii and Florida in the United States of America. Data are presented from the literature on this species’ distribution, host plants, and biological information.
Taxonomic supplement (2001 to 2015) to the catalogue of New Zealand Carabidae (Insecta: Coleoptera)
(2016)
A supplement to the “Carabidae (Insecta: Coleoptera): catalogue” published by Larochelle and Larivière (2001; Fauna of New Zealand 43), is provided. A total of 99 genera and 547 species and subspecies belonging to 21 tribes and 8 subfamilies of Carabidae (including Cicindelini and Rhysodini), is recorded for New Zealand. Endemism is high, with 93% of the species and subspecies as well as 62% of the genera recorded from this country only. Changes to the 2001 catalogue are documented. The synonymy and type locality of taxa described between 2001 and 2015 are also provided.
The description of a new species of Kessleria (Lepidoptera: Yponomeutidae) is presented, based on male and female specimens obtained from laboratory rearing of material collected on their host, Maytenus boaria, of the central region of Chile.
Andaspis recurrens Takagi and Kawai, Hypaspidiotus jordani (Kuwana), Lepidosaphes kamakurensis (Kuwana) and Selenomphalus distylii Takagi from warm temperate forests are newly documented in the Korean fauna of armored scale insects (Hemiptera: Diaspididae). Characteristics of these species are briefl y given and illustrative photographs and information on their distribution and hosts are provided.
Nine new species of Hydroptilidae (Trichoptera) are described and illustrated from the western United States, Canada, Mexico, and Belize: Seven new species in the genus Neotrichia Morton, N. buenoi, N. chihuaha, N. contrerasi, N. maya, N. palitla, N. pinnacles, and N. sandersoni, one new species in the genus Oxyethira Eaton, O. pembertonensis, and one new species in the genus Metrichia Ross, M. mastelleri. As well, new records for N. mobilensis and Mayatrichia tuscaloosa and new illustrations of the male genitalia of Neotrichia jarochita Bueno-Soria and Mayatrichia tuscaloosa Harris and Sykora are provided.
The Iranian fauna of Cucujidae, Laemophloeidae, and Silvanidae (Coleoptera: Cucujoidea) are summarized in this paper. In total 2 species of Cucujidae (1 genus: Pediacus Shuckard), 6 species of Laemophloeidae (3 genera: Cryptolestes Ganglbauer, Laemophloeus Dejean, and Placonotus MacLeay) and 7 species of Silvanidae (6 genera: Uleiota Latreille, Psammoecus Latreille, Ahasverus Gozis, Nausibius Lentz, Oryzaephilus Ganglbauer, Psammoecus Latreille, and Silvanus Latreille) are listed in this paper. Synonymies and distribution data are given.
The previously published list of Coleoptera holotypes in the Museo de Historia Natural, Noel Kempff Mercado (MNKM), Santa Cruz, Bolivia is updated to include those deposited in the Museo since then though the end of 2015. Literature citations for the original descriptions of each listed holotype are also provided along with summary comments regarding family composition and authorship of included species. Photographs of collector, authors, habitats, and major Bolivian type repositories are provided.
Descriptions or diagnoses are given for 36 species of New World Eremoleon including 12 new species:
Eremoleon attenuatus, E. durangoensis, E. jacumba, E. jamaica, E. inca, E. monagas, E. morazani, E. pygmaeus, E. samne, E. tanya, E. tepuyiensis and E. venezolanus. A neotype is designated for Hesperoleon atomarius Navás 1933.
The larvae of 25 species are described and keyed. Keys to the adults and larvae are given, and biological notes are provided. Twenty-five species were reared from larvae found in cave mouths, rock overhangs, or other less common habitats; for example, E. nigribasis were found in deep recesses of mammal burrows, E. gracile were reared from reptile holes in the ground, E. punctipennis were found in beetle frass beneath logs, and E. femoralis in small twig holes or abandoned termite galleries in termite frass. Many new bombyliid and chalcidid parasites are listed.
Die Empfehlung des Corporate Governance-Kodex (Ziff. 5.4.2), „dem Aufsichtsrat soll eine nach seiner Einschätzung angemessene Anzahl unabhängiger Mitglieder angehören“, wirft in der Praxis nach wie vor Fragen auf. Im Folgenden sollen einige Thesen zur Auslegung dieser Empfehlung aufgestellt werden. Eine rechtspolitische Auseinandersetzung mit ihr und Änderungsvorschläge sind an dieser Stelle nicht beabsichtigt.
André Prüm has asked me to talk about “La Théorie de l´organe” supposing that this is a German invention. Well, we cannot claim the authorship or copyright for that, but it is true that this doctrine is still dominating German doctrinal thinking in company law. Let me first look at the historical development and background of this theory and then ask for its actual meaning and practical consequences.
„Corporate groups are a fact of life“.1 This was the starting point for a group of renowned European experts to deliver a report on a possible Directive on corporate group law in 2000.2 We all know that no such Directive has been issued.3 However, these days a fresh group of eminent experts has started, among other things, to develop an initiative „on groups of companies“.4 One reason for a European regulation to take its time might be the enormous national differences in dealing with group situations. While some countries, notably the UK,5 rely on general company law to deal with corporate groups, others provide most detailed rules specifically for groups of companies.6 German law provides an example for the latter. Do we need a law of corporate groups? Most countries regulate one or another aspect of group law.7
This is probably most common for tax and for accounting law. Insolvency law will often take group situations into account and the same is true for labour law. Regulatory oversight for financial institutions or insurance companies usually includes a group dimension. Competition law necessarily does so as well. However, in what follows when we speak about „group law“ we will focus on regulation more specifically tuned to genuine questions of company law such as the protection of minority shareholders or creditors, the standards for managerial behavior and the „enabling“ function of legal structures.
Capital maintenance rules are part of a legal capital regime that consists of rules on raising capital and rules on maintaining it. The function of these rules is the protection of the corporation’s creditors. This is evidenced by the fact that in public as well as private companies the provisions on legal capital are not open to disapplication or variation even with unanimous shareholder consent. Thus, providing the company with a minimum of funding and ensuring equal treatment of shareholders are mere reflexes of creditor protection or, at best, ancillary purposes of legal capital. Legal capital is part of a corporation’s equity. The key feature of equity is that it ranks behind the claims of other stakeholders in the distribution of a corporation’s assets. Consequently, equity will also be the first part of a corporation’s funds to be depleted by losses. Capital maintenance rules seek to enforce this order of priority of different groups of stakeholders by restricting distributions to shareholders. Such restrictions are not unique to legal systems that have adopted a legal capital regime. A prominent example of a statute that has eliminated mandatory legal capital is the Delaware General Corporation Law. § 154 DCGL leaves it up to the directors to decide whether any part of the consideration received by the corporation for its shares shall be attributed to capital. Thus, a Delaware corporation need not have any stated capital. This has significant impact on the funds available for distribution to shareholders. Pursuant to § 170 (a) DGCL dividends may only be paid out of surplus or, in the absence of surplus, out of net profits of the current or the preceding fiscal year. § 154 DGCL defines surplus as the excess of a corporation’s net assets over the amount of its capital, and net assets as the amount by which total assets exceed total liabilities. A corporation without stated capital may, therefore, distribute all of its net assets to its shareholders and continue business without any equity on its balance sheet. This highlights the difference between the different approaches to creditor protection in Germany and the U.S. Both legal systems acknowledge the priority of creditors over shareholders in corporate distributions. However, German law seeks to give creditors additional comfort by requiring companies to raise and maintain additional layers of assets above and beyond those corresponding to the company’s liabilities that may not be depleted by way of distributions to shareholders. While private companies must merely raise and maintain their stated capital, public companies are required to raise and maintain additional equity accounts unavailable for distributions to shareholders such as the share premium account1 and the legal reserve.2
In recent years a number of objections have been raised against this concept of creditor protection. Critics argue that contractual arrangements are a more efficient means for protecting the interests of creditors.3 Capital maintenance does not prevent creditors from negotiating for more stringent protection of their claims such as collateral or financial covenants. It does, however, provide a minimum standard of protection for the benefit of creditors who lack the commercial experience or the bargaining power or who, like tort victims, are simply unable to negotiate for contractual safeguards. Capital maintenance ensures that their protection against excessive distributions does not depend on large creditors who are free to waive covenants that, in effect, benefit all creditors in exchange for individual arrangements that work exclusively in their favour.
Anleihen werden in der Regel in zahlreiche Teilschuldverschreibungen aufgespalten und diese an verschiedene Investoren verkauft. Dies begründet, der Zahl der umlaufenden Teilschuldverschreibungen entsprechend, jeweils unterschiedliche Schuldverhältnisse zwischen dem Emittenten und dem jeweiligen Investor. Hält ein Investor mehrere Teilschuldverschreibungen, so entstehen dementsprechend mehrere rechtlich voneinander zu unterscheidende Schuldverhältnisse mit gleichem Inhalt.1 Diese können jeweils ein unterschiedliches rechtliches Schicksal haben, z. B. getrennt voneinander übertragen werden. Sie können auch, von atypischen Gestaltungen abgesehen, je einzeln vom Gläubiger gekündigt werden, wenn die Anleihebedingungen insoweit keine Vorkehrungen treffen. Die folgenden Bemerkungen dazu befassen sich zunächst mit der umstrittenen Frage, ob auch eine Kündigung aus wichtigem Grund seitens eines Gläubigers gemäß §§ 490 Abs. 1, 314 BGB in Betracht kommt (im Folgenden I. - VII.)
Coccolithophores are an abundant phytoplankton group that exhibit remarkable diversity in their biology, ecology, and calcitic exoskeletons (coccospheres). Their extensive fossil record is testament to their important biogeochemical role and is a valuable archive of biotic responses to environmental change stretching back over 200 million years. However, to realise the potential of this archive requires an understanding of the physiological processes that underpin coccosphere architecture. Using culturing experiments on four modern coccolithophore species (Calcidiscus leptoporus, Calcidiscus quadriperforatus, Helicosphaera carteri and Coccolithus braarudii) from three long-lived families, we investigate how coccosphere architecture responds to shifts from exponential (rapid cell division) to stationary (slowed cell division) growth phases as cell physiology reacts to nutrient depletion. These experiments reveal statistical differences in cell size and the number of coccoliths per cell between these two growth phases, specifically that cells in exponential-phase growth are typically smaller with fewer coccoliths, whereas cells experiencing growth-limiting nutrient depletion have larger coccosphere sizes and greater numbers of coccoliths per cell. Although the exact numbers are species-specific, these growthphase
shifts in coccosphere geometry demonstrate that the core physiological responses of cells to nutrient depletion results in increased cell sizes and coccoliths per cell across four different coccolithophore families (Calcidiscaceae, Coccolithaceae, Isochrysidaceae, Helicosphaeraceae), a representative diversity of this phytoplankton group. Building on this, direct comparison of coccosphere geometries in modern and fossil coccolithophores enables a proxy for growth phase to be developed that allows growth responses to environmental change to be investigated throughout their evolutionary history. Our data also shows that changes in growth rate and coccoliths per cell associated with growth-phase shifts can substantially alter cellular calcite production. Coccosphere geometry is therefore a valuable tool for accessing growth information in the fossil record that provides unprecedented insights into the biotic responses of species to environmental change and its potential biogeochemical consequences.
Die sog. Business Judgment Rule wurde durch Art. 1 Nr. 1a des UMAG1 auf entsprechende Vorschläge im Schrifttum2 als neuer § 93 Abs. 1 Satz 2 in das Aktiengesetz eingefügt. Der Sache nach war sie bereits zuvor in Rechtsprechung3 und Lehre4 anerkannt. Nach gängigem Verständnis soll die Business Judgment Rule einen „sicheren Hafen“ bieten, der Organmitglieder davor schützt, dass unternehmerische Misserfolge auf der Grundlage nachträglicher besserer Erkenntnis als Sorgfaltspflichtverstöße sanktioniert werden. Nach ganz überwiegen-der Auffassung beschränkt sich die Bedeutung von § 93 Abs. 1 Satz 2 AktG nicht darauf, durch ausdrückliche Regelung von Elementen der Sorgfaltspflicht klarzustellen, dass das Gesetz mit dem strengen Sorgfaltsmaßstab des ordentlichen und gewissenhaften Geschäftslei-ters nicht etwa eine Erfolgshaftung statuiert. Die Business Judgment Rule wird vielmehr als Privilegierung gegenüber dem ansonsten geltenden Haftungsmaßstab des § 93 Abs. 1 Satz 1 AktG verstanden. Ausdrückliche Stellungnahmen zur Wirkungsweise dieses Privilegs reichen von der Annahme eines der richterlichen Nachprüfung entzogenen unternehmerischen Ermes-sensspielraums5 über die Einordnung als unwiderlegliche Vermutung objektiv rechtmäßigen Verhaltens6 bis hin zu der Annahme, dass im Anwendungsbereich der Business Judgment Rule eine Haftung gegenüber der Gesellschaft nur ab der Grenze der groben Fahrlässigkeit in Betracht komme.7 Aber auch die zahlreichen Stellungnahmen, die sich nicht ausdrücklich zur Frage der Haftungserleichterung äußern, setzen eine privilegierende Wirkung der Business Judgment Rule voraus. Anderenfalls hätten die eingehenden Überlegungen zur Abgrenzung unternehmerischer von anderen, insbesondere rechtlich gebundenen Entscheidungen, für die offenbar ein strengerer Sorgfalts- und Haftungsmaßstab gelten soll, keinerlei praktische Bedeutung.
1.Hinsichtlich der Haftung von Organmitgliedern gegenüber der Gesellschaft für Fehlein-schätzungen der Rechtslage gilt kein anderer Maßstab als hinsichtlich der Haftung für Fehler bei unternehmerischen Entscheidungen (dazu sogleich, II).
2.Die Business Judgment Rule des § 93 Abs. 1 Satz 2 AktG enthält kein Haftungsprivileg; insbesondere stellt sie Organmitglieder nicht grundsätzlich von der Haftung für grobe Fahr-lässigkeit frei. Sie konkretisiert vielmehr lediglich die Sorgfaltsanforderungen an einen or-dentlichen und gewissenhaften Geschäftsleiter und stellt klar, dass dessen Haftung nicht mit nachträglicher besserer Erkenntnis begründet werden kann. Aus diesem Grund ist es unbe-denklich, dass sich die Haftung für unternehmerische, rechtliche und sonstige Fehler nach einheitlichen Haftungsgrundsätzen richtet (dazu unten, III.).
In der Experimentierhalle der Physik am Campus Riedberg der Goethe – Universität wird gegenwärtig die Beschleunigeranlage FRANZ aufgebaut. FRANZ steht für Frankfurter Neutronenquelle am Stern-Gerlach-Zentrum. Die Anlage bietet vielfältige Experimentiermöglichkeiten in der Untersuchung intensiver, gepulster Protonenstrahlen. Ein Forschungsschwerpunkt an den sekundären Neutronenstrahlen sind Messungen zur nuklearen
Astrophysik. Die Neutronen werden durch einen 2 MeV Protonenstrahl mittels der Reaktion 7Li (p, n) 7Be erzeugt. Die geplanten Experimente erfordern sowohl eine hier weltweit erstmals realisierte Pulsrepetitionsrate von bis zu 250 kHz bei Pulsströmen im 100 mA – Bereich als auch eine extreme Pulskompression auf eine Nanosekunde bei dann auftretenden Pulsströmen im Ampere – Bereich. Daneben ist auch ein Dauerstrich – Strahlbetrieb im mA – Strombereich möglich. Auch viele einzelne Beschleunigerkomponenten wie die Ionenquelle, der Chopper zur Pulsformung, die hochfrequent gekoppelte RFQ-IH-Kombination, der Rebuncher in Form einer CH – Struktur und der Bunchkompressor sind Neuentwicklungen. Mittlere Strahlleistungen von bis zu 24 kW treten im Niederenergiestrahltransportbereich auf, da die Ionenquelle grundsätzlich im Dauerstrich zu betreiben ist, auch bei Hochstrom mit hohen Pulsrepetitionsraten. Der Personen- und Geräteschutz spielt damit auch eine wesentliche Rolle bei der Auslegung des Kontrollsystems für FRANZ. Der Aufbau von FRANZ und seine wesentlichen Komponenten werden in Kapitel 2 erläutert. Die vielen unterschiedlichen Komponenten wie Hochspannungsbereich, Magneten, Hochfrequenzbauteile und Kavitäten, Vakuumbauteile, Strahldiagnose und Detektoren machen plausibel, dass auch das Kontrollsystem für eine solche Anlage speziell ausgelegt werden muss. In Kapitel 4 werden zum Vergleich die Konzepte zur Steuerung und Regelung aktueller, großer Beschleunigerprojekte aufgezeigt, nämlich für die „European Spallation Source ESS“ und für die „Facility for Antiproton and Ion Research FAIR“. In der vorliegenden Arbeit wurde die Ionenquelle als komplexe Beschleunigerkomponente ausgewählt, um Entwicklungen zur Steuerung und Regelung durchzuführen und zu testen. Zum Anfahren und Betreiben der Ionenquelle wurde ein Flussdiagramm (Abb. 5.15) entwickelt und realisiert. Im Detail wurden Untersuchungen zur Abhängigkeit der Heizkathodenparameter von der Betriebsdauer gemacht. Daraus konnte ein Algorithmus zur Vorhersage eines rechtzeitigen Filamentaustausches abgeleitet werden. Weiterhin konnte die Nachregelung des Kathodenheizstromes automatisiert werden, um damit die Bogenentladungsspannung innerhalb eines Intervalls von ± 0.5 V zu stabilisieren. Das Anfahren des Filamentstroms wurde ebenfalls automatisiert. Dazu wird die Vakuumdruckänderung in Abhängigkeit der Filamentstromerhöhung gemessen, ausgewertet und daraus der nächste erlaubte Stromerhöhungsschritt abgeleitet. Auf diese Weise wird der Betriebszustand schneller und kontrollierter erreicht als bei manuellem Hochfahren. Das Ziel eines unbemannten Ionenquellenbetriebs ist damit näher gerückt. In einem ersten Test zur Komponentensteuerung und zur Datenaufnahme wurde ein Ionenstrahl extrahiert und durch den ersten Fokussierungsmagneten – einen Solenoiden – transportiert. Es wurde der Erregungsstrom des Solenoiden sowie die Strahlenergie automatisch durchgefahren, die Daten abgespeichert und daraus ein Kontourplot zum gemessenen Strahlstrom hinter der Fokussierlinse erstellt (Abb. 5). Die vorliegende Arbeit beschäftigt sich nur mit den „langsamen“ Steuerungs- und Regelungsprozessen, während die schnellen Prozesse im Hochfrequenzregelungssystem unabhängig geregelt werden. Neben der Überwachung des Betriebszustandes aller Komponenten werden auch alle für den Service und die Personensicherheit benötigten Daten weggeschrieben. Das System basiert auf MNDACS (Mesh Networked Data Acquisition and Control System) und ist in JAVA geschrieben. MNDACS besteht aus einem Kernel, welcher die Komponententreiber-Software sowie den Netzwerkserver und das graphische Netzwerkinterface (GUI) betreibt. Weterhin gehört dazu das Driver Abstraction Layer (DAL), welches den Zugang zu weiteren Computern oder zu lokalen Treibern ermöglicht. CORBA stellt die Middleware für Netzwerkkommunikation dar. Dadurch wird Kommunikation mit externer Software geregelt, weiterhin wird die Umlegung von Kommunikation im Fall von Leitungsunterbrechungen oder einem lokalen Computerabsturz festgelegt. Es gibt bei FRANZ zwei Kontrollebenen: Über Ethernet läuft die „High Level Control“ und die Datenverarbeitung. Über die „Low Level Control“ läuft das Interlock – und Sicherheitssystem. Die Netzwerkverbindungen laufen über 1 Gb Ethernet Links, womit ein schneller Austausch auch bei lokalen Netzwerkstörungen noch möglich ist. Um bei Stromausfällen das Computersystem am Laufen zu halten, wurde im Rahmen dieser Arbeit ein „Uninterruptable Power Supply“ UPS beschafft und erfolgreich am Hochspannungsterminal getestet.
Ribosomes are the central cellular assembly lines for protein synthesis. To cope with the translational needs, a proliferating mammalian cell can produce up to 7500-ribosomes per minute. However, under growth limiting conditions, such as nutrient depletion, ribosome synthesis is rapidly shut down exemplifying the importance of a tight coordination between ribosome supply and cellular energy status. In addition to the quantitative regulation, a strict quality control of ribosome synthesis is equally important, because alterations in the composition or function of ribosomes can lead to a variety of pathologies. To cope with these challenges a highly regulated, multi-step pathway of ribosome biogenesis has evolved. In mammals this pathway generates the mature 80S ribosomes that comprise the large 60S and the small 40S subunits. Together they contain around 80 ribosomal proteins and the 28S, 18S, 5.8S and 5S rRNAs. The 28S, 5.8S and 5S rRNAs are assembled into the large subunit, while the 18S rRNA is part of the small subunit. The pathway of ribosome biogenesis is a multi-step cellular process, where specific stages occur in distinct subcellular compartments. Transcription of the 47S rRNA, which is the precursor for the 28S, 18S and 5.8S species, occurs in the nucleolus. Modification of distinct bases and early processing of this precursor also take place in the nucleolus. Subsequently, the 40S and 60S pre-ribosomes take separate maturation routes through the nucleoplasm before their export and final assembly in the cytoplasm. The various stages of preribosomal maturation require the constant and sequential action of a large number of non-ribosomal proteins, known as trans-acting factors. These factors coordinate the delicate remodeling of the pre-ribosomal intermediates and thereby ensure proper progression of the maturation process. The remodeling events largely depend on the dynamics of post-translational modifications, such as phosphorylation or SUMOylation. This requires that the enzymes controlling these modifications are properly targeted to their sites of activity as they fulfill their functions within specific compartments. Here we studied the regulatory principles that govern the subcellular partitioning of the SUMO-specific isopeptidase SENP3 and its associated factor PELP1. Previous work from our laboratory has delineated the importance of the SUMO system for proper ribosome biogenesis in mammalian cells. In particular, we have shown that SENP3 is critically involved in 28S rRNA formation, which is a key step for pre-60S subunit maturation. A critical involvement of SENP3 at this stage of the maturation process is in agreement with the observed enrichment of SENP3 in the nucleolus, since 28S rRNA processing is considered to occur in the nucleolus. Our subsequent work identified the nucleolar scaffold protein NPM1 and the ribosomal trans-acting factor PELP1 as bona fide substrates of SENP3. For both proteins we could demonstrate modification by SUMO2/3 and define SENP3 as the demodifying enzyme. Depletion of SENP3 enhanced the conjugation of SUMO to both proteins and concomitantly reduced conversion of the 32S pre-rRNA to the mature 28S rRNA. PELP1 is part of a larger protein complex consisting of the core components PELP1, TEX10 and WDR18. We could show that the balanced SUMOylation/deSUMOylation of PELP1 controls the nucleolar/nucleoplasmic distribution of this complex. Enhanced SUMOylation, which is observed in the absence of SENP3, triggers the nucleolar release of the complex suggesting that SENP3-mediated deSUMOylation controls the dynamics of nucleolar trans-acting factors. Based on these findings we first wanted to understand, in which cellular compartment(s) SENP3 exerts its function on 28S maturation. Next, we wanted to tackle the question how the subcellular distribution of SENP3 is controlled. Finally
we addressed the question how the SUMOylation of PELP1 determines the subnuclear distribution of the PELP1 complex. This work initially revealed that the nucleolar localization of SENP3 is crucial for proper 28S rRNA formation and 60S ribosome maturation. Importantly, we could demonstrate that the nucleolar compartmentalization of SENP3 depends on its direct physical interaction with NPM1. Further, we could show that the amino-terminal region of SENP3 is necessary for its binding to NPM1 and nucleolar recruitment. Strikingly, this interaction requires the phosphorylation of SENP3, which is brought about by the mTOR kinase. By in-vitro kinase assays and mass-spectrometric approaches we identified five serine/threonine residues within the amino-terminal region of SENP3 that are targeted by mTOR (S/T 25, 26, 141, 142, 143). We could further demonstrate by mutagenesis that these sites in SENP3 are in fact critical for the phospho-dependent binding of SENP3 to NPM1 and its nucleolar recruitment.
Consistent with these data, we found that chemical inhibitors of the mTOR kinase trigger the nucleolar release of SENP3 and impair its interaction with NPM1. Strikingly, this goes along with severe 28S rRNA maturation defects demonstrating the physiological importance of mTOR signaling in the regulation SENP3 function and rRNA processing. By specifically depleting components of the either mTORC1 or mTORC2, we could attribute the observed effects to signaling by mTORC1 rather than mTORC2. In an attempt to find the negative regulators of SENP3 phosphorylation, we identified PP1-γ as the candidate phosphatase in this pathway. We found a strong physical interaction of SENP3 with PP1-γ and observed a loss of SENP3 nucleolar localization upon ectopic expression of PP1-γ. Thus we could define mTOR/PP1-γ mediated phosphorylation/dephosphorylation of SENP3 as an important
mechanism in the control of ribosome maturation. Given that mTOR activity is controlled by nutrient availability, SENP3 functions as a sensor that couples ribosome synthesis with nutrient availability. The second part of this work delineated the role of SUMOylated PELP1 in nucleoplasmic partitioning of the SENP3-PELP1 complex. It was revealed that the AAA-ATPase MDN1 binds preferentially to SUMO modified PELP1 and likely segregates SUMOylated PELP1 from nucleolar pre-60S particles. We initially found that the PELP1 complex associates with MDN1, a factor known to be involved in the 28S rRNA maturation. Notably, depletion of MDN1 led to an enhanced accumulation of the PELP1 complex in the nucleolus and a strong association of PELP1 with pre-60S particles, suggesting that MDN1 is required for the release of this complex from the pre-ribosomes. Intriguingly, the interaction of PELP1 with MDN1 requires SUMO2/3 and SUMOylated PELP1 shows enhanced binding to MDN1 when compared to unmodified PELP1. Taken together this work provides new insights in the control of the SENP3-PELP1 complex dynamics. We could define several layers for the coordinated spatial regulation of SENP3 and the PELP1 complex. This work therefore underscores the crucial importance of dynamic post-translational modifications for the control of ribosome maturation.
The prevalence of food allergies has increased in the westernized countries during the past decades. Clinical manifestations of food allergies involve the skin (e.g. atopic dermatitis), the respiratory tract (e.g. rhinitis, and asthma), the ocular area (e.g. conjunctivitis), the gastrointestinal tract (e.g. food-protein-induced enterocolitis syndrome, food-induced proctocolitis, and eosinophilic gastroenteropathies), and the cardiovascular system (e.g. anaphylaxis). A curative treatment of these diseases has not been established yet. Oral immunotherapy (OIT) has gained attention as a potential therapy for food allergies. Continuous feeding of allergenic diet applied in the model described here mirrors to a certain extent an OIT treatment. It might be therefore useful to investigate efficacy and safety of OIT pre-clinically.
Mouse models have been widely used to analyse novel treatment approaches. Unfortunately, most of them have focussed on IgE-mediated hyperreactivity. Only a limited number of mouse models presenting mixed IgE- and non-IgE-mediated gastrointestinal symptoms and inflammation upon allergen-challenge are available. To study the mechanisms underlying the induction of food-induced gastrointestinal inflammation and subsequent oral tolerance induction, a mouse model of food-induced gastrointestinal allergy was established. BALB/c mice were sensitised with Ovalbumin (OVA) plus ALUM and subsequently challenged by feeding a diet containing egg white (EW diet). During the first seven days on EW diet, OVA-sensitised mice (OVA/ALUM EW mice) developed gastrointestinal symptoms (e.g. weight loss, ruffed fur, soft stool and less mobility) and inflammation in the small intestines accompanied by a strong induction of OVA-specific IgE antibodies and mouse mast cell protease-1 (mMCP-1). Proliferation of CD4+ T cells from spleen of OVA/ALUM EW mice was reduced compared controls. The result indicated that feeding EW diet induced T cell tolerance systemically. In contrast, CD4+ T cells isolated from MLN of OVA/ALUM EW mice showed stronger proliferation upon OVA stimulation in vitro than mice OVA-sensitised but fed a conventional diet, indicating that tolerance was not induced by short-term EW diet. Histological analysis of the small intestinal tissue of OVA/ALUM EW mice revealed strong inflammation present in the duodenum, jejunum and ileum at this time point.
Interestingly, the observed symptoms in OVA/ALUM EW mice resolved spontaneously after 7 days on EW diet, if the feeding was continued. In the next steps the CD4+ T cell-mediated immune response after 28 days continuous EW diet was assessed and revealed that tolerance was induced systemically as well as locally. This was shown by reduced proliferation and cytokine secretion of CD4+ T cells from MLN of OVA/ALUM EW mice after long-term EW diet. However, the inflammation in the jejunum was aggravated instead of resolved at this time point of allergenic diet. Our results suggest that application of OIT in food-allergic patients with gastrointestinal inflammation may need to be reconsidered, since continuous administration of allergenic food may aggravate inflammation in the local tissue. Interestingly, only the jejunum was affected by a worsened condition, whereas duodenum and ileum resolved inflammation. In accordance to the observed jejunal inflammation mMCP-1 levels in the sera were not changed. Allergen-specific IgE levels did not reach baseline level after long-term EW diet, although they were reduced compared to levels in mice after 7 days on EW diet. This result suggests that residual OVA-specific IgE antibodies would promote the jejunal inflammation by sustained activation of mast cells. Furthermore, our results suggest that IL-4 produced by activated Th2 cells could be an effector molecule to induce intestinal inflammation.
The second part of this thesis was aimed at verifying the hypothesis that IgE-mediated mast cell activation is a major effector mechanism in induction of chronic inflammation induced by long-term EW diet. For that mice deficient for FcεRI, a high affinity IgE receptor, were used. These mice were sensitised with OVA and fed EW diet as described for WT mice. Although FcεRI-deficient mice showed an intact Th2 immunity with IgE production, weight loss in the receptor-deficient mice was moderately induced by EW diet compared to WT mice, suggesting that this clinical symptom during the acute phase of allergic response is associated with IgE-mediated mechanisms. Surprisingly, the deficient mice presented comparable intestinal inflammation on day seven of EW diet as WT mice did. However, if EW diet was continued, recovery of intestinal inflammation was observed in FcεRI-deficient mice in contrast to WT mice. These results suggest that the induction of intestinal inflammation is not IgE-dependent. Nevertheless, this does not rule out a potential role of mast cells in the inflammation, because of their IgE-independent activation pathways. It also suggests the involvement of T cell-mediated mechanisms during induction of jejunal inflammation. Interestingly, the aggravated inflammation seen after long-term EW diet in WT mice seems to be IgE-dependent, considering that it was not observed in FcεRI-deficient mice. The elevated number of mast cells in the intestine of WT mice further led to a hypothesis that their continuous activation might be responsible for the chronification of allergic inflammation observed after long-term EW diet. In the context of OIT it further implies that IgE might be a poor prognostic factor for recovery of intestinal inflammation during and after an OIT treatment. In the third part of this thesis regulatory mechanisms employed by the immune system were analysed. Initial results from CD4+ T cells isolated from MLN from OVA/ALUM EW mice showed elevated IL-10 levels in their supernatants after short-term EW diet. IL-10-deficient mice were used to analyse the effect of this immunosuppressive cytokine in the mouse model presented here. However, IL-10-deficient mice tend to develop a strong Th1-dominated immune response. Nevertheless, an accelerated weight loss and slight inflammation of the jejunum was observed after short-term EW diet. Analysis of OVA-specific proliferation and cytokine production CD4+ T cells from Spleen and MLN of IL-10-deficient mice on EW diet suggested that systemic as well as local tolerance was induced after short-term and long-term EW diet feeding, respectively. The result suggests that IL-10 is dispensable for induction of T cell tolerance in our mouse model.
However, the presence of functionally active Tregs was observed during this study in WT mice fed short-term EW diet, suggesting that Tregs might have an important role in regulating the systemic or local immune response. T cell deletion as an alternative immune regulatory mechanism was also observed. Additionally, the efficacy of continuous EW diet (mirroring to a certain extent an OIT treatment) in induction of permanent tolerance was assessed. In OVA-sensitised WT mice continuous allergenic diet was stopped after resolution of clinical symptoms and reintroduced after a defined period on conventional diet. Evaluating the weight development showed that reintroduction of EW diet induced weight loss again, but not as pronounced as seen after short-term EW diet. Also the CD4+ T cell-mediated response was elevated again upon allergen stimulation in vitro. The results suggested that permanent tolerance was not induced in the chosen feeding regime.
The mouse model established and analysed here was used to investigate inflammatory and regulatory mechanisms underlying food-induced gastrointestinal allergy. It presents clinical symptoms and intestinal inflammation (Burggraf et al., 2011). This model is easy to be reproduced in different laboratories, and is useful for testing novel therapy approaches (Schülke et al., 2011; Bohnen et al., 2013). It further provides an opportunity to investigate basic mechanisms underlying OIT. This therapy approach is currently extensively investigated and our mouse model would help to understand the therapeutic mechanism of OIT.
Während des Zellzykluses werden spezifische regulatorische Proteine, die Cycline exprimiert, die mit ihren spezifischen CDK (Cyclin Dependent Kinases) interagieren und sie hierdurch aktivieren. So interagiert in der frühen G1 Phase Cyclin D1 mit CDK4 und CDK6. Die D-Cyclin kontrollieren gemeinsam mit Cyclin E den G1 Restriktionspunkt. Rb wird durch diese D-Cycline und die assoziierten Kinasen CDK4/6 mehrfach phosphoryliert und kann nun Transkriptionsfaktoren wie E2F nicht mehr inhibieren und die nun freie E2F/ DP-Untereinheit ( = DNS-Bindungsprotein) kann Promotoraktivierung vermitteln und Gene aktivieren, die die S-Phase einleiten. Hiermit wird der Zelle der Fortschritt durch den Zellzyklus ermöglicht bis Rb gegen Ende des Zellzyklus durch Phosphatasen dephoshoryliert wird und die aus der Mitose hervorgegangenen Tochterzellen nach Ende der M-Phase erneut in der G1-Phase sind. CDK-Inhibitoren (CDKI) können diese Cyclin/CDK Komplexe in jeder Zellzyklusphase hemmen und Zellzyklusarrest auslösen. In der vorliegenden Arbeit sollte die Expression von Cyclin D1 und Retinoblastomgens immunhistochemisch untersucht werden. Es wurde versucht, mit der Avidin-Biotin-Enzymkomplexmethode die Proteinexpression des Retinoblastomgens mit einem monoklonalem Antikörper in Probeexzisionen von Mammakarzinomen der Jahre 1983 bis 1987 dazustellen, die in Paraffinum eingebettet waren. Trotz vielfacher Versuchswiederholungen gelang es nicht, eine Kernfärbung hervorzubringen, die wissenschaftlichem Standard genügte. Zum damaligen Zeitpunkt stand noch nicht viel know-how bezüglich der Kernfärbung mittels Antikörpern zur Verfügung. Vor allem nicht bei Präparaten, die bis zu 15 Jahre in Paraffinum eingebetet waren. Somit konnte eine verwertbare Kernfärbung der Gewebeschnitte, das Retinoblastomgen betreffend, nicht nachgewiesen werden und damit war es bedauerlicherweise auch nicht möglich, eine Korrelation zwischen Cyclin D1 und Retinoblastomgen im Mammakarzinom nachzuweisen. Bei der nun verbliebenen Analyse des Cyclin D1 wiesen von 198 Tumoren 10,6% (21 Präparate) eine positive Kernfärbung auf. Hierbei wurden die Präparate, die bei der lichtmikroskopischen Beurteilung der immunhistochemisch gefärbten Zellen einen Prozentsatz von 10% oder größer aufwiesen, wurden als positiv gewertet.13 von den 198 Tumoren zeigten eine Färbbarkeit zwischen 1%-10% auf und wurden per definitionem als negativ gewertet. Hieraus folgt, dass bei 164 Tumoren überhaupt keine Zellkernfärbung stattfand. Es zeigte sich, dass aufgrund der niedrigen positiven Fallzahlen nur schwer eine statische Signifikanz erreichbar sein würde. Das spiegelte unter anderem die Korrelation mit dem Menopausenstatus wieder, die einen p-Wert von 0,273 aufwies und sich hiermit einer statistischen Signifikanz entzog. Auch beim Vergleich von Cyclin D1 mit dem Ostrogen/Progesteron- Rezeptorstatus ist ein verwertbares Ergebnis nicht erreichbar (p=0,08) Eine prognostische Signifikanz des TNM-Stagings konnte bei T:p= 0,496; N:p=0,052 und M:p=0,720 nicht bestätigt werden. Zwar zeigte sich bei der Cyclin D1-Expression der Lymphknoten primär ein grenzwertig positiver Wert von p=0,047. Dieser wurde jedoch durch den kontrollierenden Fisher Exact-Test nicht bestätigt (p=0,052). Ebenfalls konnte keine signifikante Beziehung zum histologischen Tumortyp (p=0,553) und zum Differenzierungsgrad (p=0,575) nachgewiesen werden. Bei den Kaplan-Meier-Analysen in Bezug auf das rezidivfreie Intervall
(p=0,934), das metastasenfreie Intervall (p=0,386) sowie das krankheitsfreie Intervall (p=0,709), konnte kein signifikanter Parameter erhoben werden. Der Einfluss von Cyclin D1 auf das Gesamtüberleben spiegelt letztendlich auch keinen signifikanten Zusammenhang wider (p=0,830). Insgesamt zeigte sich bei keinem Parameter ein signifikanter Bezug. Dies ist wohl, wie auch bei der Versuchsreihe mit dem Retinoblastom, bei dem es ja zu überhaupt keiner verwertbaren Kernfärbung kam, auf das Alter der Probeexcisionen und der damals noch in Entwicklung befindlichen Verfahren zu erklären. Wobei hier nur gemutmaßt werden kann. Eine etablierte Methode jedoch, stand noch nicht zur Verfügung. In den letzten Jahren ist zunehmend wenig Augenmerk dem Gebiet der Cycline und des Retinoblastomgens, besonders im Hinblick auf das Mammakarzinom, gelegt worden. Vielleicht lässt sich mit den jetzigen etablierten Methoden eine Renaissance dieser interessanten Forschungsrichtung erwecken.
On October the 2nd the Colombian people rejected the peace agreement between the government and the FARC in a referendum with a very thin majority of 0.4%. With this unexpected rejection, the referendum was in some ways similar to the Brexit referendum, for the results of which David Cameron was as little prepared as Juan Manuel Santos for his rejection; there was obviously no Plan B. In the last weeks, the government undertook ten changes to the agreement, but it will not go through a referendum again. Santos, as he said, has learned his lesson from the rejection and will seek to have the amended peace agreement approved in Congress. This will likely lead to the implementation of the peace agreement and the furtherance of its goals, such as a DDR process, land reforms, a transitional justice process and reparations for victims, just to mention a few. But this progress in peace will be seen as being at odds with popular opinion. Many of the “no” voters are still not satisfied with the adjustments made by the government and the FARC, and neither are the sectors of the opposition mainly responsible for the rejection. Nevertheless, the government and the FARC are progressing with the implementation, and peace talks with the second-largest – and now the last standing – guerrilla group, the ELN, are scheduled to start in 2017. The prospects for 2018 and onwards, when the presidency election will be held, are more questionable.
The constantly increasing memory density and performance of recent Field Programmable Gate Arrays (FPGA) has boosted a usage in many technical applications such as particle accelerators, automotive industry as well as defense and space. Some of these fields of interest are characterized by the presence of ionizing radiation as caused by natural decay or artificial excitation processes. Unfortunately, this type of radiation affects various digital circuits, including transistors forming Static Random Access Memory (SRAM) storage cells that constitute the technology node for high performance FPGAs. Various digital misbehavior in temporal or permanent manner as well as physical destruction of transistors are the consequence. Therefore, the mitigation of such effects becomes an essential design rule when using SRAM FPGAs in ionizing radiation environments. Tolerance against soft errors can be handled across various layers of modern FPGA design, starting with the most basic silicon manufacturing process, towards configuration, firmware, and system design, until finally ending up with application and software engineering. But only a highly optimized, joint concept of system-wide fault tolerance provides sufficient resilience against ionizing radiation effects without losing too much valuable device resources to the safety approach. This concept is introduced, analyzed, improved and validated in the present work. It includes, but is not limited to, static configuration scrubbing, various firmware redundancy approaches, dynamic memory conservation as well as state machine protection. Guidelines are given to improve manual design practices concerning fault tolerance and tools are shown to reduce necessary efforts. Finally, the SysCore development platform has been maintained to support the recommended design methods and act as Device Under Test (DUT) for all particle irradiation experiments that prove the efficiency of the proposed concept of system-wide fault tolerance for SRAM FPGAs in ionizing radiation environments.