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This dissertation connects two independent fields of theoretical neuroscience: on the one hand, the self-organization of topographic connectivity patterns, and on the other hand, invariant object recognition, that is the recognition of objects independently of their various possible retinal representations (for example due to translations or scalings). The topographic representation is used in the presented approach, as a coordinate system, which then allows for the implementation of invariance transformations. Hence this study shows, that it is possible that the brain self-organizes before birth, so that it is able to invariantly recognize objects immediately after birth. Besides the core hypothesis that links prenatal work with object recognition, advancements in both fields themselves are also presented. In the beginning of the thesis, a novel analytically solvable probabilistic generative model for topographic maps is introduced. And at the end of the thesis, a model that integrates classical feature-based ideas with the normalization-based approach is presented. This bilinear model makes use of sparseness as well as slowness to implement "optimal" topographic representations. It is therefore a good candidate for hierarchical processing in the brain and for future research.
We present simulations with the Chemical Lagrangian Model of the Stratosphere (CLaMS) for the Arctic winter 2002/2003. We integrated a Lagrangian denitrification scheme into the three-dimensional version of CLaMS that calculates the growth and sedimentation of nitric acid trihydrate (NAT) particles along individual particle trajectories. From those, we derive the HNO3 downward flux resulting from different particle nucleation assumptions. The simulation results show a clear vertical redistribution of total inorganic nitrogen ( ), with a maximum vortex average permanent removal of over 5ppb in late December between 500 and 550K and a corresponding increase of of over 2ppb below about 450K. The simulated vertical redistribution of is compared with balloon observations by MkIV and in-situ observations from the high altitude aircraft Geophysica. Assuming a globally uniform NAT particle nucleation rate of 7.8x10-6cm-3h-1 in the model, the observed denitrification is well reproduced.
In the investigated winter 2002/2003, the denitrification has only moderate impact (≤14%) on the simulated vortex average ozone loss of about 1.1ppm near the 460K level. At higher altitudes, above 600K potential temperature, the simulations show significant ozone depletion through -catalytic cycles due to the unusual early exposure of vortex air to sunlight.
This paper discusses the effect of capital regulation on the risk taking behavior of commercial banks. We first theoretically show that capital regulation works differently in different market structures of banking sectors. In lowly concentrated markets, capital regulation is effective in mitigating risk taking behavior because banks' franchise values are low and banks have incentives to pursue risky strategies in order to increase their franchise values. If franchise values are high, on the other hand, the effect of capital regulation on bank risk taking is ambiguous as banks lack those incentives. We then test the model predictions on a cross-country sample including 421 commercial banks from 61 countries. We find that capital regulation is effective in mitigating risk taking only in markets with a low degree of concentration. The results remain robust after accounting for financial sector development, legal system effciency, and for other country and bank-specific characteristics. Keywords: Banks, market structure, risk shifting, franchise value, capital regulation
Background: The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study. Methods: Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated. Results: The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of kappa=0.71 with no significant difference between experienced and less experienced raters. Conclusions: In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future.
Dynamics of relativistic heavy-ion collisions is investigated on the basis of a simple (1+1)-dimensional hydrodynamical model in light-cone coordinates. The main emphasis is put on studying sensitivity of the dynamics and observables to the equation of state and initial conditions. Low sensitivity of pion rapidity spectra to the presence of the phase transition is demonstrated, and some inconsistencies of the equilibrium scenario are pointed out. Possible non-equilibrium effects are discussed, in particular, a possibility of an explosive disintegration of the deconfined phase into quark-gluon droplets. Simple estimates show that the characteristic droplet size should decrease with increasing the collective expansion rate. These droplets will hadronize individually by emitting hadrons from the surface. This scenario should reveal itself by strong non-statistical fluctuations of observables. Critical Point and Onset of Deconfinement 4th International Workshop July 9-13 2007 GSI Darmstadt,Germany
Event-by-event multiplicity fluctuations in nucleus-nucleus collisions from low SPS up to RHIC energies have been studied within the HSD transport approach. Fluctuations of baryonic number and electric charge also have been explored for Pb+Pb collisions at SPS energies in comparison to the experimental data from NA49. We find a dominant role of the fluctuations in the nucleon participant number for the final hadron multiplicity fluctuations and a strong influence of the experimental acceptance on the final results. Critical Point and Onset of Deconfinement - 4th International Workshop July 9 - 13, 2007 Darmstadt, Germany
Statistical physics of power flows on networks with a high share of fluctuating renewable generation
(2010)
Renewable energy sources will play an important role in future generation of electrical energy. This is due to the fact that fossil fuel reserves are limited and because of the waste caused by conventional electricity generation. The most important sources of renewable energy, wind and solar irradiation, exhibit strong temporal fluctuations. This poses new problems for the security of supply. Further, the power flows become a stochastic character so that new methods are required to predict flows within an electrical grid. The main focus of this work is the description of power flows in a electrical transmission network with a high share of renewable generation of electrical energy. To define an appropriate model, it is important to understand the general set-up of a stable system with fluctuating generation. Therefore, generation time series of solar and wind power are compared to load time series for whole Europe and the required balancing or storage capacities analyzed. With these insights, a simple model is proposed to study the power flows. An approximation to the full power flow equations is used and evaluated with Monte-Carlo simulations. Further, approximations to the distributions of power flows along the links are analytically derived. Finally, the results are compared to the power flows calculated from the generation and load data.
Nanggroe Aceh Darussalam is a multicultural province within a multicultural state. Hence, its political leaders not only face the need to integrate ethnic and cultural diversity into a regional framework, but also have to define Aceh’s role within the Indonesian nation. During its violent past which was characterized by exploitation and military oppression, there were good reasons to emphasize sameness over diversity and to build up the consciousness of a unified Acehnese identity. From both an emic and an etic perspective, it is today widely accepted that there is such a thing as a homogeneous Acehnese culture which is rooted in a glorious, though troublesome, history of repression and rebellion and shaped by a strong Islamic piety. Even if it is true that Acehnese history has created a strong regional identity, it must not be forgotten that people living in this area belong to various ethnic and cultural groups and that they represent a rich variety of different cultures rather than simply a single homogeneous culture. As a matter of fact, the practises and discourses of Islam here also vary depending on the cultural background of the people. As elsewhere in Indonesia and beyond, world religions have to adapt to local customs, have to be appropriated by the local people, and have to be indigenized. This is the reason why adat still continues to play a role in every local context, even if it has been treated with suspicion in many parts of Indonesia since the Dutch colonial administration began using it as a counterforce against Islam in order to implement their divide-and-rule strategy. With this article, I wish to shed some light on the complexities of Acehnese culture, as it encompasses numerous very distinct local cultures and this reflects on the general significance of culture for the construction and reconstruction of post-tsunami Aceh.
Yuniyanti Chuzaifah is one of the founders of "Voice of Concerned Mothers" (Suara Ibu Peduli or SIP) and later joined the "Coalition of Indonesian Women" (Koalisi Perempuan Indonesia or KPI). She studied at the Universities of Leiden and Amsterdam in the Netherlands, and later returned to Indonesia. Since March 2010 she has been the Director of the "Indonesian National Commission on Violence against Women" (Komnas Perempuan). This interview was conducted on 15 March 2010 at the organisation’s premises in Jakarta.
Indonesia is a multicultural and multireligious nation whose heterogeneity is codified in the state doctrine, the Pancasila. Yet the relations between the various social, ethnic, and religious groups have been problematic down to the present day, and national unity has remained fragile. In several respects, Christians have a precarious role in the struggle for shaping the nation. They are a small minority (about 9% of the population) in a country predominantly inhabited by Muslims; in the past they were interconnected in manifold ways with the Dutch colonial government; they exert great influence in economy and the military, and constitute the majority of the population in some parts of the so-called Outer Islands (such as Flores, Sumba, and Timor), which are characterized by an attitude fraught with ambivalence towards the state apparatus perceived as ‘Javanese’ and ‘Muslim’. In the aftermath of the former president Suharto’s resignation and in the course of the ensuing political changes – in particular the independence of East Timor – Christians were repeatedly discredited for allegedly posing a threat to Indonesian unity, and have been involved both as victims and perpetrators in violent regional clashes with Muslims that claimed thousands of lives. Since the beginning of the new millennium the violent conflicts have lessened, yet the pressure exerted on Christians by Islamic fundamentalists still continues undiminished in the Muslim-majority regions. The future of the Christians in Indonesia remains uncertain, and pluralist society is still on trial. For this reason the situation of Christians in Indonesia is an important issue that goes far beyond research on a minority, touching on general issues relating to the formation of the nation-state.
From the very outset of European expansion, scholars have been preoccupied with the impact of proselytization and colonization on non-European societies. Anthropologists such as Margaret Mead and Bronislaw Malinowski, who witnessed these processes at the beginning of the twentieth century while at the same time benefitting from the colonial structure, were convinced that the autochthonous societies could not possibly withstand the onslaught of the dominant European cultures, and thus were doomed to vanish in the near future. The fear of losing their object of research, which had just recently been discovered, hung above the heads of the scholars like a sword of Damocles ever since the establishment of anthropology as a discipline. They felt hurried to document what seemed to be crumbling away. Behind these fears there was the notion that the indigenous cultures were comparatively static entities that had existed untouched by any external influences for many centuries, or even millennia, and were unable to change. This idea was shared by proponents of other disciplines; in religious studies, for example, up to the late 1980s the view prevailed that the contact between the great world religions and the belief systems of small, autochthonous societies doomed the latter to extinction. However, more recent studies have shown that this assumption, according to which indigenous peoples have not undergone any changes in the course of history, is untenable. It became apparent that groups supposedly living in isolation have extensive contact networks, and that migration, trade, and conquest are not privileges of modern times. Myths and oral traditions bore witness of journeys to faraway regions, new settlements founded in unknown territories, or the arrival of victorious foreigners who introduced new ways and customs and laid claim to a place of their own within society.
Der L-Carnitin/gamma-Butyrobetain Antiporter CaiT ist ein Mitglied der Betain/Carnitin/Cholin Transporter (BCCT) Familie. Sekundärtransporter der BCCT Familie transportieren Substrate, die eine positiv-geladene quartäre Ammoniumgruppe besitzen. CaiT besteht aus 504 Amiosäuren und besitzt ein moleculares Gewicht von etwa 56 kDa. In Enterobakterien wie Escherichia coli, Proteus mirabilis und Salmonella typhimurium wird die Expression des caiTABCDE Operons unter anaeroben Bedingungen induziert. Unter diesen Bedinungen ist CaiT der Haupttransporter des Betain-Derivates L-Carnitin. In Enterobakterien wird L-Carnitin unter anaeroben Bedingungen aufgenommen und dehydratisiert wobei Crotonobetain ensteht. Crotonobetain wird anschließend zum Endprodukt gamma-Butyrobetain reduziert. Gamma-Butyrobetain ist das Gegensubstrat, das aus der Zelle hinaustransportiert wird, wenn L-Carnitin in die Zelle aufgenommen wird. Der Austauschmechanismus von LCarnitin gegen gamma-Butyrobetain geschieht ohne das Vorhandensein eines elektrochemischen Gradients, d.h. CaiT ist sowohl H+- als auch Na+-unabhängig. Ein Ziel dieser Arbeit war es die drei-dimensionale (3D) Struktur von CaiT mittels Röntgenstrukturanalyse zu lösen. Weiterhin sollten mit Hilfe der 3D-Struktur und funktionellen Studien detailiertere Erkenntnisse über den kationenunabhängigen Antiportmechanismus von CaiT ermittelt werden. Im Rahmen dieser Arbeit wurden die 3D-Röntgenkristallstrukturen von drei CaiT-Homologen der Enterobakterien P. mirabilis (PmCaiT), E. coli (EcCaiT) und S. typhimurium (StCaiT) mittels molekularem Ersatz (engl.: molecular replacement, MR) mit einem Alanin-Model des CaiT verwandten Na+/Glycinbetain Symporters BetP gelöst. PmCaiT konnte mit einer Auflösung von 2.3 Å gelöst werden. Das Protein kristallisierte in der Kristallraumgruppe H3, mit drei Molekülen in der asymmetrischen Einheit (engl.: asymmetric unit, AU). Die drei PmCaiT-Moleküle ordneten sich innerhalb der AU um eine kristallographische dreifach Symmetrieachse an. EcCaiT wurde mittels MR mit einem Alanin-Model von PmCaiT bei einer Auflösung von 3.5 Å gelöst. EcCaiT kristallisierte in der Kristallraumgruppe P32, ebenfalls mit drei Molekülen in der AU, jedoch ohne kristallographische Symmetry. Während der Verfeinerung des EcCaiT-Models wurde eine strenge dreifache nichtkristallographische Symmetry (engl.: non-crystallographic symmetry, NCS) angewandt. StCaiT, das ebenfalls mittels MR mit einem Alanin-Model von PmCaiT, aber bei einer Auflösung von 4.0 Å gelöst wurde, kristallisierte in der Kristallraumgruppe P65, ebenfalls mit drei StCaiT-Molekülen in der AU, ohne kristallographische Symmetry. Bei der Verfeinerung des StCaiT-Modells wurde wie bei EcCaiT eine strenge NCS angewandt. Da die Auflösung von 4.0 Å bei StCaiT zu niedrig ist um detailierte moleculare Erkenntnisse zu gewinnen, wurden Protein- sowie Substratinteraktionen nur an den Strukturen von PmCaiT und EcCaiT analysiert. Alle drei CaiT-Homologe weisen jedoch einen ähnlichen strukturellen Aufbau auf. In der Röntgenkristallstruktur bildet CaiT ein symmetrisches Trimer, das über ionische und polare Wechselwirkungen zwischen den Protomeren stabilisiert wird. Der trimere Oligomerisierungszustand von CaiT in Detergenzlösung sowie in zweidimensionalen Lipidmembrankristallen wurde bereits in früheren Arbeiten gezeigt. Jedes der drei CaiT-Protomere besteht aus zwölf Transmembranhelices (TMH), die N- und C-terminalen Domänen des Proteins befinden sich auf der cytoplasmatischen Seite. Zehn der TMH bilden zwei invertierte Wiederholungseinheiten aus jeweils fünf TMH. Die erste Einheit besteht aus den TMH 3 – 7, die invertierte zweite Einheit besteht aus den TMH 8 – 12. Beide Wiederholungseinheiten sind strukturell nahezu identisch und lassen sich fast vollständig übereinanderlegen, jedoch weisen die Aminosäuren der beiden Einheiten keine signifikante Sequenzidentität auf. Die ersten beiden Helices der Wiederholungseinheiten, die TMH 3 – 4 und die TMH 8 – 9, bilden ein antiparalleles vier-Helix-Bündel, in dem in CaiT zwei Substratbindestellen lokalisiert sind. Eine derartige Transporterarchitektur wurde erstmals in der Struktur des Na+/Alanin Symporters LeuTAa des thermophilen Bakteriums Aquifex aeolicus gezeigt. Bislang wurden, inklusive CaiT, sieben Sekundärtransporterstrukturen gelöst, die diese LeuT-Transporterarchitektur aufweisen. Ungewöhnlich dabei ist, dass diese sieben Sekundärtransporter fünf verschiedenen Transporterfamilien angehören und eine Verwandschaft auf Basis der Aminosäuren nicht zu finden ist. Da jedoch die tertiäre Struktur dieser Tansporter konserviert ist, kann davon ausgegangen werden, dass sie alle von einem Urprotein entstanden sind, welches zunächst aus fünf TMH bestanden haben muss. Im Laufe der Evolution hat sich das Urgen des Urproteins zunächst dupliziert und die weitere Evolution hat zwar die Aminosäuresequenz verändert und den Umweltbedingungen angepasst, jedoch ist die tertiäre Struktur erhalten geblieben. Da sich die tertiäre Struktur der sieben Sekundärtransporter so stark ähnelt, ist zu vermuten, dass auch der Transportmechanismus ähnlich, jedoch nicht identisch ist. Nach dem strukturellen Aufbau der Transporter, der Lage der Substratbindestellen in den jeweiligen Transportern und der Tatsache, dass es sich bei diesen Proteinen um Membranproteine handelt, wurde ein Transportmechanismus aufgestellt, in dem die Bindestelle des zu transportierende Substrats alternierend zu beiden Seiten der Membran zugänglich ist, ohne jedoch jemals den Substratweg innerhalb des Proteins vollständig zu öffnen. Dieser Mechanismus wurde als “alternating access mechanism” beschrieben. Anhand der unterschiedlichen Zustände, in denen einige der Transporter kristallisierten, kann abgeleitet werden, welche Konformationsänderungen erforderlich sind um das Substrat von einer Seiter der Membran auf die andere zu transportieren. Bisher kristallisierten einzelne der sechs Transporter in der nach außen gerichteten offenen Form, der nach außen gerichteten Form, in der die Substratbindestelle jedoch nicht mehr zugänglich ist, in einer Form, die keine Öffnungspräferenz der Substratbindestelle zu einer Seite der Membran hat und in der nach innen gerichteten Form, in der die Substratbindestelle jedoch nicht geöffnet ist. CaiT kristallisierte in der noch fehlenden Konformation, der nach innen gerichteten Form, in der die Substratbindestelle zugänglich ist. Mit dieser noch fehlenend Konformation kann der Transportzyklus des “alternating access mechanism” vollständig beschrieben werden. Alle drei CaiT-Homologe kristallisierten in der nach innen gerichteten, offenen Konformation. Im Gegensatz zur EcCaiT-Struktur kristallisierte PmCaiT in der substratungebundenen Form. In der StCaiT-Struktur konnte aufgrund der niedrigen Auflösung kein Substrat nachgewiesen werden. In der EcCaiT-Struktur sind zwei gamma-Butyrobetain-Moleküle gebunden. Das erste Molekül wurde in der zentralen Substratbindestelle, der sogenannten Tryptophan-Box bestehend aus vier Tryptophanen, im Zentrum des Protein lokalisiert. Das zweite gamma-Butyrobetain-Molekül wurde in einer Vertiefung an der extrazellulären Proteinoberfläche gefunden. Beide Substrate werden hauptsächlich über Kation-Pi-Interaktionen zwischen der positiv geladenen quatären Ammoniumgruppe des Substrats und des Pi-Elektronensystems der Tryptophane in den jeweiligen Bindestellen gebunden. Eine besondere Eigenschaft von CaiT ist der H+- bzw. Na+-unabhängige Substrattransport. Die CaiT-Struktur erklärt warum kein zusätzliches Kation benötigt wird um Substrat zu binden oder zu transportieren. In der EcCaiT-Struktur ist eine wichtige polare nicht-bindende Interaktion zwischen der Carboxylgruppe des gamma-Butyrobetains und dem Schwefelatom eines Methionins in der zentrale Bindestelle zu erkennen. Dieses Methionin ist konserviert in den prokaryotischen CaiTs und in den Na+-unabhängigen eukaryotischen L-Carnitin Transportern (OCTN), jedoch ist es nicht konserviert im Na+-abhängigen verwandten Glycinbetain Transporter BetP. In BetP ist diese Position des Methionins durch ein Valin ersetzt. Die Mutation des Methionins in CaiT zu Valin ermöglicht zwar immernoch die H+- bzw. Na+-unabhängige Bindung des Substrates durch die Tryptophan-Box, jedoch ist der Substrattransport nahezu vollständig zerstört. Eine derart wichtige Substratkoordinierende Funktion des Schwefelatoms eines Methionins wurde bisher nicht beschrieben. Eine weitere Stelle, die in H+- bzw. Na+-abhängigen Transporter mit H+ bzw. Na+ besetzt ist, ist in CaiT von einem positiv geladenen Arginin eingenommen. Eine positive Ladung an dieser Stelle stabilisiert den Bereich im Protein in der Nähe der zentralen Substratbindestelle. Die Mutation des Arginins zu Glutamat in CaiT erzielt eine vollständige Inaktivierung des Substrattansports. Durch Zugabe von Na+ im Transportansatz kann die Substrattransportaktivität der Glutamat-Mutante jedoch teilweise zurückerlangt werden. Diese eben beschriebenen Aminosäurereste in den beiden Stellen des Proteins erklären die Kationenunabhängigkeit von CaiT. Die Aktivierung des Antiportmechanismus in CaiT wurde mit Hilfe von Bindungsstudien an rekonstituiertem Protein ermittelt. Diese Messungen ergaben für das Wildtypprotein ein sigmoidales Substratbindungsverhalten, was auf ein positiv-kooperatives Bindungsverhalten hindeutet. Die beiden Substratbindestellen im Protein sowie die beiden unterschiedlichen Substrate, L-Carnitin und gamma-Butyrobetain, lassen auf einen heterotropen positiv-kooperativen Bindungs- und einen allosterisch regulierten Transportmechanismus schließen. Bei diesem Mechanismus erhöht die Bindung eines Substrats in der regulatorischen Bindestelle durch induzierte Konformationsänderungen die Affinität eines anderen Substrats in einer weiteren Substratbindestelle. Die regulatorische Bindestelle in CaiT befindet sich an der extrazellulären Proteinoberfläche. Eine Schwächung der Substrataffinität in dieser Bindestelle durch Einführung einer Mutation, verstärkt das sigmoidale Substratbindungsverhalten und hat einen negativen Einfluss auf den Substrattransport. Durch die in dieser Arbeit gelösten 3D-Röntgenkristallstrukturen der zwei CaiT-Homologen, PmCaiT und EcCaiT, sowie den durchgeführten funktionellen Studien sowohl an Wildtypprotein wie auch an Mutanten konnte ein L-Carnitin/gamma-Butyrobetain Antiport-Mechanismus für CaiT vorzuschlagen werden.
Over the past two decades the “one drug – one target – one disease” concept became the prevalent paradigm in drug discovery. The main idea of this approach is the identification of a single protein target whose inhibition leads to a successful treatment of the examined disease. The predominant assumption is that highly selective ligands would avoid unwanted side effects caused by binding to secondary non-therapeutic targets. In recent years the results of post-genomic and network biology showed that proteins rarely act in isolated systems but rather as a part of a highly connected network [1]. In addition this connectivity leads to more robust systems that cannot be interfered by the inhibition of a single target of that network and consequently might not lead to the desired therapeutic effect [2]. Furthermore studies prove that robust systems are rather affected by weak inhibitions of several parts than by a complete inhibition of a single selected element of that system [3]. Therefore there is an increasing interest in developing drugs that take effect on multiple targets simultaneously but is concurrently a great challenge for medicinal chemists. There has to be a sufficient activity on each target as well as an adequate pharmacokinetic profile [4]. Early design strategies tried to link the pharmacophors of known inhibitors, however these methods often lead to high molecular weight and low ligand efficacy. We present a new rational approach based on a retrosynthetic combinatorial analysis procedure [5] on approved ligands of multiple targets. These RECAP fragments are used to design a large combinatorial library containing molecules featuring chemical properties of each ligand class. The molecules are further validated by machine learning models, like random forests and self-organizing maps, regarding their activity on the targets of interest.
Introduction: Systemic inflammation (e.g. following surgery) involves Toll-like receptor (TLR) signaling and leads to an endocrine stress response. This study aims to investigate a possible influence of TLR2 and TLR4 single nucleotide polymorphisms (SNPs) on perioperative adrenocorticotropic hormone (ACTH) and cortisol regulation in serum of cardiac surgical patients. To investigate the link to systemic inflammation in this context, we additionally measured 10 different cytokines in the serum. Methods: 338 patients admitted for elective cardiac surgery were included in this prospective observational clinical cohort study. Genomic DNA of patients was screened for TLR2 and TLR4 SNPs. Serum concentrations of ACTH, cortisol, interferon (IFN)-, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)- and granulocyte macro-phage-colony stimulating factor (GM-CSF) were determined before surgery, immediately post surgery and on the first postoperative day. Results: 13 patients were identified as TLR2 SNP carrier, 51 as TLR4 SNP carrier and 274 pa-tients as non-carrier. Basal levels of ACTH, cortisol and cytokines did not differ between groups. In all three groups a significant, transient perioperative rise of cortisol could be ob-served. However, only in the non-carrier group this was accompanied by a significant ACTH rise, TLR4 SNP carriers had significant lower ACTH levels compared to non-carriers ((mean[95% confidence intervals]) non-carriers: 201.9[187.7 to 216.1]pg/ml; TLR4 SNP car-riers: 149.9[118.4 to 181.5]pg/ml; TLR2 SNP carriers: 176.4[110.5 to 242.3]pg/ml). Compared to non-carriers, TLR4 SNP carriers showed significant lower serum IL-8, IL-10 and GM-CSF peaks ((mean[95% confidence intervals]): IL-8: non-carriers: 42.6[36.7 to 48.5]pg/ml, TLR4 SNP carriers: 23.7[10.7 to 36.8]pg/ml; IL-10: non-carriers: 83.8[70.3 to 97.4]pg/ml, TLR4 SNP carriers: 54.2[24.1 to 84.2]pg/ml; GM-CSF: non-carriers: 33.0[27.8 to 38.3]pg/ml, TLR4 SNP carriers: 20.2[8.6 to 31.8]pg/ml). No significant changes over time or between the groups were found for the other cytokines. Conclusions: Regulation of the immunoendocrine stress response during systemic inflamma-tion is influenced by the presence of a TLR4 SNP. Cardiac surgical patients carrying this ge-notype showed decreased serum concentrations of ACTH, IL-8, IL-10 and GM-CSF. This finding might have impact on interpreting previous and designing future trials on diagnosing and modulating immunoendocrine dysregulation (e.g. adrenal insufficiency) during systemic inflammation and sepsis.
Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae
(2011)
Bartonella henselae, the agent of cat scratch disease and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis, contains to date two groups of described pathogenicity factors: adhesins and type IV secretion systems. Bartonella adhesin A (BadA), the Trw system and possibly filamentous hemagglutinin act as promiscous or specific adhesins, whereas the virulence locus (Vir)B/VirD4 type IV secretion system modulates a variety of host cell functions. BadA mediates bacterial adherence to endothelial cells and extracellular matrix proteins and triggers the induction of angiogenic gene programming. The VirB/VirD4 type IV secretion system is responsible for, e.g., inhibition of host cell apoptosis, bacterial persistence in erythrocytes, and endothelial sprouting. The Trw-conjugation system of Bartonella spp. mediates host-specific adherence to erythrocytes. Filamentous hemagglutinins represent additional potential pathogenicity factors which are not yet characterized. The exact molecular functions of these pathogenicity factors and their contribution to an orchestral interplay need to be analyzed to understand B. henselae pathogenicity in detail.
PERIOD proteins are central components of the Drosophila and mammalian circadian clocks. The crystal structure of a Drosophila PERIOD (dPER) fragment comprising two PER-ARNT-SIM (PAS) domains (PAS-A and PAS-B) and two additional C-terminal alpha-helices (alphaE and alphaF) has revealed a homodimer mediated by intermolecular interactions of PAS-A with tryptophane 482 in PAS-B and helix alphaF. Here we present the crystal structure of a monomeric PAS domain fragment of dPER lacking the alphaF helix. Moreover, we have solved the crystal structure of a PAS domain fragment of the mouse PERIOD homologue mPER2. The mPER2 structure shows a different dimer interface than dPER, which is stabilized by interactions of the PAS-B beta-sheet surface including tryptophane 419 (equivalent to Trp482dPER). We have validated and quantitatively analysed the homodimer interactions of dPER and mPER2 by site-directed mutagenesis using analytical gel filtration, analytical ultracentrifugation, and co-immunoprecipitation experiments. Furthermore we show, by yeast-two-hybrid experiments, that the PAS-B beta-sheet surface of dPER mediates interactions with TIMELESS (dTIM). Our study reveals quantitative and qualitative differences between the homodimeric PAS domain interactions of dPER and its mammalian homologue mPER2. In addition, we identify the PAS-B beta-sheet surface as a versatile interaction site mediating mPER2 homodimerization in the mammalian system and dPER-dTIM heterodimer formation in the Drosophila system.
The title I have chosen seems to signal a tension, even a contradiction, in a number of respects. Democracy appears to be a form of political organisation and government in which, through general and public participatory procedures, a sufficiently legitimate political will is formed which acquires the force of law. Justice, by contrast, appears to be a value external to this context which is not so much linked to procedures of “input” or “throughput” legitimation but is understood instead as an output- or outcome-oriented concept. At times, justice is even understood as an otherworldly idea which, when transported into the Platonic cave, merely causes trouble and ends up as an undemocratic elite project. In methodological terms, too, this difference is sometimes signalled in terms of a contrast between a form of “worldly” political thought and “abstract” and otherworldly philosophical reflection on justice. In my view, we are bound to talk past the issues to be discussed under the heading “transnational justice and democracy” unless we first root out false dichotomies such as the ones mentioned. My thesis will be that justice must be “secularised” or “grounded” both with regard to how we understand it and to its application to relations beyond the state.
In this thesis, laboratory investigations have been conducted to investigate several processes occurring during the melt segregation (crystal settling and compaction processes), as well as during emplacement of plutons. With the help of three different sets of centrifuge experiments rates of these three magmatic processes have been evaluated. In the first series of the centrifuge experiments, the diapiric ascent of buoyant material from two source layers at different depths was studied. Through five models, the hypothesis of ascending diapirs was tested and it was demonstrated whether a rising diapir ascends straight upward or if its ascent might be deviated by another buoyant, softer – and consequently easier to travel through – layer which is located within the overburden strata. We were interested under which conditions they can be formed. For this purpose we placed perturbations on top of both the buoyant layers; either with a set-off of both the protrusions (for three of these experiments), or with both protrusion sitting directly on top of each other (for one of the experiments). In the first experiment, we omitted the perturbations, to test which pathways diapirs take which grow from natural Rayleigh-Taylor instabilities. Three others experiments differed in the viscosity contrast between the overburden and the buoyant material. Through the experimental runs, the effects of different overburden viscosities and perturbation positions on the number of the diapirs were observed. The modeling results show that two diapirs rising from the offset perturbations do not take the same pathway through the overburden layer. Rather, each diapir takes a different pathway, with the deeper diapir piercing through its overburden while rising, regardless if it was a buoyant layer or denser overburden layers. However, when the two perturbations were situated directly above each other in the different PDMS layers, this resulted in the formation of one big diapir rather than several smaller ones, and the overburden layer was less deformed than with offset perturbations. Diapiric structures as those derived from the models without perturbation and where the perturbation are offset occur within Great Kavir Basin (Iran), where numerous salt diapirs grew from several salt horizons, which show a similar spatial distribution. The resulting structure observed in the model where the two perturbations situated directly above each other, is close to what is observed in composite batholiths such as the Flasergranitoid Zone within the Bergsträßer Odenwald Crystalline Complex (Germany). The second series of models were aimed to study crystal settling within a magma. For this purpose experiments with an artificial magma of 30 vol% olivine in 70 vol% basaltic melt were conducted to elucidate the formation mechanisms and time scales of gravitational cumulates. Through the experiments, two physical processes have been observed: (i) purely mechanical compaction, and (ii) chemical compaction induced by dissolution and re-precipitation of settled crystals. The results reveals that the mechanical settling of the dense olivine suspension occurs at about 1/6 the speed of simple Stokes settling, and a sedimentation exponent n of 4.1 is found. Evidences of chemical compaction induced by dissolution and re-precipitation of settled crystals have been highlighted by a detailed analysis of the fine structure of olivine grain boundaries. This last has revealed (1) the presence of Ca, which is characteristic only for MORB-melt, at the interface of two adjacent Ol-grains even when no melt is present; (2) a not fully crystallized boundary layer between two adjacent olivine grains. The crystal size distribution curves and the grain size growth exponent n ~3.6 indicate that diffusion controlled Ostwald ripening is the dominant crystal growth mechanism in concentrated magmatic suspensions. Finally, the formation times in natural olivine adcumulates have been calculated. The last series of centrifuge experiments deals with the crystal-melt settling-floating mechanism in a system composed of natural two pyroxene gabbro. The results have revealed a vertical evolution of the major and trace elements in the melt phase. Then, a numerical modelling of the sedimentation process of the crystals has been made in order to describe the compaction evolution with time. In comparing the numerical simulation with the centrifuge modelling, the stratification of the compacted layer in the runs is reproduced in numerical models. Moreover, on the base of the numerical and centrifuge modelling, a sedimentation exponent describing a deviation of settling in concentrated suspensions from Stokes sedimentation has been evaluated. Finally, the numerical simulation is applied to the Muskox intrusion to estimate the formation time and the melt fraction evolution in using the hindered sedimentation model calculations.
In the next years the Facility for Antiproton and Ion Research FAIR will be constructed at the GSI Helmholtzzentrum fur Schwerionenforschung in Darmstadt, Germany. This new accelerator complex will allow for unprecedented and pathbreaking research in hadronic, nuclear, and atomic physics as well as in applied sciences. This manuscript will discuss some of these research opportunities, with a focus on few-body physics.
The energy dependence of the local and violation in Au+Au and Cu+Cu collisions in a large energy range is estimated within a simple phenomenological model. It is expected that at LHC the chiral magnetic effect will be about 20 times weaker than at RHIC. At lower energy range, covered by the low-energy scan at RHIC and future NICA/FAIR facilities, the created magnetic field strength and energy density of deconfined matter are rather high providing necessary conditions for the chiral magnetic effect. However, the particular model for the chiral magnetic effect predicts that this effect should vanish sharply at energy somewhere above the top SPS one. To elucidate CME background effects the Hadron-String-Dynamics (HSD) transport model including electromagnetic fields is put forward. Importance of new planning experiments at LHC and for the low-energy RHIC scan program is emphasized.
Effects of nuclear orientation on fusion and fission in the reaction using 238U target nucleus
(2010)
Fission fragment mass distributions in the reaction of 30Si+238U were measured around the Coulomb barrier. At the above-barrier energies, the mass distribution showed a Gaussian shape. At the subbarrier energies, triple-humped distribution was observed, which consists of symmetric fission and asymmetric fission peaked at AL/AH ~ 90/178. The asymmetric fission should be attributed to quasifission from the results of the measured evaporation residue (ER) cross-sections for 30Si+238U. The cross-section for 263Sg at the abovebarrier energy agree with the statistical model calculation which assumes that the measured fission cross-section originates from fusion-fission, whereas the one for 264 Sg measured at the sub-barrier energy is smaller than the calculation, which suggests the presence of quasifission.
We examine the scaling trends in particle multiplicity and flow observables between SPS, RHIC and LHC, and discuss their compatibility with popular theoretical models. We examine the way scaling trends between SPS and RHIC are broken at LHC energies, and suggest experimental measurements which can further clarify the situation.
The mass-dependent structure of the composite nucleus is shown based on three-dimensional timedependent Hartree-Fock calculations with Skyrme interactions (SLy4d and SkM*). One remarkable result is that the isovector monopole excitation dominantly appears for collisions of heavy nuclei, and the isovector dipole excitation for those of light ones. Such a difference found in the dynamical structure of composite nucleus plays a role in the equilibration of charge.
We derive the equations of second order dissipative fluid dynamics from the relativistic Boltzmann equation following the method of W. Israel and J. M. Stewart [1]. We present a frame independent calculation of all first- and second-order terms and their coefficients using a linearised collision integral. Therefore, we restore all terms that were previously neglected in the original papers of W. Israel and J. M. Stewart.