Myoglobin from the burrowing reptile Amphisbaena alba: concentrations and functional characteristics

1. 1. Myoglobin from the subterranean reptile Amphisbaena alba was isolated for measurement of concentrations and physico-chemical properties. 2. 2. The concentrations (averaging 12.1 mg.g-1 wet weight in the temporal muscles and 5.8-6.0 in the muscles that motivate the wedge-shaped head which forms the burrowing tool) far exceed those earlier reported for reptiles and other terrestrial vertebrates. 3. 3. The myoglobin has a low O2 affinity compared to mammals (P50 = 2mmHg at 25°C). In the presence of the same myoglobin O2 tension as in mammals this appears to favour similar in vivo O2 saturations at the lower reptilian body temperature. 4. 4. The temperature sensitivity of P50 reflect a heat of oxygenation, ΔH near -13 kcal· mol-1. The myoglobin is monomeric and thus lacks cooperativity in O2 binding and there is no Bohr effect. 5. 5. The pattern of microheterogeneity is similar to that of myoglobin of terrestrial vertebrates but different to aquatic mammals and reptiles. The major and two minor components exhibit very similar O2 affinities. 6. 6. The concentrations and oxygen-binding characteristics of Amphisbaena myoglobin are discussed with regard to the flow of O2 to the mitochondria during digging activity in hypoxic burrow environments. © 1981.

Spectroscopic Study on the Structural Differences of Thermally Induced Cross-Linking Segments in Emeraldine Salt and Base Forms of Polyaniline

This paper reports the spectroscopic study on the structural differences of thermally induced cross-linking segments in polyaniline in its emeraldine salt (PANI-ES) and base (PANI-EB) forms. Casting films of PANI-ES (ES-film) and PANI-EB (EB-film) were prepared and heated at 150 degrees C under atmospheric air for 30 min. Raman spectra excited at 632.8 nm of heated ES-film presented the characteristic bands of phenazine-like structures at 1638, 1392, and 575 cm(-1), whereas EB-film showed lower relative intensities for these bands. The lower content of phenazine-like segments in heated EB-film is related to residual polaronic segments from preparation procedures, as revealed by Raman. This statement was confirmed by a sequence of thermal and doping experiments in both films. Quantum-chemical calculations by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) showed that the phenazine-like structure presents the intense Raman band at 1350 cm(-1) due to heterocycle breathing mode, and the non-phenazine-like structure (substituted hydrophenazine-type) presents higher energy for HOMO-LUMO transition, indicating the lack of conjugation in the heterocycle compared with the phenazine-like structure. According to experimental and theoretical data reported here, it is proposed that only thermally treated PANI-ES presents phenazine-like rings, whereas PANI-EB presents heterocyclic non-aromatic structures.

Architectures and design patterns for functional design of logic control and diagnostics in industrial automation

Recently in most of the industrial automation process an ever increasing degree of automation has been observed. This increasing is motivated by the higher requirement of systems with great performance in terms of quality of products/services generated, productivity, efficiency and low costs in the design, realization and maintenance. This trend in the growth of complex automation systems is rapidly spreading over automated manufacturing systems (AMS), where the integration of the mechanical and electronic technology, typical of the Mechatronics, is merging with other technologies such as Informatics and the communication networks. An AMS is a very complex system that can be thought constituted by a set of flexible working stations, one or more transportation systems. To understand how this machine are important in our society let considerate that every day most of us use bottles of water or soda, buy product in box like food or cigarets and so on. Another important consideration from its complexity derive from the fact that the the consortium of machine producers has estimated around 350 types of manufacturing machine. A large number of manufacturing machine industry are presented in Italy and notably packaging machine industry,in particular a great concentration of this kind of industry is located in Bologna area; for this reason the Bologna area is called “packaging valley”. Usually, the various parts of the AMS interact among them in a concurrent and asynchronous way, and coordinate the parts of the machine to obtain a desiderated overall behaviour is an hard task. Often, this is the case in large scale systems, organized in a modular and distributed manner. Even if the success of a modern AMS from a functional and behavioural point of view is still to attribute to the design choices operated in the definition of the mechanical structure and electrical electronic architecture, the system that governs the control of the plant is becoming crucial, because of the large number of duties associated to it. Apart from the activity inherent to the automation of themachine cycles, the supervisory system is called to perform other main functions such as: emulating the behaviour of traditional mechanical members thus allowing a drastic constructive simplification of the machine and a crucial functional flexibility; dynamically adapting the control strategies according to the different productive needs and to the different operational scenarios; obtaining a high quality of the final product through the verification of the correctness of the processing; addressing the operator devoted to themachine to promptly and carefully take the actions devoted to establish or restore the optimal operating conditions; managing in real time information on diagnostics, as a support of the maintenance operations of the machine. The kind of facilities that designers can directly find on themarket, in terms of software component libraries provides in fact an adequate support as regard the implementation of either top-level or bottom-level functionalities, typically pertaining to the domains of user-friendly HMIs, closed-loop regulation and motion control, fieldbus-based interconnection of remote smart devices. What is still lacking is a reference framework comprising a comprehensive set of highly reusable logic control components that, focussing on the cross-cutting functionalities characterizing the automation domain, may help the designers in the process of modelling and structuring their applications according to the specific needs. Historically, the design and verification process for complex automated industrial systems is performed in empirical way, without a clear distinction between functional and technological-implementation concepts and without a systematic method to organically deal with the complete system. Traditionally, in the field of analog and digital control design and verification through formal and simulation tools have been adopted since a long time ago, at least for multivariable and/or nonlinear controllers for complex time-driven dynamics as in the fields of vehicles, aircrafts, robots, electric drives and complex power electronics equipments. Moving to the field of logic control, typical for industrial manufacturing automation, the design and verification process is approached in a completely different way, usually very “unstructured”. No clear distinction between functions and implementations, between functional architectures and technological architectures and platforms is considered. Probably this difference is due to the different “dynamical framework”of logic control with respect to analog/digital control. As a matter of facts, in logic control discrete-events dynamics replace time-driven dynamics; hence most of the formal and mathematical tools of analog/digital control cannot be directly migrated to logic control to enlighten the distinction between functions and implementations. In addition, in the common view of application technicians, logic control design is strictly connected to the adopted implementation technology (relays in the past, software nowadays), leading again to a deep confusion among functional view and technological view. In Industrial automation software engineering, concepts as modularity, encapsulation, composability and reusability are strongly emphasized and profitably realized in the so-calledobject-oriented methodologies. Industrial automation is receiving lately this approach, as testified by some IEC standards IEC 611313, IEC 61499 which have been considered in commercial products only recently. On the other hand, in the scientific and technical literature many contributions have been already proposed to establish a suitable modelling framework for industrial automation. During last years it was possible to note a considerable growth in the exploitation of innovative concepts and technologies from ICT world in industrial automation systems. For what concerns the logic control design, Model Based Design (MBD) is being imported in industrial automation from software engineering field. Another key-point in industrial automated systems is the growth of requirements in terms of availability, reliability and safety for technological systems. In other words, the control system should not only deal with the nominal behaviour, but should also deal with other important duties, such as diagnosis and faults isolations, recovery and safety management. Indeed, together with high performance, in complex systems fault occurrences increase. This is a consequence of the fact that, as it typically occurs in reliable mechatronic systems, in complex systems such as AMS, together with reliable mechanical elements, an increasing number of electronic devices are also present, that are more vulnerable by their own nature. The diagnosis problem and the faults isolation in a generic dynamical system consists in the design of an elaboration unit that, appropriately processing the inputs and outputs of the dynamical system, is also capable of detecting incipient faults on the plant devices, reconfiguring the control system so as to guarantee satisfactory performance. The designer should be able to formally verify the product, certifying that, in its final implementation, it will perform itsrequired function guarantying the desired level of reliability and safety; the next step is that of preventing faults and eventually reconfiguring the control system so that faults are tolerated. On this topic an important improvement to formal verification of logic control, fault diagnosis and fault tolerant control results derive from Discrete Event Systems theory. The aimof this work is to define a design pattern and a control architecture to help the designer of control logic in industrial automated systems. The work starts with a brief discussion on main characteristics and description of industrial automated systems on Chapter 1. In Chapter 2 a survey on the state of the software engineering paradigm applied to industrial automation is discussed. Chapter 3 presentes a architecture for industrial automated systems based on the new concept of Generalized Actuator showing its benefits, while in Chapter 4 this architecture is refined using a novel entity, the Generalized Device in order to have a better reusability and modularity of the control logic. In Chapter 5 a new approach will be present based on Discrete Event Systems for the problemof software formal verification and an active fault tolerant control architecture using online diagnostic. Finally conclusive remarks and some ideas on new directions to explore are given. In Appendix A are briefly reported some concepts and results about Discrete Event Systems which should help the reader in understanding some crucial points in chapter 5; while in Appendix B an overview on the experimental testbed of the Laboratory of Automation of University of Bologna, is reported to validated the approach presented in chapter 3, chapter 4 and chapter 5. In Appendix C some components model used in chapter 5 for formal verification are reported.

Structural and functional analysis of centromeric chromatin

Animal neocentromeres are defined as ectopic centromeres that have formed in non-centromeric locations and avoid some of the features, like the DNA satellite sequence, that normally characterize canonical centromeres. Despite this, they are stable functional centromeres inherited through generations. The only existence of neocentromeres provide convincing evidence that centromere specification is determined by epigenetic rather than sequence-specific mechanisms. For all this reasons, we used them as simplified models to investigate the molecular mechanisms that underlay the formation and the maintenance of functional centromeres. We collected human cell lines carrying neocentromeres in different positions. To investigate the region involved in the process at the DNA sequence level we applied a recent technology that integrates Chromatin Immuno-Precipitation and DNA microarrays (ChIP-on-chip) using rabbit polyclonal antibodies directed against CENP-A or CENP-C human centromeric proteins. These DNA binding-proteins are required for kinetochore function and are exclusively targeted to functional centromeres. Thus, the immunoprecipitation of DNA bound by these proteins allows the isolation of centromeric sequences, including those of the neocentromeres. Neocentromeres arise even in protein-coding genes region. We further analyzed if the increased scaffold attachment sites and the corresponding tighter chromatin of the region involved in the neocentromerization process still were permissive or not to transcription of within encoded genes. Centromere repositioning is a phenomenon in which a neocentromere arisen without altering the gene order, followed by the inactivation of the canonical centromere, becomes fixed in population. It is a process of chromosome rearrangement fundamental in evolution, at the bases of speciation. The repeat-free region where the neocentromere initially forms, progressively acquires extended arrays of satellite tandem repeats that may contribute to its functional stability. In this view our attention focalized to the repositioned horse ECA11 centromere. ChIP-on-chip analysis was used to define the region involved and SNPs studies, mapping within the region involved into neocentromerization, were carried on. We have been able to describe the structural polymorphism of the chromosome 11 centromeric domain of Caballus population. That polymorphism was seen even between homologues chromosome of the same cells. That discovery was the first described ever. Genomic plasticity had a fundamental role in evolution. Centromeres are not static packaged region of genomes. The key question that fascinates biologists is to understand how that centromere plasticity could be combined to the stability and maintenance of centromeric function. Starting from the epigenetic point of view that underlies centromere formation, we decided to analyze the RNA content of centromeric chromatin. RNA, as well as secondary chemically modifications that involve both histones and DNA, represents a good candidate to guide somehow the centromere formation and maintenance. Many observations suggest that transcription of centromeric DNA or of other non-coding RNAs could affect centromere formation. To date has been no thorough investigation addressing the identity of the chromatin-associated RNAs (CARs) on a global scale. This prompted us to develop techniques to identify CARs in a genome-wide approach using high-throughput genomic platforms. The future goal of this study will be to focalize the attention on what strictly happens specifically inside centromere chromatin.

Rare and complicated forms of infantile hemangiomas: new therapeutic outlooks

Infantile hemangiomas (IHs) are the most common benign neoplastic pathology of childhood; their natural history generally involves three phases: after the onset, which usually occurs in the first weeks of life, there is the proliferation phase where the IH reaches its maximum development and it is followed by the spontaneous involution which leads to the IH regression. The duration and the extent of these phases may vary widely even though in most of the cases the involution process begins around twelve months of life and the regression, complete or partial, is completed around seventh-ninth year of life. The majority of the IHs does not require any treatment. However, 10%-20% is likely to develop serious complications, functional impairments or aesthetic alterations and entail a timely treatment. Although there is no treatment protocol currently shared, therapies usually used in cases with a complication risk consist in: systemic or intralesional steroids as a first choice; interferon α, vincristine and/or bleomicin as second or third choice and/or surgical treatment. Propranolol, a non-selective beta-blocker, has been used for cardiovascular diseases even in childhood for decades. Since 2008 it has been widely used in the IHs treatment, although it is still "off-label". In literature there are hundreds of cases and some clinical studies that show the effectiveness and safety of this drug for this indication. Thanks to a multidisciplinary team (Dermatologists, Cardiologists, Paediatricians, and Radiologists) of S. Orsola-Malpighi Hospital, a clinical study, which has been previously approved by the ethics committee, is carried out in order to evaluate the efficacy and safety of systemic propranolol in the treatment of IHs in paediatric age. At the end of 2012, 78 patients underwent this treatment: the results we have obtained so far show a good efficacy and safety profile in agreement with the data provided by the literature.

Electrical scanning probe microscopy on organic optoelectronic structures

In the field of organic optoelectronics, the nanoscale structure of the materials has huge im-pact on the device performance. Here, scanning force microscopy (SFM) techniques become increasingly important. In addition to topographic information, various surface properties can be recorded on a nanometer length scale, such as electrical conductivity (conductive scanning force microscopy, C-SFM) and surface potential (Kelvin probe force microscopy, KPFM).rnrnIn the context of this work, the electrical SFM modes were applied to study the interplay be-tween morphology and electrical properties in hybrid optoelectronic structures, developed in the group of Prof. J. Gutmann (MPI-P Mainz). In particular, I investigated the working prin-ciple of a novel integrated electron blocking layer system. A structure of electrically conduct-ing pathways along crystalline TiO2 particles in an insulating matrix of a polymer derived ceramic was found and insulating defect structures could be identified. In order to get insights into the internal structure of a device I investigated a working hybrid solar cell by preparing a cross cut with focused ion beam polishing. With C-SFM, the functional layers could be identified and the charge transport properties of the novel active layer composite material could be studied. rnrnIn C-SFM, soft surfaces can be permanently damaged by (i) tip induced forces, (ii) high elec-tric fields and (iii) high current densities close to the SFM-tip. Thus, an alternative operation based on torsion mode topography imaging in combination with current mapping was intro-duced. In torsion mode, the SFM-tip vibrates laterally and in close proximity to the sample surface. Thus, an electrical contact between tip and sample can be established. In a series of reference experiments on standard surfaces, the working mechanism of scanning conductive torsion mode microscopy (SCTMM) was investigated. Moreover, I studied samples covered with free standing semiconducting polymer nano-pillars that were developed in the group of Dr. P. Theato (University Mainz). The application of SCTMM allowed non-destructive imag-ing of the flexible surface at high resolution while measuring the conductance on individual pillarsrnrnIn order to study light induced electrical effects on the level of single nanostructures, a new SFM setup was built. It is equipped with a laser sample illumination and placed in inert at-mosphere. With this photoelectric SFM, I investigated the light induced response in function-alized nanorods that were developed in the group of Prof. R. Zentel (University Mainz). A block-copolymer containing an anchor block and dye moiety and a semiconducting conju-gated polymer moiety was synthesized and covalently bound to ZnO nanorods. This system forms an electron donor/acceptor interface and can thus be seen as a model system of a solar cell on the nanoscale. With a KPFM study on the illuminated samples, the light induced charge separation between the nanorod and the polymeric corona could not only be visualized, but also quantified.rnrnThe results demonstrate that electrical scanning force microscopy can study fundamental processes in nanostructures and give invaluable feedback to the synthetic chemists for the optimization of functional nanomaterials.rn

Spatial and temporal flower presentation in Apiaceae-Apioideae

Alle Doldengewächse (Apiaceae), darunter die größte, weltweit verbreitete Unterfamilie der Apioideen, weisen in ihren Blütenständen sehr einheitliche Merkmale auf. Die ‚Doppeldolden´ werden aus kleinen, weißen oder gelben Blüten gebildet und von vielen unspezialisierten Insekten besucht. Der uniforme Eindruck, der damit erweckt wird, ist unter Umständen ein Grund, dass die zugrundeliegende Morphologie bislang wenig untersucht wurde. Gegenstand der vorliegenden Dissertation ist es daher, die ‚verborgene Diversität´ im Blütenstandsbereich der Apiaceae -Apioideen mit dem Ziel darzustellen, den Einfluss der Architektur der Pflanzen auf die Art der Blütenpräsentation in Raum und Zeit und damit auf das Reproduktionssystem der Art zu ermitteln. Im ersten Kapitel zeigt der Vergleich von neun ausgewählten Arten, dass in den selbstfertilen und unspezifisch bestäubten Pflanzen durch Synchronisation und Rhythmik in der Präsentation von Blüten Fremdbefruchtung gefördert wird. Entweder durchlaufen die Pflanzen dabei nur eine getrennte männliche und weibliche Blühphase (Xanthoselinum alsaticum) oder der moduläre Bau der Pflanzen führt zu einer Folge männlicher und weiblicher Blühphasen (multizyklische Dichogamie). Die Diözie in Trinia glauca kann in diesem Zusammenhang als eine Trennung der Blühphasen auf verschiedengeschlechtliche Individuen gesehen werden. Für die andromonözischen Arten wird gezeigt, dass der Anteil funktional männlicher Blüten mit steigender Doldenordnung nicht einheitlich zu- oder abnimmt. Dadurch fungieren die Pflanzen zu verschiedenen Zeiten und mit unterschiedlicher Stärke eher als Pollenrezeptoren oder Pollendonatoren. Es wird deutlich, dass das ‚uniforme Muster‘ der Apioideen mit Dolden verschiedener Ordnungen, dichogamen Blüten und deren diversen Geschlechtsausbildungen ein komplexes Raum-Zeit-Gefüge zur Optimierung des Reproduktionssystems darstellt. Das zweite Kapitel stellt die Ergebnisse von Manipulationsexperimenten (Handbestäubung, Bestäuberabschirmung, Entfernen von Dolden niedriger Ordnung) an Chaerophyllum bulbosum dar, die zeigen, dass das Raum-Zeit-Gefüge in der Präsentation der Blüten der Art erlaubt, flexibel auf Umwelteinflüsse zu reagieren. Es stellt sich heraus, dass mechanische Beschädigungen kaum Einfluss auf den Andromonöziegrad und prozentualen Fruchtansatz der Individuen nehmen. Grundvoraussetzung der Reaktionsfähigkeit ist wiederum deren modulärer Bau. Dieser erlaubt es den Pflanzen, zusammen mit dem andromonöziebedingten Reservoir an - geschlechtlich flexiblen - männlichen Blüten, in den später angelegten Dolden fehlenden Fruchtansatz der Blüten früh blühender Dolden zu kompensieren. Im dritten Kapitel wird eine vergleichende Merkmalsanalyse an 255 Apioideen-Arten vorgelegt, die alle Verwandtschaftskreise, Wuchsformen und Verbreitungsgebiete der Gruppe repräsentieren. Ziel der Analyse war die Identifizierung von Merkmalssyndromen, die den Zusammenhang zwischen Architektur und Reproduktionssystem verdeutlichen sollten. Interessanterweise sind die einzigen Merkmale, die miteinander einhergehen, Protogynie und die graduelle Abnahme männlicher Blüten mit steigender Doldenordnung. Alle anderen Merkmale variieren unabhängig voneinander und erzeugen auf vielen verschiedenen Wegen immer wieder das gleiche Funktionsmuster, das als ‚breeding syndrome‘ der Apioideae gedeutet werden kann. Die Arbeit leistet einen wichtigen Beitrag zum Verständnis der Blütenstände der Apiaceen und darüber hinaus zu morphologischer Variation in ‚unspezialisierten‘ Reproduktionssystemen. Offensichtlich liegt in den Apioideen der Selektionsdruck auf der Aufrechterhaltung der generalisistischen Bestäubung und überprägt alle morphologisch-phylogenetischen Merkmalsvarianten.

Functional characterization of the placenta specific protein PLAC1 and its use for cancer immunotherapy

Summary Antibody-based cancer therapies have been successfully introduced into the clinic and have emerged as the most promising therapeutics in oncology. The limiting factor regarding the development of therapeutical antibody vaccines is the identification of tumor-associated antigens. PLAC1, the placenta-specific protein 1, was categorized for the first time by the group of Prof. Sahin as such a tumor-specific antigen. Within this work PLAC1 was characterized using a variety of biochemical methods. The protein expression profile, the cellular localization, the conformational state and especially the interacting partners of PLAC1 and its functionality in cancer were analyzed. Analysis of the protein expression profile of PLAC1 in normal human tissue confirms the published RT-PCR data. Except for placenta no PLAC1 expression was detectable in any other normal human tissue. Beyond, an increased PLAC1 expression was detected in several cancer cell lines derived of trophoblastic, breast and pancreatic lineage emphasizing its properties as tumor-specific antigen. rnThe cellular localization of PLAC1 revealed that PLAC1 contains a functional signal peptide which conducts the propeptide to the endoplasmic reticulum (ER) and results in the secretion of PLAC1 by the secretory pathway. Although PLAC1 did not exhibit a distinct transmembrane domain, no unbound protein was detectable in the cell culture supernatant of overexpressing cells. But by selective isolation of different cellular compartments PLAC1 was clearly enriched within the membrane fraction. Using size exclusion chromatography PLAC1 was characterized as a highly aggregating protein that forms a network of high molecular multimers, consisting of a mixture of non-covalent as well as covalent interactions. Those interactions were formed by PLAC1 with itself and probably other cellular components and proteins. Consequently, PLAC1 localize outside the cell, where it is associated to the membrane forming a stable extracellular coat-like structure.rnThe first mechanistic hint how PLAC1 promote cancer cell proliferation was achieved identifying the fibroblast growth factor FGF7 as a specific interacting partner of PLAC1. Moreover, it was clearly shown that PLAC1 as well as FGF7 bind to heparin, a glycosaminoglycan of the ECM that is also involved in FGF-signaling. The participation of PLAC1 within this pathway was approved after co-localizing PLAC1, FGF7 and the FGF7 specific receptor (FGFR2IIIb) and identifying the formation of a trimeric complex (PLAC1, FGF7 and the specific receptor FGFR2IIIb). Especially this trimeric complex revealed the role of PLAC1. Binding of PLAC1 together with FGF7 leads to the activation of the intracellular tyrosine kinase of the FGFR2IIIb-receptor and mediate the direct phosphorylation of the AKT-kinase. In the absence of PLAC1, no FGF7 mediated phosphorylation of AKT was observed. Consequently the function of PLAC1 was clarified: PLAC1 acts as a co-factor by stimulating proliferation by of the FGF7-FGFR2 signaling pathway.rnAll together, these novel biochemical findings underline that the placenta specific protein PLAC1 could be a new target for cancer immunotherapy, especially considering its potential applicability for antibody therapy in tumor patients.

Musical Training Induces Functional Plasticity in Human Hippocampus

Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for the investigation of auditory processing, we examined brain responses induced by temporal novelty in otherwise isochronous sound patterns in musicians and musical laypersons, since the hippocampus has been suggested previously to be crucially involved in various forms of novelty detection. In the first cross-sectional experiment, we identified enhanced neural responses to temporal novelty in the anterior left hippocampus of professional musicians, pointing to expertise-related differences in hippocampal processing. In the second experiment, we evaluated neural responses to acoustic temporal novelty in a longitudinal approach to disentangle training-related changes from predispositional factors. For this purpose, we examined an independent sample of music academy students before and after two semesters of intensive aural skills training. After this training period, hippocampal responses to temporal novelty in sounds were enhanced in musical students, and statistical interaction analysis of brain activity changes over time suggests training rather than predisposition effects. Thus, our results provide direct evidence for functional changes of the adult hippocampus in humans related to musical training.

The effect of arts speech therapy on cerebral oxygenation and low frequency hemodynamic oscillations measured using functional near-infrared spectroscopy

Introduction: As a previous study revealed, arts speech therapy (AST) affects cardiorespiratory interaction [1]. The aim of the present study was to investigate whether AST also has effects on brain oxygenation and hemodynamics measured non-invasively using near-infrared spectroscopy (NIRS). Material and methods: NIRS measurements were performed on 17 subjects (8 men and 9 women, mean age: 35.6 ± 12.7 y) during AST. Each measurement lasted 35 min, comprising 8 min pre-baseline, 10 min recitation and 20 min post-baseline. For each subject, measurements were performed for three different AST recitation tasks (recitation of alliterative, hexameter and prose verse). Relative concentration changes of oxyhemoglobin (Δ[O2Hb]) and deoxyhemoglobin (Δ[HHb]) as well as the tissue oxygenation index (TOI) were measured using a Hamamatsu NIRO300 NIRS device and a sensor placed on the subjects forehead. Movement artifacts were removed using a novel method [2]. Statistical analysis (Wilcoxon test) was applied to the data to investigate (i) if the recitation causes changes in the median values and/or in the Mayer wave power spectral density (MW-PSD, range: 0.07–0.13 Hz) of Δ[O2Hb], Δ[HHb] or TOI, and (ii) if these changes vary between the 3 recitation forms. Results: For all three recitation styles a significant (p < 0.05) decrease in Δ[O2Hb] and TOI was found, indicating a decrease in blood flow. These decreases did not vary significantly between the three styles. MW-PSD increased significantly for Δ[O2Hb] when reciting the hexameter and prose verse, and for Δ[HHb] and TOI when reciting alliterations and hexameter, representing an increase in Mayer waves. The MW-PSD increase for Δ[O2Hb] was significantly larger for the hexameter verse compared to alliterative and prose verse Conclusion: The study showed that AST affects brain hemodynamics (oxygenation, blood flow and Mayer waves). Recitation caused a significant decrease in cerebral blood flow for all recitation styles as well as an increase in Mayer waves, particularly for the hexameter, which may indicate a sympathetic activation. References 1. D. Cysarz, D. von Bonin, H. Lackner, P. Heusser, M. Moser, H. Bettermann. Am J Physiol Heart Circ Physiol, 287 (2) (2004), pp. H579–H587 2. F. Scholkmann, S. Spichtig, T. Muehlemann, M. Wolf. Physiol Meas, 31 (5) (2010), pp. 649–662

Numerical Computation of a Certain Dirichlet Series Attached to Siegel Modular Forms of Degree Two

The Rankin convolution type Dirichlet series D-F,D-G(s) of Siegel modular forms F and G of degree two, which was introduced by Kohnen and the second author, is computed numerically for various F and G. In particular, we prove that the series D-F,D-G(s), which shares the same functional equation and analytic behavior with the spinor L-functions of eigenforms of the same weight are not linear combinations of those. In order to conduct these experiments a numerical method to compute the Petersson scalar products of Jacobi Forms is developed and discussed in detail.

Functional flexibility of intestinal IgA - broadening the fine line

Intestinal bacteria outnumber our own human cells in conditions of both health and disease. It has long been recognized that secretory antibody, particularly IgA, is produced in response to these microbes and hypothesized that this must play an important role in defining the relationship between a host and its intestinal microbes. However, the exact role of IgA and the mechanisms by which IgA can act are only beginning to be understood. In this review we attempt to unravel the complex interaction between so-called "natural," "primitive" (T-cell-independent), and "classical" IgA responses, the nature of the intestinal microbiota/intestinal pathogens and the highly flexible dynamic homeostasis of the mucosal immune system. Such an analysis reveals that low-affinity IgA is sufficient to protect the host from excess mucosal immune activation induced by harmless commensal microbes. However, affinity-maturation of "classical" IgA is essential to provide protection from more invasive commensal species such as segmented filamentous bacteria and from true pathogens such as Salmonellatyphimurium. Thus a correlation is revealed between "sophistication" of the IgA response and aggressiveness of the challenge. A second emerging theme is that more-invasive species take advantage of host inflammatory mechanisms to more successfully compete with the resident microbiota. In many cases, the function of IgA may be to limit such inflammatory responses, either directly by coagulating or inhibiting virulence of bacteria before they can interact with the host or by modulating immune signaling induced by host recognition. Therefore IgA appears to provide an added layer of robustness in the intestinal ecosystem, promoting "commensal-like" behavior of its residents.

Immunologic and functional evidence for anti-Siglec-9 autoantibodies in intravenous immunoglobulin preparations

Human intravenous immunoglobulin (IVIg) preparations are increasingly used for the treatment of autoimmune diseases. Earlier work demonstrated the presence of autoantibodies against Fas in IVIg, suggesting that IVIg might be able to induce caspase-dependent cell death in Fas-sensitive cells. In this study, we demonstrate that sialic acid-binding Ig-like lectin 9 (Siglec) represents a surface molecule on neutrophils that is activated by IVIg, resulting in caspase-dependent and caspase-independent forms of cell death. Neutrophil death was mediated by naturally occurring anti-Siglec-9 autoantibodies present in IVIg. Moreover, the efficacy of IVIg-mediated neutrophil killing was enhanced by the proinflammatory cytokines granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma), and this additional cell death required reactive oxygen species (ROSs) but not caspases. Anti- Siglec-9 autoantibody-depleted IVIg failed to induce this caspase-independent neutrophil death. These findings contribute to our understanding of how IVIg preparations exert their immunoregulatory effects under pathologic conditions and may provide a possible explanation for the neutropenia that is sometimes seen in association with IVIg therapy.

Functional neuroimaging of emotional learning and autonomic reactions

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.