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This book constitutes a pioneering work in the field of Societas Privata Europaea. It analyzes the law applicable to SPE – from the corresponding regulation to statute sand national law. The book gives an introduction to this new type of company and deals with almost all aspects of a SPE – from basic questions of interpretation, the scope of the regulation and its concept, the system of references to the statute of the company and national law and its relationship to disputed questions such as the seat and registered office, internal structure, minimum capital and worker participation. The results are presented in intelligible graphics, theses and tables. The book is relevant for a wide range of audience. In science, it serves as a starting point for reopening the legislative procedure of the SPE in practice, it serves as a guide. It is a fundamental work on legal issues of supranational companies.

We experimentally investigated the morphology and mechanism of laser-induced damage in the ablation cutting of thin glass sheets with picosecond pulsed lasers and we compared the experimental results to our models. After several passes of laser ablation, we observed two different kinds of damage morphologies on the cross-section of the cut channel. They are distinguished to be the damage region caused by high-density free-electrons and the heat-affected zone due to the heat accumulation, respectively. Furthermore, micro-cracks can be observed on the top surface of the workpiece near the cut edge. The nano-cracks could be generated by high energy free-electrons but opened and developed to be visible micro-cracks by thermal stress generated in the heat-affected zone. The crack length was proportional to the volume of heat-affected zone. Heat-affected-zone and visible-cracks free conditions of glass cutting were achieved by controlling the repetition rate and spatial overlap of laser pulses.

BACKGROUND Collecting patient-reported outcome (PRO) data systematically enables objective evaluation of treatment and its related outcomes. Using disease-specific questionnaires developed by the International Consortium for Health Outcome Measurement (ICHOM) allows for comparison between physicians, hospitals, and even different countries. OBJECTIVE This pilot project aimed to establish a digital system to measure PROs for new patients with breast cancer who attended the Charité Breast Center This approach should serve as a blueprint to further expand the PRO measurement to other disease entities and departments. METHODS In November 2016, we implemented a Web-based system to collect PRO data at Charité Breast Center using the ICHOM dataset. All new patients at the Breast Center were enrolled and answered a predefined set of questions using a tablet computer. Once they started their treatment at Charité, automated emails were sent to the patients at predefined treatment points. Those emails contained a Web-based link through which they could access and answer questionnaires. RESULTS By now, 541 patients have been enrolled and 2470 questionnaires initiated. Overall, 9.4% (51/541) of the patients were under the age of 40 years, 49.7% (269/541) between 40 and 60 years, 39.6% (214/541) between 60 and 80 years, and 1.3% (7/541) over the age of 80 years. The average return rate of questionnaires was 67.0%. When asked about the preference regarding paper versus Web-based questionnaires, 6.0% (8/134) of the patients between 50 and 60 years, 6.0% (9/150) between 60 and 70 years, and 12.7% (9/71) over the age of 70 years preferred paper versions. CONCLUSIONS Measuring PRO in patients with breast cancer in an automated electronic version is possible across all age ranges while simultaneously achieving a high return rate.

In a combined theoretical and experimental work, we investigate X-ray Absorption Near-Edge Structure (XANES) spectroscopy of the I $L_3$ and the Pb $M_5$ edges of the methylammonium lead iodide ($\textrm{MAPbI}_3$) hybrid inorganic-organic perovskite and its binary phase $\textrm{PbI}_2$. The absorption onsets are dominated by bound excitons with sizable binding energies of a few hundred meV and pronounced anisotropy. The spectra of both materials exhibit remarkable similarities, suggesting that the fingerprints of core excitations in $\textrm{MAPbI}_3$ are essentially given by its inorganic component, with negligible influence from the organic groups. The theoretical analysis complementing experimental observations provides the conceptual insights required for a full characterization of this complex material.

The unprecedented speed at which the performance of solar cells based on solution-processed perovskite thin films has increased, in some ways, appears to violate conventional understanding of device optimization. The relatively poor coverage of the TiO2 electron transport layer by the absorber should cause shunting of the cell. This, however, is not the case. In this paper, it is attempted to explain this “discrepancy.” Insights into coverage, morphology, local elemental composition, and spatially resolved electronic structure of CH3NH3PbI(3-x)Clx perovskite absorbers wet-chemically deposited on planar compact TiO2 electron transport material (ETM) are revealed. Microscopy images indicate an incomplete coverage of the ETM. Depending on the degree of coverage, a variation in iodine oxidation and metallic lead formation is found. With the electronic structure of the absorber and the ETM established experimentally and taking literature on the commonly used hole transport material spiro-MeOTAD into account, it is revealed that excellent charge selectivity occurs at the interfaces between the absorber and both the hole and electron transport layers. It can also be surmised that, crucially, any direct interface between the TiO2 and spiro-MeOTAD would be characterized by a large recombination barrier preventing shunts; to some extent minimizing the negative effects of absorber pinholes.

We investigated the morphology and mechanism of laser-induced damage in the ablation cutting of thin glass sheets with picosecond laser. Two kinds of damage morphologies observed on the cross-section of the cut channel, are caused by high-density free-electrons and the temperature accumulation, respectively. Notches and micro-cracks can be observed on the top surface of the sample near the cut edge. The surface micro-cracks were related to high energy free-electrons and also the heat-affected zone. Heat-affected-zone and visible-cracks free conditions of glass cutting were achieved by controlling the repetition rate and spatial overlap of laser pulses.

Development of technical solutions that lead to widening the use of multi-technological products as well as in assessing ecological and economic potentials of multi-technological products have not yet been studied intensively. The activities conducted in the context of this research area focus on these aspects. The aforementioned aspects have been examined, evaluated and quantified on the basis of three example products resulting from the first funding period. The research activities conducted on the example components deliver the basis for the layout of different integrated multi-technology production systems. Technical solutions that enable coupling of different process steps with each other as well as the integration of different functionalities and different materials in final multi-technology products have been proposed. The complex interdependencies of the products themselves and their associated production processes have been researched and evaluated intensively. Finally, a profitability assessment of the proposed solutions was conducted and future research topics identified.

Single-ion lanthanide-organic complexes can provide stable magnetic moments with well-defined orientation for spintronic applications on the atomic level. Here, we show by a combined experimental approach of scanning tunneling microscopy and x-ray absorption spectroscopy that dysprosium-tris(1,1,1-trifluoro-4-(2-thienyl)-2,4-butanedionate) $(\mathrm{Dy}{(\mathrm{tta})}_{3})$ complexes deposited on a Au(111) surface undergo a molecular distortion, resulting in distinct crystal field symmetry imposed on the Dy ion. This leads to an easy-axis magnetization direction in the ligand plane. Furthermore, we show that tunneling electrons hardly couple to the spin excitations, which we ascribe to the shielded nature of the $4f$ electrons.

We present a new method for the creation of hierarchical structures by two subsequent steps of laser ablation. To create certain functionalization of surfaces hierarchical structures are often required. These structures can be considered as a microstructure with a superposed nanostructure. Therefore the approach presented in this paper divides the patterning process into two parts: The microstructures are accomplished by direct laser writing with feature sizes down to a few microns whereas the nanostructure is subsequently added by Multi-beam-interference (MBI). Multi-beaminterference is a promising tool for the generation of nanostructures on 3D surfaces. Within this work the feasibility and limitations of this method are investigated.

Medical devices and engineering products need an increasing number of micro scaled-features, such as holes for filtration, separation and ventilation or small structures e.g. for hydrophobic effects. The size of these structures is often in the range of 20 mm and below while the structured areas grow at the same time. Therefore the factors influencing the drilling process are becoming more and more important and used to generate high process stability during the laser process. This paper investigates the process limits as well as the factors influencing the application of perforation with laser radiation of a 15 mm thick aluminum foil with UV ps-pulses. The pitch of the holes within the drilling pattern is varied as is the repetition rate used for the percussion drilling of each of the holes. The holes are evaluated by means of their diameter and shape. The precision of the hole shape is examined for two characteristics: circularity and ellipticity. Holes with a diameter of < 10 mm are drilled with pitches between 14 mm and 25 mm. Depending on the repetition rate three different drilling regimes are identified: 1. thermal drilling with increasing surface-oxidation, 2. thermal drilling with decreasing surface-oxidation and 3. shadowing of laser radiation.

Zum mikrometerfeinen Strukturieren funktioneller Oberflachen eigenen sich Kurzpuls- und Ultrakurzpulslaser inzwischen ebenso gut wie die klassischen Fertigungstechnologien. Das belegt auch die Vielzahl der Anwendungen, bei denen Laser derzeit die Oberflachen strukturieren. Speziell zum wirtschaftlichen Strukturieren von groseren Flachen bedarf es aber weiterer Forschungsaktivitaten. Sie offnen den (Ultra-) Kurzpulslasern zusatzliches Einsatzpotenzial.

Seit einiger Zeit ist die Thematisierung der demografischen Entwicklung, wenn es um die Darstellung der Seniorenarbeit geht, zu einer vertrauten Einleitungsformel geworden. Hierdurch soll zumeist die Relevanz von neuen Angebotsformaten von und fur die altere Generation hervorgehoben werden, die sich mehrheitlich an den Bedarfslagen der so genannten aktiven und mobilen Seniorinnen und Senioren orientieren. Die Aktivierung dieser SeniorInnen und die Motivierung zum Einsatz von erworbenen Kenntnissen fur die Gesellschaft ist eine beachtenswerte soziale Ressource, die viel zu lange vernachlassigt worden ist.

The loci Tb927.3.4070, 927.3.4080, Tb927.3.4090, 927.3.4100 and 927.3.4110 of Trypanosoma brucei encode five similar proteins with 13–14 transmembrane domains. Corresponding mRNAs are more abundant in bloodstream-form trypanosomes than in procyclics. The 4070, 4090 and 4110 genes have almost identical 3′-intergenic regions and the predicted proteins share a short C-terminal extension; a reporter mRNA with the 4110 3′-untranslated region was more abundant in bloodstream forms than procyclic forms. The 3′-untranslated regions for 4080 and 4100 are different, and that of 4080 gave procyclic-specific reporter expression. Tb UBP1 and 2 are proteins with low-specificity RNA-binding activity. Over-expression of Tb UBP2 in bloodstream forms increased the overall abundance of mRNA encoding the transmembrane proteins, whereas Tb UBP1 and 2 RNA interference decreased it. RNAi targeting Tb UBP1 and 2 in bloodstream forms decreased mRNA with a 4110 3′-untranslated region, but increased it for 4080. Thus Tb UBP and Tb UBP2 may accentuate developmental regulation of the Tb927.3.4070–927.3.4110 mRNAs.

In the African trypanosome Trypanosoma brucei nearly all control of gene expression is posttranscriptional; sequences in the 3′-untranslated regions of mRNAs determine the steady-state mRNA levels by regulation of RNA turnover. Here we investigate the roles of two related proteins, Tb UBP1 and Tb UBP2, containing a single RNA recognition motif, in trypanosome gene expression. Tb UBP1 and Tb UBP2 are in the cytoplasm and nucleus, comprise ca. 0.1% of the total protein, and are not associated with polysomes or RNA degradation enzymes. Overexpression of Tb UBP2 upregulated the levels of several mRNAs potentially involved in cell division, including the CFB1 mRNA, which encodes a protein with a cyclin F-box domain. CFB1 regulation was mediated by the 3′-untranslated region and involved stabilization of the mRNA. Depletion of Tb UBP2 and Tb UBP1 inhibited growth and downregulated expression of the cyclin F box protein gene CFB2 ; trans splicing was unaffected. The results of pull-down assays indicated that all tested mRNAs were bound to Tb UBP2 or Tb UBP1, with some preference for CFB1 . We suggest that Tb UBP1 and Tb UBP2 may be relatively nonspecific RNA-binding proteins and that specific effects of overexpression or depletion could depend on competition between various different proteins for RNA binding.

The production and machining of micro parts were in the past mainly made by technologies developed from the electronic industry, which is particularly based on silicon etching technologies for the production of, e.g., sensor elements. Due to the increasing demand for micro products in other production area such as medical-, automotive-, optical- and chemical-industry, suitable processes for machining parts from non-silicon materials has become increasingly more important. Laser technology has been qualified for microtechnology because of its high lateral resolution by minimized focusability down to a few microns, low heat input and high flexibility. Some examples for laser applications are micro welding, soldering, selective bonding of silicon and glass, micro structuring and laser assisted forming.

Heat-shock locus VU (HslVU) is an ATP-dependent proteolytic system and a prokaryotic homolog of the proteasome. It consists of HslV, the protease, and HslU, the ATPase and chaperone. We have cloned, sequenced and expressed both protein components from the hyperthermophile Thermotoga maritima. T. maritima HslU hydrolyzes a variety of nucleotides in a temperature-dependent manner, with the optimum lying between 75 and 80 degrees C. It is also nucleotide-unspecific for activation of HslV against amidolytic and caseinolytic activity. The Escherichia coli and T. maritima HslU proteins mutually stimulate HslV proteins from both sources, suggesting a conserved activation mechanism. The crystal structure of T. maritima HslV was determined and refined to 2.1-A resolution. The structure of the dodecameric enzyme is well conserved compared to those from E. coli and Haemophilus influenzae. A comparison of known HslV structures confirms the presence of a cation-binding site, although its exact role in the proteolytic mechanism of HslV remains unclear. Amongst factors responsible for the thermostability of T. maritima HslV, extensive ionic interactions/salt-bridge networks, which occur specifically in the T. maritima enzyme in comparison to its mesophilic counterparts, seem to play an important role.

Protease HslV and ATPase HslU form an ATP-dependent protease in bacteria. We have previously determined the structure of the components of this protease. In the case of HslU, the structure was derived from HslU–HslV cocrystals, combining phase information from MAD and the previously determined HslV model. Whereas the structures of the components were confirmed in detail by later structures, the quaternary arrangement of HslV and HslU was not reproduced in later crystal forms. In a recent communication to this journal, Wang attempted a reinterpretation of our original data to account for this difference. In response, we demonstrate that difference Pattersons, difference Fouriers, molecular replacement calculations, R factors, and omit maps all support our original analysis and prove that the suggested reinterpretation is false by these criteria. In particular, we show that our crystals are essentially untwinned and that only the originally reported quaternary arrangement of HslV and HslU particles is consistent with the experimental data. We finally demonstrate that Wang's newly introduced Rtpart method to predict translational corrections for a subset of the unit cell contents is systematically flawed.

This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients.

Trypanosoma brucei TREU 927/4 has been chosen as the reference strain targeted for complete sequencing of the genome of the African trypanosome. This line is pleomorphic in mammalian hosts and is fly transmissible; however it is relatively unstable with respect to variable surface glycoprotein (VSG) expression. Therefore, we subjected TREU 927/4 to 27 rapid syringe passages through mice, and derived a cloned line which expressed Glasgow University Trypanozoon antigen type (GUTat) 10.1 with relative stability. This line also retained pleomorphism in the bloodstream, being able to generate homogeneous populations of stumpy forms in mice. Furthermore, these parasites remain able to transform to procyclic forms synchronously in vitro and can complete their life cycle in tsetse flies. The passaged cell line was also adapted to in vitro bloodstream-form culture and transfected with a construct encoding the tetracycline repressor (TETR) protein. The resulting TETR subline no longer expressed the GUTat 10.1 VSG but remained able to generate uniform populations of stumpy form cells in mice immunocompromised with cyclophosphamide. They could also differentiate to procyclic forms synchronously in vitro. The generated lines and analyses of their growth and differentiation will provide a basic resource for the analysis and interpretation of gene function in the T. brucei genome reference strain.

L’originalité du château de Marly réside avant tout dans l’ordonnance de l’architecture en un système de pavillons et dans la décoration de toutes les façades par des fresques polychromes. D’un seul point de vue quantitatif, l’ensemble des projets de ce décor représente le groupe de dessins le plus important de la première phase de construction de Marly. Non seulement ces documents, parmi les plus anciens conservés, nous renseignent sur la première phase de la conception, mais, dans le cas du Pavillon royal, ils sont aussi la preuve qu’un processus de concertation eut lieu entre Le Brun et Mansart en vue d’harmoniser l’architecture et le système de décor feint. La tradition des décors de fêtes éphémères a sans aucun doute constitué la source d’inspiration principale de ce décor : les correspondances frappantes entre le premier projet d’ensemble pour Marly et l’Illumination du jardin de Versailles organisée en 1674 et 1676 – dont nous aimerions attribuer le projet à Le Brun –, qui a fortement fasciné Louis XIV, pour lequel elle représentait une sorte d’extension idéale du jardin de Versailles, suggèrent que ce décor a fourni le modèle de l’idée initiale de Marly. Parallèlement, le rôle de Mansart apparaît clairement comme celui d’un architecte extrêmement inventif qui donna au site sa forme architecturale concrète ; son projet d’une chartreuse sécularisée à des fins de retraite pour le monarque ne présente pas moins de caractères fantastiques. Le projet et la réalisation d’un concept aussi « risqué » à tous points de vue ne furent possibles que parce que son commanditaire y voyait la transposition idéale de ses souhaits personnels et de ses goûts esthétiques, dans un lieu jouissant d’une relative intimité. The originality of the Château de Marly lies, above all, in its architecture’s order on a system of pavilions and on the polychrome frescoes decorating all its facades. With just one quantitative point of view, all of the decor’s projects represent the most important designs of the first phase of Marly’s construction. Not only do these documents, among the oldest preserved, tell us about the first phase of design, but, in the case of the Royal Pavilion, they are also proof of a consultative process that took place between Le Brun and Mansart with a view to harmonizing the architecture and the system of trompe l’oeil decoration. The tradition of ephemeral decorations for feasts undoubtedly constituted the main source of inspiration for this decoration: the striking correspondence between the first overall project for Marly and the Illumination of the garden of Versailles organized in 1674 and 1676 — that we would like to attribute to Le Brun — which greatly interested Louis XIV for whom it represented a kind of ideal extension of the garden of Versailles, suggest that this provided the model for the initial idea of Marly. Meanwhile, Mansart’s role clearly appears as one of an extremely inventive architect who gave the site its concrete architectural form: his project for the secularized charterhouse as a retreat for the monarch presents no fewer fantastic characteristics. The project and realization of a concept so “risky” from all viewpoints were only possible because his sponsor saw the ideal transposition of his personal wishes and his aesthetic tastes in a location that enjoyed relative privacy.

a Zentrum fur Molekulare Biologie, Im Neuenheimer Feld 282, Postfach 106249, D-6900 Heidelberg 1, Federal Republic of Germany b Department of Biological Chemistry and Molecular Pharmacology, Har6ard Medical School, 250 Longwood A6e., Boston, MA 02115, USA c Department of Molecular Microbiology, 760 McDonnell Science Building, Box 8230, Washington Uni6ersity School of Medicine, 660 South Euclid A6enue, St. Louis, MO 63110-1093, USA

African trypanosomes express a heterodimeric transferrin receptor that mediates iron uptake from the host bloodstream. The genes encoding the receptor, ESAG6 and ESAG7, are found at the beginning of VSG expression sites: these are telomeric, polycistronic transcription units that each terminate with a gene encoding a trypanosome variant surface glycoprotein, VSG. Approximately 20 of these VSG expression sites are found in the trypanosome genome, but only one VSG is expressed at a time. The conventional view is that one expression site promoter is extremely active whereas the others are either inactive or show very low, poorly processive activity, and that all transferrin receptor molecules are encoded by the active expression site. The 3'-end of the ESAG6 gene is more than 5 kb from the promoter. We show here that 20% of ESAG6 mRNA originates from the 'inactive' expression sites. We suggest that many expression site promoters in trypanosomes show low-level activity throughout the life cycle, and that transcription proceeds for at least 5 kb. This suggests a simplified model of VSG expression site control, whereby the only regulated event is the strong activation of a single expression site promoter in bloodstream forms.

▪ Abstract Proteasomes are large multisubunit proteases that are found in the cytosol, both free and attached to the endoplasmic reticulum, and in the nucleus of eukaryotic cells. Their ubiquitous presence and high abundance in these compartments reflects their central role in cellular protein turnover. Proteasomes recognize, unfold, and digest protein substrates that have been marked for degradation by the attachment of a ubiquitin moiety. Individual subcomplexes of the complete 26S proteasome are involved in these different tasks: The ATP-dependent 19S caps are believed to unfold substrates and feed them to the actual protease, the 20S proteasome. This core particle appears to be more ancient than the ubiquitin system. Both prokaryotic and archaebacterial ancestors have been identified. Crystal structures are now available for the E. coli proteasome homologue and the T. acidophilum and S. cerevisiae 20S proteasomes. All three enzymes are cylindrical particles that have their active sites on the inner walls of a large central cavity. They share the fold and a novel catalytic mechanism with an N-terminal nucleophilic threonine, which places them in the family of Ntn (N terminal nucleophile) hydrolases. Evolution has added complexity to the comparatively simple prokaryotic prototype. This minimal proteasome is a homododecamer made from two hexameric rings stacked head to head. Its heptameric version is the catalytic core of archaebacterial proteasomes, where it is sandwiched between two inactive antichambers that are made up from a different subunit. In eukaryotes, both subunits have diverged into seven different subunits each, which are present in the particle in unique locations such that a complex dimer is formed that has six active sites with three major specificities that can be attributed to individual subunits. Genetic, biochemical, and high-resolution electron microscopy data, but no crystal structures, are available for the 19S caps. A first step toward a mechanistic understanding of proteasome activation and regulation has been made with the elucidation of the X-ray structure of the alternative, mammalian proteasome activator PA28.

Prostaglandins are believed to play an important role in the regulation of resting cerebral blood flow and in the vasodilatory response to hypercapnia. Recently, we reported an increased CO2 reactivity (CR) in premenopausal women and, in the past, evidence has accumulated that estrogens might increase basal levels of prostaglandin secretion from endothelial cells. Therefore, one may speculate that gender differences in CR are possibly mediated by higher prostaglandin levels in women. Using transcranial Doppler sonography, we assessed CR before and 90 min after a single dose of 100 mg of indomethacin in 22 healthy volunteers (11 men, 11 women). Before intake of indomethacin, women had a significantly higher CR (4.53+/-0.49 vs. 3.61+/-0.74, P0.01). Ninety minutes after indomethacin administration, CR decreased to 1.53+/-0.93 in women and 1.60+/-0.92 in men, respectively. The change of CR was 3.00+/-1.29 in women vs. 2.01+/-1.06 in men (P=0.07). For the entire study population, the decrease of CR was linearly correlated with the initial value of CR (rs=0.74, P0.001). This gender-related difference possibly relates to higher prostaglandin levels as mediators of an increased CR in premenopausal women, although the exact features remain to be clarified.

There is still some controversy about alterations in velocity of blood flow and in cerebral vasomotor reactivity of intracranial arteries in migraineurs during the interictal phase. By means of simultaneous bilateral transcranial Doppler ultrasonography we, therefore, assessed intracranial blood flow velocities and cerebrovascular reactivity to carbon dioxide of all three basal brain arteries in 20 migraineurs during the interictal phase and 30 nonheadache-prone control subjects. Mean blood flow velocities were higher in migraineurs than in controls in all three arteries on both sides, with a significant difference (P < 0.05) for the right anterior cerebral artery and middle cerebral artery under basal conditions and for the right posterior cerebral artery during hypercapnia. Similarly, the cerebrovascular reactivity to carbon dioxide was always higher in patients than in controls, with a significant difference for the left anterior and the right middle cerebral arteries (P < 0.05) and the right posterior cerebral artery (P < 0.01). The broad overlap of cerebrovascular blood flow velocities and CO2 reactivities in patients and controls precluded identification of values diagnostic of migraine. Nevertheless, transcranial Doppler ultrasonography offers the opportunity to noninvasively monitor cerebral blood flow parameters and, therefore, represents a valuable tool for vascular research in migraine.

Background and Purpose Cerebrovascular CO 2 reactivity can be assessed easily and reliably by transcranial Doppler sonography. The objectives of the present study were to evaluate sex differences in cerebral CO 2 reactivity and to specify the relation between CO 2 and cerebral blood flow velocity. Methods CO 2 reactivity of the circulation of both middle cerebral arteries was measured by bilateral transcranial Doppler sonography in 60 healthy volunteers (30 men, 30 women) aged 21 to 58 years. End-tidal carbon dioxide tensions (P etco 2 ) were elevated with the use of carbogene gas (95% O 2 , 5% CO 2 ). In each subject the mean blood flow velocity (V mean ) was plotted as a function of P etco 2 . Results The best-fit curves for the relation of V mean /P etco 2 were exponential functions, with the following basic equation: V mean (cm/s)= a e bx , where a is a theoretical quantity representing V mean at a P co 2 of 0 mm Hg, b is the relative slope of the curve (slope divided by the value of the function) corresponding to the definition of reactivity, and x is the P etco 2 (mm Hg). The mean value of b was 0.037±0.008 in women and 0.030±0.010 in men. ANOVA demonstrated a significant difference between men and women ( P Conclusions This study demonstrates a highly significant sex-related difference in CO 2 -induced cerebral vasomotor reactivity. The relation between altered carbon dioxide tensions and blood flow velocities of both middle cerebral arteries in 60 healthy volunteers was found to be exponential.

Processing of thin and ultra-thin glass displays is becoming more important in the fast increasing market of display manufacturing. As conventional technologies such as mechanical scribing followed by manual breaking mostly lead to bad edge quality and thus to a huge amount of reject, other processes like ablation processes [1] with picosecond lasers are getting more and more interesting. However processing with ultrashort pulsed lasers partially leads to unwanted effects which should be understood in a better way by means of intensive basic research. Therefore the ablation mechanism of ultrashort pulses on transparent materials was investigated in this research project. On the one hand the ablation mechanism was analyzed in a simulative way by means of rate equations on the other hand by laboratory experiments.

The need for micro scaled features in medical devices and engineering products, like holes for filtration, separation and ventilation or small structures e.g. for hydrophobic effects, is constantly increasing. The size of these structures is often in the region of 20 µm and smaller. One important aspect of the drilling or structuring process is the process stability and its influencing factors. For the laser perforation of a 15 µm thick Aluminum foil with UV ps-pulses the process limits as well as the influencing factors are investigated. The pitch of the holes within the pattern as well as the number of pulses used for the percussion drilling of each of the holes are varied. The drilled holes are evaluated by means of hole diameter and precision of the hole shape in means of circularity and ellipticity. Holes with a diameter of < 6 µm are drilled at a minimal pitch of 12 µm. The ellipticity is mainly dependent on the heat distribution, the circularity on polarization effects. In contrast to the perforation process with ns-pulses polarization effects play a major role for the perforation process with ps-pulses.

This study presents a novel numerical model for laser ablation and laser damage in glass including beam propagation and nonlinear absorption of multiple incident ultrashort laser pulses. The laser ablation and damage in the glass cutting process with a picosecond pulsed laser was studied. The numerical results were in good agreement with our experimental observations, thereby revealing the damage mechanism induced by laser ablation. Beam propagation effects such as interference, diffraction and refraction, play a major role in the evolution of the crater structure and the damage region. There are three different damage regions, a thin layer and two different kinds of spikes. Moreover, the electronic damage mechanism was verified and distinguished from heat modification using the experimental results with different pulse spatial overlaps.

African trypanosomes are extracellular protozoan parasites that are transmitted from one mammalian host to the next by tsetse flies. Bloodstream forms express variant surface glycoprotein (VSG); the tsetse fly (procyclic) forms express instead the procyclic acidic repetitive protein (PARP). PARP mRNA is abundant in procyclic forms and almost undetectable in blood-stream forms. Post-transcriptional mechanisms are mainly responsible for PARP mRNA regulation but results of nuclear run-on experiments suggested that transcription might also be regulated. We measured the activity of genomically-integrated PARP, VSG and rRNA promoters in permanently-transformed blood-stream and procyclic form trypanosomes, using reporter gene constructs that showed no post-transcriptional regulation. When the constructs were integrated in the rRNA non-transcribed spacer, the ribosomal RNA and VSG promoters were not developmentally regulated, but integration at the PARP locus reduced rRNA promoter activity in bloodstream forms. PARP promoter activity was 5-fold down-regulated in bloodstream forms when integrated at either site. Regulation was probably at the level of transcriptional initiation, but elongation through plasmid vector sequences was also reduced.

Thin glass sheets (thickness

While the cutting of thin glass becomes more and more interesting especially for display applications, direct glass ablation with ps-lasers is a promising technology but not completely understood with respect to ablation and damage mechanisms.The principal goal of this work is to generate a basic understanding of the ablation process by a combination of simulation4, experimental diagnostics1 and process development2,3.In this publication the free electron dynamics is discussed, a numerical model is implemented including beam propagation and nonlinear absorption. Finally the results from simulation and experiment are compared.Major findings achieved with the numerical model so far are: The critical electron density is adequate / complex enough as a criterion for material removal. For small pulse durations ( 10 ps) ablation criterion is intensity based. The damage mechanism is revealed/identified and qualitatively in good comparison with the experiment. Beam propagation effects like interference play a major role in the damage mechanisms.While the cutting of thin glass becomes more and more interesting especially for display applications, direct glass ablation with ps-lasers is a promising technology but not completely understood with respect to ablation and damage mechanisms.The principal goal of this work is to generate a basic understanding of the ablation process by a combination of simulation4, experimental diagnostics1 and process development2,3.In this publication the free electron dynamics is discussed, a numerical model is implemented including beam propagation and nonlinear absorption. Finally the results from simulation and experiment are compared.Major findings achieved with the numerical model so far are: The critical electron density is adequate / complex enough as a criterion for material removal. For small pulse durations ( 10 ps) ablation criterion is intensity based. The damage mechanism is revealed/identified and qualitatively in good comparison wit...

The application of the extrusion embossing process is a fast and cost-effective way to produce large-scale films with structured surfaces. In principle, microscopic and macroscopic surface structures can be manufactured this way. Particularly for the fabrication of microscopic structures, the reproduction accuracy can be remarkably improved by applying variothermal heating concepts for the embossing roll. In this article, two possible heating concepts are investigated: one laser-based and another using an inductor. The generated temperature profile along the circumference of the embossing roll is studied, taking the material of the embossing roll as well as different processing parameters into account. Both external heating systems (laser vs. inductor) are tested and compared. Furthermore, the improvement of the accuracy of the replicated microstructures is examined.

Messenger RNAs of higher eukaryotes share a functionally essential 5' monomethyl CAP structure generated during a reaction that is linked exclusively to RNA polymerase II transcription. In unicellular parasites belonging to the Kinetoplastida, however, mRNAs acquire their 5' CAP through a trans-splicing reaction which effectively uncouples pol II transcription and capping. Consequently functional mRNAs can be produced by endogenous RNA polymerase I. Here we demonstrate the extension of this flexibility to heterologous bacteriophage polymerases. Transgenic Trypanosoma brucei cell lines stably expressing functional, nuclearly localized T3 or T7 RNA polymerase were established and assayed using reporter plasmids bearing the corresponding phage promoters. In these cell lines the levels of phage promoter-driven gene expression ranges from one half to greater than 5 times that mediated by endogenous pol I. Analysis of 5' ends of transcripts synthesized by the T7 polymerase revealed that they are trans-spliced. Thus the usual eukaryotic link between mRNA production and pol II transcription can be by-passed by the introduced phage polymerases, thereby significantly expanding the critically small panel of promoters currently available for exploitation in reverse genetic approaches in T. brucei.

While virtual product development allows great freedom in terms of design, actual development processes are rather restricted. Those boundary conditions are at best hardly possible to exert influence on. Therefore, future research has to focus both on the realisation of the concept of one-piece-flow while simultaneously increasing flexibility and productivity and on the technological advancement. Hence, hybridisation of manufacturing processes is a promising approach, which often allows tapping potentials in all the aforementioned dimensions.

Micro-structured and thus functionalized surfaces offer high potentials for new approaches in processing techniques and product design. However, for mass production purposes quite a few challenges regarding the manufacturing of these surfaces have to be overcome. For the fast and economic production of large quantities of structured polymer films the extrusion embossing process is suitable. For embossing microstructures there are special requirements on temperature control because of the double function of the embossing roll. On the one hand the roll is used as an embossing roll with a high surface temperature to improve the embossing accuracy. On the other hand it is used as a cooling roll with a low surface temperature. Only by using variothermal heating systems these contradictory demands on the temperature control can be met. In order to achieve a high quality of the produced micro-structured films an integrative analysis and optimization of the entire process chain is required. This includes the manufacturing of suitable embossing rolls, the development of coating systems and the adaption of the extrusion process. This paper deals with the entire process chain for functionalized, super hydrophobic plastic parts with contact angles up to 165°. Therefore, conelike surface structures, mimicking the structure of lotus leaves, are replicated. Functionalized parts are produced in the injection molding as well as in the extrusion process; however, this paper focuses on the process chain of the extrusion process.

The usual way of realizing microstructured features on metallic surfaces is to generate the designated pattern on each single part by means of laser ablation, electro discharge machining or micro milling. A disadvantage of these process chains is the limited productivity due to the additional processing of each part. The approach taken by this project is to replicate microstructured surfaces via investment casting. The main research objective deals with the investigation of single process steps of the investment casting process with regard to the molding accuracy. To demonstrate the potential of microcast surfaces, current results for the casting of a microstructured hydrophobic surface will be shown.