Refine
Year of publication
- 2016 (73) (remove)
Document Type
- Doctoral Thesis (46)
- Article (27)
Language
- English (73) (remove)
Has Fulltext
- yes (73)
Is part of the Bibliography
- no (73)
Keywords
- - (25)
- Genetik (3)
- Pancreatic cancer (3)
- Atmosphärendruckplasma (2)
- Biokatalyse (2)
- Enzyme (2)
- Molecular biology (2)
- Molekularbiologie (2)
- Plasmadiagnostik (2)
- Plasmamedizin (2)
- Plasmaphysik (2)
- Protein-Engineering (2)
- Proteomics (2)
- Prävention (2)
- Schleimpilze (2)
- Slime molds (2)
- Slime moulds (2)
- Staphylococcus aureus (2)
- Thrombozyt (2)
- Thrombozytopenie (2)
- fMRI (2)
- plasma medicine (2)
- 1-deoxy sphingolipids (1)
- 3DM (1)
- <span style="font-variant:small-caps; text-transform:lowercase">L</span>-Carnitine (1)
- ASDEX (1)
- Abdominal fat (1)
- Abiraterone (1)
- Afrika (1)
- Akt (1)
- Alcohol dehydrogenases (1)
- Alexithymia (1)
- Angiogenesis (1)
- Animal models (1)
- Antibacterial efficacy (1)
- Antikörper (1)
- Aquatic Interfaces (1)
- Art (1)
- Arxula adeninivorans (1)
- Atomspektrum (1)
- BDNF (1)
- BK-virus (1)
- Bacillus (1)
- Bacterial infection (1)
- Band (1)
- Beckenboden (1)
- Bernoulli convolutions (1)
- Bernoulli-Faltungen (1)
- Binaural beats (1)
- Biocatalysis (1)
- Biogeochemie (1)
- Biogeografie (1)
- Biomarkers (1)
- Biotechnologie (1)
- Bose-Einstein-Kondensation (1)
- CP7_E2alf (1)
- Calcium regulation (1)
- Caries decline (1)
- Cell surface molecules (1)
- Central Europe (1)
- Ceramide (1)
- Cerebral angiogram (1)
- Cerebral cavernous malformations (1)
- Cerebrovascular disease (1)
- Changai (1)
- Chemotherapy (1)
- Childhood trauma (1)
- Children (1)
- Chiral alcohols (1)
- Classical swine fever virus (1)
- Cluster (1)
- Cold atmospheric pressure plasma (1)
- Community dentistry (1)
- Community-based Health Insurance (1)
- Complement (1)
- Cytoprotection (1)
- DIVA-Impfstoff (1)
- Demenz (1)
- Dental profiles (1)
- Dental public health (1)
- Deutschland (1)
- Diabetes mellitus (1)
- Differentialgleichung (1)
- Diffusion (1)
- Dilated cardiomyopathy (1)
- Disease management (1)
- Dissociation (1)
- Dual-task (1)
- Dusty Plasma (1)
- ECC (1)
- EPR (1)
- ERK1/2 (1)
- Ecology (1)
- Efficacy (1)
- Effizienz (1)
- Eisenoxid-Nanopartikels (1)
- Eisflussmodellierung (1)
- Elastizitätstheorie (1)
- Electroencephalography (1)
- Elektronenemission (1)
- Elektronenparamagnetische Resonanz (1)
- Endomyokardbiopsien und Plasma (1)
- Enteral nutrition (1)
- Enzym (1)
- Enzyme identification (1)
- Enzymidentifizierung (1)
- Epidemiologie (1)
- Epilepsy (1)
- Epoxid-Hydrolase (1)
- Esterasen (1)
- Extracellular matrix (1)
- Exziton (1)
- FOLFIRINOX (1)
- FTIR (1)
- Ficus species (1)
- Ficus-Arten (1)
- Fidschi (1)
- Flüssigkeiten (1)
- Fusion plasma (1)
- Fusionsplasma (1)
- General Anesthesia (1)
- Genetics (1)
- Geochronologie (1)
- Geomorphologie (1)
- Germany (1)
- Gesundheitssysteme (1)
- Gesundheitssystementwicklung (1)
- Gesundheitsökonomie (1)
- Glucocorticoid receptor (1)
- Guided Streamer (1)
- Haemorrhagic cystitis (1)
- Haloalkan-Dehalogenase (1)
- Hansenula polymorpha (1)
- Heart Failure (1)
- Heat shock protein 27 (1)
- Heißes Plasma (1)
- Heparin (1)
- Herzchirurgie (1)
- Herzinsuffizienz (1)
- Hot plasma (1)
- Hue (1)
- Human (1)
- Hutchinson Operator (1)
- Hutchinson-Operator (1)
- Hydrolasen (1)
- Immobilisierung (1)
- Immobilization (1)
- Immunantwort (1)
- Immunbiologie (1)
- Immune response (1)
- Immunkomplex (1)
- Immunoadsorptionstherapie (1)
- Immunsystem (1)
- Impfstoff (1)
- Imunoadsorption therapy (1)
- Inanspruchnahme (1)
- Infektionen (1)
- Informeller Sektor (1)
- Innate immunity (1)
- Innere Energie (1)
- Insulin (1)
- Integrierte Soziale Sicherung (1)
- Internet (1)
- Intracerebral haemorrhage (1)
- Ionenstrahlfalle (1)
- Iterated Function System (1)
- Iteriertes Funktionensystem (1)
- Kardiovaskuläre Krankheit (1)
- Kernfusion (1)
- Kinder (1)
- Kinetische Gastheorie (1)
- Krankenversicherung (1)
- Krankheitskosten (1)
- LSR (1)
- Lebendmarker-Vakzine (1)
- Leptin (1)
- Limnologie (1)
- Linear Elasticity (1)
- Lipoprotein (1)
- Lévy processes (1)
- Lévy-prozess (1)
- MRP3 (1)
- Magnetohydrodynamik (1)
- Massenspektrometrie (1)
- Maus (1)
- Mediation analysis (1)
- Metabolismus (1)
- Metabolomics (1)
- Methicillin-resistant (1)
- Microarrays (1)
- Modellbildung (1)
- Modenübergang (1)
- Molecular Modelling (1)
- Molecular modelling (1)
- Mongolei (1)
- Mongolia (1)
- Mongolischer Altai (1)
- Monitoring (1)
- Myodes glareolus (1)
- N-Acyl-L-Homoserinlakton (1)
- NOD/SCID mouse model (1)
- Nab-paclitaxel (1)
- Narkose (1)
- Neonatal outcome (1)
- Neonates (1)
- Nephropathy (1)
- Netz (1)
- Neue Medien (1)
- Neukaledonien (1)
- Neutrophil extracellular traps (1)
- Niedertemperaturplasma (1)
- Nuckelflaschenkaries (1)
- Oberflächendatierung (1)
- Omega-3 fatty acids (1)
- Optimal Control (1)
- Optimale Kontrolle (1)
- Organic Matter (1)
- Organischer Stoff (1)
- P-Glykoprotein (1)
- PDAC (1)
- PDE (1)
- PI3K (1)
- PLK1 (1)
- PRP (1)
- PTSD (1)
- Palliative chemotherapy (1)
- Paläoklima (1)
- Pancreatitis (1)
- Panton-Valentin-Leukozidin (1)
- Panton-Valentine Leukocidin (1)
- Parenteral nutrition (1)
- Pazifischer Ozean <Süd > (1)
- Perinatal infection (1)
- Pharmakogenetik (1)
- Pharmakokinetik (1)
- Phosphoproteomik (1)
- Phylogenie (1)
- Physik (1)
- Physiologie (1)
- Pilz-Endophyten (1)
- Pilz-Vielfalt (1)
- Plasma-Flüssigkeits-Wechselwirkung (1)
- Plasmachemie (1)
- Polaron (1)
- Polymorphism (1)
- Polynesien (1)
- Population genetics (1)
- Populationsgenetik (1)
- Precision medicine (1)
- Preterm infants (1)
- Prevalence (1)
- Prevention (1)
- Process engineering (1)
- Progenitor cells (1)
- Progenitorzellen (1)
- Prostate cancer (1)
- Protamine (1)
- Protease (1)
- Proteine (1)
- Proteinphosphorylierung (1)
- Proteinreinigung (1)
- Proteomik (1)
- Prozesstechnik (1)
- Psychiatrie (1)
- Puumala virus (1)
- Quantendot (1)
- Quantengruppe (1)
- Quantenwahrscheinlichkeitstheorie (1)
- Quorum quenching (1)
- Quorum sensing (1)
- RNS (1)
- ROS (1)
- Radiation (1)
- Radiofrequenz (1)
- Random matrices (1)
- Reaktionskaskade (1)
- Recurrent depression (1)
- Redox Biogeochemie (1)
- Redox Biogeochemistry (1)
- Referred (1)
- Rekrutierung (1)
- Responder und Nicht-Responder (1)
- SPIONs (1)
- Schale (1)
- Schlaganfall (1)
- Schlieren (1)
- Schlinge (1)
- Schnecken (1)
- Schweineleber-Esterase (1)
- Screening (1)
- Sekundärmetaboliten (1)
- Shells (1)
- Sicherheit (1)
- Simulation (1)
- Social Health Insurance (1)
- Socio-economic status (1)
- Soziale Krankenversicherung (1)
- Sozialversicherung (1)
- Spektroskopie (1)
- Spektrum (1)
- Sphingolipide (1)
- Spin Trap (1)
- Spin Trapping (1)
- Statistik (1)
- Staubiges Plasma (1)
- Stem cell transplantation (1)
- Stereotactic surgery (1)
- Synthetic Biology (1)
- Synthetische Biologie (1)
- THP-1 cells (1)
- TRP channels (1)
- Talinolol (1)
- Targeted delivery (1)
- Temperatur (1)
- Theranostics (1)
- Thyroid function (1)
- Thyroid-stimulating hormone (1)
- Tokamak (1)
- Tolerability (1)
- Tomographie (1)
- Tourismus (1)
- Tracer particles (1)
- Tracerpartikel (1)
- Transaminasen (1)
- Transfer Operator (1)
- Transfer-Operator (1)
- Transportproteine (1)
- Tropen (1)
- Truncatelloidea (1)
- Tumor spezifischer Transport (1)
- Universal Health Coverage (1)
- Universelle Abdeckung (1)
- Urological complications (1)
- Vanuatu (1)
- Vergletscherung (1)
- Verhaltensmodifikation (1)
- Vietnam (1)
- Virulence (1)
- Virus der klassischen Schweinepest (1)
- Visceral adipose tissue (1)
- Visceral body fat (1)
- Vitronectin (1)
- Waves (1)
- Wellen (1)
- Wirt-Erreger Interaktion (1)
- Wirtsorganismus (1)
- Yeast (1)
- Zahnstatus (1)
- Zeeman and Stark effects (1)
- Zeeman- und Stark-Effekte (1)
- Zerstörung (1)
- Zufallsmatrizen (1)
- Zylinderschale (1)
- adhesin A (1)
- affective neuroscience (1)
- alloplastische Materialien (1)
- amygdala (1)
- aquatische Grenzzonen (1)
- arousal (1)
- atomic spectra (1)
- bank vole (1)
- caries prevelance (1)
- catalytic promiscuity (1)
- cell signaling (1)
- climate extremes (1)
- dendritic spine function (1)
- dendrometer measurements (1)
- destination image (1)
- destination loyalty (1)
- diffusion weighted imaging (1)
- dilatative Kardiomyopathie (1)
- duktale Adenokarzinom des Pankreas (1)
- dystrophin deficient (1)
- efficacy (1)
- electron emission (1)
- emotion (1)
- emotion perception (1)
- endemic region (1)
- endoscope-assisted (1)
- enzyme evolution (1)
- event coincidence analysis (1)
- evolutionary lineage (1)
- face perception (1)
- free probability (1)
- fungal diversity (1)
- fungal endophytes (1)
- gamma (1)
- gemeindebasierte Krankenversicherung (1)
- geochronology (1)
- gerichtete Evolution (1)
- glaciers (1)
- group prevention (1)
- growth response (1)
- guided streamer (1)
- hemifacial spasm (1)
- host pathogen interactions (1)
- hydrolases (1)
- ice flow model (1)
- individual differences (1)
- internal energy (1)
- intestinale Absorption (1)
- intraoperative monitoring (1)
- invariant measure (1)
- invariantes Maß (1)
- ion-beam trap (1)
- katalytische Promiskuität (1)
- lateral spread (1)
- life-span development (1)
- live marker vaccine (1)
- microvascular decompression (1)
- motivation (1)
- motor outcome (1)
- multilayers (1)
- neural circuits and behavior (1)
- neuroimmune interactions (1)
- outbreak (1)
- p38 (1)
- phagocytosis (1)
- phonon localization (1)
- phonon propagation (1)
- pig liver esterase (1)
- plasma-liquid-interaction (1)
- prediction (1)
- protein engineering (1)
- proteomics (1)
- psychiatric disorders (1)
- pulsed laser deposition (1)
- pump-probe spectroscopy (1)
- quantum groups (1)
- quantum probability (1)
- recovery (1)
- reinforcement learning (1)
- resting state fMRI (1)
- safety (1)
- secondary metabolites (1)
- sexual dimorphism (1)
- social relationships in school (1)
- spectrum (1)
- stroke (1)
- sub-Saharan Africa (1)
- surface exposure dating (1)
- synaptic function (1)
- synaptic remodeling (1)
- synaptic transmission (1)
- temperature (1)
- tourism (1)
- tourist satisfaction (1)
- transbilayer lipid (flip-flop) motion (1)
- tropics (1)
- visual processing (1)
- Ökologie (1)
Institute
- Institut für Physik (9)
- Institut für Biochemie (7)
- Abteilung für Mikrobiologie und Molekularbiologie (5)
- Institut für Botanik und Landschaftsökologie & Botanischer Garten (4)
- Institut für Mathematik und Informatik (3)
- Institut für Psychologie (3)
- Klinik für Psychiatrie und Psychotherapie (3)
- Klinik und Poliklinik für Neurologie (3)
- Poliklinik für Kieferorthopädie, Präventive Zahnmedizin und Kinderzahnheilkunde (3)
- Institut für Geographie und Geologie (2)
Publisher
- S. Karger AG (15)
- Frontiers Media S.A. (8)
- De Gruyter (1)
- IOP Publishing (1)
The aim of this retrospective observational study is to describe and discuss various complications that can arise after insertion of alloplastic materials in the field of urogynecology that require further surgical interventions in order to manage them or to at least improve the quality of life in those women. We were able to collect data on 77 patients who fulfilled the criteria. Medical history, data of clinical findings, and outcomes were collected and analyzed. The most common complication seen as an indication for resecting slings or meshes was de novo overactive bladder syndrome (40%). Other indications seen were lower urinary tract obstruction or obstructive voiding symptoms (21%), chronic pain (21%), and de novo dyspareunia (13%). 36% of the patients had recurrent symptoms (failure) after insertion of alloplastic materials in the form of urinary incontinence or prolapse, 32% presented with vaginal erosions, 2 women had severe signs of infection with abscess formation, another 3 women had urogenital fistulae. Other rare complications after mesh or sling insertion are perforations of the urinary bladder or urethra. Proper case selection is the key factor. The use of meshes and slings seems justified only in patients with known connective tissue weakness and recurrences after native tissue repair. Otherwise, patients will be exposed to unnecessary risk without any expectable improvement to their quality of life. Most of the complications are mainly caused by wrong and inadequate surgical techniques, wrong indications, or missed diagnosis of the underlying problem. In addition, lack of long-term follow-up is usually the cause behind the negligence towards many complications. Therefore, only experienced physicians should be allowed to perform such procedures, and long-term postoperative follow-up is strongly recommended. As slings and meshes are used for procedures of choice as means to improve quality of life, and not for life threatening situations, there is a need for intensive informed consent. All possible alternatives have to be discussed, as do the pros and cons of selected procedures, even the rare complications. Mesh or sling resection is considered to be an effective solution for the management of such complications. It has shown a high success rate in comparison to conservative treatment, and the majority of patients were satisfied and experienced a big improvement in their quality of life. The most common complication after resection is the recurrence of primary symptoms, either urinary incontinence or prolapse. Major or serious intra- or postoperative complications are very rare. All complications were classified and given a code according to the classification system of the international urogynecological association and the international continence society (IUGA/ICS) on 2011. The applicability and practicability of this code were evaluated, looking for ways to possibly improve it or to identify missing parameters. Many patients had more than one code, a problem that entirely torpedoed the idea of “simple” classification. Some complications are not covered individually in the classification, such as failure and recurrence or overactive bladder syndrome. These complications should be included. Many cases began with the same code, despite having different complications. Further sub-classifications should be considered to enable the reader to easily recognize the complication at hand. Patients who came with complications more than one year after mesh or sling insertion were categorized as (T4), regardless of whether the complication arose after 1 year of after 10. Therefore, sub-classifications in the (T4) category are recommended. The “site” category was not applicable in many cases. Furthermore, it is necessary that the severity of a complication is discernible, and should be mentioned in the code. We did not find any correlation between the code given and patient satisfaction. After re-modification and completion, the IUGA/ICS code could be more practical for clinical use, which would allow for the comparison of complications and make the assessment of adverse effects easier for research purposes.
Dilated cardiomyopathy (DCM) is a myocardial disorder characterised by ventricular dilation with reduced left ventricular ejection fraction (LVEF). Immunoadsorption (IA) followed by immunoglobulin (IgG) substitution (IA/IgG) has been shown to be a promising therapeutic intervention to recover myocardial functions in DCM patients. The beneficial effects of IA/IgG therapy are associated with increased LVEF, decreased left ventricular inner diameter at diastole (LVIDd) and reduced myocardial inflammation. Despite knowing the cardiac benefits of IA/IgG, the precise molecular mechanism induced by therapy is still elusive. Additionally, only ≈60 % DCM patients treated with IA/IgG demonstrated improved heart function. Moreover, the reasons for this differential outcome among DCM patients after treatment have not been clearly understood. In this study, efforts were made to uncover the therapy induced proteomic changes in the heart of responders (relative change in LVEF ≤ 20%, LVEF < 5% absolute value) and non-responders using a global proteomic approach. Apart from it, proteomic profiling of endomyocardial biopsies and plasma was performed to find protein biomarker candidates which might be useful to distinguish responder and non-responder DCM patients before immunoadsorption therapy and support a selective and individualized treatment. To reveal therapy induced myocardial proteomic changes, endomyocardial biopsies of DCM patients before and after therapy were compared. LVEF increased (32 ± 8 to 45±7, p<0.002) and LVIDd decreased (66 ± 6 to 60±6, p<0.040) after therapy in responders, whereas non-responders did not show any significant changes in these clinical parameters. To address the changes in the myocardial proteome induced by therapy, a label-free proteomic approach was applied. The most prominent proteomic differences between both subgroups were observed in cytoskeletal, fibrosis, and extracellular matrix proteins. Therapy linked benefit in responders seems to be highly associated with the lower abundance of fibrotic and extracellular matrix proteins which seems to reflect a lower activity of transforming growth factor-β signaling. To elucidate proteomic differences between responders and non-responders at baseline, endomyocardial biopsies and plasma proteome profiling were performed. Responder and non-responder DCM patients did not show any significant differences in the clinical parameters (LVEF, LVIDd, age, inflammation, etc.) before IA/IgG therapy except for disease duration that was in tendency higher among non-responders. Proteomics profiling of endomyocardial biopsies revealed 54 differentially abundant proteins between responders and non-responders. Among those proteins, Protein S100-A8 and kininogen-1 was found higher whereas perilipin-4 was found lower abundant in responders. Plasma profiling of these subgroups revealed five proteins (S100-A8, S100-A9, C-Reactive protein, lipopolysaccharide-binding protein, and cysteine-rich secretory protein) displaying strong discriminative power between responders and non-responders. Higher abundance of Protein S100-A8 was observed in myocardium as well as in plasma among responders. Protein S100-A8 might be a potential candidate to distinguish responders and non-responders at baseline, and its potential utility at clinical levels must be evaluated. The last objective of the thesis was to establish a workflow for the relative quantitation of phosphopeptides for samples generally obtained in small amounts like myocardial biopsies. To address this question, optimization was performed with HL-1 cardiomyocytes using a PolyMAC phosphopeptide enrichment kit and the effect of TGF-β1 on the phosphoproteome was evaluated as a proof-of-principle study. Using only 200µg protein of each sample up to 2000 phosphopeptides with an efficiency of >90 percent could be covered. In total, upon TGF-β1 incubation alterations of 214, 92, and 53 phosphopeptides were observed after 1, 6 and 24 hours, respectively. Differentially altered phosphopeptides belonged to many signaling pathways including the ubiquitin-proteasome pathway, cytoskeletal regulation by Rho GTPase, calcium signaling, and TGF-β signaling. Thus, in this study a workflow for relative quantitation of phosphopeptides was established that may be later applied to precious biopsy samples. Along with this, TGF- β1 induced phosphoproteome was analysed in HL-1 cardiomyocytes.
The thesis deals with ions stored in an electrostatic ion beam trap. In the first part of the thesis the so-called self-synchronization effect is discussed. It is demonstrated that the time a bunch of injected ions is conserved by the self-synchronization effect depends on the number of injected ions. In the second part of the thesis the cooling of small anionic cobalt and copper clusters is addressed. Measurements on anionic copper clusters consisting of four to seven atoms are presented and the decay of hot clusters is observed in order to draw conclusions on the internal temperature and the cooling process itself. Afterwards measurements on Co4- are discussed and a measurement scheme based on laser induced delayed electron emission is presented enabling to monitor the internal energy distribution of the clusters over storage time in a temperature-controlled environment. The cooling of initially hot clusters as well as the heating of initially cold clusters were observed.
Achieving commercial production of electricity by magnetic confinement fusion requires improvements in energy and particle confinement. In order to better understand and optimise confinement, numerical simulations of plasma phenomena are useful. One particularly challenging regime is that in which long wavelength MHD phenomena interact with kinetic phenomena. In such a regime, global electromagnetic gyrokinetic simulations are necessary. In this regime, computational requirements have been excessive for Eulerian methods, while Particle-in-Cell (PIC) methods have been particularly badly affected by the "cancellation problem", a numerical problem resulting from the structure of the electromagnetic gyrokinetic equations. A number of researchers have been working on mitigating this problem with some significant successes. Another alternative to mitigating the problem is to move to a hybrid system of fluid and gyrokinetic equations. At the expense of reducing the physical content of the numerical model, particularly electron kinetic physics, it is possible in this way to perform global electromagnetic PIC simulations retaining ion gyrokinetic effects but eliminating the cancellation problem. The focus of this work has been the implementation of two such hybrid models into the gyrokinetic code EUTERPE. The two models treat electrons and the entire bulk plasma respectively as a fluid. Both models are additionally capable of considering the self-consistent interaction of an energetic ion species, described gyrokinetically, with the perturbed fields. These two models have been successfully benchmarked in linear growth rate and frequency against other codes for a Toroidal Alfvén Eigenmode (TAE) case. The m=1 internal kink mode, which is particularly challenging in terms of the fully gyrokinetic cancellation problem, has also been successfully benchmarked using the hybrid models with the MHD eigenvalue code CKA. Non-linear simulations in this TAE case have been performed confirming the analytical prediction of a quadratic relationship between the linear growth rate of the TAE and the saturated amplitude of the TAE for a range of moderate values of the linear growth rate. At higher linear growth rate, a slower scaling of saturated amplitude with linear growth rate is observed. This analysis has been extended to include the non-linear wave-wave coupling between multiple TAE modes. It has been shown that wave-wave coupling results in a significant reduction in the saturated amplitude. It has been demonstrated that both plasma elongation and ion kinetic effects can exert a stabilising influence on the internal kink mode. A population of energetic particles can also exert a stabilising influence at low normalised pressure. At high normalised fast particle pressure the stabilised kink mode has been shown to give way to the m=1 EPM, which has been simulated both linearly and non-linearly (the "fishbone" mode). The first self-consistent simulations of global modes in the magnetic geometry of the optimised stellarator Wendelstein 7-X have been performed both linearly and non-linearly. Limitations have been encountered in performing simulations in 3D geometry. A hypothesis for the cause of these problems is outlined and ideas for mitigation are briefly described. In addition to the hybrid model simulations, some of the first utilisations of a new scheme for mitigating the cancellation problem in the fully gyrokinetic regime have been carried out in the framework of this thesis. This scheme, which was developed separately, is concisely described in this work. The new scheme has been benchmarked with existing gyrokinetic and hybrid results. The linear Wendelstein 7-X simulations and linear and single mode non-linear TAE simulations have been repeated with the new model. It is shown that bulk plasma kinetics can suppress the growth rate of global modes in Wendelstein 7-X. The results of fully gyrokinetic TAE simulations, the first to have been performed to our knowledge, are shown to be in close agreement with those results obtained using hybrid models. In the TAE case, the hybrid models are an order of magnitude less computationally demanding than the new gyrokinetic scheme, which is in turn at least an order of magnitude less computationally demanding than the previous gyrokinetic scheme.
Myxomycetes are fungus-like protists of the supergroup Amoebozoa found to be abundant in all terrestrial ecosystems. Mainly based on its macroscopically visible fruit bodies, our knowledge on ecology and diversity of myxomycetes is better than for most other protistean groups, but there is still a lacking knowledge about global diversity patterns since tropical regions, especially the old world tropics, are still understudied. In this thesis a combination of classical ecological analyses and modern molecular methods were used to expand the current knowledge on myxomycete diversity and biogeography in the Paleotropics. A number of surveys in the Philippine archipelago are conducted to provide and to add information about the distribution of myxomycetes in the Southeast Asian region. A combination of field collecting and ca. 2500 moist chamber cultures from four unexplored areas in the Philippines, namely, the Bicol Peninsula (746 records, 57 taxa), Puerto Galera (926 records, 42 taxa), Quezon National Park (205 records, 35 taxa), and Negros Province (193 records, 28 taxa), now brings the number of species recorded for Philippines to 150; with one record, Stemonaria fuscoides, noted as new for the Asian Paleotropics. Collecting localities that have more diverse plant communities showed as well higher species diversity of myxomycetes. In congruence with studies from the Neotropical forests, it seems also that anthropogenic disturbances and the type of forest structure affect the occurrence of myxomycetes for the Philippines. Another survey carried out in another paleotropical region, the highlands of Ethiopia, revealed a total of 151 records, with all 39 species found as new for the country. Three records of Diderma cf. miniatum with a strong bright red peridium and one record of Didymium cf. flexuosum with a conspicuous broad reticulation in the spore ornamentation were described and barcoded, since both may represent morphospecies new to science. A number of rarely recorded species, like Didymium saturnus, Metatrichia floripara, Perichaena areolata, and Physarina echinospora showed that resembling to its unique flora, the east African mountain ranges harbor a diverse and distinctive myxomycete assemblage. One incentive of this study was to compile a solid large dataset for the Paleotropical region that is comparable to data obtained from comprehensive studies performed in the Neotropical areas a decade ago. A total of eight surveys (with four comprehensive regional surveys, two from lowland and two from highland, for each region, the Neo- and the Paleotropics) were used, to compare the myxomycete assemblages of both regions. Each survey comes from a region with fairly homogenous vegetation, and includes specimens from both field and moist chamber cultures component. A statistical analysis of species accumulation curves revealed that only between 70 and 95% of all species to be expected have been found. Even for >1000 specimens per survey these figures seem hardly to increase with increasing collection effort, since a high proportion of species is always represented by a single or a few records only. Both ordination and cluster analysis suggests that geographical separation explains differences in species composition of the myxomycete assemblages much better than elevational differences. 5 The molecular component of this thesis is a phylogeographic study of the widely distributed tropical myxomycete Hemitrichia serpula. It is a morphologically distinct species with golden-yellow fructifications forming a reticulum. However, subtle variation in spore ornamentation points to cryptic speciation within this myxomycete. Using two independent molecular markers, 135 partial sequences of the small subunit (SSU) rRNA (a nuclear but extrachromosomal gene) and 30 partial sequences of the elongation factor 1 alpha gene (EF1A) (a nuclear gene), a study of 135 Hemitrichia serpula specimens collected worldwide revealed the existence of four clades that are likely to represent reproductively isolated biospecies, since each clade shows a unique combination of SSU and EF1A genotypes. A Mantel test with the partial SSU sequences indicated geographical differentiation, giving a correlation coefficient of 0.467 between the pairwise computed geographic and genetic distances, compared with the 95% confidence interval from 999 permutations (-0.013 to 0.021). Biogeographical analysis of the 40 SSU ribotypes showed clear intraspecific variation and geographic differentiation demonstrating a limited gene flow among the world population. We argue that the distribution of cryptic species in the different clade can be explained by ongoing, but still incomplete speciation. An event-based ancestral area reconstruction using the software S-DIVA employed in RASP showed that the probable origin of the ribotypes was a global dispersal event in the Neotropics. Additional species distribution models that were implemented for the three most prominent clades show different putative ranges. As such H. serpula supports the moderate endemicity hypothesis for protists. In summary, myxomycete assemblages in the Paleotropics (1) displayed a higher diversity than for Neotropical forests, (2) harbor unique taxa that differentiates those assemblages in spite of the expected similar macroecological all over the Tropics, (3) are affected by geographical barriers that likely causes speciation both at a morphospecies and biospecies level, and (4) follow the ubiquitous model in the sense that gene flow mediated by long-distance dispersal of spores is high enough that a species can fill out its entire putative range, but (5) the gene flow is not high enough to prevent variation in regional gene pools, which may lead to speciation and is better explained by the moderate endemicity model. Our data are still too limited to draw a comprehensive picture of the diversity of tropical myxomycetes, but the baseline information compiled with the aid of both classical ecology and molecular approaches from this study are first major steps towards this goal.
The antigen in heparin-induced thrombocytopenia (HIT) is expressed on platelet factor 4 (PF4) when PF4 complexes with polyanions. In recent years, biophysical tools (e.g. circular dichroism spectroscopy, atomic force microscopy, isothermal titration calorimetry, x-ray crystallography, electron microscopy) have gained an important role to complement immunological and functional assays for better understanding the interaction of heparin with PF4. This allowed identification of those features that make PF4 immunogenic (e.g. a certain conformational change induced by the polyanion, a threshold energy of the complexes, the existence of multimeric complexes, a certain number of bonds formed by PF4 with the polyanion) and to characterize the morphology and thermal stability of complexes formed by the protein with polyanions. These findings and methods can now be applied to test new drugs for their potential to induce the HIT-like adverse drug effect by preclinical in vitro testing. The methods and techniques applied to characterize the antigen in HIT may also be helpful to better understand the mechanisms underlying other antibody-mediated disorders in thrombosis and hemostasis (e.g. acquired hemophilia, thrombotic thrombocytopenic purpura). Furthermore, understanding the mechanisms making the endogenous protein PF4 immunogenic may help to understand the mechanisms underlying other autoimmune disorders.
Hantaviruses are enveloped viruses with a single-stranded RNA genome of negative polarity. The genome consists of three segments: small (S), medium (M) and large (L). As zoonotic pathogen, hantaviruses are worldwide responsible for 150,000 to 200,000 human disease cases per year. Two forms of human disease are currently distinguished: In the Americas the hantavirus cardiopulmonary syndrome (HCPS) and in Europe and Asia the hemorrhagic fever with renal syndrome (HFRS). Since the introduction of the German Protection against Infection Act in 2001 until now a total of 10,082 disease cases have been reported. As a result, hantavirus infections currently rank as the fifth frequent notifiable disease in Germany. More than 80% of these infections were caused by the hantavirus species Puumala virus (PUUV), transmitted by the bank vole Myodes glareolus. Besides temporal oscillations, an unequal geographical distribution of human PUUV cases was noticed in Germany and in other countries of Central Europe. This is reflected in the presence of endemic and non-endemic regions as well as of so-called outbreak years. Therefore, the overall objective of this study was to find out possible reasons for the inhomogeneous distribution of PUUV in Central Europe, in particular in Poland, Germany and certain districts of Baden-Wuerttemberg. The basic working hypothesis was that PUUV spread in Central Europe after the last glaciation with different evolutionary lineages of the bank vole and that the current emergence of PUUV in bank vole populations is determined by local geographical and ecological factors. Very little was known about the presence of PUUV in Poland. Earlier studies were based exclusively on serological detection of PUUV, but a molecular detection with subsequent phylogenetic investigation was missing so far. Therefore, 45 bank voles from the northeastern part of Poland were investigated by serological and molecular assays. In three animals from a forest region close to the city of Miko³ajki PUUV-reactive antibodies and/or PUUV RNA were detected. Phylogenetic analysis indicated the presence of a Latvian (LAT) PUUV strain. Viral RNA was detected in one bank vole of the Eastern evolutionary lineage and two animals of the Carpathian lineage. Thereby it could be demonstrated for the first time that the distribution of the LAT PUUV lineage ranges from Latvia south-west to the northeastern part of Poland. An inhomogeneous spatial distribution of human disease cases has been observed even for Baden-Wuerttemberg, a long time known endemic federal state of Germany. Therefore 660 bank voles were trapped during the outbreak and non-outbreak years 2012 and 2013 in four districts with high incidences (H) and in four districts with low incidences or lacking PUUV cases (L). During the outbreak year 2012 PUUV-positive bank voles were detected by serological and molecular investigations in seven of eight districts. In contrast, in the following year only in one district PUUV infected bank voles were detected. Furthermore, it was demonstrated that after a beech mast, i.e., a massive fructification of beech trees, in H districts with a higher percentage of beech forest coverage a higher number of human cases was notified, but not in L districts with a lower percentage of beech forest coverage. For the future development of early warning modules it is therefore necessary to have a long-term bank vole monitoring established that incorporates beech mast data and information on beech forest coverage. High endemic regions for PUUV are mainly located in the southern and western parts of Germany, whereas in the eastern and northern parts only low numbers or even no human cases are recorded. To find out possible reasons for this inhomogeneous distribution, 1,774 bank voles from different regions of Germany were investigated for PUUV infections and in parallel for the corresponding bank vole evolutionary lineage (Western, Eastern, Carpathian). The PUUV investigations indicated positive voles in the known endemic regions with an easternmost and northernmost occurrence in western Saxony-Anhalt, western Thuringia and in Osnabrück. In the northern and eastern part of Germany none of the 1,210 investigated bank voles showed a PUUV infection. In the southern and western parts of Germany only the Western bank vole lineage was identified, whereas the Eastern lineage was exclusively found in the eastern and northern part and the Carpathian lineage in the South-East and North-East of Germany. PUUV infections were found almost exclusively in bank voles of the Western lineage. Individuals of the other two vole lineages were found to be PUUV infected only in regions with sympatric occurrence of the Western lineage. The previously described contact zone of the different bank vole phylogroups ranges from Poland to the entire northern part of Germany. In conclusion, the results of this investigation indicate two potential major reasons for the inhomogeneous distribution of PUUV in Germany: First, PUUV of the CE lineage seems to be associated with the Western bank vole lineage. The current geographical distribution of virus and host might be explained by a post-glacial northern expansion of the bank vole starting at the western refuge. Second, the missing detection of PUUV in bank voles of the Western lineage in areas close to high endemic regions might be explained by the extinction of the virus due to a limited winter survival of infected animals during long and harsh winters. The virus stability outside the host or ecological barriers, such as isolated forest areas or broad rivers, might also influence the distribution of PUUV in bank vole populations.
The presented study was dedicated to outstanding issues in regard to the safety and efficacy of the LAV “CP7_E2alf”, during the final licensing process and towards its putative implementation in outbreak scenarios as emergency vaccine. (I) For application of a genetically engineered virus under field conditions, knowledge about its genetic stability is mandatory. Therefore, the genetic stability of “CP7_E2alf” needed to be assessed in vivo and in vitro. Mutation rates were compared to the parental pestivirus strains (BVDV-1 “CP7” and CSFV “Alfort/187”), and BVDV or CSFV field-strains. There was no indication that “CP7_E2alf” could be more prone to mutational events than its parental viruses or representative field-strains. Moreover, no recombination events were observed in in vitro experiments. In conclusion, the data obtained in this study confirm a strong genetic stability of “CP7_E2alf” as an important safety component. (II) Since vaccination of breeding animals is often discussed, this study was conducted to assess the safety of “CP7_E2alf” vaccination of breeding male pigs. The study with “CP7_E2alf” vaccinated boar demonstrated that the new CSFV marker vaccine is suitable for application in reproductive boar. Neither in organs of the uro-genital tract related to sperm production nor in urine or feces, vaccine virus genome was detectable. Dissemination of “CP7_E2alf” through semen, and shedding with urine and feces, is therefore highly unlikely. (III) In order to investigate the influence of pre-existing pestivirus antibodies of the efficacy of “CP7_E2alf”, a vaccination-challenge-trial was conducted with “CP7_E2alf” (Suvaxyn® CSF Marker) and the “gold-standard” of live-modified CSFV vaccines, the C-strain (RIEMSER® Schweinepestvakzine). Pre-existing antibodies against BVDV-1 were provoked through intramuscular inoculation of a recent field isolate from Germany. Seven days after the vaccination, all animals were challenged with highly virulent CSFV strain “Koslov”. It was demonstrated that pre-existing anti- BVDV-1 antibodies do not impact the efficacy of both live attenuated vaccines against CSFV. Both C-strain “Riems” and marker vaccine “CP7_E2alf” were able to confer full protection against the highly virulent challenge. However, slight interference was seen with serological DIVA diagnostics accompanying “CP7_E2alf”. Amended sample preparation and combination of test systems was able to resolve most cases of false positive reactions. However, in such a coinfection scenario, optimization and embedding in a well-defined surveillance strategy is clearly needed for marker vaccination scenarios. (IV) To supplement the data about the kinetic of maternally derived antibodies in piglets from sows vaccinated during outbreaks, a single “emergency-type” vaccination of two pregnant sows was done. Focus was laid on the kinetics of maternally derived antibodies (MDA) in the screening assays of their offspring with screening assays that would be used in case of CSFV outbreaks, i.e. CSFV E2 and Erns antibody ELISA. Upon vaccination with “CP7_E2alf” 21 days before farrowing, MDAs were measurable in all piglets born to vaccinated sows. The E2- ELISA reactivities showed an almost linear decrease over ten weeks after which all piglets were tested negative in the ELISA. Future studies should investigate, if MDA are able to protect offspring of vaccinated sows or whether the piglets should also be vaccinated.
Abstract
Nanoscale multilayer thin films of W and PC (Polycarbonate) show, due to the great difference of the components’ characteristics, fascinating properties for a variety of possible applications and provide an interesting research field, but are hard to fabricate with low layer thicknesses. Because of the great acoustic mismatch between the two materials, such nanoscale structures are promising candidates for new phononic materials, where phonon propagation is strongly reduced. In this article we show for the first time that W/PC-multilayers can indeed be grown with high quality by pulsed laser deposition. We analyzed the polymer properties depending on the laser fluence used for deposition, which enabled us to find best experimental conditions for the fabrication of high-acoustic-mismatch W/PC multilayers. The multilayers were analyzed by fs pump-probe spectroscopy showing that phonon dynamics on the ps time-scale can strongly be tailored by structural design. While already periodic multilayers exhibit strong phonon localization, especially aperiodic structures present outstandingly low phonon propagation properties making such 1D-layered W/PC nano-structures interesting for new phononic applications.
Background: Microvascular Decompression represents an effective treatment for hemifacial spasm. The use of lateral spread responses (LSRs) monitoring remains a useful intraoperative tool to ensure adequate decompression of the facial nerve. Objective: To assess the value of LSRs intraoperative monitoring as a prognostic indicator for the outcome of microvascular decompression in hemifacial spasm. Methods: Our study included 100 patients prospectively. The patients were classified into 4 groups whether LSRs were totally, partially, not relieved or not detected from the start. According to clinical outcome, the patients were classified into 4 groups depending on the clinical course after surgery and the residual symptoms if any. Then, correlations were made between LSRs events and treatment outcome to detect its reliability as a prognostic indicator. Results: LSRs were relieved totally in 56% of the patients, partially relieved in 14%, not relieved in 10% and were not detected in 20% of the patients from the start. HFS was relieved directly after operation in 62% with clinical improvement of 90-100%. 31% described 50-90% improvement over the next 3 months after surgery. Almost all of these 31% (28 out of 31 patients) reported further clinical improvement of 90-100% within one year after surgery. 3% suffered from a relapse after a HFS-free period and 4% reported minimal or no improvement describing 0-50% of the preoperative state. The percentage of the satisfied patients with the clinical outcome who reported after one year a clinical improvement of 90-100% was 90%. Statistical analysis did not find a significant correlation between the relief of LSRs and clinical outcome. Conclusion: LSRs may only represent an intraoperative tool to guide for an adequate decompression but failed to represent a reliable prognostic indicator for treatment outcome.