Metallinitierte Ringöffnungspolymerisation von funktionalisierten Lactonen und cyclischen Carbonaten

In der vorliegenden Arbeit wurden verschiedene Metallkomplexe als Initiatoren für die RÖP von Lactonen und cyclischen Carbonaten vorgestellt. Zunächst gelang die Darstellung von Poly(trimethylencarbonat) mit Hilfe von Triscyclopentadienylverbindungen der Seltenerdmetallen. NMR-spektroskopische Untersuchungen ergaben keine Hinweise auf Decarboxylierungsreaktionen während der Polymerisation. Des weiteren konnte gezeigt werden, dass Tris(bis(phosphanyl)amid)komplexe von Yttrium, Lanthan, Neodym und Erbium die RÖP von 6-Caprolacton und TMC initiieren, wobei die entstehenden Polymere in sehr guten Ausbeuten und mit hohen Molekulargewichten erhalten werden. Im folgenden wurde eine vergleichende Untersuchung der Komplexe [Sm{N(SiMe3)2}3] und [Sm(NPtBu3)(NHPtBu3){N(SiMe3)2}2] durchgeführt, die die hohe Aktivität beider Verbindungen in der RÖP von CL verdeutlicht. Die Molekulargewichte, die signifikant über den erwarteten Werten liegen, und die breiten Verteilungen weisen auf relativ geringe Unterschiede in den Geschwindigkeiten für Anlagerungs- und Wachstumsschritt hin. Weiterhin konnte das System SmI2/Sm in die RÖP von TMC und DTMC eingeführt werden. Die Molekulargewichte der Homopolymere sind im Falle der Substanzpolymerisationen niedriger verglichen mit denen der Lösungspolymerisationen in Toluol. Ein Einfluss der Temperatur kann nicht festgestellt werden. Die Molekulargewichte steigen mit wachsendem Monomer-Initiator-Verhältnis an, bleiben aber aufgrund von Nebenreaktionen hinter den erwarteten Werten zurück Im weiteren Verlauf gelang die Darstellung von statistischen Copolymeren aus TMC und Dilactid sowie TMC und DTMC. Die Zusammensetzung der Polymere zeigt große Übereinstimmung mit der vorgelegten Monomermischung. Der statistische Charakter konnte mittels DSC-Untersuchungen unterlegt werden. SmI2/Sm eignet sich weiterhin für die Copolymerisation von EC mit TMC bzw. DTMC. Der Anteil von EC im Polymeren liegt unabhängig vom vorgegebenen Verhältnis bei maximal 6 %. Die Mikrostrukturanalyse mittels NMR-Spektroskopie belegt, dass TMC-Blöcke durch genau eine EC-Monomereinheit verbunden sind. Weiterhin war es möglich statistische Copolymere von 4-Brom-6-Caprolacton und 6-Caprolacton initiiert mit Neodym(III)-isoproxid zu synthetisieren. Die resultierenden Poly(gamma-haloester) eignen sich als Initiatoren für die lebende radikalische Polymerisation von Methylmethacrylat, wobei Propfcopo-lymere bestehend aus einem PCL-Rückgrat mit PMMA-Seitenketten gebildet werden. Außerdem lassen sich Polyester mit ungesättigten Seitenketten durch statistische Copolymerisation von 2-Allyl-5-valerolacton mit 5-Valerolacton herstellen. Der Initiation mit Nd[N(PPh2)2]3 führt im Vergleich zu SmI2/Sm zu höheren Ausbeuten und höheren Molekulargewichten. Weiterhin ließen sich ungesättigte Polyestercarbonate auf der Basis von AVL und TMC in guten Ausbeuten gewinnen. Die chemische Vernetzbarkeit der ungesättigten Polyester konnte mit Hilfe torsionsrheologischer Un-tersuchungen demonstriert werden. Abbau-Studien ergaben, dass sich die PTMC-PAVL-Copolymere unter dem Einfluss von Proteinase K abbauen lassen. Die Molekulargewichte änderten sich dabei nur geringfügig, was auf einen oberflächlichen Abbau hindeutet. Die Copolymere bestehend aus TMC und EC zeigen lediglich einen hydrolytischen jedoch keinen durch Proteinase K vermittelten Abbau. Die Abnahme der Molekulargewichte lässt auf einen Substanzabbau schließen

Deriving genetic programming fitness properties by static analysis

Deriving Genetic Programming Fitness Properties by Static Analysis Colin G. Johnson The aim of this paper is to introduce the idea of using static analysis of computer programs as a way of measuring fitness in genetic programming. Such techniques extract information about the programs without explicitly running them, and in particular they infer properties which hold across the whole of the input space of a program. This can be applied to measure fitness, and has a number of advantages over measuring fitness by running members of the population on test cases. The most important advantage is that if a solution is found then it is possible to formally trust that solution to be correct across all inputs. This paper introduces these ideas, discusses various ways in which they could be applied, discusses the type of problems for which they are appropriate, and ends by giving a simple test example and some questions for future research

Safety aspects of infliximab in inflammatory bowel disease patients - A retrospective cohort study in 100 patients of a German University Hospital

Background: Infliximab, a chimeric anti-tumour necrosis factor monoclonal antibody with potent anti-inflammatory effects, represents an effective treatment option in patients with severe inflammatory bowel disease (IBD). Serious side-effects of such an immunomodulating therapy are speculated and therefore we reviewed our clinical experience in a retrospective safety study looking upon a single cohort of 100 IBD patients from a large German University Hospital. Methods: 100 patients with severe Crohn's disease (n = 92), ulcerative colitis (n = 7) or indeterminate colitis (n = 1) treated with infliximab (5 mg/kg) from January 2000 to December 2003 were retrospectively analysed for acute and subacute adverse events by chart review. Results: Overall, infliximab therapy was generally well tolerated. No fatal complications, malignancies, autoimmune diseases, neurologic or cardiovascular complications were observed in the cohort during the study period. Overall, adverse events were observed in 10 patients: 2 patients showed an acute infusion reaction, 1 patient a serum sickness-like reaction, in 4 patients a bacterial or viral infection occurred, in 1 patient pancytopenia and 2 patients developed surgical complications. Only 6 patients with adverse events required admission to hospital. A case of tuberculosis after infliximab was not found. The lack of adverse side-effects was associated with young median age and infrequent comorbidities of the cohort. Conclusion: Regarding its strong immunomodulating capacity, infliximab appears to be an efficient and relatively safe therapeutic option for patients with severe IBD. However, the use of infliximab requires careful screening and close patient monitoring to identify patients at risk and the infrequent, but sometimes serious complications of infliximab. Copyright (C) 2004 S. Karger AG, Basel

Markers of Angiogenesis Associated with Surgical Attenuation of Congenital Portosystemic Shunts in Dogs

BACKGROUND: Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the intrahepatic portal veins. Surgical CPSS attenuation results in the development of the intrahepatic portal vasculature, the precise mechanism for which is unknown, although new vessel formation by angiogenesis is suspected. HYPOTHESIS: That the degree of portal vascular development and the increase in portal vascularization after CPSS attenuation is significantly associated with hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) gene expression and serum VEGF concentration. ANIMALS: Client‐owned dogs with CPSS undergoing surgical treatment. Forty‐nine dogs were included in the gene expression data and 35 in the serum VEGF data. MATERIALS AND METHODS: Dogs surgically treated by partial or complete CPSS attenuation were prospectively recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver biopsy samples taken at initial and follow‐up surgery using quantitative polymerase chain reaction. Serum VEGF concentration was measured before and after CPSS attenuation using a canine specific ELISA. Statistical significance was set at the 5% level (P ≤ .05). RESULTS: There was a significant increase in the mRNA expression of VEGFR2 after partial attenuation (P = .006). Dogs that could tolerate complete attenuation had significantly greater VEGFR2 mRNA expression than those that only tolerated partial attenuation (P = .037). Serum VEGF concentration was significantly increased at 24 (P < .001) and 48 (P = .003) hours after attenuation. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that intrahepatic angiogenesis is likely to occur after the surgical attenuation of CPSS in dogs, and contributes to the development of the intrahepatic vasculature postoperatively

Short-term pretreatment with a dual 5α-reductase inhibitor before bipolar transurethral resection of the prostate (b-turp): evaluation of prostate vascularity and decreased surgical blood loss in large prostates

Objective: To investigate if short-term treatment with dutasteride (8 weeks) before bipolar transurethral resection of the prostate (B-TURP) can reduce intraoperative bleeding, as dutasteride a dual 5α-reductase inhibitor (5-ARI) blocks the conversion of testosterone into its active form dihydrotestosterone (DHT), and reduces prostate volume and prostate-specific antigen (PSA) levels, while increasing urinary flow rate. Patients and Methods: In all, 259 patients were enrolled and randomised to two groups: Group A, receiving placebo and Group B, receiving dutasteride (0.5mg daily for 8 weeks). Blood samples were taken before and after B-TURP for serum chemistry evaluation. In particular we evaluated blood parameters associated with blood loss [haemoglobin (Hb) and haematocrit (Ht)] and prostate vascularity [vascular endothelial growth factor (VEGF) immunoreactivity and microvessel density (MVD) using cluster of differentiation 34 (CD34) immunoreactivity]. Results: Total testosterone, DHT, PSA level and prostate volume were evaluated and with the exception of DHT and PSA level there was no statistically significant differences between the groups. When comparing changes in Hb and Ht between Group A and Group B before and after B-TURP, there was a statistically significant difference only in patients with large prostates of ≥50mL (ΔHb 3.86 vs 2.05g/dL and ΔHt 4.98 vs 2.64%, in Groups A and B, respectively). There was no significant difference in MVD and VEGF index in prostates of &lt;50mL, conversely in large prostates the difference become statistically significant. Conclusions: Dutasteride was able to reduce operative and perioperative bleeding only in patients with large prostates (≥50mL) that underwent B-TURP. Our findings are confirmed by Hb and Ht values reported before and after the B-TURP and reductions in the molecular markers for VEGF and CD34 in the dutasteride-treated specimens

SEU Characterization of Three Successive Generations of COTS SRAMs at Ultralow Bias Voltage to 14.2 MeV Neutrons

This paper presents a SEU sensitivity characterization at ultra-low bias voltage of three generations of COTS SRAMs manufactured in 130 nm, 90 nm and 65 nm CMOS processes. For this purpose, radiation tests with 14.2 MeV neutrons were performed for SRAM power supplies ranging from 0.5 V to 3.15 V. The experimental results yielded clear evidences of the SEU sensitivity increase at very low bias voltages. These results have been cross-checked with predictions issued from the modeling tool MUlti-SCAles Single Event Phenomena Predictive Platform (MUSCA-SEP3). Large-scale SELs and SEFIs, observed in the 90-nm and 130-nm SRAMs respectively, are also presented and discussed

Quantitative coronary plaque analysis predicts high-risk plaque morphology on coronary computed tomography angiography: results from the ROMICAT II trial

Semi-automated software can provide quantitative assessment of atherosclerotic plaques on coronary CT angiography (CTA). The relationship between established qualitative high-risk plaque features and quantitative plaque measurements has not been studied. We analyzed the association between quantitative plaque measurements and qualitative high-risk plaque features on coronary CTA. We included 260 patients with plaque who underwent coronary CTA in the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) II trial. Quantitative plaque assessment and qualitative plaque characterization were performed on a per coronary segment basis. Quantitative coronary plaque measurements included plaque volume, plaque burden, remodeling index, and diameter stenosis. In qualitative analysis, high-risk plaque was present if positive remodeling, low CT attenuation plaque, napkin-ring sign or spotty calcium were detected. Univariable and multivariable logistic regression analyses were performed to assess the association between quantitative and qualitative high-risk plaque assessment. Among 888 segments with coronary plaque, high-risk plaque was present in 391 (44.0%) segments by qualitative analysis. In quantitative analysis, segments with high-risk plaque had higher total plaque volume, low CT attenuation plaque volume, plaque burden and remodeling index. Quantitatively assessed low CT attenuation plaque volume (odds ratio 1.12 per 1 mm3, 95% CI 1.04-1.21), positive remodeling (odds ratio 1.25 per 0.1, 95% CI 1.10-1.41) and plaque burden (odds ratio 1.53 per 0.1, 95% CI 1.08-2.16) were associated with high-risk plaque. Quantitative coronary plaque characteristics (low CT attenuation plaque volume, positive remodeling and plaque burden) measured by semi-automated software correlated with qualitative assessment of high-risk plaque features

Statistical Deviations from the Theoretical only-SBU Model to Estimate MCU rates in SRAMs

This paper addresses a well-known problem that occurs when memories are exposed to radiation: the determination if a bitflip is isolated or if it belongs to a multiple event. As it is unusual to know the physical layout of the memory, this paper proposes to evaluate the statistical properties of the sets of corrupted addresses and to compare the results with a mathematical prediction model where all of the events are SBUs. A set of rules easy to implement in common programming languages can be iteratively applied if anomalies are observed, thus yielding a classification of errors quite closer to reality (more than 80% accuracy in our experiments)

The effectiveness of manipulation of the wrist in the management of lateral epicondylitis

The purpose of this study was to explore the effectiveness of chiropractic manipulative therapy on the wrist, in treating lateral epicondylitis. It also aimed to determine the effectiveness of Mills’ manipulation applied to elbow, and whether adjusting both the elbow and the wrist would be more effective than simply adjusting the elbow or the wrist in isolation. Thirty patients suffering from lateral epicondylitis who conformed to specific diagnostic criteria were accepted for the trial. The patients were stratified according to age and sex and placed into three groups of ten. The first group received chiropractic manipulative therapy directed to the wrist. The second group received chiropractic manipulative therapy directed to the elbow complex, and the third group received chiropractic manipulative therapy directed at both areas. The treatment consisted of four sessions over a period of 2 weeks. The groups were assessed and compared in terms of objective and subjective measurements to determine the most beneficial treatment. The data was collected at the beginning of each treatment session. Subjective data consisted of the Numerical Pain Rating Scale 101 (Vernon in Liebenson, 1996:61) and the short form Mc Gill Pain Questionnaire (Melzack, 1987:192), which assessed patients’ discomfort levels. Objective data was collected by means of the Jamar Grip Strength Dynamometer (Kaufman, 2000:619) and the Pressure Algometer (Fischer, 1987:213), which measured the grip strength and pressure pain threshold respectively. The results showed that both wrist and Mills’ manipulation in isolation as well as in combination are beneficial in treating lateral epicondylitis, in that they all showed subjective and objective improvements. The Mills’ manipulation alone and in combination with wrist manipulations had superior clinical effects compared to the wrist manipulations in isolation. The statistical results of the inter-group analysis revealed that there was no significant difference between the outcomes of the wrist manipulation, Mills’ manipulation and combined treatment protocols and therefore none are expressly recommended above the other.Dr. C. Yelverton Dr. C. Lyon