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Future robotic manipulators mounted on small satellites are expected to perform important tasks in space, like servicing other satellites or automating extravehicular activities on a space station. In a free-floating space manipulator, the motion of the manipulator affects the carrier satellite’s position and attitude. Spin-stabilization improves the system performance, but further complicates the dynamics. The combination of satellite and multi-link manipulator is modeled as a rigid multi-body system. A Maximum Principle based approach is used to calculate optimal reference trajectories with high precision. To convert the optimal control problem into a nonlinear multi-point boundary value problem, complicated adjoint differential equations have to be formulated and the full apparatus of optimal control theory has to be applied. For that, an accurate and efficient access to first- and higher-order derivatives is crucial. The special modeling approach described in this paper allows it to generate all the derivative information in a structured and efficient way. Nonlinear state and control constraints are treated without simplification by transforming them into linear equations; they do not have to be calculated analytically. By these means, the modeling of the complete optimal control problem and the accompanying boundary value problem is automated to a great extent. The fast numerical solution is by the advanced multiple shooting method JANUS.

Decreased concentrations of the circulating angiogenic factors, free placental growth factor (PLGF) and free vascular endothelial growth factor (VEGF), and increased concentrations of the anti-angiogenic factor, soluble fms-like tyrosine kinase 1 (sFLT-1) have been observed during clinical preeclampsia. We established a new PLGF-ELISA kit for the measurement of PLGF in sera. In the present study, we demonstrated the assay characteristics by measurement of PLGF expression in normal and preeclamptic pregnancies as compared to an established research kit.Blood samples were taken from 64 women with singleton uncomplicated pregnancies for longitudinal measurement of PLGF in the course of pregnancy. In 30 preeclamptic patients, serum levels of PLGF and sFLT-1 were measured by Human PLGF-ELISA and Human sVEGF R1 ELISA according to the described test principles. The assay characteristics of the new PLGF-ELISA were determined and the results were compared to those performed with an available research kit.The PLGF concentration in normal pregnancies showed a steady increase starting at the beginning of the second trimester with a peak at 28-32 weeks and a consistent decline thereafter. The preeclamptic pregnancies had significant lower serum concentrations of PLGF and significant higher serum concentrations of sFLT-1 as compared to the non-preeclamptic pregnancies. All the measured assay characteristics fulfilled the required specifications. Comparison of the values of the new PLGF-ELISA and the established research kit resulted in a correlation coefficient of 0.921.Our results support the hypothesis that an imbalance between factors promoting angiogenesis, such as PLGF, and factors antagonizing angiogenesis, such as sFLT-1, has a fundamental role in the pathogenesis of preeclampsia. The new established ELISA test can be considered reliable and it offers many advantages. As it is authorized for routine diagnostic testing, it may offer new possibilities in the prediction of preeclampsia in clinical routine.

Purpose: Expression of the antiapoptotic and antiproliferative protein Bcl-2 has been repeatedly shown to be associated with better clinical outcome in breast cancer. We recently showed a novel regulatory (−938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Experimental Design: Paraffin-embedded neoplastic and nonneoplastic tissues from 274 patients (161 still alive after a follow-up period of at least 80 months) with primary unilateral invasive breast carcinoma were investigated. Bcl-2 expression of tumor cells was shown by immunohistochemistry; nonneoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (−938C>A) genotypes were correlated with the patients' survival. Results: Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (P = 0.030) in lymph node–negative breast cancer patients, whereas no genotype effect could be observed in lymph node–positive cases. Ten-year survival rates were 88.6% for the AA genotype, 78.4% for the AC genotype, and 65.8% for the CC genotype. Multivariable Cox regression identified the BCL2 (−938CC) genotype as an independent prognostic factor for cancer-related death in lymph node–negative breast carcinoma patients (hazard ratio, 3.59; P = 0.032). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome of lymph node–positive but not of lymph node–negative breast cancer patients. In lymph node–negative cases, the (−938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression (P = 0.044) and the survival of patients with Bcl-2–expressing carcinomas (P = 0.006). Conclusions: These results suggest the (−938C>A) polymorphism as a survival prognosticator as well as indicator of a high-risk group within patients with lymph node–negative breast cancer.

Antibiotic prophylaxis is a standard procedure in obstetric surgery and has been discussed in various investigations. Use of treatment is judged by high efficacy and good tolerance.In 300 patients undergoing cesarean sections we compared results of application of Piperacillin 4 g and Piperacillin/Tazobactam 4.5 g after cut of umbilical cord. Tazobactam/Piperacillin is a combination of a broad-spectrum penicillin and a beta-lactamase inhibitor with increased toxicity against staph. aureus, enterobacter, and other germs responsible for local and systemic infections in obstetric surgery.We did not observe any severe adverse effects. Rate of severe wound infections was 1.3 % (Tazobactam/Piperacillin) and 2 % (Piperacillin alone). The difference showed no statistic significance (p0.01). During postoperative course we found a higher increase of CRP (p0.01) in the Piperacillin group. CRP proved to be a useful objective parameter to distinguish between patients with or without postoperative infections. No differences were found in the number of leucocytes, time in hospital and other parameters.

Miniaturized robotic manipulators are a key element in future highprecision minimally invasive surgery and telesurgery. This development is supported by the rapidly decreasing size of robotic sensors and actuators. Severe limitations are currently induced by the drives of the micro-joints.

Optimal path-constrained trajectories of an ISS-based, three-link robot are investigated with a monorail as an additional fourth and prismatic joint. This results in a problem of optimal control for a multiple constrained nonlinear system of differential-algebraic equations. After transformation into minimum coordinates, the only remaining control is the acceleration of the end-effector along the prescribed trajectory, replacing four actuator torques/forces in the original formulation. The simpler structure is achieved at the price of introducing piecewise defined equations of motion, two highly nonlinear control constraints and two state constraints of first order. Switching points between partly linear and fully rotational motion are optimized. Solutions are presented including touch points of the state constraints with the two control constraints being active simultaneously. For the mathematical treatment of those problems, new interior point conditions are derived.

Background and aim: The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways—namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu—is assessed in a series of 113 node-negative breast cancers. Results: COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis. Conclusions: The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed—COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.

Mammography is an appropriate method for the detection of early forms of cancer of the breast, and for reducing mortality. Whether this actually succeeds depends upon the quality of the early detection strategies employed. Currently the data on reduction of mortality by mammographic screening remain ambivalent.

INTRODUCTION: Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy. METHODS: We analyzed 162 node-negative breast cancer cases to determine the prognostic relevance of FAK expression, and we investigated the relationship of FAK with major associated signaling pathways (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and western blot analysis. RESULTS: Elevated FAK expression did not predict patient outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383) and estrogen receptor status (P = 0.0033). Significant positive correlations were observed between elevated FAK expression and HER2 overexpression (P = 0.001), as well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01). CONCLUSIONS: Immunohistochemical detection of FAK expression is of no prognostic significance in node-negative breast cancer but provides evidence that HER2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src.

Nuclear magnetic resonance offers the possibility of noninvasive in situ observation of (15)N pulse labeling in the presence of light. In vivo, exclusively the delta-nitrogen of Gln is labeled in the cyanobacterium Microcystis firma when glutamate synthase is inhibited by azaserine. In contrast, the green alga Chlorella fusca is additionally capable of incorporating nitrogen into Glu, thus providing evidence for an anabolic function of glutamate dehydrogenase in this organism.

Cellular adhesion molecules ICAM-1 and VCAM-1 have been implicated in tumor progression and metastasis. As the sequential interaction of neoplastic cells with the endothelium of tumor neovascularisation is believed to be essential for tumor metastasizing processes, we analysed the concentration of ICAM-1 and VCAM-1 in the cytosol of patients with human breast cancers and their corresponding sera. We compared the obtained values with established prognostic parameters for breast cancer. Benign breast tissues were also analyzed.Levels of ICAM-1 and VCAM-1 of 62 patients with invasive breast cancer and 17 patients with benign breast tissue were measured using commercially available sandwich enzyme-linked immunoassays with monoclonal antibodies. To establish a reference and control group, levels of ICAM-1 and VCAM-1 were measured in the sera of 66 women without breast tumors.The mean cytosol concentration of ICAM-1 and VCAM-1 was significantly higher in the breast cancer specimens than in the tissue of patients with benign breast diseases. This could be found not only in the tumor cytosol but also in the corresponding sera of the patients. No correlations between the ICAM-1 and VCAM-1 expressions and established prognostic parameters could be observed.Our findings suggest that malignant breast cancer cells could induce neovascularisation with subsequent high expressions of ICAM-1 and VCAM-1. These upregulations of adhesion molecules might contribute to changes in invasive phenotypes by promoting endothelial cell adhesion and angiogenesis, as well as being responsible for the recognition of tumor cells by the human immune system. Prognostic relevance for the development of breast cancer could not be established.

The rare case of a decidualized endometriosis of the appendix vermiformis is reported in a woman who developed HELLP syndrome during the 32nd week of a twin pregnancy. Cesarean section and simultaneous appendectomy were performed. An inspection of the appendix should always be carried out if an endometriosis-associated anamnesis is known. No pathophysiological correlations between the HELLP syndrome and the endometriosis of the appendix vermiformis could be found.

BACKGROUND AND QUESTION: A retrospective study was performed. To check the hypothesis whether there is an inverse connection between age and prognosis.We investigated a total group of 1000 cases with breast cancer primarily and consecutively treated between 1968 and 1986. After grouping the patients by tumor stage and median age various life table analyses were performed to calculate and compare the overall survival. Entry date was the date at diagnosis of a first breast cancer or date at first diagnosis of distant metastasis.Young patients with a tumor size T1 and T2 had a significantly better prognosis than older patients with the same tumor stage. Influence of age became significantly weaker in patients with a T3 and T4 tumor. At least in the patients with a primarily M1 stage hardy any more dependence of age could be demonstrated. Similar results were obtained for the 198 patients which presented a distant recurrence.Better general life expectancy of young patients is the cause of substantially better overall survival in curable stages. Advanced breast cancer is a strongly life-threatening factor. The fatal influence of large tumor mass is independent of age.

A new and improved version of the multiple shooting method is presented. The new features include the use of dynamic nodes, improved convergence strategies, and hierarchical, adaptive approximation techniques significantly simplifying the numerical treatment of complicated problems in aerospace engineering. As a demanding application of the new algorithm, an optimal 3D ascent trajectory including singular subarcs is calculated for a single-stage, suborbital hypersonic demonstrator system. The mathematical model describing the motion of the rocket-powered vehicle is based on the 3D equations of motion of a point mass with reference to the spherical rotating Earth. Only a simplified model has to be formulated; the realistic model is then iteratively approximated by the algorithm. As a result of the calculations, the suitability of a VTVL single stage demonstrator system as a testbed for advanced airbreathing propulsion systems (ramjet, scramjet) is shown. (Author)

Mutations of the tumor suppressor gene p53 are common in multiple cancer forms, including breast cancer. Data are available that suggest, that the loss of the wild type form of p53 and the appearance of the mutant forms of p53 are correlated with a poorer overall survival rate in patients with breast cancer. The accumulation of the mutant forms of p53 in the cytoplasmatic rooms of the tumor cells leads to the production of human auto-antibodies against these mutant p53 proteins. Therefore, the aim of this study was to analyse and quantify the levels of serum auto-antibodies against p53 protein in patients with an intact immunological system having an active and new recurrence of breast cancer and to compare the obtained results with the recurrence free interval and with established prognostic parameters at the time of first diagnosis, to see if patients with a positive p53 auto-antibody status had a poorer prognosis than those who were p53 auto-antibody positive.The ser of 61 patients with breast cancer, who experienced a new, clinical and biophysically identified local or distant recurrence and that showed an intact immunological system were analysed with an ELISA assay of Dianova to determine the concentration of auto-antibodies against mutant p53.14.5% of the patients showed a positive p53 auto-antibody serum status. The recurrence free interval between the p53 auto-antibody positive and negative patients was almost the same: 4.12 years for the p53 auto-antibody positive patients versus 3.72 years for the p53 auto-antibody negative patients (independent t-test value = 0.224 and p value = 0.824; statistically not a significant difference). When comparing the p53 auto-antibody status with established prognostic parameters we could only find a statistically significant correlation with tumor size. No correlations were obtained when comparing the p53 auto-antibody status with the N- and M status, the ER- and PR status, the menopausal status and the cathepsin-D status.We were able to demonstrate that the expression of serum auto-antibodies against mutant p53 can not be used as a prognostic parameter in patients with breast cancer as the recurrence free interval between the p53 auto-antibody positive and negative patients did not differ. The determination of the auto-antibodies against p53, though easy to perform, is therefore not a test that helps clinicians in their treatment options, but it remains a useful test for the description of the biological mechanisms of breast cancer.

With progress in microelectronics and -mechanics there is a growing interest in relatively small, robotic spacecrafts for precisely defined and limited scientific missions. These space systems are competitive especially for highly developed scientific payloads with a large fraction of state-of-the-art microelectronics. The advantage of such spacecrafts is the rapid and often cheaper access to space. But this is true only as long as strict limitations of the overall size and mass are observed and system complexity is kept low. On the other hand, every decrease in system performance will result in a further decrease of the payload fraction, which is rather low anyhow.

To compare in mammography the image quality of digital luminescence radiography (DLR) to that of usual film screen mammography and xeromammography.Three single emulsion film-screen combinations, one double coated high resolution film and xeroradiography, were tested for this purpose. In our phantom study the detectability of microcalcifications, fibrils and low contrast details were first of all studied separately. Image processing techniques were, for example, contrast variation by grey scale level windowing, "unsharp mask" filtering and regulatable edge enhancement. Phantom images were made and then the image quality was evaluated by observer performance study using a receiver operating characteristic (ROC analysis).Best results in respect of detection of microcalcifications and fibrils were found in xeroradiography, luminescent image plate and double-coated film-screen combination. These systems showed more favourable ROC curves than the single emulsion film-screen combinations.Our results indicate that image quality of digital images in the field of image processing is equal to that of conventional mammographic techniques and partially superior to detection of low contrast details.

The concentration of c-erbB-2 oncoprotein (HER-2/neu) was examined in the membrane fraction of 196 breast cancer and 39 benign breast specimens using a recently introduced ELISA-assay. The results were compared with established clinical and laboratory prognostic factors, 19% of all breast cancer specimens showed a c-erbB-2 protein level above 10 HNU/micrograms extract protein and were so classified as positive. Considering only the samples of primary tumors the rate was 21%. Surprisingly the rate was only 13.5% in the tissue samples of recurrent disease. Significant correlations were found between high c-erbB-2 protein levels and the tumor diameter, the axillary lymph node status and the progesterone receptor status. In contrast no correlation was found with estrogen receptor or menopausal status. All specimens of benign tumors showed levels10 HNU/micrograms extract protein and were classified as negative. The measurement of the c-erbB-2 protein using this ELISA assay was simple to perform and revealed reliable results. Nevertheless the prognostic power of the c-erbB-2 protein seems to be of minor relevance in comparison with established clinical and laboratory parameters, as the positive rates are too small in regard to the much higher recurrence rates of breast cancer. Probably the serum levels of this oncoprotein will be of greater clinical interest in the course of breast cancer.

Modern techniques of optimization and control considerably increase the performance of robotic satellites. As an example, a small Venus mission is presented for such a spacecraft. Not only a point-mass model is considered, but the full rigid body dynamics of a highly realistic model spacecraft is taken into account. The arising problems are formulated mathematically as boundary-value problems for complex systems of highly nonlinear differential equations. All scientific and technological constraints are exactly included as state and control constraints and interior point conditions. The numerical solution of the boundary-value problems is by a modified multiple shooting method. Problems of scaling and extremely small convergence areas require new solution techniques. For the first time the proof of mission feasibility is given. Design optimization leads to a cheap, robust satellite.

Modern techniques of optimization and control considerably increase the performance of small, robotic satellites. As an example, an advanced near-Earth mission is presented for such a spacecraft. Not only a point-mass model is considered, but the full rigid body dynamics of a highly realistic model spacecraft is taken into account. The arising problems are formulated mathematically as boundary-value problems for complex systems of highly nonlinear differential equations. All scientific and technological constraints are exactly included as state and control constraints and interior point conditions. The numerical solution of the boundary-value problems is by a modified multiple shooting method. Problems of scaling and extremely small convergence areas require new solution techniques. For the first time the proof of mission feasibility is given. Moreover maximum thrust level is reduced by a factor of 4, cheap thrusters are used that are fixed to their positions, optimal momentum steering replaces conventional thrust vector steering -all this with a performance reduction of less than 2 per cent, but a dramatic decrease in mechanical complexity. Single stage design results in a further decrease of operation complexity and costs.

1991 berichteten Badwe et al in einer sehr beachteten Veroffentlichung uber einen Zusammenhang zwischen dem Zykluszeitpunkt bei Operation und dem weiteren Verlauf. Es handelte sich dabei um das Ergebnis einer retrospektiven Studie an 249 pramenopausalen Fallen mit operablem Mammakarzinom. Diese bemerkenswerte Aussage war der Anlass, eine ahnliche Untersuchung am Krankengut unserer Klinik durchzufuhren.

For an interplanetary spacecraft from the Earth to the planet of Neptune trajectory optimization and the optimization of spacecraft design are tightly coupled to increase overall system performance.

Optimization problems in technical simulation often lead to boundary value problems for systems of highly nonlinear ordinary differential equations with piecewise defined right hand sides and a large number of exceptional points with reduced differentiability. Classical integration schemes show a poor performance due to the large number of restarts of the integrator; integration intervals end before the stepsize control has stabilized. The new approach does not only use the information of the preceeding integration step for stepsize control, but also information from the preceeding iteration step, if the boundray value problem is solved by an iterative algorithm. Multistage search techniques improve the efficiency of the determination of the exceptional points. These new techniques are tightly coupled with the progress of the Newton process. The numerical solution of the boundary value problem is by the new multiple shooting code JANUS which fully exploits the new integration techniques.

Nuclear magnetic resonance offers the possibility of noninvasive in situ observation of (15)N pulse labeling in the presence of light. In vivo, exclusively the delta-nitrogen of Gln is labeled in the cyanobacterium Microcystis firma when glutamate synthase is inhibited by azaserine. In contrast, the green alga Chlorella fusca is additionally capable of incorporating nitrogen into Glu, thus providing evidence for an anabolic function of glutamate dehydrogenase in this organism.

The analgesic effectiveness of physical therapy in rheumatology is dependent on the differentiated clinical picture (joint, soft parts, spinal column, musculature) and on the differentiated therapeutic remedy (intensity, duration of single treatments, frequency, duration of therapeutic series). Physico- and kinesitherapy can be distinguished with regard to objective and subjective doses; manual therapy is between them. During the last decade, particular advances were achieved in the field of medical gymnastics (muscular stretching technique), patients' schools (back school) and of cryotherapy (cold-air therapy). The pulsed high-frequency therapy and particularly laser therapy, magnetic-field therapy and high-voltage therapy are critically judged. The problem "rheumatism and pain" mainly exists at the level of "chronic"; diagnostics of movement function (articular and muscular functions) on one hand and dosage of therapeutic remedies (drugs and remedies of physiotherapy) on the other are the guidelines. Course (rehabilitation) as well as onset (prevention) of rheumatic clinical pictures determine the further strategy of pain therapy.

Bisher wurden im Cytosol des primaren Mammakarzinoms hauptsachlich die Konzentrationen des Ostrogen-(ER) und des Gestagenrezeptors (PR) gemessen. Seit einigen Jahren gewinnt auch die Bestimmung anderer Marker wie von Tumormarkern, Enzymen etc. zunehmende Bedeutung. Dabei bleibt die Suche nach therapeutisch verwertbaren Parametern ein vorrangiges Ziel. In diesem Sinne wurde die nachfolgende Untersuchung vorgenommen.

11073 Background: Recently, two polymorphisms in CASP8 were independently identified as factors influencing cancer susceptibility. A non-synonymous single nucleotide polymorphism (SNP) in exon 9 (D...

Inpatients with progressive systemic scleroderma were submitted to ultrasound application several times every day. This type of ultrasonic therapy is practicable. Pain decreased in 18 of 24 patients. At the end of therapy, pain had not increased in any of the patients. The strength of the hands was significantly improved in all patients.