THEORETICAL STUDIES OF BILIPROTEIN CHROMOPHORES AND RELATED BILE PIGMENTS BY MOLECULAR ORBITAL AND RAMACHANDRAN TYPE CALCULATIONS

Ramachandran calculations have been used to gain insight into steric hindrance in bile pigments related to biliprotein chromophores. The high optical activity of denatured phycocyanin, as compared to phycoerythrin, has been related to the asymmetric substitution at ring A, which shifts the equilibrium towards the P-helical form of the chromophore. Geometric effects on the electronic structures and transitions have then been studied by molecular orbital calculations for several conjugation systems including the chromophores of phycocyanin. phytochrome P,, cations, cation radicals and tautomeric forms. For these different chromophores some general trends can be deduced. For instance, for a given change in the gross shape (e.g. either unfolding of the molecule from a cyclic-helical to a fully extended geometry, or upon out-of-plane twists of the pyrrole ring A) of the molecules under study, the predicted absorption spectra all change in a simikar way. Nonetheless, there are characteristic distinctions between the different n-systems, both in the transition energies and the charge distribution, which can be related to their known differences in spectroscopic properties and their reactivity

Life Cycle of Multi Technology Machine Tools – Modularization and Integral Design

AbstractFor reasons of high flexibility but still maximum productivity, machine tools integrating various production technologies have recently received particular attention. Combining and integrating multiple manufacturing techniques into one single system in early stages of the product emergence process is challenging. To keep the effort for implementation to a minimum, an initiation already in the concept phase is being actively pursued. Design guidelines are currently investigated based on the examination of different technology combinations.This approach focuses on systematic conceptual design for such hybrid machine technologies. Product architectures are used to describe the modularity and create a specific delimitation for standardization. Reference product architectures for Multi Technology Machine Tools (MTMT) carry high potential for saving expenses in product development. The main emphasis is on technology and system integration. A technological similarity assessment of the single processes involved forms the basis of this approach to assure potential for synergies. Monetary aspects in early stages of product development are considered. Based on the analysis a generic system model is connected with general product architectures for MTMT.The method introduced is validated by a Multi-Technology Machining Centre with two simultaneously usable workspaces integrating a milling spindle and two laser processing units. The research undertaken is part of the Cluster of Excellence “Integrative Production Technology for High-Wage Countries” and has been funded by German Research Foundation (DFG)

Gravitational decoherence of planetary motions

We study the effect of the scattering of gravitational waves on planetary motions, say the motion of the Moon around the Earth. Though this effect has a negligible influence on dissipation, it dominates fluctuations and the associated decoherence mechanism, due to the very high effective temperature of the background of gravitational waves in our galactic environment.Comment: 6 pages, no figure, to appear in EuroPhysics Letters; needs `epl.cls

Mechanochemical feedback regulates the dynamics of the PAR system in C. elegans zygotes

The interplay between regulatory biochemistry and cell mechanics is critical for a broad range of morphogenetic changes. Cell mechanics can induce transport via growth and flow-fields, which in turn affect concentration-fields of regulators. Such systems exhibit an intrinsic feedback-architecture between regulators of cell mechanics and mechanical deformation. While we anticipate that this feedback between biochemistry and cell mechanics is widespread in Morphogenesis, there are few examples that are studied with respect to their potential for generating spatiotemporal patterns. Here we establish at a quantitative level that PAR polarization of C. elegans zygotes represents a coupled mechanochemical system. Using Fluorescence Recovery After Photobleaching (FRAP) and RNA interference (RNAi), we first demonstrate that the biochemistry in form of the PAR domains feeds back on the mechanics by establishing and maintaining a non-muscle myosin II (nmy-2) gradient. Additionally, we characterize the effect of the polarity cue associated with the centrosome of the male pronucleus on the local myosin concentration at the posterior pole. We show that it induces a reduction in myosin concentration and thereby triggers the onset of cortical flows. Furthermore we measure the spatiotemporal profile of the anterior and posterior PAR concentration, the myosin II concentration and the induced flow-field. Finally, we capture the feedback-architecture of the coupled actomyosin – PAR system in a quantitative model, based on coupling a thin film active fluid description of cortical mechanics [1] to a reaction-diffusion PAR patterning system [2]. We show that this mathematical model can quantitatively recapitulate the spatiotemporal profile of PAR polarity establishment. Furthermore, we demonstrate that the model predicts the existence of a threshold in cortical flow velocity, which separates the nonpolarizing and the polarizing regime and confirm the existence of this threshold velocity in the living C. elegans zygote

Surgery in recurrent ovarian cancer

Ovarian cancer is one of the most challenging diseases in gynecologic oncology. The presentation of frequent recurrences requires the establishment and further development of therapy standards for this patient group. Surgery is crucial in the therapy of patients with primary ovarian cancer, and the postoperative residual tumor mass is the most relevant clinical prognostic factor. The surgical management of recurrent disease is still subject to an emotional international discussion. Only a few prospective clinical trials focused on the effects of surgery in relapsed ovarian cancer have been published. The available data show improvements in the prognosis due to complete cytoreduction in the setting of recurrence. However, the selection of eligible patients is the essential issue. Therefore, the establishment of reliable predictive factors for complete tumor resection as well as a definition of the group of patients who might profit from this approach remains a field for research. Further randomized trials designed to develop and incorporate operative standards for recurrent ovarian cancer should follow

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m−2 DL), combined with cisplatin (standard dose 75 mg m−2). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m−2 DL; at the 110 mg m−2 DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m−2, but not through the 150 mg m−2 DL. The mean±SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317±60 ml min−1 m−2, 258±96 l m−2 and 30.8±7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m−2 (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m−2

Variations on the Pear Tree Experiment : different variables, new results?

Inspired by the Pear Stories Project, the Pear Tree Project has investigated how different cultures and languages describe the same film in order to apply its findings to audio description (AD). Participants from different countries were asked to "write down what they saw" in a controlled setting. This article proposes an alternative experiment, also based on the original Pear Stories Project, which aims to shed light on two issues: how different describer profiles (translation students with AD training/without AD training) and different instructions concerning the target audience profiles (blind/non-blind) could alter the final production. The results are analysed in this paper, taking into account the elements covered in the original Pear Stories Project as well as some additional elements proposed by the authors

Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer.

The early detection of breast cancer is the best means to minimise disease-related mortality. Current screening techniques have limited sensitivity and specificity. Breast nipple aspirate fluid can be obtained noninvasively and contains proteins secreted from ductal and lobular epithelia. Nipple aspirate fluid proteins are breast specific and generally more concentrated than corresponding blood levels. Proteomic analysis of 1 microl of diluted nipple aspirate fluid over a 5-40 kDa range from 20 subjects with breast cancer and 13 with nondiseased breasts identified five differentially expressed proteins. The most sensitive and specific proteins were 6500 and 15 940 Da, found in 75-84% of samples from women with cancer but in only 0-9% of samples from normal women. These findings suggest that (1) differential expression of nipple aspirate fluid proteins exists between women with normal and diseased breasts, and (2) analysis of these proteins may predict the presence of breast cancer

ESMO-ESGO consensus conference recommendations on ovarian cancer: Pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically-relevant and evidence-based guidelines in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO-ESGO consensus conference on ovarian cancer was held on 12-14 April 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO-ESGO consensus conference, together with a summary of evidence supporting each recommendation

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page