Malonylation/Decarbalkoxylation of Furan Derivatives as Key Steps for the Preparation of Nonactic Acid Derivatives. Part I [1]

Summary.: A malonylation/decarbalkoxylation sequence from 2-substituted furans was investigated in view of developing a scalable synthesis of hydrophobic nonactic acid analogue

Ozone LIDAR as an Analytical Tool in Effective Air Pollution Management: The Geneva 96 Campaign

The LIDAR (LIght Detection And Ranging) technique has developed into one of the practical high performance techniques for conducting air quality and meteorological measurements. DIfferential Absorption Lidar (DIAL) is used for measuring trace gases, including pollutants like ozone at low concentrations. Multiple wavelengths backscatter and depolarization measurements give information about particles in the atmosphere, and single wavelength lidar can be used for meteorological measurements like wind velocity and temperature. Range resolved in situ data obtained by lidar can play a significant role in our understanding of the air quality in the planetary boundary layer, particularly when applied in conjunction with air quality models. This is because DIAL can be used to measure concentrations in three dimensions in real time with a spatial resolution that corresponds well to that used in the model calculations. Thus one obtains an advantage when comparing with point measurements at or near ground level which are often perturbed by local emissions. A summary of the lidar principle is presented here, followed by different examples of vertical ozone profiles and time series obtained with a new optical layout of the EPFL-LPAS DIAL system using dual telescope detection. These data were obtained during the summer 96 field campaign in the Geneva area. Results are then compared with the mesoscale Eulerian model calculations performed in our laboratory. The overall results provide new insight into air pollution dynamics in the Geneva area and calculations are under way, using the model adjusted by the measurements, to optimize air pollution abatement strategies under certain atmospheric conditions in this part of Switzerland

Tumour-derived and host-derived nitric oxide differentially regulate breast carcinoma metastasis to the lungs

To study the role of nitric oxide (NO) in lung metastasis of breast carcinoma, we isolated two cell clones (H and J) from the parental EMT-6 murine breast carcinoma cell line, based on their differential NO production. In vitro, EMT-6 J cells, but not EMT-6H cells, constitutively expressed inducible NO synthase (NOS II) and secreted high levels of NO. IL-1β increased NO production in both clones, and TNF-α had a synergistic effect on IL-1β-induced NO production, but NO production by EMT-6 J cells was always higher than by EMT-6H cells. Proliferation, survival and adhesion to lung-derived endothelial cells of both clones were similar and were not affected by NO. In vivo, both clones similarly located in the lungs of syngeneic mice 48 h after injection. However, EMT-6H cells were significantly more tumorigenic than EMT-6 J cells as assessed at later time points. Injection of EMT-6 J cells and simultaneous treatment of mice with aminoguanidine (AG), a NOS II inhibitor, significantly increased tumour formation. Injection of EMT-6H and EMT-6 J cells into NOS II-deficient mice resulted in a significant survival increase as compared with wild-type animals. Simultaneous administration of AG increased the death rate of NOS II-deficient mice injected with EMT-6 J cells. These results demonstrate that: (i) NO does not influence the early stages of tumour metastasis to the lungs and (ii) NOS II expression in tumour cells reduces, while NOS II expression in host cells enhances, tumour nodule development. In conclusion, the cellular origin and the local NO production are critical in the metastatic proces

Convertible Debt and Shareholder Incentives

Given equity’s convex payoff function, shareholders can transfer wealth from bondholders by increasing firm risk. We test the existing hypothesis that convertible debt reduces this classical agency problem of risk-shifting. First, we derive a measure of shareholders’ risk incentives induced by convertible debt using a contingent claims framework. We then document that when risk-shifting incentives are high, the propensity to issue convertible (rather than straight) debt increases and the negative stock market reaction following convertible debt issue announcements is amplified. We further highlight that convertible debt is the only type of security that affects business risk durably downwards. Our conclusions support the agency theoretic rationale for convertible debt financing especially for financially distressed firms

Improving Breast Cancer Education: The Case of an Evolving Multidisciplinary Module for Undergraduate Medical Students (Lausanne Medical School, 1993-2008)

Breast cancer is a public health issue in numerous countries. Multidisciplinary collaboration is required for patient care, research, and also education of future physicians. This paper uses Kern's framework for curriculum design to demonstrate how a breast diseases module for undergraduate medical students created in 1993 evolved over 15years. The main outcomes of program refinements were better integrated course content, the development of electronic course documents, and implementation of computer-aided small group learning. A main future challenge is to further develop efficient instructional strategies in line with well-defined learning needs for undergraduate student

Evaluation of the Interaction Between TGF β and Nitric Oxide in the Mechanisms of Progression of Colon Carcinoma

It is recognised that stromal cells determine cancer progression. We have previously shown that active TGFβ produced by rat colon carcinoma cells modulated NO production in rat endothelial cells. To elucidate the role of TGFβ and NO in the mechanisms of interaction of colon carcinoma cells with stromal cells and in cancer progression, we transfected REGb cells, a regressive colon carcinoma clone secreting latent TGFβ, with a cDNA encoding for a constitutively-secreted active TGFβ. Out of 20 injected rats only one tumour progressed, which was resected and sub-cultured (ReBeta cells). ReBeta cells secreted high levels of active TGFβ. The adhesive properties of REGb and Rebeta cells to endothelial cells were similar, showing that the secretion of active TGFβ is not involved in tumour cell adhesion to endothelial cells. ReBeta, but not REGb, cell culture supernatants inhibited cytokine-dependent NO secretion by endothelial cells, but inhibition of NO production was similar in co-cultures of REGb or ReBeta cells with endothelial cells. Therefore, secretion of active TGFβ regulated endothelial NO synthase activity when tumour cells were distant from, but not in direct contact with, endothelial cells. However, only ReBeta cells inhibited cytokine-dependent secretion of NO in coculture with macrophages, indicating that the active-TGFβ-NO axis confers an advantage for tumour cells in their interaction with macrophages rather than endothelial cells in cancer progressio

The Reasons for Discrepancies in TargetVolume Delineation: A SASRO Study on Head-and-Neck and Prostate Cancers

Purpose: : To understand the reasons for differences in the delineation of target volumes between physicians. Material and Methods: : 18 Swiss radiooncology centers were invited to delineate volumes for one prostate and one head-and-neck case. In addition, a questionnaire was sent to evaluate the differences in the volume definition (GTV [gross tumor volume], CTV [clinical target volume], PTV [planning target volume]), the various estimated margins, and the nodes at risk. Coherence between drawn and stated margins by centers was calculated. The questionnaire also included a nonspecific series of questions regarding planning methods in each institution. Results: : Fairly large differences in the drawn volumes were seen between the centers in both cases and also in the definition of volumes. Correlation between drawn and stated margins was fair in the prostate case and poor in the head-and-neck case. The questionnaire revealed important differences in the planning methods between centers. Conclusion: : These large differences could be explained by (1) a variable knowledge/interpretation of ICRU definitions, (2) variable interpretations of the potential microscopic extent, (3) difficulties in GTV identification, (4) differences in the concept, and (5) incoherence between theory (i.e., stated margins) and practice (i.e., drawn margins

Méthode de libération d'une pièce micromécanique et pièce micromécanique comprenant des attaches sacrificielles

A method for fabricating a micromechanical part from a substrate in which the part is fabricated by providing a plurality of fasteners between the part and the substrate, the fasteners being sacrificial, characterized in that the fasteners include at least one hinge at the end of each fastener located beside the part, and in that the method includes a step of breaking the sacrificial fasteners. The micromechanical parts employing this type of sacrificial fastener are also described

A Novel Approach to Better Characterize Medication Adherence in Oral Anticancer Treatments.

Purpose: This study aims to describe a 12-month medication adherence with oral anticancer medications (OAMs) in a routine care medication adherence program, and to better characterize non-persistence. Patients and methods:In this observational, one-centered, longitudinal study, medication adherence was monitored electronically while patients were taking part in a medication adherence program for 12 months or until treatment stop. Patients were >18 years and starting or taking one of the following OAMs: letrozole, exemestane, imatinib, sunitinib, capecitabine, or temozolomide. Non-persistence was defined as any premature treatment interruption due to patient's unilateral decision or to a medical decision because of adverse effects. The Kaplan Meier survival function estimate was used to characterize persistence, and Generalized Estimating Equations (GEE) were adopted to fit implementation. Statistical analyses were performed using the R software package. Results: Forty-three outpatients with various tumor entities were enrolled. Reasons for quitting the medication adherence program and/or OAM medication were characterized as OAM discontinuation due to adverse effects or toxicity (n = 5), planned OAM completion time (n = 10), OAM failure (cancer relapse) (n = 5) and non-compliance to the adherence program (n = 3). In persistent patients, the implementation rates were high (from 98% at baseline to 97% at 12 months). The probability of being persistent at 12 months was estimated at 85%. Conclusion: A better characterization of both persistence and implementation to OAMs in real life settings is crucial for understanding and optimizing medication adherence to OAMs. The complex identification of non-persistence underlines the need to carefully and prospectively assess OAM interruption or treatment switch reasons. The GEE analysis for describing implementation to OAMs will allow researchers and professionals to take advantage of the richness of longitudinal real-time data, to avoid reducing such data through thresholds and to put them into perspective with OAM blood levels