Studies on the ability of minor groove binders to induce supercoiling in DNA

AbstractThe effect of various non-intercalating minor groove binders on closed circular DNA in the presence of topoisomerase I has been studied by means of agarose gel electrophoresis. Analogues of the netropsin series (lexitropsins) and SN-6999 can effectively produce positive supercoils, as indicated by analysis of the topoisomers in the presence of chloroquine and the evaluated linking number changes. Analogues of the distamycin series are less effective, and bisquaternary ammonium heterocycles, as well as DAPI and pentamidine, were found to be ineffective ligands. The large differences observed in the ability of minor groove binders to induce positive supercoils are discussed

On the Behaviour of General-Purpose Applications on Cloud Storages

Managing data over cloud infrastructures raises novel challenges with respect to existing and well studied approaches such as ACID and long running transactions. One of the main requirements is to provide availability and partition tolerance in a scenario with replicas and distributed control. This comes at the price of a weaker consistency, usually called eventual consistency. These weak memory models have proved to be suitable in a number of scenarios, such as the analysis of large data with Map-Reduce. However, due to the widespread availability of cloud infrastructures, weak storages are used not only by specialised applications but also by general purpose applications. We provide a formal approach, based on process calculi, to reason about the behaviour of programs that rely on cloud stores. For instance, one can check that the composition of a process with a cloud store ensures `strong' properties through a wise usage of asynchronous message-passing

Über Rindenexzisionen als Beitrag zur operativen Therapie der Psychosen

PDF is a seperate copy of the origina

Verifying linearizability on TSO architectures

Linearizability is the standard correctness criterion for fine-grained, non-atomic concurrent algorithms, and a variety of methods for verifying linearizability have been developed. However, most approaches assume a sequentially consistent memory model, which is not always realised in practice. In this paper we define linearizability on a weak memory model: the TSO (Total Store Order) memory model, which is implemented in the x86 multicore architecture. We also show how a simulation-based proof method can be adapted to verify linearizability for algorithms running on TSO architectures. We demonstrate our approach on a typical concurrent algorithm, spinlock, and prove it linearizable using our simulation-based approach. Previous approaches to proving linearizabilty on TSO architectures have required a modification to the algorithm's natural abstract specification. Our proof method is the first, to our knowledge, for proving correctness without the need for such modification

An annotated checklist of the jumping plant-lice (Insecta: Hemiptera: Psylloidea) from the Mercantour National Park, with seven new records for France and one new synonymy

A total of 68 psyllid species are listed from the Mercantour National Park in Southeast France, where a targeted collecting campaign was conducted between 2009 and 2012, as part of the project "ATBI+M" Mercantour. The insects were collected using Malaise traps, flight intercept traps and sweep nets to sample in the vegetation. Additional information on distribution, biology and host-plants is provided for each species. Seven species are recorded for the first time from France: Craspedolepta artemisiae (Foerster, 1848), Craspedolepta nebulosa (Zetterstedt, 1828), Cacopsylla propinqua (Schaefer, 1949), Cyamophila prohaskai (Priesner, 1927), Eryngiofaga cf. refuga (Loginova, 1966), Bactericera parastriola Conci, Ossiannilsson & Tamanini, 1988 and Trioza flixiana Burckhardt & Lauterer, 2002. Trioza (Trioza) rapisardai Conci & Tamanini, 1984 is a new subjective synonym of Trioza brachyceraea Hodkinson & White, 1979, which was previously known only from the male holotype. The abundance, distribution and introduction status of some species are discussed

Pharmacokinetics of Pamidronate in Patients With Bone Metastases

Background: Pamidronate is a secondgeneration bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. Purpose: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. Methods: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. Results: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (±SD) half-life of the distribution phase was 0.8 hour (±0.3), the mean (±SD) of the area under the curve for drug concentration in plasma × time at 0-24 hours was 22.0 × 8.8 μmol/L × hours, and the mean (±SD) of the maximum plasma concentration was 9.7 μmol/L (±3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. Conclusions: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases. [J Natl Cancer Inst 84: 788-792, 1992

Interplaying Cassandra NoSQL Consistency and Performance: A Benchmarking Approach

This experience report analyses performance of the Cassandra NoSQL database and studies the fundamental trade-off between data consistency and delays in distributed data storages. The primary focus is on investigating the interplay between the Cassandra performance (response time) and its consistency settings. The paper reports the results of the read and write performance benchmarking for a replicated Cassandra cluster, deployed in the Amazon EC2 Cloud. We present quantitative results showing how different consistency settings affect the Cassandra performance under different workloads. One of our main findings is that it is possible to minimize Cassandra delays and still guarantee the strong data consistency by optimal coordination of consistency settings for both read and write requests. Our experiments show that (i) strong consistency costs up to 25% of performance and (ii) the best setting for strong consistency depends on the ratio of read and write operations. Finally, we generalize our experience by proposing a benchmarking-based methodology for run-time optimization of consistency settings to achieve the maximum Cassandra performance and still guarantee the strong data consistency under mixed workloads

Pharmacokinetics of pamidronate in patients with bone metastases

BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases