Exact relations between damage spreading and thermodynamic functions for the N-color Ashkin-Teller model

Exact results are derived relating quantities computable by the so-called damage spreading method and thermodynamic functions for the N-color Ashkin-Teller model. The results are valid for any ergodic dynamics. Since we restrict our analysis to the ferromagnetic case the results are also valid for any translational invariant lattice. The derived relations should be used in order to determine numerically the N-color Ashkin-Teller critical exponents with better accuracy and less computational efforts than standard Monte Carlo simulations.Comment: 6 pages, to be published in JSTAT (Journal of Statistical Mechanics: Theory and Experiment). The results of a computer simulation were included for N=3 as an example on how to use the analytical relations derived in the paper as a guide to obtain the critical temperature and critical exponent

Scalar meson production in nucleon-nucleon collisions near threshold

We establish the model-independent spin structure of the matrix elements for the near-threshold scalar meson production in $pp-$ and $np$-collisions, when the final particles are emitted in S-state. Polarization phenomena are derived in a general form. The properties of the $t-$channel dynamics, which is based on different meson exchanges, are studied in terms of the $s-$channel parametrization of the matrix element. The prediction of a 'realistic' model, based on $\pi+\sigma$-exchanges are also presented.Comment: 16 pages 6 figure

Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m−2 week−1 and trastuzumab: 4 mg kg−1 on day 1 as a loading dose followed by 2 mg kg−1 week−1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6–12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4–32.6). This regimen was safe: grade 3–4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005

Integration of Expressed Sequence Tag Data Flanking Predicted RNA Secondary Structures Facilitates Novel Non-Coding RNA Discovery

Many computational methods have been used to predict novel non-coding RNAs (ncRNAs), but none, to our knowledge, have explicitly investigated the impact of integrating existing cDNA-based Expressed Sequence Tag (EST) data that flank structural RNA predictions. To determine whether flanking EST data can assist in microRNA (miRNA) prediction, we identified genomic sites encoding putative miRNAs by combining functional RNA predictions with flanking ESTs data in a model consistent with miRNAs undergoing cleavage during maturation. In both human and mouse genomes, we observed that the inclusion of flanking ESTs adjacent to and not overlapping predicted miRNAs significantly improved the performance of various methods of miRNA prediction, including direct high-throughput sequencing of small RNA libraries. We analyzed the expression of hundreds of miRNAs predicted to be expressed during myogenic differentiation using a customized microarray and identified several known and predicted myogenic miRNA hairpins. Our results indicate that integrating ESTs flanking structural RNA predictions improves the quality of cleaved miRNA predictions and suggest that this strategy can be used to predict other non-coding RNAs undergoing cleavage during maturation

Normal tissue toxicity after small field hypofractionated stereotactic body radiation

Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics

Taking Two-Photon Excitation to Exceptional Path-Lengths in Photonic Crystal Fiber

The well-known, defining feature of two-photon excitation (TPE) is the tight, three-dimensional confinement of excitation at the intense focus of a laser beam. The extremely small excitation volume, on the order of 1 μm3 (1 femtoliter), is the basis of far-reaching applications of TPE in fluorescence imaging, photodynamic therapy, nanofabrication, and three-dimensional optical memory. Paradoxically, the difficulty of detecting photochemical events in such a small volume is a barrier to the development of the two-photon-activated molecular systems that are essential to the realization of such applications. We show, using two-photon-excited fluorescence to directly visualize the excitation path, that confinement of both laser beam and sample solution within the 20 μm hollow core of a photonic crystal fiber permits TPE to be sustained over an extraordinary path-length of more than 10 cm, presenting a new experimental paradigm for ultrasensitive studies of two-photon-induced processes in solution. (Figure Presented).We are grateful to the Koerber Foundation (Germany) and the EPSRC (UK) for financial support. G.O.S.W. is a recipient of an EPSRC Prize Postdoctoral Fellowshi

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes

Regulation of MicroRNA Biogenesis: A miRiad of mechanisms

microRNAs are small, non-coding RNAs that influence diverse biological functions through the repression of target genes during normal development and pathological responses. Widespread use of microRNA arrays to profile microRNA expression has indicated that the levels of many microRNAs are altered during development and disease. These findings have prompted a great deal of investigation into the mechanism and function of microRNA-mediated repression. However, the mechanisms which govern the regulation of microRNA biogenesis and activity are just beginning to be uncovered. Following transcription, mature microRNA are generated through a series of coordinated processing events mediated by large protein complexes. It is increasingly clear that microRNA biogenesis does not proceed in a 'one-size-fits-all' manner. Rather, individual classes of microRNAs are differentially regulated through the association of regulatory factors with the core microRNA biogenesis machinery. Here, we review the regulation of microRNA biogenesis and activity, with particular focus on mechanisms of post-transcriptional control. Further understanding of the regulation of microRNA biogenesis and activity will undoubtedly provide important insights into normal development as well as pathological conditions such as cardiovascular disease and cancer