Soliton ratchets

The mechanism underlying the soliton ratchet, both in absence and in presence of noise, is investigated. We show the existence of an asymmetric internal mode on the soliton profile which couples, trough the damping in the system, to the soliton translational mode. Effective soliton transport is achieved when the internal mode and the external force are phase locked. We use as working model a generalized double sine-Gordon equation. The phenomenon is expected to be valid for generic soliton systems.Comment: 4 pages, 4 figure

DNA transport by a micromachined Brownian ratchet device

We have micromachined a silicon-chip device that transports DNA with a Brownian ratchet that rectifies the Brownian motion of microscopic particles. Transport properties for a DNA 50mer agree with theoretical predictions, and the DNA diffusion constant agrees with previous experiments. This type of micromachine could provide a generic pump or separation component for DNA or other charged species as part of a microscale lab-on-a-chip. A device with reduced feature size could produce a size-based separation of DNA molecules, with applications including the detection of single nucleotide polymorphisms.Comment: Latex: 8 pages, 4 figure

Force and Motion Generation of Molecular Motors: A Generic Description

We review the properties of biological motor proteins which move along linear filaments that are polar and periodic. The physics of the operation of such motors can be described by simple stochastic models which are coupled to a chemical reaction. We analyze the essential features of force and motion generation and discuss the general properties of single motors in the framework of two-state models. Systems which contain large numbers of motors such as muscles and flagella motivate the study of many interacting motors within the framework of simple models. In this case, collective effects can lead to new types of behaviors such as dynamic instabilities of the steady states and oscillatory motion.Comment: 29 pages, 9 figure

Molecular motor that never steps backwards

We investigate the dynamics of a classical particle in a one-dimensional two-wave potential composed of two periodic potentials, that are time-independent and of the same amplitude and periodicity. One of the periodic potentials is externally driven and performs a translational motion with respect to the other. It is shown that if one of the potentials is of the ratchet type, translation of the potential in a given direction leads to motion of the particle in the same direction, whereas translation in the opposite direction leaves the particle localized at its original location. Moreover, even if the translation is random, but still has a finite velocity, an efficient directed transport of the particle occurs.Comment: 4 pages, 5 figures, Phys. Rev. Lett. (in print

Disorder Induced Diffusive Transport In Ratchets

The effects of quenched disorder on the overdamped motion of a driven particle on a periodic, asymmetric potential is studied. While for the unperturbed potential the transport is due to a regular drift, the quenched disorder induces a significant additional chaotic ``diffusive'' motion. The spatio-temporal evolution of the statistical ensemble is well described by a Gaussian distribution, implying a chaotic transport in the presence of quenched disorder.Comment: 10 pages, 4 EPS figures; submitted to Phys. Rev. Letter

Brownian motion exhibiting absolute negative mobility

We consider a single Brownian particle in a spatially symmetric, periodic system far from thermal equilibrium. This setup can be readily realized experimentally. Upon application of an external static force F, the average particle velocity is negative for F>0 and positive for F<0 (absolute negative mobility).Comment: 4 pages, 3 figures, to be published in PR

Framework Report: The AIDS Accountability Workplace Scorecard, September 2011

The aim of the AIDS Accountability Workplace Scorecard is to improve HIV and AIDS workplace programmes in the countries and sectors most affected by the disease, and improve the health of employees, their families and communities. Through this initiative we will: / 1. Provide tools for HIV and AIDS workplace programme monitoring and evaluation AAI has developed scorecard tools for small, medium and large workplaces, which can be used to assess a global, regional or national HIV and AIDS programme or interventions at a specific workplace site. The scorecards can serve as both internal monitoring and evaluation tools and as assessments to present to stakeholders within and outside the organization. / 2. Publish annual Rankings of HIV and AIDS Workplace Programmes Scorecard users who wish to receive a ranking analysis and recommendations for how to improve their programmes can submit their scorecards to AAI. AAI ‘s ranking analysis will allow users to compare their performance with others and over time also measure their own progress. Respondents will be encouraged to publish their ranking in AAI’s yearly Ranking Reports. / 3. Share good practice The knowledge and good practices generated through the published rankings will be used to stimulate improved HIV and AIDS Workplace Programmes worldwide. Large networks of companies, trade union confederations, and national and international organizations can use the scorecard as a common framework for monitoring and evaluation of workplace programmes

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic

New dosing schedules of dasatinib for CML and adverse event management

Resistance to imatinib in patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has emerged as a significant clinical issue. Dasatinib is a tyrosine kinase inhibitor that has 325-fold greater in vitro activity against native BCR-ABL (breakpoint cluster region-Abelson leukemia virus) compared with imatinib and can overcome primary (intrinsic) and secondary (acquired) imatinib resistance. Here, we review the clinical profile of dasatinib in imatinib-resistant and -intolerant patients and share clinical approaches for managing adverse events (AEs) to ensure maximum patient benefit. References were obtained through literature searches on PubMed as well as from the Proceedings of Annual Meetings of the American Society of Clinical Oncology, the American Society of Hematology, and European Hematology Association. Phase II and III studies of dasatinib in patients with imatinib-resistant or -intolerant CML in any phase or Ph+ ALL were selected for discussion. Dasatinib is currently indicated for the treatment of patients with imatinib-resistant or -intolerant CML or Ph+ ALL. AEs associated with dasatinib are typically mild to moderate, and are usually resolved with temporary treatment interruption and/or dose adjustments. A Phase III dose optimization study showed that in patients with chronic phase (CP) CML, 100 mg once-daily dasatinib improves the safety profile, particularly pleural effusion and thrombocytopenia, while maintaining efficacy compared with the previously recommended dose of 70 mg twice-daily. Dasatinib has a manageable safety profile. For patients with CP CML, a new recommended starting dose of 100 mg once daily has recently been approved. The recommended dose for patients with advanced CML or Ph+ ALL remains 70 mg twice daily