331 research outputs found
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
A screen to identify drug resistant variants to target-directed anti-cancer agents
The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec), a specific inhibitor of the Chronic Myeloid Leukemia (CML)-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair
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
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
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