Positive Feedback Regulation Results in Spatial Clustering and Fast Spreading of Active Signaling Molecules on a Cell Membrane

Positive feedback regulation is ubiquitous in cell signaling networks, often leading to binary outcomes in response to graded stimuli. However, the role of such feedbacks in clustering, and in spatial spreading of activated molecules, has come to be appreciated only recently. We focus on the latter, using a simple model developed in the context of Ras activation with competing negative and positive feedback mechanisms. We find that positive feedback, in the presence of slow diffusion, results in clustering of activated molecules on the plasma membrane, and rapid spatial spreading as the front of the cluster propagates with a constant velocity (dependent on the feedback strength). The advancing fronts of the clusters of the activated species are rough, with scaling consistent with the Kardar-Parisi-Zhang (KPZ) equation in one dimension. Our minimal model is general enough to describe signal transduction in a wide variety of biological networks where activity in the membrane-proximal region is subject to feedback regulation.Comment: 37 pages, 8 figures. Journal of Chemical Physics (in press

Responsible Scholarship in a Crisis: A Plea For Fairness in Academic Discourse on Carbon Pricing References

This article offers a critical review of a paper Professor Dwight Newman recently published on the constitutionality of the federal government’s national carbon pricing legislation and the Saskatchewan and Ontario court decisions upholding the law. Rather than engage with the substance of Professor Newman’s article, the authors consider whether it respects the norms of rigorous and fair inquiry that enable constructive scholarly debate. The authors conclude that it does not, and that the consequences for the Supreme Court’s resolution of the carbon pricing reference cases could be significant. Le présent article propose une analyse critique d’un texte publié récemment par le professeur Dwight Newman sur la constitutionnalité de la loi du gouvernement fédéral relative à la tarification du carbone et des décisions des tribunaux de la Saskatchewan et de l’Ontario confirmant la loi. Plutôt que de s’engager sur le fond de l’article du professeur Newman, les auteurs examinent s’il respecte les normes d’une enquête rigoureuse et équitable qui permettent un débat scientifique constructif. Les auteurs concluent que ce n’est pas le cas, et que les conséquences pour la résolution par la Cour suprême des affaires relatives au renvoi sur la tarification du carbone pourraient être importantes

Associated Charm Production in Neutrino-Nucleus Interactions

In this paper a search for associated charm production both in neutral and charged current $\nu$-nucleus interactions is presented. The improvement of automatic scanning systems in the {CHORUS} experiment allows an efficient search to be performed in emulsion for short-lived particles. Hence a search for rare processes, like the associated charm production, becomes possible through the observation of the double charm-decay topology with a very low background. About 130,000 $\nu$ interactions located in the emulsion target have been analysed. Three events with two charm decays have been observed in the neutral-current sample with an estimated background of 0.18$\pm$0.05. The relative rate of the associated charm cross-section in deep inelastic $\nu$ interactions, $\sigma(c\bar{c}\nu)/\sigma_\mathrm{NC}^\mathrm{DIS}= (3.62^{+2.95}_{-2.42}({stat})\pm 0.54({syst}))\times 10^{-3}$ has been measured. One event with two charm decays has been observed in charged-current $\nu_\mu$ interactions with an estimated background of 0.18$\pm$0.06 and the upper limit on associated charm production in charged-current interactions at 90% C.L. has been found to be $\sigma (c\bar{c} \mu^-)/\sigma_\mathrm{CC} < 9.69 \times 10^{-4}$.Comment: 10 pages, 4 figure

Leading order analysis of neutrino induced dimuon events in the CHORUS experiment

We present a leading order QCD analysis of a sample of neutrino induced charged-current events with two muons in the final state originating in the lead-scintillating fibre calorimeter of the CHORUS detector. The results are based on a sample of 8910 neutrino and 430 antineutrino induced opposite-sign dimuon events collected during the exposure of the detector to the CERN Wide Band Neutrino Beam between 1995 and 1998. % with $E_{\mu 1},E_{\mu 2} > 5$ GeV and $Q^2 > 3$ GeV$^2$ collected %between 1995 and 1998. The analysis yields a value of the charm quark mass of \mc = (1.26\pm 0.16 \pm 0.09) \GeVcc and a value of the ratio of the strange to non-strange sea in the nucleon of $\kappa = 0.33 \pm 0.05 \pm 0.05$, improving the results obtained in similar analyses by previous experiments.Comment: Submitted to Nuclear Physics

Charged-Particle Multiplicities in Charged-Current Neutrino-- and Anti-Neutrino--Nucleus Interactions

The CHORUS experiment, designed to search for $\nu_{\mu}\to\nu_{\tau}$ oscillations, consists of a nuclear emulsion target and electronic detectors. In this paper, results on the production of charged particles in a small sample of charged-current neutrino-- and anti-neutrino--nucleus interactions at high energy are presented. For each event, the emission angle and the ionization features of the charged particles produced in the interaction are recorded, while the standard kinematic variables are reconstructed using the electronic detectors. The average multiplicities for charged tracks, the pseudo-rapidity distributions, the dispersion in the multiplicity of charged particles and the KNO scaling are studied in different kinematical regions. A study of quasi-elastic topologies performed for the first time in nuclear emulsions is also reported. The results are presented in a form suitable for use in the validation of Monte Carlo generators of neutrino--nucleus interactions.Comment: 17 pages, 5 figure

Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

<p>Abstract</p> <p>Background</p> <p>The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally.</p> <p>Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose.</p> <p>Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment.</p> <p>Methods/design</p> <p>The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy.</p> <p>A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border), heart, vertebral bodies and pelvic bones.</p> <p>Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival.</p> <p>Discussion</p> <p>Intensity-modulated WAR provides a new promising option in the consolidation treatment of ovarian carcinoma in patients with a complete pathologic remission after adjuvant chemotherapy. Further consequent studies will be needed to enable firm conclusions regarding the value of consolidation radiotherapy within the multimodal treatment of advanced ovarian cancer.</p> <p>Trial registration</p> <p>Clinicaltrials.gov: <a href="http://clinicaltrials.gov/ct2/show/NCT01180504">NCT01180504</a></p

Test System Stability and Natural Variability of a Lemna Gibba L. Bioassay

BACKGROUND: In ecotoxicological and environmental studies Lemna spp. are used as test organisms due to their small size, rapid predominantly vegetative reproduction, easy handling and high sensitivity to various chemicals. However, there is not much information available concerning spatial and temporal stability of experimental set-ups used for Lemna bioassays, though this is essential for interpretation and reliability of results. We therefore investigated stability and natural variability of a Lemna gibba bioassay assessing area-related and frond number-related growth rates under controlled laboratory conditions over about one year. METHODOLOGY/PRINCIPAL FINDINGS: Lemna gibba L. was grown in beakers with Steinberg medium for one week. Area-related and frond number-related growth rates (r(area) and r(num)) were determined with a non-destructive image processing system. To assess inter-experimental stability, 35 independent experiments were performed with 10 beakers each in the course of one year. We observed changes in growth rates by a factor of two over time. These did not correlate well with temperature or relative humidity in the growth chamber. In order to assess intra-experimental stability, we analysed six systematic negative control experiments (nontoxicant tests) with 96 replicate beakers each. Evaluation showed that the chosen experimental set-up was stable and did not produce false positive results. The coefficient of variation was lower for r(area) (2.99%) than for r(num) (4.27%). CONCLUSIONS/SIGNIFICANCE: It is hypothesised that the variations in growth rates over time under controlled conditions are partly due to endogenic periodicities in Lemna gibba. The relevance of these variations for toxicity investigations should be investigated more closely. Area-related growth rate seems to be more precise as non-destructive calculation parameter than number-related growth rate. Furthermore, we propose two new validity criteria for Lemna gibba bioassays: variability of average specific and section-by-section segmented growth rate, complementary to average specific growth rate as the only validity criterion existing in guidelines for duckweed bioassays

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum