Isospin non-equilibrium in heavy-ion collisions at intermediate energies

We study the equilibration of isospin degree of freedom in intermediate energy heavy-ion collisions using an isospin-dependent BUU model. It is found that there exists a transition from the isospin equilibration at low energies to non-equilibration at high energies as the beam energy varies across the Fermi energy in central, asymmetric heavy-ion collisions. At beam energies around 55 MeV/nucleon, the composite system in thermal equilibrium but isospin non-equilibrium breaks up into two primary hot residues with N/Z ratios closely related to those of the target and projectile respectively. The decay of these forward-backward moving residues results in the strong isospin asymmetry in space and the dependence of the isotopic composition of fragments on the N/Z ratios of the target and projectile. These features are in good agreement with those found recently in experiments at NSCL/MSU and TAMU, implications of these findings are discussed.Comment: 9 pages, latex, + 3 figures available upon reques

Targeted removal of blood cancer cells from mixed cell populations by cell recognition with matching particle imprints

We report a new approach for separation of blood cancer cells from healthy white blood cells based on cell recognition by surface functionalised particle imprints. We prepared polymeric particle imprints from a layer of suspension of monodisperse PMMA microbeads which closely match the size of in vitro cultured human leukaemia cells (HL60). The imprints were replicated on a large scale with UV curable polyurethane resin using nanoimprinting lithography and surface functionalized with a cationic polymer, a branched polyethylene imine (bPEI), and a Pluronic surfactant, Poloxamer 407, to engineer a weak attraction towards the cells. The latter is amplified several orders of magnitude when a cell of a closely matching size and shape fits into the imprint cavity which multiplies the contact area between the cell surface and the imprint. The particle imprints were optimised for their specificity toward blood cancer cells by treatment with oxygen plasma and then subsequent coatings with bPEI and Poloxamer 407 with various functionalisation concentrations. We tested the surface functionalised imprints for their specificity in retaining in vitro cultured human leukaemic cells (HL60) over healthy human peripheral blood mononuclear cells (PBMCs) in a flow through chamber. The effect of the flushing flow rate of the mixed cell suspension over the particle imprint and the imprint length were also investigated. At each step the selectivity towards HL60 was assessed. Selective isolation of an increased amount of HL60 tumour cells over PBMC was ultimately achieved as a function of the cell seeding ratio on the particle imprint. The effect is attributed to the substantial size difference between the HL60 cell and the PBMCs. The data presented show that relatively inexpensive PMMA microbeads imprints can be utilised as a cell separation technique which could ultimately lead to novel therapies for removal of neoplastic cells from the peripheral blood of acute myeloid leukaemia patients

Isospin Physics in Heavy-Ion Collisions at Intermediate Energies

In nuclear collisions induced by stable or radioactive neutron-rich nuclei a transient state of nuclear matter with an appreciable isospin asymmetry as well as thermal and compressional excitation can be created. This offers the possibility to study the properties of nuclear matter in the region between symmetric nuclear matter and pure neutron matter. In this review, we discuss recent theoretical studies of the equation of state of isospin-asymmetric nuclear matter and its relations to the properties of neutron stars and radioactive nuclei. Chemical and mechanical instabilities as well as the liquid-gas phase transition in asymmetric nuclear matter are investigated. The in-medium nucleon-nucleon cross sections at different isospin states are reviewed as they affect significantly the dynamics of heavy ion collisions induced by radioactive beams. We then discuss an isospin-dependent transport model, which includes different mean-field potentials and cross sections for the proton and neutron, and its application to these reactions. Furthermore, we review the comparisons between theoretical predictions and available experimental data. In particular, we discuss the study of nuclear stopping in terms of isospin equilibration, the dependence of nuclear collective flow and balance energy on the isospin-dependent nuclear equation of state and cross sections, the isospin dependence of total nuclear reaction cross sections, and the role of isospin in preequilibrium nucleon emissions and subthreshold pion production.Comment: 101 pages with embedded epsf figures, review article for "International Journal of Modern Physics E: Nuclear Physics". Send request for a hard copy to 1/author

Carbonyl sulfide : comparing a mechanistic representation of the vegetation uptake in a land surface model and the leaf relative uptake approach

Land surface modellers need measurable proxies to constrain the quantity of carbon dioxide (CO2) assimilated by continental plants through photosynthesis, known as gross primary production (GPP). Carbonyl sulfide (COS), which is taken up by leaves through their stomates and then hydrolysed by photosynthetic enzymes, is a candidate GPP proxy. A former study with the ORCHIDEE land surface model used a fixed ratio of COS uptake to CO2 uptake normalised to respective ambient concentrations for each vegetation type (leaf relative uptake, LRU) to compute vegetation COS fluxes from GPP. The LRU approach is known to have limited accuracy since the LRU ratio changes with variables such as photosynthetically active radiation (PAR): while CO2 uptake slows under low light, COS uptake is not light limited. However, the LRU approach has been popular for COS-GPP proxy studies because of its ease of application and apparent low contribution to uncertainty for regional-scale applications. In this study we refined the COS-GPP relationship and implemented in ORCHIDEE a mechanistic model that describes COS uptake by continental vegetation. We compared the simulated COS fluxes against measured hourly COS fluxes at two sites and studied the model behaviour and links with environmental drivers. We performed simulations at a global scale, and we estimated the global COS uptake by vegetation to be -756 Gg S yr(-1) , in the middle range of former studies (-490 to -1335 Gg S yr(-1)). Based on monthly mean fluxes simulated by the mechanistic approach in ORCHIDEE, we derived new LRU values for the different vegetation types, ranging between 0.92 and 1.72, close to recently published averages for observed values of 1.21 for C-4 and 1.68 for C-3 plants. We transported the COS using the monthly vegetation COS fluxes derived from both the mechanistic and the LRU approaches, and we evaluated the simulated COS concentrations at NOAA sites. Although the mechanistic approach was more appropriate when comparing to high-temporal-resolution COS flux measurements, both approaches gave similar results when transporting with monthly COS fluxes and evaluating COS concentrations at stations. In our study, uncertainties between these two approaches are of secondary importance compared to the uncertainties in the COS global budget, which are currently a limiting factor to the potential of COS concentrations to constrain GPP simulated by land surface models on the global scale.Peer reviewe

Unprecedented Incorporation of alpha-Emitter Radioisotope 213Bi into Porphyrin Chelates with Reference to a Daughter Isotope Mediated Assistance Mechanism

For the first time, alphaemitter radioisotope 213Bi has been 10 incorporated into porphyrin chelates, with rates matching with the short period of the radionuclide. An in-situ transmetalation mechanism involving the daughter isotope 209Pb is expected to boost the 213Bi radiolabeling process.JRC.E.5-Nuclear chemistr

Notch and Prospero Repress Proliferation following Cyclin E Overexpression in the Drosophila Bristle Lineage

Understanding the mechanisms that coordinate cell proliferation, cell cycle arrest, and cell differentiation is essential to address the problem of how “normal” versus pathological developmental processes take place. In the bristle lineage of the adult fly, we have tested the capacity of post-mitotic cells to re-enter the cell cycle in response to the overexpression of cyclin E. We show that only terminal cells in which the identity is independent of Notch pathway undergo extra divisions after CycE overexpression. Our analysis shows that the responsiveness of cells to forced proliferation depends on both Prospero, a fate determinant, and on the level of Notch pathway activity. Our results demonstrate that the terminal quiescent state and differentiation are regulated by two parallel mechanisms acting simultaneously on fate acquisition and cell cycle progression

Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

Fault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging-wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP-2). We present observational evidence for extensive fracturing and high hanging-wall hydraulic conductivity (∼10−9 to 10−7 m/s, corresponding to permeability of ∼10−16 to 10−14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP-2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging-wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off-fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation

Removing critical gaps in chemical test methods by developing new assays for the identification of thyroid hormone system-disrupting chemicals—the athena project

The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These gaps put the public at risk and risk assessors in a difficult position. Decisions about the status of chemicals as thyroid hormone system disruptors currently are based on inadequate toxicity data. The ATHENA project (Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies) has been conceived to address these gaps. The project will develop new test methods for the disruption of thyroid hormone transport across biological barriers such as the blood–brain and blood–placenta barriers. It will also devise methods for the disruption of the downstream effects on the brain. ATHENA will deliver a testing strategy based on those elements of the thyroid hormone system that, when disrupted, could have the greatest impact on diminished or enhanced thyroid hormone action and therefore should be targeted through effective testing. To further enhance the impact of the ATHENA test method developments, the project will develop concepts for better international collaboration and development in the area of thyroid hormone system disruptor identification and regulation

Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer

<p>Abstract</p> <p>Background</p> <p>Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.</p> <p>Methods</p> <p>This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/²/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.</p> <p>Results</p> <p>Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (<it>DPYD</it>) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).</p> <p>Conclusion</p> <p>Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.</p