Transverse-Longitudinal Coupling by Space Charge in Cyclotrons

A method is presented that enables to compute the parameters of matched beams with space charge in cyclotrons with emphasis on the effect of the transverse-longitudinal coupling. Equations describing the transverse-longitudinal coupling and corresponding tune-shifts in first order are derived for the model of an azimuthally symmetric cyclotron. The eigenellipsoid of the beam is calculated and the transfer matrix is transformed into block-diagonal form. The influence of the slope of the phase curve on the transverse-longitudinal coupling is accounted for. The results are generalized and numerical procedures for the case of an AVF cyclotron are presented. The algorithm is applied to the PSI Injector II and Ring cyclotron and the results are compared to TRANSPORT.Comment: 8 pages, 2 figure

A minimal-length approach unifies rigidity in under-constrained materials

We present a novel approach to understand geometric-incompatibility-induced rigidity in under-constrained materials, including sub-isostatic 2D spring networks and 2D and 3D vertex models for dense biological tissues. We show that in all these models a geometric criterion, represented by a minimal length $\bar\ell_\mathrm{min}$, determines the onset of prestresses and rigidity. This allows us to predict not only the correct scalings for the elastic material properties, but also the precise {\em magnitudes} for bulk modulus and shear modulus discontinuities at the rigidity transition as well as the magnitude of the Poynting effect. We also predict from first principles that the ratio of the excess shear modulus to the shear stress should be inversely proportional to the critical strain with a prefactor of three, and propose that this factor of three is a general hallmark of geometrically induced rigidity in under-constrained materials and could be used to distinguish this effect from nonlinear mechanics of single components in experiments. Lastly, our results may lay important foundations for ways to estimate $\bar\ell_\mathrm{min}$ from measurements of local geometric structure, and thus help develop methods to characterize large-scale mechanical properties from imaging data.Comment: 10 pages, 5 figure

Polar stratospheric cloud observations by MIPAS on ENVISAT: Detection method, validation and analysis of the northern hemisphere winter 2002/2003

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on ENVISAT has made extensive measurements of polar stratospheric clouds (PSCs) in the northern hemisphere winter 2002/2003. A PSC detection method based on a ratio of radiances (the cloud index) has been implemented for MIPAS and is validated in this study with respect to ground-based lidar and space borne occultation measurements. A very good correspondence in PSC sighting and cloud altitude between MIPAS detections and those of other instruments is found for cloud index values of less than four. Comparisons with data from the Stratospheric Aerosol and Gas Experiment (SAGE) III are used to further show that the sensitivity of the MIPAS detection method for this threshold value of cloud index is approximately equivalent to an extinction limit of 10-3km-1 at 1022nm, a wavelength used by solar occultation experiments. The MIPAS cloud index data are subsequently used to examine, for the first time with any technique, the evolution of PSCs throughout the Arctic polar vortex up to a latitude close to 90° north on a near-daily basis. We find that the winter of 2002/2003 is characterised by three phases of very different PSC activity. First, an unusual, extremely cold phase in the first three weeks of December resulted in high PSC occurrence rates. This was followed by a second phase of only moderate PSC activity from 5-13 January, separated from the first phase by a minor warming event. Finally there was a third phase from February to the end of March where only sporadic and mostly weak PSC events took place. The composition of PSCs during the winter period has also been examined, exploiting in particular an infra-red spectral signature which is probably characteristic of NAT. The MIPAS observations show the presence of these particles on a number of occasions in December but very rarely in January. The PSC type differentiation from MIPAS indicates that future comparisons of PSC observations with microphysical and denitrification models might be revealing about aspects of solid particle existence and location

Systemically Administered Ligands of Toll-Like Receptor 2, -4, and -9 Induce Distinct Inflammatory Responses in the Murine Lung

Objective. To determine whether systemically administered TLR ligands differentially modulate pulmonary inflammation. Methods. Equipotent doses of LPS (20 mg/kg), CpG-ODN (1668-thioat 1 nmol/g), or LTA (15 mg/kg) were determined via TNF activity assay. C57BL/6 mice were challenged intraperitoneally. Pulmonary NFκB activation (2 h) and gene expression/activity of key inflammatory mediators (4 h) were monitored. Results. All TLR ligands induced NFκB. LPS increased the expression of TLR2, 6, and the cytokines IL-1αβ, TNF-α, IL-6, and IL-12p35/p40, CpG-ODN raised TLR6, TNF-α, and IL12p40. LTA had no effect. Additionally, LPS increased the chemokines MIP-1α/β, MIP-2, TCA-3, eotaxin, and IP-10, while CpG-ODN and LTA did not. Myeloperoxidase activity was highest after LPS stimulation. MMP1, 3, 8, and 9 were upregulated by LPS, MMP2, 8 by CpG-ODN and MMP2 and 9 by LTA. TIMPs were induced only by LPS. MMP-2/-9 induction correlated with their zymographic activities. Conclusion. Pulmonary susceptibility to systemic inflammation was highest after LPS, intermediate after CpG-ODN, and lowest after LTA challenge

First in situ measurement of the vertical distribution of ice volume in a mesospheric ice cloud during the ECOMA/MASS rocket-campaign

We present in situ observations of mesospheric ice particles with a new particle detector which combines a classical Faraday cup with the active photoionization of particles and subsequent detection of photoelectrons. Our observations of charged particles and free electrons within a decaying PMSE-layer reveal that the presence of charged particles is a necessary but not sufficient condition for the presence of PMSE. That is, additional requirements like a sufficiently large electron density – which we here estimate to be on the order of ~100 cm−3 – and the presence of small scale structures (commonly assumed to be caused by turbulence) need to be satisfied. Our photoelectron measurements reveal a very strong horizontal structuring of the investigated ice layer, i.e., a very broad layer (82–88 km) seen on the upleg is replaced by a narrow layer from 84.5–86 km only 50 km apart on the downleg of the rocket flight. Importantly, the qualitative structure of these photoelectron profiles is in remarkable qualitative agreement with photometer measurements on the same rocket thus demonstrating the reliability of this new technique. We then show that the photoelectron currents are a unique function of the ice particle volume density (and hence ice mass) within an uncertainty of only 15% and we derive corresponding altitude profiles of ice volume densities. Derived values are in the range ~2–8×10−14 cm3/cm3 (corresponding to mass densities of ~20–80 ng/m3, and water vapor mixing ratios of 3–12 ppm) and are the first such estimates with the unique spatial resolution of an in situ measurement

Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma

Purpose: In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods: Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results: Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion: Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived