The Mid-Infrared Instrument for the James Webb Space Telescope, III: MIRIM, The MIRI Imager

In this article, we describe the MIRI Imager module (MIRIM), which provides broad-band imaging in the 5 - 27 microns wavelength range for the James Webb Space Telescope. The imager has a 0"11 pixel scale and a total unobstructed view of 74"x113". The remainder of its nominal 113"x113" field is occupied by the coronagraphs and the low resolution spectrometer. We present the instrument optical and mechanical design. We show that the test data, as measured during the test campaigns undertaken at CEA-Saclay, at the Rutherford Appleton Laboratory, and at the NASA Goddard Space Flight Center, indicate that the instrument complies with its design requirements and goals. We also discuss the operational requirements (multiple dithers and exposures) needed for optimal scientific utilization of the MIRIM.Comment: 29 pages, 9 figure

Characterizing Exoplanets in the Visible and Infrared: A Spectrometer Concept for the EChO Space Mission

Transit-spectroscopy of exoplanets is one of the key observational techniques to characterize the extrasolar planet and its atmosphere. The observational challenges of these measurements require dedicated instrumentation and only the space environment allows an undisturbed access to earth-like atmospheric features such as water or carbon-dioxide. Therefore, several exoplanet-specific space missions are currently being studied. One of them is EChO, the Exoplanet Characterization Observatory, which is part of ESA's Cosmic Vision 2015-2025 program, and which is one of four candidates for the M3 launch slot in 2024. In this paper we present the results of our assessment study of the EChO spectrometer, the only science instrument onboard this spacecraft. The instrument is a multi-channel all-reflective dispersive spectrometer, covering the wavelength range from 400 nm to 16 microns simultaneously with a moderately low spectral resolution. We illustrate how the key technical challenge of the EChO mission - the high photometric stability - influences the choice of spectrometer concept and drives fundamentally the instrument design. First performance evaluations underline the fitness of the elaborated design solution for the needs of the EChO mission.Comment: 20 pages, 8 figures, accepted for publication in the Journal of Astronomical Instrumentatio

Survival following coronary angioplasty versus coronary artery bypass surgery in anatomic subsets in which coronary artery bypass surgery improves survival compared with medical therapy Results from the Bypass Angioplasty Revascularization Investigation (BARI)

AbstractOBJECTIVESWe sought to compare survival after coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in high-risk anatomic subsets.BACKGROUNDCompared with medical therapy, CABG decreases mortality in patients with three-vessel disease and two-vessel disease involving the proximal left anterior descending artery (LAD), particularly if left ventricular (LV) dysfunction is present. How survival after PTCA and CABG compares in these high-risk anatomic subsets is unknown.METHODSIn the Bypass Angioplasty Revascularization Investigation (BARI), 1,829 patients with multivessel disease were randomized to an initial strategy of PTCA or CABG between 1988 and 1991. Stents and IIb/IIIa inhibitors were not utilized. Since patients in BARI with diabetes mellitus had greater survival with CABG, separate analyses of patients without diabetes were performed.RESULTSSeven-year survival among patients with three-vessel disease undergoing PTCA and CABG (n = 754) was 79% versus 84% (p = 0.06), respectively, and 85% versus 87% (p = 0.36) when only non-diabetics (n = 592) were analyzed. In patients with three-vessel disease and reduced LV function (ejection fraction <50%), seven-year survival was 70% versus 74% (p = 0.6) in all PTCA and CABG patients (n = 176), and 82% versus 73% (p = 0.29) among non-diabetic patients (n = 124). Seven-year survival was 87% versus 84% (p = 0.9) in all PTCA and CABG patients (including diabetics) with two-vessel disease involving the proximal LAD (n = 352), and 78% versus 71% (p = 0.7) in patients with two-vessel disease involving the proximal LAD with reduced LV function (n = 72).CONCLUSIONIn high–risk anatomic subsets in which survival is prolonged by CABG versus medical therapy, revascularization by PTCA and CABG yielded equivalent survival over seven years

Null mutation for Macrophage Migration Inhibitory Factor (MIF) is associated with less aggressive bladder cancer in mice

<p>Abstract</p> <p>Background</p> <p>Inflammatory cytokines may promote tumorigenesis. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We studied the development of bladder cancer in wild type (WT) and MIF knockout (KO) mice given N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), a known carcinogen, to determine the role of MIF in bladder cancer initiation and progression.</p> <p>Methods</p> <p>5-month old male C57Bl/6 MIF WT and KO mice were treated with and without BBN. Animals were sacrificed at intervals up to 23 weeks of treatment. Bladder tumor stage and grade were evaluated by H&E. Immunohistochemical (IHC) analysis was performed for MIF and platelet/endothelial cell adhesion molecule 1 (PECAM-1), a measure of vascularization. MIF mRNA was analyzed by quantitative real-time polymerase chain reaction.</p> <p>Results</p> <p>Poorly differentiated carcinoma developed in all BBN treated mice by week 20. MIF WT animals developed T2 disease, while KO animals developed only T1 disease. MIF IHC revealed predominantly urothelial cytoplasmic staining in the WT control animals and a shift toward nuclear staining in WT BBN treated animals. MIF mRNA levels were 3-fold higher in BBN treated animals relative to controls when invasive cancer was present. PECAM-1 staining revealed significantly more stromal vessels in the tumors in WT animals when compared to KOs.</p> <p>Conclusion</p> <p>Muscle invasive bladder cancer with increased stromal vascularity was associated with increased MIF mRNA levels and nuclear redistribution. Consistently lower stage tumors were seen in MIF KO compared to WT mice. These data suggest that MIF may play a role in the progression to invasive bladder cancer.</p

Hydrothermal dolomitization of basinal deposits controlled by a synsedimentary fault system in Triassic extensional setting, Hungary

Dolomitization of relatively thick carbonate successions occurs via an effective fluid circulation mechanism, since the replacement process requires a large amount of Mg-rich fluid interacting with the CaCO3 precursor. In the western end of the Neotethys, fault-controlled extensional basins developed during the Late Triassic spreading stage. In the Buda Hills and Danube-East blocks, distinct parts of silica and organic matter-rich slope and basinal deposits are dolomitized. Petrographic, geochemical, and fluid inclusion data distinguished two dolomite types: (1) finely to medium crystalline and (2) medium to coarsely crystalline. They commonly co-occur and show a gradual transition. Both exhibit breccia fabric under microscope. Dolomite texture reveals that the breccia fabric is not inherited from the precursor carbonates but was formed during the dolomitization process and under the influence of repeated seismic shocks. Dolomitization within the slope and basinal succession as well as within the breccia zones of the underlying basement block is interpreted as being related to fluid originated from the detachment zone and channelled along synsedimentary normal faults. The proposed conceptual model of dolomitization suggests that pervasive dolomitization occurred not only within and near the fault zones. Permeable beds have channelled the fluid towards the basin centre where the fluid was capable of partial dolomitization. The fluid inclusion data, compared with vitrinite reflectance and maturation data of organic matter, suggest that the ascending fluid was likely hydrothermal which cooled down via mixing with marine-derived pore fluid. Thermal gradient is considered as a potential driving force for fluid flow

The immunosuppressive cytokine interleukin-4 increases the clonogenic potential of prostate stem-like cells by activation of STAT6 signalling

Interleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumour microenvironment of cancer patients, where concentrations correlate with the grade of malignancy. In prostate cancer, interleukin-4 has been associated with activation of the androgen receptor, increased proliferation and activation of survival pathways such as Akt and NF-κB. However, its role in therapy resistance has not yet been determined. Here we investigate the influence of interleukin-4 on primary epithelial cells from prostate cancer patients. Our data demonstrate an increase in the clonogenic potential of these cells when cultured in the presence of interleukin-4. In addition, a Phospho-Kinase Array revealed that in contrast to previously published work, signal transducer and activator of transcription6 (STAT6) is the only signalling molecule activated after interleukin-4 treatment. Using the STAT6-specific inhibitor AS1517499 we could confirm the role of STAT6 in increasing colony-forming frequency. However, clonogenic recovery assays revealed that interleukin-4 does not rescue the effects of either irradiation or docetaxel treatment. We therefore propose that although the interleukin-4/STAT6 axis does not appear to be involved in therapy resistance, it does play a crucial role in the colony-forming abilities of the basal cell population in prostate cancer. IL-4 may therefore contribute to disease relapse by providing a niche that is favourable for the clonogenic growth of prostate cancer stem cells

Magnetic resonance imaging of brain angiogenesis after stroke

Stroke is a major cause of mortality and long-term disability worldwide. The initial changes in local perfusion and tissue status underlying loss of brain function are increasingly investigated with noninvasive imaging methods. In addition, there is a growing interest in imaging of processes that contribute to post-stroke recovery. In this review, we discuss the application of magnetic resonance imaging (MRI) to assess the formation of new vessels by angiogenesis, which is hypothesized to participate in brain plasticity and functional recovery after stroke. The excellent soft tissue contrast, high spatial and temporal resolution, and versatility render MRI particularly suitable to monitor the dynamic processes involved in vascular remodeling after stroke. Here we review recent advances in the field of MR imaging that are aimed at assessment of tissue perfusion and microvascular characteristics, including cerebral blood flow and volume, vascular density, size and integrity. The potential of MRI to noninvasively monitor the evolution of post-ischemic angiogenic processes is demonstrated from a variety of in vivo studies in experimental stroke models. Finally, we discuss some pitfalls and limitations that may critically affect the accuracy and interpretation of MRI-based measures of (neo)vascularization after stroke

What the radiologist needs to know about the diabetic patient

Diabetes mellitus (DM) is recognised as a major health problem. Ninety-nine percent of diabetics suffer from type 2 DM and 10% from type 1 and other types of DM. The number of diabetic patients worldwide is expected to reach 380 millions over the next 15 years. The duration of diabetes is an important factor in the pathogenesis of complications, but other factors frequently coexisting with type 2 DM, such as hypertension, obesity and dyslipidaemia, also contribute to the development of diabetic angiopathy. Microvascular complications include retinopathy, nephropathy and neuropathy. Macroangiopathy mainly affects coronary arteries, carotid arteries and arteries of the lower extremities. Eighty percent of deaths in the diabetic population result from cardiovascular incidents. DM is considered an equivalent of coronary heart disease (CHD). Stroke and peripheral artery disease (PAD) are other main manifestations of diabetic macroangiopathy. Diabetic cardiomyopathy (DC) represents another chronic complication that occurs independently of CHD and hypertension. The greater susceptibility of diabetic patients to infections completes the spectrum of the main consequences of DM. The serious complications of DM make it essential for physicians to be aware of the screening guidelines, allowing for earlier patient diagnosis and treatment