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Islet transplantation for the treatment of type 1 diabetes mellitus is limited in its clinical application mainly due to early loss of the transplanted islets, resulting in low transplantation efficiency. NKT cell-dependent IFN-γ production by [Gr-1.sup.+][CD11b.sup.+] cells is essential for this loss, but the upstream events in the process remain undetermined. Here, we have demonstrated that high-mobility group box 1 (HMGB1) plays a crucial role in the initial events of early loss of transplanted islets in a mouse model of diabetes. Pancreatic islets contained abundant HMGB1, which was released into the circulation soon after islet transplantation into the liver. Treatment with an HMGB1-specific antibody prevented the early islet graft loss and inhibited IFN-γ production by NKT cells and [Gr-1.sup.+][CD11b.sup.+] cells. Moreover, mice lacking either of the known HMGB1 receptors TLR2 or receptor for advanced glycation end products (RAGE), but not the known HMGB1 receptor TLR4, failed to exhibit early islet graft loss. Mechanistically, HMGB1 stimulated hepatic mononuclear cells (MNCs) in vivo and in vitro; in particular, it upregulated CD40 expression and enhanced IL-12 production by DCs, leading to NKT cell activation and subsequent NKT cell-dependent augmented IFN-γ production by [Gr-1.sup.+][CD11b.sup.+] cells. Thus, treatment with either IL-12- or CD40L-specific antibody prevented the early islet graft loss. These findings indicate that the HMGB1-mediated pathway eliciting early islet loss is a potential target for intervention to improve the efficiency of islet transplantation., Introduction Pancreatic islet transplantation, although an attractive procedure for the treatment of type 1 diabetes mellitus, usually fails to achieve insulin independence of a diabetic recipient from a single donor [...]

In order to operate an 'improved' Fourier synthesis imager at higher photon energies than are accessible with solidstate detectors, we developed a new one-dimensional [gamma]-ray position sensor consisting of inorganic scintillators whose light is read out by a silicon strip detector (SSD). The SSD is read out through stripped p-electrodes (DC-coupled, 32 channels at 400 [micro]m pitch). The n-side of the SSD does not have a metallic surface, and has a relatively good optical transparancy. A stack of optically isolated thin CsI(TI) scintillator plates (10 mm x 10 mm in area and 0.3 mm thick) is attached, edge-on, to the n-side of the SSD. When a [gamma]-ray photon hits the stacked scintillator, the generated scintillation light is detected by the SSD, with the signal pulse-height largest in the p-electrode which is just beneath the CsI plate hit by the [gamma]-ray. The 32-channel outputs from the SSD are acquired simultaneously for each event with a low-noise analog ASIC. The [gamma]-ray position can be calculated as a weighted mean of pulse heights. Using this system, we have obtained a position resolution significantly finer than 1 mm for v-rays with energies greater than ~500 keV up to ~1300 keV. Index Terms--Inorganic scintillator, silicon strip detector, X-ray astronomy detectors, X-ray imaging.

The Hard X-ray Detector (HXD-II) is one of the scientific payloads on board the fifth Japanese cosmic X-ray satellite Astro-E2, scheduled for launch in 2005. The HXD-II is designed to cover a wide energy range of 10-600 keV with a high sensitivity of about [10.sup.-5] cnt/s/[cm.sup.2]/keV. In order to derive the energy response of the sensor and to estimate the background, a Monte Carlo simulator based on the Geant4 toolkit is currently being developed. This paper describes the design concept of the HXD-II software package, including the analysis tools and the Monte Carlo simulator, and its verification through a comparison with actual data taken by pre-flight radio-isotope irradiation experiments, together with calculated outputs that can demonstrate the in-orbit performance of the HXD-II. Index Terms--Astronomical satellites, gamma-ray spectroscopy detectors, Monte Carlo, simulation.

Matrix metalloproteinase-2 (MMP-2) is prominently overexpressed both after myocardial infarction (MI) and in heart failure. However, its pathophysiological significance in these conditions is still unclear. We thus examined the effects of targeted deletion of MMP-2 on post-MI left ventricular (LV) remodeling and failure. Anterior MI was produced in 10- to 12-wk-old male MMP-2 knock-out (KO) and sibling wild-type (WT) mice by ligating the left coronary artery. By day 28, MI resulted in a significant increase in mortality in association with LV cavity dilatation and dysfunction. The MMP-2 KO mice had a significantly better survival rate than WT mice (56% vs. 85%, P < 0.05), despite a comparable infarct size (50 [+ or -] 3% vs. 51 [+ or -] 3%, P = not significant), heart rate, and arterial blood pressure. The KO mice had a significantly lower incidence of LV rupture (10% vs. 39%, P < 0.05), which occurred within 7 days of MI. The KO mice exerted less LV cavity dilatation and improved fractional shortening after MI by echocardiography. The LV zymographic MMP-2 level significantly increased in WT mice after coronary artery ligation; however, this was completely prevented in KO mice. In contrast, the increase in the LV zymographic MMP-9 level after MI was similar between KO and WT mice. MMP-2 activation is therefore considered to contribute to an early cardiac rupture as well as late LV remodeling after MI. The inhibition of MMP-2 activation may therefore be a potentially useful therapeutic strategy to manage post-MI hearts. matrix metalloproteinase; cardiac rupture; heart failure; myocyte; extracellular matrix; mouse

Model-based control has great potential for use in real robots due to its high sampling efficiency. Nevertheless, dealing with physical contacts and generating accurate motions are inevitable for practical robot control tasks, such as precise manipulation. For a real-time, model-based approach, the difficulty of contact-rich tasks that requires precise movement lies in the fact that a model needs to accurately predict forthcoming contact events within a limited length of time rather than detect them afterward with sensors. Therefore, in this study, we investigate whether and how neural network models can learn a task-related model useful enough for model-based control, that is, a model predicting future states, including contact events. To this end, we propose a structured neural network model predictive control (SNN-MPC) method, whose neural network architecture is designed with explicit inertia matrix representation. To train the proposed network, we develop a two-stage modeling procedure for contact-rich dynamics from a limited number of samples. As a contact-rich task, we take up a trackball manipulation task using a physical 3-DoF finger robot. The results showed that the SNN-MPC outperformed MPC with a conventional fully connected network model on the manipulation task. [ABSTRACT FROM AUTHOR]

Acute and fulminant liver failure induced by viral hepatitis, alcohol or other hepatotoxic drugs, are associated with tumor necrosis factor (TNF) production. In a mouse model of lethal hepatitis induced by TNF, apoptosis and necrosis of hepatocytes, but also lethality, hypothermia and influx of leukocytes into the liver, are prevented by a broad-spectrum matrix metalloproteinase (MMP) inhibitor, BB-94. Mice deficient in MMP-2, MMP-3 or MMP-9 had lower levels of apoptosis and necrosis of hepatocytes, and better survival. We found induction of MMP-9 activity and fibronectin degradation. Our findings suggest that several MMPs play a critical role in acute, fulminant hepatitis by degrading the extracellular matrix and allowing massive leukocyte influx in the liver. BB-94 also prevented lethality in TNF/interferon-[gamma] therapy in tumor-bearing mice. A broad-spectrum MMP inhibitor may be potentially useful for the treatment of patients with acute and perhaps chronic liver failure, and in cancer therapies using inflammatory cytokines., Author(s): Ben Wielockx [1]; Katrien Lannoy [1]; Steven D. Shapiro [2]; Takeshi Itoh [3]; Shigeyoshi Itohara [4]; Joel Vandekerckhove [5]; Claude Libert (corresponding author) [1] The abrupt or chronic loss [...]