Characterisation of a Thin Fully Depleted SOI Pixel Sensor with High Momentum Charged Particles

This paper presents the results of the characterisation of a thin, fully depleted pixel sensor manufactured in SOI technology on high-resistivity substrate with high momentum charged particles. The sensor is thinned to 70 $\mu$m and a thin phosphor layer contact is implanted on the back-plane. Its response is compared to that of thick sensors of same design in terms of signal and noise, detection efficiency and single point resolution based on data collected with 300 GeV pions at the CERN SPS. We observe that the charge collected and the signal-to-noise ratio scale according to the estimated thickness of the sensitive volume and the efficiency and single point resolution of the thinned chip are comparable to those measured for the thick sensors.Comment: 8 pages, 3 figures, submitted to Nucl. Instr. and Meth., section

Characterisation of a Thin Fully-Depleted SOI Pixel Sensor with Soft X-ray Radiation

This paper presents the results of the characterisation of a back-illuminated pixel sensor manufactured in Silicon-On-Insulator technology on a high-resistivity substrate with soft X-rays. The sensor is thinned and a thin Phosphor layer contact is implanted on the back-plane. The response to X-rays from 2.12 up to 8.6 keV is evaluated with fluorescence radiation at the LBNL Advanced Light Source.Comment: 9 pages, 5 figures, submitted to Nuclear Instruments and Methods

Studies of Vertex Tracking with SOI Pixel Sensors for Future Lepton Colliders

This paper presents a study of vertex tracking with a beam hodoscope consisting of three layers of monolithic pixel sensors in SOI technology on high-resistivity substrate. We study the track extrapolation accuracy, two-track separation and vertex reconstruction accuracy in pion-Cu interactions with 150 and 300 GeV/c pions at the CERN SPS. Results are discussed in the context of vertex tracking at future lepton colliders.Comment: 15 pages, 8 figures, submitted to Nuclear Instruments and Methods

Monolithic Pixel Sensors in Deep-Submicron SOI Technology with Analog and Digital Pixels

This paper presents the design and test results of a prototype monolithic pixel sensor manufactured in deep-submicron fully-depleted Silicon-On-Insulator (SOI) CMOS technology. In the SOI technology, a thin layer of integrated electronics is insulated from a (high-resistivity) silicon substrate by a buried oxide. Vias etched through the oxide allow to contact the substrate from the electronics layer, so that pixel implants can be created and a reverse bias can be applied. The prototype chip, manufactured in OKI 0.15 micron SOI process, features both analog and digital pixels on a 10 micron pitch. Results of tests performed with infrared laser and 1.35 GeV electrons and a first assessment of the effect of ionising and non-ionising doses are discussed.Comment: 5 pages, 7 figures, submitted to Nuclear Instruments and Methods

N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans.

Emerging research seeking novel analgesic drugs focuses on agents targeting group-II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors). N-Acetylcysteine (NAC) enhances the endogenous activation of mGlu2/3 receptors by activating the glial glutamate:cystine membrane exchanger. Here, we examined whether NAC inhibits nociceptive responses in humans and animals. We tested the effect of oral NAC (1.2 g) on thermal-pain thresholds and laser-evoked potentials in 10 healthy volunteers, according to a crossover, double-blind, placebo-controlled design, and the effect of NAC (100 mg/kg, i.p.) on the tail-flick response evoked by radiant heat stimulation in mice.In healthy subjects, NAC treatment left thermal-pain thresholds unchanged, but significantly reduced pain ratings to laser stimuli and amplitudes of laser-evoked potentials. NAC induced significantly greater changes in these measures than placebo. In the tail-flick test, NAC strongly reduced the nocifensive reflex response to radiant heat. The action of NAC was abolished by the preferential mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.).Our findings show for the first time that NAC inhibits nociceptive transmission in humans, and does the same in mice by activating mGlu2/3 receptors. These data lay the groundwork for investigating the therapeutic potential of NAC in patients with chronic pain

Analgesia induced by the epigenetic drug, L-acetylcarnitine, outlasts the end of treatment in mouse models of chronic inflammatory and neuropathic pain

Background: L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results: A seven-day treatment with L-acetylcarnitine ( 100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain. L-Acetylcarnitine-induced analgesia persisted for at least 14 days after drug withdrawal. In contrast, the analgesic effect of pregabalin, amitryptiline, ceftriaxone, and N-acetylcysteine disappeared seven days after drug withdrawal. L-acetylcarnitine treatment enhanced mGlu2/3 receptor protein levels in the dorsal region of the spinal cord. This effect also persisted for two weeks after drug withdrawal and was associated with increased levels of acetylated histone H3 bound to the Grm2 gene promoter in the dorsal root ganglia. A long-lasting analgesic effect of L-acetylcarnitine was also observed in mice subjected to chronic constriction injury of the sciatic nerve. In these animals, a 14-day treatment with pregabalin, amitryptiline, tramadol, or L-acetylcarnitine produced a significant antiallodynic effect, with pregabalin displaying the greatest efficacy. In mice treated with pregabalin, tramadol or L-acetylcarnitine the analgesic effect was still visible 15 days after the end of drug treatment. However, only in mice treated with L-acetylcarnitine analgesia persisted 37 days after drug withdrawal. This effect was associated with an increase in mGlu2/3 receptor protein levels in the dorsal horns of the spinal cord. Conclusions: Our findings suggest that L-acetylcarnitine has the unique property to cause a long-lasting analgesic effect that might reduce relapses in patients suffering from chronic pain

Characterisation of a Pixel Sensor in 0.20 micron SOI Technology for Charged Particle Tracking

This paper presents the results of the characterisation of a pixel sensor manufactured in OKI 0.2 micron SOI technology integrated on a high-resistivity substrate, and featuring several pixel cell layouts for charge collection optimisation. The sensor is tested with short IR laser pulses, X-rays and 200 GeV pions. We report results on charge collection, particle detection efficiency and single point resolution.Comment: 15 pages, 11 figures, submitted to Nuclear Instruments and Methods

Elevated soluble receptor for advanced glycation end product levels in patients with acute coronary syndrome and positive cardiac troponin I

Objectives High levels of soluble receptor for advanced glycation end products (sRAGE) have been shown to have an atheroprotective role; however, no data are available on this molecule in acute coronary syndromes (ACS). We evaluated sRAGE levels in patients with non-ST segment elevation ACS (NSTE-ACS) or with chronic stable angina. Methods We studied 265 patients, 190 of whom had NSTE-ACS and 75 had chronic stable angina. Results Plasma sRAGE values were comparable in the two groups (P= 0.19). However, in the patients with NSTEACS,sRAGE levels were significantly higher in patients with cardiac troponin-I (cTnI) of more than or equal to 0.04 lg/l compared with those with cTnI of less than 0.04 lg/l [758 pg/ml (493-1536 pg/ml) vs. 454 pg/ml (167-899 pg/ml); P = 0.0037]. A significant correlation(r= 0.323, P = 0.0045) was found between sRAGE and cTnI levels in patients with NSTE-ACS.Conclusion Plasma sRAGE levels are elevated in patients with NSTE-ACS with positive cTnI, suggesting that they could be related to myocardial cell damage

mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors

In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1α receptors were barely detectable. The developmental decline of mGlu5 receptors coincided with the appearance of mGlu1α receptors in PCs, and both processes were associated with specular changes in CpG methylation in the corresponding gene promoters. It was the mGlu1 receptor that drove the elimination of mGlu5 receptors from PCs, as shown by data obtained with conditional mGlu1α receptor knockout mice and with targeted pharmacological treatments during critical developmental time windows. The suppressing activity of mGlu1 receptors on mGlu5 receptor was maintained in mature PCs, suggesting that expression of mGlu1α and mGlu5 receptors is mutually exclusive in PCs. These findings add complexity to the the finely tuned mechanisms that regulate PC biology during development and in the adult life and lay the groundwork for an in-depth analysis of the role played by mGlu5 receptors in PC maturation