Planar geometry silicon pixel and strip sensors for the high luminosity upgrade of the LHC (HL-LHC) require a high bias voltage of 1000V in order to withstand a radiation damage caused by particle ...fluences of 1×1016 1MeVneq/cm2 and 1×1015 1MeVneq/cm2 for pixel and strip detectors, respectively. In order to minimize the inactive edge space that can withstand a bias voltage of 1000V, edge regions susceptible to microdischarge (MD) should be carefully optimized. We fabricated diodes with various edge distances (slim-edge diodes) and with 1–3 multiple guard rings (multi-guard diodes). AC coupling insulators of strip sensors are vulnerable to sudden heavy charge deposition, such as an accidental beam splash, which may destroy the readout AC capacitors. Thus various types of punch-through-protection (PTP) structures were implemented in order to find the most effective structure to protect against heavy charge deposition. These samples were irradiated with 70MeV protons at fluences of 5×1012 1MeVneq/cm2–1×1016 1MeVneq/cm2. Their performances were evaluated before and after irradiation in terms of an onset voltage of the MD, a turn-on voltage of the PTP, and PTP saturation resistance.
► We have evaluated radiation tolerance of n-in-p sensors up to 1×1016 1MeVneq/cm2. ► Both n-bulk and p-bulk require a field width≥450μm in order to withstand 1000V. ► The MD onset voltage was found to be independent of the edge width. ► With increasing number of guard rings, bias voltage tolerance improved before irrad. ► BZ4D-5 (with full extension) performs the best among the samples.
We have tested the performance of two types of the latest Multi-Pixel Photon Counters (MPPCs; measuring 3×3mm2 in size) developed by Hamamatsu Photonics K.K. The new S12572-050C is a successor to the ...S10362-33-050C (i.e., conventional 3×3-mm2 pixel MPPC of 50μm pitch), comprises 3600 Geiger mode avalanche photodiodes (APDs), and also features high gain (up to 1.25×106), a low dark count (up to 106cps), and improved photon detection efficiency (PDE) by up to 30%. The S12572-015C is a new type of fine-pitch (15μm) MPPC featuring a wide dynamic range and fast timing response. This paper first presents the detailed performance of these latest MPPCs as photon counting devices. It then describes our fabrication of a prototype detector consisting of a MPPC optically coupled with a Ce:GAGG scintillator. We obtained average FWHM energy resolutions of 7.3% (15μm) and 6.7% (new-50μm), as compared to 6.9% (old-50μm) for 662-keV gamma rays from the 137Cs source, as measured at 20°C. Moreover, the number of fired pixels for 662-keV gamma rays increased by 30% for the new-50μm (as compared to the old-50μm). We confirmed that the low energy threshold improved from 10keV to 4keV, when using the latest MPPC device (new-50μm). We also confirmed that the timing resolution of the new MPPC is 50ps or even better, as compared to 89ps of the old MPPC. The results thus confirm that these new types of MPPCs are promising for various applications as scintillation detectors.
•We tested the performance of the latest MPPC.•We confirmed that the new MPPC is superior to the old MPPC.•We plan to apply the new MPPC for a next-generation PET and a handy Compton camera.
Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of ...oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P=0.016). Angiogenesis was significantly higher in treatment group (P=0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P=0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.
We have developed a new type of large-area monolithic Multi-Pixel Photon Counter (MPPC) array consisting of a 4×4 matrix of 3×3
mm
2 pixels. Each pixel comprises 3600 Geiger mode avalanche ...photodiodes (APDs) that achieve an average gain of 9.68×10
5 at 71.9
V at 0
°C with variations of only ±7.2% over 4×4 pixels. Excellent uniformity was also obtained for photon detection efficiencies (PDE) of ±6.4%, whilst dark count rates at the single photoelectron (1 p.e.) level amounted to
≃
2
Mcps
/
pixel
, measured at 0
°C. As the first step toward using the device in scintillation photon detectors, we fabricated a prototype gamma-ray camera consisting of an MPPC array optically coupled with a scintillator matrix, namely a 4×4 array of 3×3 ×10
mm
3 crystals. Specifically, we tested the performance with Ce-doped (Lu, Y)
2(SiO
4)O (Ce:LYSO), Pr-doped Lu
3Al
5O
12 (Pr:LuAG) and “surface coated” Pr:LuAG (Pr:LuAG (WLS)) matrices whereby the emission peak of Pr:LuAG was shifted from 310 to 420
nm via a wavelength shifter (WLS). Average energy resolutions of 13.83%, 14.70% and 13.96% (FWHM) were obtained for 662
keV gamma-rays, as measured at 0
°C with Ce:LYSO, Pr:LuAG and Pr:LuAG (WLS) scintillator matrices, respectively. We confirmed that the effective PDE for Pr:LuAG (WLS) had improved by more than 30% compared to original, non-coated Pr:LuAG matrix. These results suggest that a large-area monolithic MPPC array developed here could be promising for future medical imaging, particularly in positron emission tomography (PET).
Background. Research in Western countries has shown most centenarians to be survivors with multiple comorbidities. However, Japanese centenarians' morbidity and its relationship to functional status ...has yet to be elucidated. The aim of this study is to clarify the association of morbidity with the physical and cognitive function of centenarians. We examined Tokyo-area centenarians to determine their kinds of morbidity profiles and how such morbidity related to their functional status. Methods. We studied 302 centenarians living in Tokyo (101.2 ± 1.8 years; 65 men, 237 women), and assessed their physical status, morbidity, and use of medication. Activities of daily living and cognitive function were also assessed using the Barthel Index and the Clinical Dementia Rating. Results. More than 95% of the centenarians had chronic diseases. Both the physical and cognitive functions were significantly higher in men. The present and previous illnesses most frequently included hypertension, heart disease, stroke, fractures, and cataracts. Fractures were observed significantly more frequently in women. Diabetes mellitus was uncommon. The physical and cognitive function of centenarians with a history of stroke or fracture were particularly poor, whereas those centenarians with hypertension tended to show a high level of physical and cognitive function. Conclusions. Almost all centenarians had chronic diseases. Stroke and fracture were correlated with poorer function; therefore, we hypothesize that prevention of stroke and fracture might improve functional status in the oldest-old.
The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) ...activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1-/- mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo.
The objective of this study was to retrospectively investigate the influence of cerebral fluid drainage on the serum concentrations and pharmacokinetic parameters of vancomycin (VCM). We analyzed 55 ...patients with normal renal function who had been hospitalized in the neurosurgical ward and received intravenous infusions of VCM. We compared the daily doses of VCM, serum VCM concentrations, serum concentration/dose ratio (C/D ratio), and pharmacokinetic parameters calculated using the Sawchuk-Zaske method between patients who underwent cerebral fluid drainage (drainage group) and controls (non-drainage group). The patients in the drainage group showed a significantly lower trough concentration of VCM (5.8 ± 3.3 μg/mL) than that shown by the non-drainage group (9.9 ± 5.4 μg/mL, p = 0.017). Further, the patients in the drainage group showed a significantly lower trough C/D ratio (0.32 ± 0.17) than that shown by the non-drainage group (0.50 ± 0.31, p = 0.047). In conclusion, cerebral fluid drainage may influence VCM pharmacokinetics. Our findings strongly suggest that a high dose of VCM is required to maintain optimal serum concentrations of VCM in patients managed with cerebral fluid drainage.
Two cell lines have been established from insulinomas obtained by targeted expression of the simian virus 40 T antigen gene in transgenic mice. These cell lines, designated MIN6 and MIN7, produce ...insulin and T antigen and have morphological characteristics of pancreatic beta cells. MIN6 cells exhibit glucose-inducible insulin secretion comparable with cultured normal mouse islet cells, whereas MIN7 cells do not. Both cell lines produce liver-type glucose transporter (GT) mRNA at high level. Brain-type GT mRNA is also present at considerable level in MIN7 cells, but is barely detectable in MIN6 cells, suggesting that exclusive expression of the liver-type GT is related to glucose-inducible insulin secretion. MIN6 cells do not express either major histocompatibility (MHC) class I or class II antigens on the cell surface. However, treatment with interferon-gamma induces high levels of MHC class I antigens, and a combination of interferon-gamma and tumor necrosis factor-alpha induces a MHC class II antigen on the cell surface. These results emphasize that the MIN6 cell line retains physiological characteristics of normal beta cells. The MIN6 cell line will be especially useful to analyze the molecular mechanisms by which beta cells regulate insulin secretion in response to extracellular glucose concentrations. We discuss a possible role of GT isoforms in glucose sensing by beta cells.
Childhood fractures involving the physis potentially result in premature physeal closure that can lead to growth disturbances. Growth disturbances are challenging to treat with associated ...complications. Current literature focusing on physeal injuries to lower extremity long bones and risk factors for growth disturbance development is limited. The purpose of this study was to provide a review of growth disturbances among proximal tibial, distal tibial, and distal femoral physeal fractures.
Data were retrospectively collected from patients undergoing fracture treatment at a level I pediatric trauma center between 2008 and 2018. The study was limited to patients 0.5 to 18.9 years with a tibial or distal femoral physeal fracture, injury radiograph, and appropriate follow-up for determination of fracture healing. The cumulative incidence of clinically significant growth disturbance (CSGD) (a growth disturbance requiring subsequent physeal bar resection, osteotomy, and/or epiphysiodesis) was estimated, and descriptive statistics were used to summarize demographics and clinical characteristics among patients with and without CSGD.
A total of 1,585 patients met the inclusion criteria. The incidence of CSGD was 5.0% (95% confidence interval, 3.8% to 6.6%). All cases of growth disturbance occurred within 2 years of initial injury. The risk of CSGD peaked at 10.2 years for males and 9.1 years for females. Complex fractures that required surgical treatment, distal femoral and proximal tibial fractures, age, and initial treatment at an outside hospital were significantly associated with an increased risk of a CSGD.
All CSGDs occurred within 2 years of injury, indicating that these injuries should be followed for a period of at least 2 years. Patients with distal femoral or proximal tibial physeal fractures that undergo surgical treatment are at highest risk for developing a CSGD.
Level III Retrospective Cohort Study.
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