Pulse Shape Discrimination of CsI(Tl) with a Photomultiplier Tube and MPPCs

In this study, we evaluate and compare the pulse shape discrimination (PSD) performance of multipixel photon counters (MPPCs, also known as silicon photomultiphers - SiPMs) with that of a typical photomultiplier tube (PMT) when testing using CsI(Tl) scintillators. We use the charge comparison method, whereby we discriminate different types of particles by the ratio of charges integrated within two time-gates (the delayed part and the entire digitized waveform). For a satisfactory PSD performance, a setup should generate many photoelectrons (p.e.) and collect their charges efficiently. The PMT setup generates more p.e. than the MPPC setup does. With the same digitizer and the same long time-gate (the entire digitized waveform), the PMT setup is also better in charge collection. Therefore, the PMT setup demonstrates better PSD performance. We subsequently test the MPPC setup using a new data acquisition (DAQ) system. Using this new DAQ, the long time-gate is extended by nearly four times the length when using the previous digitizer. With this longer time-gate, we collect more p.e. at the tail part of the pulse and almost all the charges of the total collected p.e. Thus, the PSD performance of the MPPC setup is improved significantly. This study also provides an estimation of the short time-gate (the delayed part of the digitized waveform) that can give a satisfactory PSD performance without an extensive analysis to optimize this gate

CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses

A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected CA9 and PRELID2 as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment

The current state of marine debris on the seafloor in offshore area around Japan

Marine debris on the seafloor has not been thoroughly investigated, and there is little information compared to other types of marine debris. We conducted bottom trawl surveys to determine the present situation of marine debris on the seafloor in offshore areas around Japan. The survey was conducted in three sea areas with different characteristics. As a result, it was found that the amount of marine debris in submarine canyons (2926.1 items/km2) was higher than on the continental shelf. It was revealed that most marine debris on the seafloor is comprised of plastic products, and that debris on the seafloor retains its condition for a long time (over 30 years) without deterioration. In addition, the type of marine debris is affected by the industries operating in each area. Continuing to investigate marine debris on the seafloor in more areas will contribute to solving the problem of marine debris

Long-term monitoring of sediment runoff for an active sediment control in Joganji River

There were huge sediment yielding and deposition due to debris flows by breaking natural landslide dams which were formed by earthquake in 1858 at upstream reach of Joganji River. Sediment transportation is still active by debris flow and flow with bedload due to rainfall, though a lot of erosion control dams have been constructed. Continuously measuring sediment runoff for long term along a main river is necessary to evaluate the propagation of sediment after the huge events for sediment management in the basin using well hydrological information. Appropriate tools are selected and applied to monitoring in the area managed by Tateyama Mountain Area Sabo Office along Joganji River, using a Reid-type bedload slot sampler, robust-type hydrophone and velocity meter on the bed for bedload and turbidity meter for washload. Monitored data is concentratedly collected at the office to apply risk management for sediment movement due to heavy rainfall and so on. Several typical data and problems to solved were shown because it passed around twenty years since sediment monitoring started, and those are reported in present study

Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy

Background and Purpose: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. Methods: Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined. Results: Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. Conclusion: The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. © 2013 Kitano et al

Current state of hypnotic use disorders: Results of a survey using the Japanese version of Benzodiazepine Dependence Self-Report Questionnaire

Aims Benzodiazepine receptor agonists (BZ-RAs) are frequently prescribed to treat insomnia; however, their long-term use is not recommended. To introduce an appropriate pharmaco-therapy, the current state and background factors of BZ-RAs\u27 dependence must be elucidated. In this study, we developed a Japanese version of the Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ-J) and conducted a study of BZ-RAs\u27 use disorder. Methods The Bendep-SRQ-J was created with permission from the original developer. Subjects were inpatients and outpatients receiving BZ-RAs between 2012 and 2013. Clinical data collected were Bendep-SRQ-J scores, sleep disorders for which BZ-RAs were prescribed, physical comorbidities, psychotropic drugs, and lifestyle factors. Logistic analysis was performed to extract factors associated with severe symptoms. Results Of the 707 patients prescribed BZ-RAs, 324 had voluntarily tapered or discontinued their drugs. Logistic analysis showed that the total number of drugs administered in the last 6 months correlated with both worsening of symptoms or conditions. This was more notable among younger patients, and the proportion of patients with severe symptoms or conditions increased with the increasing number of drugs. Conclusion Using the Bendep-SRQ-J, we elucidated the current state of BZ-RA dependence. Nearly half of the patients were non-compliant. The proportion of patients with severe symptoms or disease conditions increased with the increase in the number of drugs administered. These findings highlight the need for clinicians to be aware of the likelihood of benzodiazepine dependence, especially in young patients and patients prescribed multiple hypnotics

Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.Etude de cohorte sur la santé des étudiantsStopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young student