Histomorphological species identification of tiny bone fragments from a Paleolithic site in the Northern Japanese Archipelago

AbstractBone histomorphology is an effective method for species identification of fragmentary osseous remains. The 1997–1998 excavations of the Kashiwadai 1 Upper Paleolithic site (ca. 22–20.5 kyBP) in Hokkaido (the northern island of the Japanese Archipelago) yielded tiny bone fragments, which had been burned to white and broken into pieces less than 1 cm in size, making their species identification by gross morphology alone impossible. For the purpose of species identification, histomorphological analyses were performed on thin sections of the Kashiwadai 1 bone fragments. Compact bone cross sections taken from medium- to large-sized land mammals in the Pleistocene and Holocene Hokkaido were prepared for comparison. The structures of the Kashiwadai 1 samples consisted of secondary osteons and plexiform bone. Consideration of the presence versus absence of plexiform bone and quantitative assessments of osteon sizes and bone cortical thickness allows for distinction between medium-sized deer, large-sized artiodactyls, small- to medium-sized carnivores, large-sized carnivores, elephants, and humans. The histomorphological characteristics of the Kashiwadai 1 samples were quite similar to those of both sika deer and ancient sika deer. A probable conclusion is that medium-sized deer was the primary game hunted by Paleolithic people at the Kashiwadai 1 site. Interestingly, the samples did not include elephant or large-sized artiodactyls, which were the predominant species in other Paleolithic sites of the Japanese Archipelago. This is the first evidence of human hunting medium-sized animals in the Upper Paleolithic period of the Japanese Archipelago based on faunal remains

Radiation hardness testing of an organic liquid scintillator detector for use in high dose rate accident response scenarios

Organic liquid scintillation detectors offer the advantage relative to many alternatives that they are sensitive to both fast neutrons and gamma rays, whilst radiation type can be discerned on the basis of pulse-shape discrimination. Mixed radiation fields of this type can arise in the context of reactor accidents via, for example, 137Cs (gamma) and 244Cm (neutrons). However, performance degradation of such scintillators, such as EJ-301, is a significant possibility that might limit the use of this technology in accident response applications. The premise behind the high dose rate testing of such a liquid scintillator described in this paper is for fuel debris characterisation at Fukushima Daiichi, which has expected dose rates of up to 1000 Gy/hr in close proximity to fuel debris. The tests carried out for this investigation involved using the 60Co gamma irradiation facility at the Dalton Cumbria Facility, Cumbria, United Kingdom to expose the detector to a similar dose rate to that which is estimated within the primary containment vessel for survivability tests. Radiation hardness tests have rarely been reported for such devices and it is expected that the performance will be dependent on the survival of the window of the photomultiplier tube rather than the liquid scintillant itself. A major advantage of the use of this detector is its physical size, due to the limitations on access into Fukushima reactors physical space is a premium. The research described in this paper presents the results of the dose rate exposure of the detector before signal was lost with the total dose observed providing information on any degradation affecting the performance of the device post-irradiatio

On the design of a remotely-deployed detection system for reactor assessment at Fukushima Daiichi

The premise behind this research is the design of a system that will allow fuel debris characterisation at Fukushima Daiichi. The precise location of the debris is not known for example as to whether it remains within the reactor pressure vessel or it has leaked through into the base of the pedestal below, additionally the state of the fuel is also in question as to whether this has corroded from within its encasing or if it is intact. The most likely scenario is a combination of all four of these situations. The flooding of the reactor floors immediately following the Fukushima accident adds an extra element of complexity for the detection system requiring it to be submersible and to hold any detector system in water tight confinement. The research carried out has involved extensive modifications to a previously-designed low-cost small-scale AVEXIS submersible inspection vehicle and the incorporation of a variety of radiation detectors. The latter has been designed to allow for mapping and determination of the situation that is present within the primary containment vessels. The challenges addressed with the detection system arise from the high dose rates that have been recorded around the reactor pressure vessels which can be as high as 1000 Gy/hr. In such a harsh environment not only will the radiation detectors struggle to operate but the components that make up the remote-operated vehicle are also likely to suffer radiation damage after only a relatively short period of time. The research presented here evaluates the components currently incorporated into the AVEXIS system in terms of their radiation tolerability as well as presenting the combination of detectors to be used in the remote probe for the investigation of the fuel debris

Functional 1,3a,6a-triazapentalene scaffold : Design of fluorescent probes for kinesin spindle protein (KSP)

1,3a,6a-Triazapentalene is a compact fluorescent chromophore. In this study, triazapentalene was used to modify a series of biphenyl-type inhibitors of kinesin spindle protein (KSP) to develop fluorescent probes for the intracellular visualization of this protein. Microscopic studies demonstrated that these novel triazapentalene-labeled compounds exhibited inhibitory activity towards KSP in cultured cells and provided important information concerning the intracellular distribution

Construction of possible integrated predictive index based on EGFR and ANXA3 polymorphisms for chemotherapy response in fluoropyrimidine-treated Japanese gastric cancer patients using a bioinformatic method

Selected genetic and clinical parameters of gastric cancer patients. (XLS 33 kb

Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report

Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA

Haplotypes and a Novel Defective Allele of CES2 Found in a Japanese Population

ABSTRACT: Human carboxylesterase 2 (hCE-2) is a member of the serine esterase superfamily and is responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. hCE-2 also activates an anticancer drug, irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin, CPT-11), into its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In this study, a comprehensive haplotype analysis of the CES2 gene, which encodes hCE-2, in a Japanese population was conducted. Human carboxylesterases are members of the serine esterase superfamily and are responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. They metabolize esters, thioesters, carbamates, and amides to yield soluble acids and alcohols or amines Although both hCE-1 and hCE-2 show broad substrate specificities, hCE-2 is relatively specific for heroin, cocaine (benzoyl ester), 6-acetylmorphine, procaine, and oxybutynin 1865 camptothecin (SN-38), a topoisomerase inhibitor, by carboxylesterases Previously, 12 exons and their flanking regions of CES2 were sequenced from 153 Japanese subjects, who received irinotecan or steroidal drugs, and 12 novel SNPs, including the nonsynonymous SNP, 100CϾT (Arg 34 Trp), and the SNP at the splice acceptor site of intron 8 (IVS8-2AϾG) were found Materials and Methods Chemicals. Irinotecan, SN-38, and SN-38G were kindly supplied by Yakult Honsha Co. Ltd. (Tokyo, Japan). Patients. A total of 262 Japanese subjects analyzed in this study consisted of 85 patients with allergies who received steroidal drugs and 177 patients with cancer who received irinotecan. The ethical review boards of the National Cancer Center, National Center for Child Health and Development, and National Institute of Health Sciences approved this study. Written informed consent was obtained from all participants. DNA Sequencing. Total genomic DNA was extracted from blood leukocytes or Epstein-Barr virus-transformed lymphocytes and used as a template in the polymerase chain reaction (PCR). Sequence data of the CES2 gene from 72 patients and 81 cancer patients were described previously Linkage Disequilibrium and Haplotype Analyses. LD analysis was performed by the SNPAlyze software (version 5.1; Dynacom Co., Yokohama, Japan), and a pairwise two-dimensional map between SNPs was obtained for the DЈ and rho square (r 2 ) values. All allele frequencies were in HardyWeinberg equilibrium. Some haplotypes were unambiguously assigned in the subjects with homozygous variations at all sites or a heterozygous variation at only one site. Separately, the diplotype configurations (combinations of haplotypes) were inferred by LDSUPPORT software, which determines the posterior probability distribution of the diplotype configuration for each subject on the basis of estimated haplotype frequencies Administration of Irinotecan and Pharmacokinetic Analysis. The demographic data and eligibility criteria for 177 cancer patients who received irinotecan in the National Cancer Center Hospitals (Tokyo and Chiba, Japan) were described elsewhere Each patient received a 90-min i.v. infusion at doses of 60 to 150 mg/m 2 , which varied depending on regimens/coadministered drugs: i.e., irinotecan dosages were 100 or 150 mg/m 2 for monotherapy and combination with 5-FU, 150 mg/m 2 for combination with mitomycin C (MMC), and 60 (or 70) mg/m 2 for combination with platinum anticancer drugs. Heparinized blood was collected before administration of irinotecan and at 0 min (end of infusion), 20 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. Plasma concentrations of irinotecan, SN-38, and SN-38G were determined as described previously Expression of Wild-Type and Variant CES2 Proteins in COS-1 Cells. Expression of wild-type and variant CES2 proteins in COS-1 cells was examined as described previously and ZERO-Dscan software (Raytest, Straubenhardt, Germany). The relative expression levels are shown as the means Ϯ S.D. of three separate transfection experiments. Determination of CES2 mRNA by Real-Time RT-PCR. Total RNA was isolated from transfected COS-1 cells using the RNeasy Mini Kit (QIAGEN, Tokyo, Japan). After RNase-free DNase treatment of samples to minimize plasmid DNA contamination, first-strand cDNA was prepared from 1 g of total RNA using the High-Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA) with random primers. Real-time PCR assays were performed with the ABI7500 Real Time PCR System (Applied Biosystems) using the TaqMan Gene Expression Assay for CES2 (Hs01077945_m1; Applied Biosystems) according to the manufacturer's instructions. The relative mRNA levels were determined using calibration curves obtained from serial dilutions of the pooled wild-type CES2 cDNA. Samples without reverse transcriptase were routinely included in the RT-PCR reactions to measure possible contributions of contaminating DNA, which was usually less than 1% of the mRNA-derived amplification. Transcripts of ␤-actin were quantified as internal controls using TaqMan ␤-Actin Control Reagent (Applied Biosystems), and normalization of CES2 mRNA levels were based on ␤-actin concentrations. Enzyme Assay. CPT-11 hydrolyzing activity of the postmitochondrial supernatants (microsomal fraction plus cytosol) was assayed over the substrate concentration range of 0.25 to 50 M as described previously Statistical Analysis. Statistical analysis of the differences in the AUC ratios among CES2 diplotypes, coadministered drugs. or irinotecan dosages was performed using the Kruskal-Wallis test, Mann-Whitney test, or Spearman rank correlation test (Prism 4.0, GraphPad Software, Inc., San Diego, CA). The t test (Prism 4.0) was applied to the comparison of the average values of protein expression and mRNA levels between wild-type and variant CES2. Results CES2 Variations Detected in a Japanese Population. Previously, the promoter region, all 12 exons, and their flanking introns of the CES2 gene were sequenced from 72 allergic patients and 81 cancer patients and resulted in the identification of 12 novel SNPs The nonsynonymous SNP 424GϾA (V142M) reported by our group LD and Haplotype Analysis. Using the detected SNPs, LD analysis was performed, and the pairwise values of r 2 and DЈ were obtained. A perfect linkage (r 2 ϭ 1.00) was observed between SNPs Ϫ363CϾG and IVS10-87GϾA. A close association (r 2 ϭ 0.85) was found between SNPs IVS10-108GϾA and 1749AϾG. Other associations were much lower (r 2 Ͻ 0.1). Therefore, the entire CES2 gene was analyzed as one LD block. The determined/inferred haplotypes are summarized i