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Background Abdominal aortic aneurysm (AAA) is a life-threatening disease, and the decision to treat relies on the exact detection and size of AAA, which is time-consuming and prone to high inter-reader variability. Artificial intelligence (AI) has revealed new insights into the management of AAA, but it needs large amounts of contrast-enhanced CT data. Moreover, there has been few studies about the fully automatic detection and measurement of AAA. Purpose The aim of this study is to evaluate the accuracy of AI for the detection and measurement of AAA using small amounts of non-contrast CT. Methods We retrospectively collected 145 non-contrast CT scans of suspected AAA. The first step was to manually segment the 30 non-contrast CT scans to create training data for the AI, and the second step was to improve accuracy using 9 of non-contrast CT scans. Image processing is used to identify the AAA area and automatically measure the size. The AAA region was identified from the amount of change in the minor-axis, and the maximum minor-axis diameter was calculated using elliptical fitting. To evaluate the diagnostic utility of AI for the detection of AAA, the sensitivity and positive predictive value were calculated referred for the diagnostic report. The reproducibility in the size of AAA was assessed using intraclass correlation coefficients (ICCs) between the diagnostic report and AI. Results Among 145 of non-contrast CT scans, 111 had AAA. The sensitivity and positive predictive value of AI for the detection of AAA were 94.6% and 53.8%, respectively (Picture 1). The size of AAA calculated by the AI (42.5±8.8 mm) showed a strong correlation with the those of diagnostic reports (44.6±8.4 mm; ICCs = 0.97) (Picture 2). Conclusions AI represents a useful tool in the fully automatic detection and measurement of AAA using small amounts of non-contrast CT. Funding Acknowledgement Type of funding sources: None. Picture 1Picture 2

The structure of Ni50V50 amorphous alloy was investigated by using neutron, X-ray diffraction and reverse Monte Carlo (RMC) modelling. The RMC configuration was decomposed into polyhedral holes whose faces are all triangles consisting of chemical bonds. Free volumes in the respective polyhedral holes were evaluated with reference to the packing efficiency of Ni-V metastable BCC phase. The tetrahedral holes, which account for about 70% of the whole space, are regarded as densely packed units because the average packing efficiency of them is approximately equal to that of the corresponding crystal phase. On the other hand, various types of polyhedral holes, which have a certain free volume, are observed and some of them are connected with each other. The densely packed coordination polyhedra consisting only of tetrahedral holes tend to be clustered.

PURPOSE/OBJECTIVE(S) Reducing radiation doses to the heart and/or cardiac segments are crucial to decrease the risk of radiation-induced coronary artery diseases (RICAD) for patients with left-sided breast cancer. However, dosimetric advantages for these structures between three-dimensional conformal radiation therapy plus electron boost (3D-CRT+EB) and simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) remain unclear, especially in the patients with a potential risk of RICAD. The aim of this study was to compare some dosimetric parameters between the 3D-CRT + EB and SIB-VMAT in left-sided breast cancer patients with a potential risk of RICAD. MATERIALS/METHODS A total of 57 patients with left-sided breast cancer treated with SIB-VMAT between 2018 and 2020 were enrolled. All patients were identified as the potential risk of RICAD by radiation oncologists using maximum heart distance (MHD), and met the MHD ≧ 1 cm. All patients were prescribed a dose of 42.56 Gy/ 16 fractions to planning target volume and a total dose of 53.2 Gy (N = 21) or 51.2 Gy (N = 36) for a concomitant-boosted target. The 3D-CRT + EB plans were retrospectively created for a comparison purpose, using field-in-field technique followed by electron beam irradiations. Some dosimetric parameters for clinical target volume (CTV), heart, left anterior descending coronary artery (LAD), middle LAD (mLAD), lungs, and contralateral breast were compared using the Wilcoxon signed rank test. RESULTS The Dmean, Dmax and D98% for CTV were significantly improved in the SIB-VMAT plans. For cardiac-related structures, the median doses of SIB-VMAT versus 3D-CRT + EB were as follows: Dmean for heart, 2.9 Gy vs. 1.9 Gy (P < 0.001); Dmean, V20 and V30 for LAD, 12.6 Gy vs. 15.4 Gy (P < 0.001), 23.0% vs. 33.3% (P = 0.0049) and 2.0% vs. 24.7% (P < 0.001); Dmean, V20 and V30 for mLAD, 16.0 Gy vs. 21.1 Gy (P = 0.0014), 29.9% vs. 51.4% (P = 0.0040) and 0.5% vs. 31.1% (P < 0.001), respectively. The Dmean, V5 and V20 for the lungs and the Dmean for contralateral breast were significantly reduced in the 3D-CRT + EB plans (P < 0.001, for all). The doses to the LAD and mLAD tended to be higher in lateral cohort (upper outer and lower outer quadrants of breast) than in medial cohort (upper inner and lower inner quadrants of breast), while these doses were significantly reduced by the SIB-VMAT. CONCLUSION Although 3D-CRT + EB technique can reduce the mean dose to the heart, the doses to LAD and mLAD can be significantly decreased by SIB-VMAT, which could be a benchmark for selecting the most appropriate irradiation technique in the patients with a potential risk of RICAD.

Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO32-) in its crystal structure.

We present the first observation by the Telescope Array Surface Detector (TASD) of the effect of thunderstorms on the development of cosmic ray single count rate intensity over a 700 km$^{2}$ area. Observations of variations in the secondary low-energy cosmic ray counting rate, using the TASD, allow us to study the electric field inside thunderstorms, on a large scale, as it progresses on top of the 700 km$^{2}$ detector, without dealing with the limitation of narrow exposure in time and space using balloons and aircraft detectors. In this work, variations in the cosmic ray intensity (single count rate) using the TASD, were studied and found to be on average at the $\sim(0.5-1)\%$ and up to 2\% level. These observations were found to be both in excess and in deficit. They were also found to be correlated with lightning in addition to thunderstorms. These variations lasted for tens of minutes; their footprint on the ground ranged from 6 to 24 km in diameter and moved in the same direction as the thunderstorm. With the use of simple electric field models inside the cloud and between cloud to ground, the observed variations in the cosmic ray single count rate were recreated using CORSIKA simulations. Depending on the electric field model used and the direction of the electric field in that model, the electric field magnitude that reproduces the observed low-energy cosmic ray single count rate variations was found to be approximately between 0.2-0.4 GV. This in turn allows us to get a reasonable insight on the electric field and its effect on cosmic ray air showers inside thunderstorms.

Bone quality is defined by structural and material characteristics. Most studies on the mandible have focused on the analysis of structural characteristics, with insufficient investigation of material characteristics. This study tested whether zoledronate affects the material characteristics of newly formed mandibular bone. Thirty-six female Wistar rats were assigned to three groups: sham-ovariectomized rats (SHAM, n=12), ovariectomized rats (OVX, n=12), and ovariectomized rats treated with zoledronate (ZOL, n=12). The left side of the mandibular ramus of all rats was drilled bicortically. Twenty-eight days after surgery, all surviving rats were euthanized and all mandibles were removed. Raman microspectroscopy was performed, and five spectra per specimen of newly formed mandibular bone were analysed. Compared with OVX rats, the mineral/matrix ratio in ZOL rats was significantly increased (5.43±1.88 vs. 7.86±2.05), while crystallinity (0.055±0.002 vs. 0.050±0.002), relative proteoglycan content (0.43±0.10 vs. 0.31±0.05), and collagen structural integrity (1.16±0.21 vs. 0.72±0.06) were significantly decreased. These changes in material characteristics may explain why rats that received zoledronate exhibited peculiar biological phenomena such as bisphosphonate-related osteonecrosis of the jaw.

Exosomes are potent players in the development of metastases and they play an important role in cancer angiogenesis and exacerbation. However, it is unclear how proteins on exosomes affect development of blood vessel networks. In this study, we focused on relationships between membrane proteins on exosomes and angiogenesis using human umbilical vein endothelial cells (HUVEC). Lung tumor cell-derived exosomes induced tube formation and growth of endothelial cells

In this study, we investigated the terahertz radiation from a truncated edge square mesa structure made from a superconducting Bi_{2}Sr_{2}CaCu_{2}O_{8+{\delta}} . Using a commercial software, the polarization characteristics were determined, and introduced, while accounting for the skin effect. The axial ratio was enhanced in the simulation by performing a parametric study on the design., Comment: Proceedings of the 28th International Symposium on Superconductivity, ISS 2015, November 16-18, 2015, Tokyo, Japan

Background Methotrexate (MTX) is a well-known anchor drug for rheumatoid arthritis (RA); however, dose regimens vary. We previously reported in EULAR2015 that split dose weekly oral methotrexate induced elevation of AST and ALT in association with elevation of MTX with 2 glutamates (MTX-PG2) in a single-centre trial. Objectives We performed a multi-centre randomised controlled trial to compare the incidence of adverse events using single and split dose regimens. Methods Six hospitals and 2 rheumatology clinics participated in this study. Seventy-eight patients with insufficient control on MTX 8 mg/week were randomly assigned to 2 groups, i.e., a single weekly dose regimen with 39 patients and a 3 dose per week regimen with 39 patients. The MTX dose in all patients was gradually increased to 16 mg/week. The primary endpoint was the occurrence of liver dysfunction during the observation period (20 weeks). Other endpoints included the incidence of adverse events and the changes from baseline in the disease activity score (DAS28) based on ESR or CRP, the Simplified Disease Activity Index (SDAI), and MTX-PG at week 20. Results There were no differences between the groups in baseline data and MTX dose at 20 weeks (single dose: 10.2±0.8 vs. 3-dose: 10.2±0.9 mg/week). Liver dysfunction occurred in 3 patients (7.7%) receiving the single dose regimen and in 5 patients (13.2%) receiving the 3-dose regimen, but there was no significant difference in the incidence in both groups (p=0.455). There was a significant difference in the incidence of adverse events (gastrointestinal disorder was most common) between single dose (11 patients, 28.9%) and 3-dose (20 patients, 52.6%) regimens (p=0.036). There was no significant difference in the changes from baseline in DAS28-ESR (−1.55 vs. −1.36), DAS28-CRP (−1.31 vs. −1.26), or SDAI (−9.45 vs. −10.11). Compared to the single dose regimen, MTX-PG2 was significantly increased in the 3-dose regimen, and MTX-PG3, -PG4, and -PG5 were significantly increased in the single dose regimen (table 1). Conclusions There were no differences in the incidence of liver dysfunction and efficacy according to the oral MTX dose regimen; however, split weekly dosing compared with single weekly dosing reduced polyglutamylation and increased the risk of adverse events. Acknowledgements Clinical registration: UMIN000021157 Disclosure of Interest Y. Yoshioka: None declared, K. Katayama: None declared, T. Kasama: None declared, M. Sato: None declared, S. Ohno: None declared, Y. Amasaki: None declared, H. Kataoka: None declared, D. Kanai: None declared, A. Suda: None declared, M. Okamoto Employee of: AYUMI Pharmaceutical Corporation, M. Sasano: None declared, S. Nagaoka: None declared, A. Sagawa: None declared

Background Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome is a rare inflammatory arthritis, characterised by absence of rheumatoid factor, symmetrical distal synovitis, pitting oedema of the hands and feet. In recent years the use of dipeptidyl peptidase-4 (DPP4) inhibitor has increased and some reports have described the association of RS3PE syndrome with DPP4 inhibitor. Objectives: We have tried to investigate the association of RS3PE syndrome with DPP4 inhibitor in our hospital. Methods: In Japan DPP4 inhibitor was released in December 2009, so we retrospectively analysed background, treatment and clinical course of 25 patients with RS3PE syndrome diagnosed between December 2009 and December 2016 in our hospital. We divided them in two groups according to DPP4 inhibitor prescription and compared two groups. Results: Our cases included 18 males and 7 females, and the mean age of RS3PE syndrome onset was 76 years old. The mean follow-up period was 32.5 months. Six patients had diabetes mellitus and DPP4 inhibitor was prescribed in five of six patients (83.3%). (sitagliptin 3 cases, teneligliptin 1 case, alogliptin 1case). The duration of RS3PE syndrome onset after DPP4 inhibitor prescription was mean 22.9 months, and two cases developed within a half year, two cases after two years. Compared with non DPP4 inhibitor group, the mean age of RS3PE syndrome onset was significantly low (70 vs 78.5, p=0.023), and HbA1c (NGSP) was high (7.3% vs 6.02%, p=0.00022) in DPP4 inhibitor group. The occurrence of flare was four cases in non DPP4 inhibitor group and zero in DPP4 inhibitor group, but was not statistically different (p=0.275). Other clinical features were not significantly different. Conclusions: DPP4 inhibitor group was significantly younger than non DPP4 inhibitor group, and the possibility that DPP4 inhibitor contributed to the early onset of RS3PE syndrome was suggested. References [1] Oyama K, Taniguchi J, et al. Remitting seronegative symmetrical synovitis with pitting edema syndrome in individuals with type 2 diabetes mellitus or impaired glucose tolerance. Diabetes Res Clin Pract. 2015Oct;110(1):e5–8. [2] McCarty DJ, O’Duffy JD, et al. Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE Syndrome). JAMA 1985; 254: 2763–2767. Disclosure of Interest None declared

In this study, measurement of wall shear stress on an airfoil surface under the lifting condition by using oil film interferometry (OFI) is performed. Reynolds number of the airfoil flow is 8 × 104. Silicon oil and sodium lamp are used for Fizeau fringes formation. The 300–600 images with time interval snap shot in 1–2 s depends on velocity by digital camera are acquired for the calculation of thickness of oil film and moving velocity on surface of it. Also, airfoil surface is covered with PET film for more clearly Fizeau fringes. Time-averaged wall shear stress measured by OFI are compared to numerical simulation by the LES. Maximum difference in the distributions between by the OFI and by the LES has at x/C = 0.58, and it has C f = 0.00439 by the OFI and C f = 0.00455 by the LES.

The aim of this study was to investigate the chemical composition and the antiinflammatory/antinociceptive properties of the hydroalcoholic extract derived from the leaves of Phyllanthus brasiliensis (HEPB) in rodents. A new arylnaphthalene lignan glycoside, 5-O-β-d-glucopyranosyljusticidin B, together with six known lignans, were isolated from HEPB. 1D and 2D NMR experiments and HRMS were used to elucidate the structure of the new compound. HEPB toxicity and antinociceptive activity were evaluated through acute oral toxicity and formalin models in mice, respectively. The anti-inflammatory effects of HEPB were assessed using carrageenan- and dextran-induced paw edema models in rats. HEPB showed low toxicity. Oral administration of HEPB reduced paw edema induced by carrageenan, but not by dextran. HEPB and its fractions from FR6 to FR10 (FR6-10) inhibited the neurogenic and inflammatory phases of formalin-induced linking, demonstrating its antinociceptive activity. These results indicated that lignans from Phyllanthus brasiliensis exerted antinociceptive/anti-inflammatory effects not related to the histaminergic pathway.

Nanomaterials are frequently used in microelectronics, cosmetics, and sunscreens. Platinum reagents are commonly used in disease diagnosis, cosmetics, and the food industry. Although research into the development of nanomaterialbased drug delivery systems has yielded promising results, the toxicity of these materials is not fully understood. We investigated the toxicity and drug interactions of 1- and 8-nm diameter platinum nanoparticles (nPt1 and nPt8, respectively) in mice. Acute hepato-renal toxicity of intravenously administered platinum nanoparticles was evaluated biochemically and histologically. Dose-dependent increases in serum markers of hepato-renal function (serum aminotransferases and blood urea nitrogen) were observed following administration of nPt1, whereas nPt8 had no effect, even at 20 mg/kg. Moreover, nPt1 induced interleukin (IL)-6 and IL-1β production 3 and 6 hours after administration. The effect of nPts on drug-induced toxicity was evaluated in mice injected intraperitoneally with carbon tetrachloride or cisplatin, with or without intravenous administration of platinum nanoparticles. All treatments in the absence of nanoparticles were non-lethal and resulted in moderate toxicity. However, exacerbated toxicity was observed in mice injected with carbon tetrachloride or cisplatin together with nPt1, but not in mice co-injected with nPt8. We found that nPt1 cause hepato-renal damage, and the effect is enhanced by chemical inducers of hepatotoxicity and nephrotoxicity. This is the first report demonstrating that nPt1 not only are hepatotoxic and nephrotoxic but also exacerbate drug toxicity. These findings will be useful for future nanotechnology and nanoscience research.

We propose an approach to control the polarization of terahertz (THz) radiation from intrinsic Josephson-junction stacks in single crystalline high-temperature superconductor $Bi_2Sr_2CaCu_2O_{8+\delta}$. By monolithically controlling the surface current distributions in the truncated square mesa structure, we can modulate the polarization of the emitted THz wave as a result of two orthogonal fundamental modes excited inside the mesa. Highly polarized circular terahertz waves with a degree of circular polarization of more than 99% can be generated using an electrically controlled method. The emitted radiation has a high intensity and a low axial ratio (AR, Comment: Submitted to PRApplied

Intermittent parathyroid hormone (PTH) administration is known to promote bone healing after surgical procedures. However, the mechanism and influence of PTH on the mineral and collagen quality of the jaw are not well understood. Most studies have focused on analyzing the bone density and microstructure of the mandible, and have insufficiently investigated its mineral and collagen quality. Oxidative stress activates osteoclasts, produces advanced glycation end products, and worsens mineral and collagen quality. We hypothesized that PTH induces oxidation and affects the mineral and collagen quality of newly formed mandibular bone. To test this, we examined the mineral and collagen quality of newly formed mandibular bone in rats administered PTH, and analyzed serum after intermittent PTH administration to examine the degree of oxidation. PTH administration reduced mineralization and worsened mineral and collagen quality in newly formed bone. In addition, total anti-oxidant capacity in serum was significantly decreased and the oxidative-INDEX was increased among PTH-treated compared to vehicle-treated rats, indicating serum oxidation. In conclusion, intermittent administration of PTH reduced mineral and collagen quality in newly formed mandibular bone. This effect may have been induced by oxidation.

We present a case of paediatric Stage IV sporadic Burkitt's leukaemia presenting as cheek enlargement with osteolysis of the maxilla. An 8-year-old boy was referred to our department with diffuse swelling of both cheeks. Head and neck examination revealed bilateral diffuse nontender swelling, non-fluctuant but slightly compressible. Computed tomography imaging showed enhancing bilateral bulky lesions expanding the maxillary sinuses, with associated osteolysis in the posterior walls of both sinuses. Laboratory results included blast cells in the peripheral blood, suggesting a haematopoietic tumour. We referred the patient to the Department of Paediatric Haematology and Oncology. Additional examinations eventually led to the diagnosis of Stage IV sporadic Burkitt's leukaemia.

Background The p53 tumor-suppressor gene is one of the most frequently mutated genes in cancers, and its mutations affect various biological actions, such as tumor growth, apoptosis, and so on. During hypoxia, p53 is stabilized by interaction with hypoxia-inducible factor-1 (HIF-1). This interaction raised the possibility for regulating HIF-1 activity by p53, which is still to be elucidated. Methods First, we introduced various types of the p53 mutant gene into Hep3B and evaluated the role of p53 in hypoxic responses, including vascular endothelial growth factor (VEGF) production and HIF-1 activation. Second, Hep3B-vector cells and Hep3B-p53 cells were subcutaneously injected into BALB/c (nu/nu) mice, and tumor progression and the hypoxic responses were analyzed. Finally, we investigated the role of the p53 mutant genes in the level of vascularity in human pancreatic neoplasia. Results Here, we showed that expression of wild-type p53, but not null or mutated p53, significantly suppressed HIF-1 activity and production of VEGF, which mostly depends on the HIF-1β protein level. In a tumor xenograft model, we consistently found that loss of p53 promotes VEGF production, neovascularization, and tumor progression via accumulation of HIF-1β protein. Furthermore, in clinical pancreatic neoplasia, tumors with mutated p53 have significantly higher levels of vascularity than those with wild-type p53. Conclusion These results indicate that loss of p53 contributes to neovascularization through regulation of HIF-1.

The validity of chemical reaction mechanistic domains defined by skin sensitisation in the Quantitative Structure-Activity Relationship (QSAR) ecotoxicity system, KAshinhou Tools for Ecotoxicity (KATE), March 2009 version, has been assessed and an external validation of the current KATE system carried out. In the case of the fish end-point, the group of chemicals with substructures reactive to skin sensitisation always exhibited higher root mean square errors (RMSEs) than chemicals without reactive substructures under identical C- or log P-judgements in KATE. However, in the case of the Daphnia end-point this was not so, and the group of chemicals with reactive substructures did not always have higher RMSEs: the Schiff base mechanism did not function as a high error detector. In addition to the RMSE findings, the presence of outliers suggested that the KATE classification rules needs to be reconsidered, particularly for the amine group. Examination of the dependency of the organism on the toxic action of chemicals in fish and Daphnia revealed that some of the reactive substructures could be applied to the improvement of the KATE system. It was concluded that the reaction mechanistic domains of toxic action for skin sensitisation could provide useful complementary information in predicting acute aquatic ecotoxicity, especially at the fish end-point.

We report emissions of circular polarized electromagnetic waves from cylindrically shaped mesa structures of the high-temperature superconductor Bi2Sr2CaCu2O8+δ. The frequency range of circularly polarized emission of a cylindrical mesa with notched sides is between 400 and 430 GHz, which is wider than expected by the patch antenna theory. Three maxima recognized in emission intensity are presumably attributed to excitations of fundamental orthogonal modes and circularly polarized modes. Along with the demonstration of circularly polarized emission from truncated edge square mesas, the obtained results provide a wide variety of engineering designs of compact and solid-state electromagnetic sources which are able to generate circularly-polarized terahertz waves.

Fruit texture, which can be assessed using characteristics such as firmness and crispness, is one of the most important targets in cucumber breeding, because it is directly related to the commercial value of the product. Breeding efforts to improve fruit texture, although somewhat successful, have been largely based on rough, qualitative evaluations based solely on human perceptions. However, this evaluation of texture sometimes results in unacceptable human errors and training and experience are required for accurate and consistent assessment. Therefore, effective quantitative indicator has been desired to increase the objectivity of data collection while reducing subjective characterization that is typically prone to bias. In this study, we investigated variability among cucumber cultivars in the texture parameter based on secondary differentiation of the force-deformation plots produced by puncture test, and to assess the efficacy of this parameter as a candidate indicator for use in breeding to improve cucumber fruit texture. We found wide variations in the texture parameter among the 13 cultivars or lines from 5 cucumber types. There was a significant genotypic (cultivar) effect on the texture parameter, and a significant relationship between the texture parameter and human textural evaluations. Furthermore, the lack of a significant correlation between the texture parameter and fruit firmness indicated that the texture parameter evaluates a different property than firmness. Based on these results, it is possible to make a conclusion that the texture parameter calculated based on secondary differentiation of the force-deformation plots is as effective, quantitative indicator of fruit texture, and has considerable promise for application in scientific research and breeding programs.

The KAshinhou Tool for Ecotoxicity (KATE) system, including ecotoxicity quantitative structure-activity relationship (QSAR) models, was developed by the Japanese National Institute for Environmental Studies (NIES) using the database of aquatic toxicity results gathered by the Japanese Ministry of the Environment and the US EPA fathead minnow database. In this system chemicals can be entered according to their one-dimensional structures and classified by substructure. The QSAR equations for predicting the toxicity of a chemical compound assume a linear correlation between its log P value and its aquatic toxicity. KATE uses a structural domain called C-judgement, defined by the substructures of specified functional groups in the QSAR models. Internal validation by the leave-one-out method confirms that the QSAR equations, with r(2 )0.7, RMSEor= 0.5, and n5, give acceptable q(2) values. Such external validation indicates that a group of chemicals with an in-domain of KATE C-judgements exhibits a lower root mean square error (RMSE). These findings demonstrate that the KATE system has the potential to enable chemicals to be categorised as potential hazards.

Cancer gene therapy by adenovirus vectors (Advs) for metastatic cancer is limited because systemic administration of Adv produces low therapeutic effect and severe side effects. In this study, we generated a dual cancer-specific targeting vector system by using PEGylation and the telomere reverse transcriptase (TERT) promoter and attempted to treat experimental metastases through systemic administration of the vectors. We first optimized the molecular size of PEG and modification ratios used to create PEG-Ads. Systemic administration of PEG-Ad with 20-kDa PEG at a 45% modification ratio (PEG[20K/45%]-Ad) resulted in higher tumor-selective transgene expression than unmodified Adv. Next, we examined the effectiveness against metastases and side effects of a TERT promoter-driven PEG[20K/45%]-Ad containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk). Systemic administration of PEG-Ad-TERT/HSVtk showed superior antitumor effects against metastases with negligible side effects. A cytomegalovirus (CMV) promoter-driven PEG[20K/45%]-Ad also produced antimetastatic effects, but these were accompanied by side effects. Combining PEG-Ad-TERT/HSVtk with etoposide or 5-fluorouracil enhanced the therapeutic effects with negligible side effects. These results suggest that modification with 20-kDa PEG at a 45% modification ratio is the optimal condition for PEGylation of Adv, and PEG-Ad-TERT/HSVtk is a prototype Adv for systemic cancer gene therapy against metastases.

Vibration caused by mechanical resonance and time delay caused by signal detection and transmission degrade the control performance of a servo controller for a multimass mechanical system. A precise numerical model that represents resonance characteristics and time delay is necessary to design a desired control system. This paper presents an identification method using the iterative process of the linearized and weighted total least-squares method. The proposed method derives a transfer function without any prior knowledge of resonance characteristics and time delay. The order of the transfer function is determined with a coefficient diagram that shows coefficients of the denominator of the transfer function. Identification results with an experimental setup are shown to demonstrate the performance of the proposed method. A velocity servo controller with vibration-suppression control is designed with the transfer function, and control performance is verified with the experimental setup to validate the transfer function.

Glass ampoule breakage during the freeze-drying process was prevented by the addition of sodium chloride to the formulation of lyophilization products of sodium thiopental. In order to clarify the ampoule breakage prevention mechanism, the physicochemical behavior of the freeze-drying process was monitored by simultaneous XRD-DSC measurements and thermal mechanical analysis (TMA). During the freezing process of formulated solution, the smaller heat of fusion of crystallized ice with the addition of sodium chloride was observed in comparison to that without sodium chloride. Although a greater amorphous portion remained, a higher crystal habit of hexagonal ice was reproducibly observed in the XRD patterns with the addition of sodium chloride during the freezing process. In the measurement of TMA, the scattering of the thermal expansion rate of formulated solution was significantly reduced by the addition of sodium chloride. These observations indicated that the addition of sodium chloride minimized the scattering of the thermal expansion rate and might be a cause for the inhibition of glass ampoule breakage during the freeze-drying process.

We have developed the vacuum dryer attached XRD-DSC system and monitored manufacturing process of freeze-dried pharmaceutical product. The aim of this study is to apply the XRD-DSC system for the preformulation of freeze-dried injections. Gabexate mesilate was used as a model drug. Drug solution was frozen then heated to annealing temperature according to the process-controlling program. The XRD-DSC analyses were performed to monitor the crystallized spicies and their crystallinity of sample. When the solution was cooled slowly, peaks of gabexate mesilate and mannitol polymorph had been already observed during the cooling process while those crystallinity were low at fast cooling rate. As the drying underwent, intensity of ice peaks were getting weaker. At the cooling rate of 0.1°C min–1, the XRD profile of final product was revealed that the characteristic peaks of gabexate mesilate, mannitol δ-form and β-form were appeared. When the cooling rate was increased, the crystallinity of final products was decreased. From these results, it was confirmed that the XRD profiles during freeze-drying process significantly related to the final freeze-dried product. It is obvious that monitoring by XRD-DSC system is a quite effective way to simulate the manufacturing process and to optimize the qualified product.

We study the universal relationship between the hot-spot size and the intensity of terahertz emission from intrinsic Josephson junctions by dynamically controlling the temperature distributions in mesas of Bi2Sr2CaCu2O8þδ. The uniform current bias leads to a significant increase in local temperature compared to the nonuniform current bias. The thermal response of emission differs between the high- and low-bias regimes. We find a strong positive correlation between the emission intensity and the volume of the superconducting parts in the emitting stack. We identify the remarkable increase in the emission intensity by up to 20% by eliminating the excess Joule heat from the mesa.

Detection of drug-target proteins and biomarkers that are expressed in cancer tissue has significant potential for both diagnosis and treatment of cancer. However, current immuno-histochemical and cytogenetic analyses of biopsy specimens for pre-operational diagnosis are highly invasive and often difficult to apply to lung cancer patients. The purpose of this study was to evaluate the possible utility of determining epidermal growth factor receptor (EGFR) expression on exosomal membranes using a targeted ELISA with an anti-CD81 antibody as a capture antibody for lung cancer diagnosis. While soluble EGFR (sEGFR) levels in plasma were not remarkably different between lung cancer patients and normal controls, significantly higher exosomal EGFR expression levels were observed in 5/9 cancer cases compared to normal controls. These results suggest that measurement of exosomal protein levels could be useful for in vitro diagnosis, and that exosomal EGFR is a possible biomarker for characterization of lung cancer.

Rapid analysis of steelmaking slag by the combination of a new sampling technique and EDX has been developed.In the present method, the analysis time has been shortened to about 5 min. Moreover, the features of the present method are low cost, easy operation and useful accuracy for the process control.By using the present method, it has been possible to control the process by feedback of the slag composition in nearly real time in the steelmaking process.