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The main purpose of this research was to determine the hydraulic properties of evaporitic rocks using geotechnical engineering concepts. A detailed characterization protocol was enacted to understand fluid retention and migration under saturated–unsaturated states using representative samples of Midale evaporites from southern Saskatchewan, Canada. Evolved from geological setting and environmental conditions, the investigated samples comprised low-porosity anhydrites and high-porosity dolomites. Generally, the air entry value measured 1000 kPa and the residual suction value ranged from 6000 to 8000 kPa. The saturated hydraulic conductivity (based on Ito and Azam (Q J Eng Geo 51: 49–62, 2017) and Lebron (Water Resour Res, 35:3149–3158, 1999)) was estimated to be from 2 × 10−10 to 8 × 10−10 m/s for anhydrites and from 1 × 10−8 to 5 × 10−8 m/s for dolomites. The well-established fitting equations for hydraulic conductivity function closely matched up to 10−11 m/s. The fit from van Genuchten (Soil Sci Soc Am J 44: 892–898, 1980) became asymptotic around 10−20 m/s whereas that from Fredlund et al. (Can Geotech J 31:533–546, 1994) showed a lower rate of decrease with suction increase and exhibited a better correlation with vapour flow.

Urbanization is a globally shared challenge and Nepal, a small developing country in the foot of the Himalayas, is no exception. For Lalitpur Metropolitan City (LMC), the country’s second ranked city in terms of population density, the situation is complex as numerous historic and artistic monuments including a UNESCO World Heritage property make structural adjustment prohibitive. As a practical and sustainable response to the mobility challenge, then, LMC has teamed up with the City’s stakeholders to transform into a cyclable city. Based on a case study that employed in-depth qualitative interviewing of specialized populations, this study attempted to validate City’s course of actions in light of global trend in the use of bicycles, and discussed the movement from the perspective of sustainable urban governance. The study found that the case city is on the right trajectory for tackling urbanization challenges with sustainable means, aided by the collective wit of the political, administrative, and citizens’ power. Their effort was validated by the initiative’s alignment with the global benchmarking on the use of bicycle for sustainable mobility. The study concluded that factors such as collaborative public service design and local government led spatial management are holding keys for sustainable urban governance.

Defining an appropriate and efficient assessment of drug‐induced corrected QT interval (QTc) prolongation (a surrogate marker of torsades de pointes arrhythmia) remains a concern of drug developers and regulators worldwide. In use for over 15 years, the nonclinical International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) S7B and clinical ICH E14 guidances describe three core assays (S7B: in vitro hERG current & in vivo QTc studies; E14: thorough QT study) that are used to assess the potential of drugs to cause delayed ventricular repolarization. Incorporating these assays during nonclinical or human testing of novel compounds has led to a low prevalence of QTc‐prolonging drugs in clinical trials and no new drugs having been removed from the marketplace due to unexpected QTc prolongation. Despite this success, nonclinical evaluations of delayed repolarization still minimally influence ICH E14‐based strategies for assessing clinical QTc prolongation and defining proarrhythmic risk. In particular, the value of ICH S7B‐based “double‐negative” nonclinical findings (low risk for hERG block and in vivo QTc prolongation at relevant clinical exposures) is underappreciated. These nonclinical data have additional value in assessing the risk of clinical QTc prolongation when clinical evaluations are limited by heart rate changes, low drug exposures, or high‐dose safety considerations. The time has come to meaningfully merge nonclinical and clinical data to enable a more comprehensive, but flexible, clinical risk assessment strategy for QTc monitoring discussed in updated ICH E14 Questions and Answers. Implementing a fully integrated nonclinical/clinical risk assessment for compounds with double‐negative nonclinical findings in the context of a low prevalence of clinical QTc prolongation would relieve the burden of unnecessary clinical QTc studies and streamline drug development.

Background The purpose of this study was to clarify the efficacy of the combination of low-voltage coagulation plus staple line coverage with a polyglycolic acid sheet after bullectomy for primary spontaneous pneumothorax to prevent a postoperative recurrence. Methods A total of 143 patients who underwent bullectomy for primary spontaneous pneumothorax between January 2014 and December 2019 were enrolled in this study. We classified the patients into two groups based on additional procedures after bullectomy, namely, low-voltage coagulation for the margin of the staple line plus coverage with a polyglycolic acid sheet (Group A) and staple line coverage with a polyglycolic acid sheet alone (Group B). We evaluated perioperative factors and recurrence-free survival after surgery in the two groups. Results Nine patients in Group B developed postoperative recurrences. In contrast, there was no postoperative recurrence in Group A. According to the Kaplan–Meier curves, the 2-year recurrence-free survival rates of the patients were 100% and 90.3%, in Group A and Group B, respectively. The log-rank test showed a significant difference between the two groups ( p = 0.031). Conclusion Low-voltage coagulation for the margin of a staple line plus coverage with a polyglycolic acid sheet is a useful option as an additional technique after bullectomy for primary spontaneous pneumothorax to prevent a postoperative recurrence.

The purpose of this study was to develop a clear understanding of water flow through clayey slurries. Computed micro-tomography was used to quantify slurry constituents and validate index properties and hydraulic conductivity. An image analysis method was developed to capture the mechanics of flow through clayey slurries that are difficult to quantify through conventional measurement techniques. A solids ratio was defined to identify actual flow paths within a mixture of the solids, water and hydrated grains . Likewise, hydraulic radius was re-defined to describe water flow paths (pore throat) thereby eliminating the measurement of shape factor and tortuosity. More importantly, hydraulic conductivity calculated through the new method (and based on Poiseuille9s law) corroborated well with the empirical method of Pane & Schiffman (1997) for flocculated slurries.

The main objective of this paper was to investigate the dewatering behaviour of a clayey uranium ore slurry. The slurry (containing 28% clay size) exhibited moderate water adsorption (w l = 83% and w p = 30%). Primarily composed of muscovite (46%) and quartz (30%), the clay minerals included illite (8%), chlorite (5%) and kaolinite (2%) alongside a CEC of 41 (cmol(+)/kg) with Ca2+ and Mg2+ as the dominant cations. Likewise, the high EC (17,600 μS/cm) and ionic strength (1.15 mol/L) indicated a flocculated microstructure due to the presence of SO4 2− (22,600 mg/L) and Mg2+ (1340 mg/L) in the slurry water. Settling included sedimentation and consolidation at low initial solids condition (25–35%) whereas only consolidation was observed at high initial solids contents (40–50%). The average k reduced from 1.2 × 10−6 m/s (initial s = 25%) to 5.3 × 10−8 m/s (initial s = 50%) along with a void ratio reduction from 7.4 to 2.6. Due to thixotropic strength, volume compressibility during consolidation showed apparent pre-consolidation at low effective stress (0.3–2 kPa) with a reduction in void ratio from 2.6 to 2.5. The e s was found to be 2.46 at σ′ = 2 kPa and was followed by a steeper slope with the void ratio reducing to 2.1 at σ′ = 31 kPa. Likewise, the hydraulic conductivity during consolidation decreased from 2.6 × 10−9 m/s (at e = 2.6) to 2.0 × 10−10 m/s (at e = 2.1).

Geology and climate govern the evolution and behavior of natural expansive soils in the semi-arid Canadian Prairies. The Regina clay deposit has a flat topography, a homogenous composition, and contains hair-line fissures. This research focuses on understanding the relation between flow through and volumetric changes in the natural expansive soil. Based on analysis of test data, it is concluded that flow occurs through macro-pores or fissures (5 × 10−8 m/s) during structural volume change and through micro-pores or matrix (10−9 m/s) during normal and residual volume changes. The hydraulic conductivity decreases by several orders of magnitude and becomes asymptotic vapor flow (2 × 10−14 m/s) during residual volume change. A complete assessment of soil behavior requires water retention, swell-shrink, and hydraulic conductivity curves. The proposed straight-line representation of the functions' components is useful for predicting field response of expansive soils.

Stochastic analysis procedure was developed to predict the probability and range of volume changes in expansive soils. The plastic limit is an appropriate datum for estimating volume changes in the absence of continuous water content data. Results indicated that the soil usually exhibits swelling (30 mm) due to the prevalent dry conditions. The volume changes ranged between − 44 and + 104 mm for the investigated soil. Similarly, the likelihood to have − 30, + 30, and + 60 mm volume change was 5, 50, and 20%, respectively.

Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX.We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers.We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors.There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease.

文部科学省の「教育の情報化に関する手引き」や学習指導要領にICT化を押し図る動きと呼応するように、安価で便利な機器の開発が進み、一般化している。本研究では、障害者の困り感をどのようにICT機器を使って解決するか、或いはICT機器を使ってどのように効果的に学習していくかについて検討したものである。ICTに関する文献検討や研究会への参加、実際に障害のある方に機器を試していただき、利用法や効果について検証した。タブレットPCは扱いやすく、アプリケーションや内臓のカメラ機能や音声機能などを活用することで、様々な障害のある生徒が有効に利用していた。タブレットPCの活用は、学習場面だけでなく人とのつながりや、社会的ルールを守る基礎作りの効果も得られていた。また、豊富なアプリケーションや携帯に便利なこと、操作が簡単なことは教員の教材研究や教材作りの時間を短縮することも期待された。ICT機器を利用して彼らが楽しみや達成感、安心できる環境を得ることは、教員側が行っていきたい支援の一つと考えられる。

The main objective of this paper was to study the swelling properties of Regina clay. The deposit comprises a topsoil (surface to 0.3 m depth), an expansive clay (0.3–8 m), and a bottom till (8–9 m). High liquid limit (70 ± 15 %) and plastic limit (33 ± 4 %) indicated high water retention and adsorption capacity for the clay. Irrespective of the cover type (vegetation and cracked road), the field water content in summer closely matched the plastic limit. The clay was characterized by medium-to-high swelling that was best predicted by SP = 0.16 (I p)1.188. The soil had 51 % clay minerals including smectite (32 %), illite (7 %), kaolinite (5 %), and chlorite (3 %). With a CEC of 40 cmol(+)/kg, Ca2+ and Mg2+ were found to be the main exchangeable cations: the specific surface area was 50 m2/g. The SP and P s for a 1.2 m deep sample measured 12 % and 260 kPa, respectively, and the estimated surface heave of 180 mm gradually diminished to 3.6 m depth. These values matched well with consistency-based correlations.

Vertisolic expansive soils are characterized by unique morphological features and extensive volume changes of swelling clay minerals. The engineering properties of such a soil deposit in Regina, Canada, were investigated under in situ conditions. Results indicated a bi-modal SWCC composing of a fissure AEV (10 kPa) and a matrix AEV (300 kPa based on water content and 6000 kPa based on degree of saturation). The latter value matched the field water content and the plastic limit, of which both occurred at Save ≈ 80%. The swell-shrink path was found to be S-shaped and included a low structural shrinkage (Save = 100% to Save = 80% at wp) followed by a sharp decline during normal shrinkage (Save = 80% to Save = 60% at ws) and then by a low decrease during residual shrinkage (Save = 60% to Save = 0%). An equilibrium soil microstructure for the undisturbed samples mean that for the field conditions (up to the matrix AEV), the soil aggregates remain fully saturated whereas drainage and volume changes primarily occur through the fissures.

In our previous works, we demonstrated that human neural stem cells (NSCs) transduced with the cytosine deaminase (CD) gene showed remarkable 'bystander killer effect' on glioma and medulloblastoma cells after administration of the prodrug 5-fluorocytosine (5-FC). In addition, herpes simplex virus thymidine kinase (TK) is a widely studied enzyme used for suicide gene strategies, for which the prodrug is ganciclovir (GCV). To apply this strategy to brain metastasis treatment, we established here a human NSC line (F3.CD-TK) expressing the dual suicide genes CD and TK. We examined whether F3.CD-TK cells intensified the antitumor effect on lung cancer brain metastases. In vitro studies showed that F3.CD-TK cells exerted a marked bystander effect on human lung cancer cells after treatment with 5-FC and GCV. In a novel experimental brain metastases model, intravenously administered F3 cells migrated near lung cancer metastatic lesions, which were induced by the injection of lung cancer cells via the intracarotid artery. More importantly, F3.CD-TK cells in the presence of prodrugs 5-FC and GCV decreased tumor size and considerably prolonged animal survival. The results of the present study indicate that the dual suicide gene-engineered, NSC-based treatment strategy might offer a new promising therapeutic modality for brain metastases.

Plastic resin pellets collected from remote islands in the Pacific, Atlantic, and Indian Oceans and the Caribbean Sea were analyzed for polychlorinated biphenyls (PCBs), dichloro-diphenyltrichloroethane and its degradation products (DDTs), and hexachlorocyclohexanes (HCHs). Concentrations of PCBs (sum of 13 congeners) in the pellets were 0.1-9.9 ng/g-pellet. These were 1-3 orders of magnitude smaller than those observed in pellets from industrialized coastal shores. Concentrations of DDTs in the pellets were 0.8-4.1 ng/g-pellet. HCH concentrations were 0.6-1.7 ng/g-pellet, except for 19.3 ng/g-pellet on St. Helena, where current use of lindane is likely influence. This study provides background levels of POPs (PCBs

2-Hydroxychalcones are known to be converted to the colored flavylium form under UV irradiation. In this study, the photochemical conversion of two 2-hydroxychalcone derivatives (4′-dimethylamino-2-hydroxychalcone and 4′-methoxy-2-hydroxychalcone) has been carried out in the solid matrix by the intercalation into the layer of the clay, montmorillonite. The 2-hydroxychalcone has been adsorbed on the clay by modifying the clay interlayer with a cationic surfactant, dodecyltrimethylammonium chloride. The addition of an acidic compound (benzenesulfonic acid) has induced the successful coloring reaction of the 2-hydroxychalcone derivatives by the conversion to the flavylium under UV irradiation between the clay interlayer. A delayed coloration has been observed on the short time irradiation of 4′-methoxy-2-hydroxychalcone included in the clay layer.

人工膝関節全置換術 (TKA) 後の歩行能力の獲得時期と手術時年齢，性別，BMI，罹患関節 (片側・両側)，手術アプローチ，日本整形外科学会変形性膝関節症治療判定基準 (以下JOA score) を調査し，歩行能力の回復に影響する予測因子を検討した．当院でTKAを施行した67 例 (男性7 例，女性60 例)，88 膝を対象とした．原因疾患は変形性膝関節症80 膝，特発性骨壊死症8 膝であった．術後歩行能力の獲得時期として平行棒歩行，T字杖歩行，手すりによる階段昇降が可能となるまでの期間を調査した．平行棒歩行が可能となった時期は平均5.7 日，T字杖歩行16.1 日，階段昇降23.0 日であった．術後の歩行能力に影響した予測因子は罹患関節(片側・両側)，手術時年齢，術前JOA score，手術アプローチであった．

Expansive soils exhibit large volume changes when their water content changes. Alternate heave and settlement due to seasonal climatic variations result in distress and damage in civil infrastructure systems. This research focuses on the understanding of swelling and shrinkage phenomenon in the surface layer of expansive soils. Undisturbed field samples were used to capture the effect of in situ conditions (geologically induced fissuring and environmentally caused saturation) on volume change properties of Regina clay. Based on laboratory investigations, the swelling potential and swelling pressure of the native clay at S = 82% were found to be 1.5% and 3.5 kPa, respectively. The swell-shrink path during progressive soil drying followed an S-shaped curve comprising of an initial low structural shrinkage followed by a sharp decline during normal shrinkage and then by a low decrease during residual shrinkage. The soil microstructure correlated well with the observed volume change behaviour as well as with the consistency limits. The presence of fissures in field samples at various degrees of saturation confirmed that the investigated deposit is at an equilibrium condition with respect to the swell-shrink phenomenon. The swelling properties at any initial saturation state were estimated using the free swelling test and the swell-shrink test data in conjunction. The swelling potential increased 12 times (from 2 to 24%) and the swelling pressure increased by two orders of magnitude (from 27 to 2500 kPa) with a change in the degree of saturation from 80% (at the plastic limit) to 60% (at the shrinkage limit).

Parent material composition, particle disintegration by glaciers and lacustrine environment govern the geological development and engineering characteristics of clay deposits in southern Saskatchewan. The pre-existing expansive clay minerals were preserved due to the restrained leaching in the Regina Lake and the prevalent aridity in the area. The main objective of this paper was to develop a fundamental understanding of the clay deposit for the use in the design and construction of civil infrastructure. The results indicated the presence of expansive clay minerals in the deposit, with smectite accounting for 35% of the material. The major exchangeable cation was found to be Ca2+ which accounted for more than half of the total measured cation exchange capacity of 40 (cmol(+)/kg). The most likely exchange complex governing water adsorption of the clay was determined to be Ca2+-smectite. Alongside a high initial saturation (86%), this complex resulted in moderate volume changes in the clay. The swelling pressure was fully developed within the first hour of the constant volume test. The corrected swelling pressure was determined to be 120 kPa leading to an estimated heave of 36 mm in the surface layer of the deposit. The compression index and the swelling index were found to be 0.25 and 0.08, respectively.

Summary Background Dermatophytes are closely related keratinophilic fungal pathogens and are the causative agents of a superficial cutaneous infection called dermatophytosis (ringworm). A lack of gene manipulation techniques has prevented detailed analyses of the mechanisms of host invasion by dermatophytes. We have introduced the tetracycline-regulatable (TR) gene expression system into dermatophytes to facilitate functional analyses of genes essential for growth and virulence. As the TR gene expression system consists of two plasmid vector components, two dominant selectable markers are required for genetic transformation. In dermatophytes, only the hygromycin B phosphotransferase gene ( hph ) is available as a selectable marker. Objective We investigated the possibility of G418 resistance as a secondary selectable marker for genetic transformation in dermatophytes. Methods A series of plasmid vectors carrying the neomycin phosphotransferase gene ( nptII ) were introduced into the protoplasts of Trichophyton mentagrophytes , one of the most clinically important dermatophyte species, by polyethylene glycol (PEG)-mediated transformation. Transformants were selected on selective medium containing G418 at 300–500 μg/ml. Results Molecular biological analyses indicated that colonies appearing on the selective medium harbored nptII in their chromosomes. Colonies produced from protoplasts transformed with the enhanced green fluorescent protein ( eGFP ) gene- T. mentagrophytes cyclophilin cDNA ( Tmcyp B) fusion vector also exhibited GFP fluorescence throughout their mycelia, but accumulation of the GFP-TmCYPB fusion protein in specific intracellular compartments was not observed. Conclusions This study has provided a new selectable marker for genetic transformation in dermatophytes.

Curcumin is a plant-derived diferuloylmethane compound extracted from Curcuma longa, possessing antioxidative and anticarcinogenic properties. Antioxidants and oxidative stress are known to induce the expression of certain classes of detoxification enzymes. Since the upregulation of detoxifying enzymes affects the drug metabolism and cell defense system, it is important to understand the gene regulation by such agents. In this study, we demonstrated that curcumin could induce the expression of human glutathione S-transferase P1 (GSTP1). In HepG2 cells treated with 20muM curcumin, the level of GSTP1 mRNA was significantly increased. In luciferase reporter assays, curcumin augmented the promoter activity of a reporter construct carrying 336bp upstream of the 5'-flanking region of the GSTP1 gene. Mutation analyses revealed that the region including antioxidant response element (ARE), which overlaps AP1 in sequence, was essential to the response to curcumin. While the introduction of a wild-type Nrf2 expression construct augmented the promoter activity of the GSTP1 gene, co-expression of a dominant-negative Nrf2 abolished the responsiveness to curcumin. In addition, curcumin activated the expression of the luciferase gene from a reporter construct carrying multiple ARE consensus sequences but not one with multiple AP1 sites. In a gel mobility shift assay with an oligonucleotide with GSTP1 ARE, an increase in the amount of the binding complex was observed in the nuclear extracts of curcumin-treated HepG2 cells. These results suggested that ARE is the primary sequence for the curcumin-induced transactivation of the GSTP1 gene. The induction of GSTP1 may be one of the mechanisms underlying the multiple actions of curcumin.

Persistent organic pollutants (i.e. PCBs, DDTs, and HCHs) were analyzed along Australia and New Zealand North Island coastlines. PCB concentrations were high in urban areas (107-294 ng/g-pellet), with Sydney Harbour the most polluted. Hepta-chlorinated PCB was abundant, with ~30% in urban areas suggesting legacy pollution. DDT concentrations showed similar pattern except in rural agricultural sites, Taupo Bay and Ahipara, New Zealand (23 and 47 ng/g-pellet). p,p'-DDE predominance at these 2 sites suggested historical input; they also had high HCH concentrations (17 and 29 ng/g-pellet). The role of International Pellet Watch (IPW) in science communication was studied through feedbacks from IPW volunteers, case studies and examples. IPW data were categorized into understandable terms and tailored reports based on volunteers' backgrounds complemented with pollution maps. The effectiveness of IPW science communication has led to its use in awareness and education activities focusing on both POPs and plastic debris issues.

A major benefit of allogeneic hematopoietic cell transplantation (HCT) in the treatment of malignancies is the graft-versus-tumor (GVT) effect conferred by lymphocytes contained within the graft. However, lymphocytes can also induce the potentially lethal complication of graft-versus-host disease (GVHD). We have previously reported a method of generating large numbers of ex vivo activated and expanded T cells with antitumor activity after culture with interferon-y, cross-linking antibodies to CD3, and interleukin-2. Murine splenocytes expanded under these conditions are a heterogeneous population of which approximately 20% to 60% of cells express natural killer (NK)-cell markers (NK1.1 and DX5) and display major histocompatibility complex (MHC)-unrestricted antitumor activity. Here we demonstrate the in vivo antitumor activity of this population of expanded CD8+ NK-T cells when transplanted across MHC barriers into tumor-bearing hosts. In cotransfer studies with purified allogeneic hematopoietic stem cells, expanded CD8+ NK-T cells confer GVT activity with minimal to no GVHD. In vitro studies show that, although expanded NK-T cells lyse normal allogeneic bone marrow cells, they preferentially mediate cytolysis against tumor targets. These cells persist in the peripheral circulation of host animals for at least 3 weeks posttransfer. GVT activity is dependent on perforin, but not on Fas-ligand. We conclude that expanded CD8+ NK-T cells may serve as a valuable adjuvant population for allogeneic HCT because they mediate GVT effects with minimal GVHD.Biol Blood Marrow Transplant 2001;7(10):532-42.

A γ-cyclodextrin (γ-CyD) derivative (1) having a pyrene moiety, connected through a 4, 13-diaza-18-crown-6 ether moiety to γ-CyD, was synthesized and evaluated for guest binding and sensing properties. In aqueous solution, 1 existed as an association dimer in which the secondary hydroxyl sides faced each other to accommodate two pyrene moieties. Photo-induced electron transfer (PET) between the amino group and the excited pyrene moiety regulated the monomer fluorescence intensity of 1. The monomer-dimer equilibrium and the PET indicated that 1 may be used as a host capable of detecting guest complexation by changes in fluorescence intensity from the pyrene moiety. Deoxycholic acids were found to be good guests for detection by 1, and deoxycholic acid itself induced different fluorescence changes compared to the other deoxycholic acids. This indicated that 1 could recognize the position of the hydroxy groups on the steroidal framework. The azacrown part may participate in the guest selectivity for the deoxycholic acids by regulating the distance between the amino group and the pyrene moiety, modifying PET efficiency.

The isothermal phase relations for the MnO-SiO 2 -TiO 2 system have been investigated at 1 673 K by a chemical equilibration technique. Iso-activity curves for MnO are drawn from the experimental results of the activities as well as those for SiO2 and TiO 2 calculated by Schuhmann's tangent intercept procedure. 1) Iso-activity curves are nearly parallel to the saturation lines for the respective components. In this system, the interaction between MnO and SiO2 is the strongest of all. The sulfide capacity mostly depends on MnO content in this ternary system. It slightly increases when SiO 2 is replaced by TiO 2 at a constant (MnO+MnS) content by molar basis, whereas γMns considerably decreases.

Isocitrate dehydrogenase 1 (IDH1), which localizes to the cytosol and peroxisomes, catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) and in parallel converts NADP(+) to NADPH. IDH1 mutations are frequently detected in grades 2-4 gliomas and in acute myeloid leukemias (AML). Mutations of IDH1 have been identified at codon 132, with arginine being replaced with histidine in most cases. Mutant IDH1 gains novel enzyme activity converting α-KG to D-2-hydroxyglutarate (2-HG) which acts as a competitive inhibitor of α-KG. As a result, the activity of α-KG-dependent enzyme is reduced. Based on these findings, 2-HG has been proposed to be an oncometabolite. In this study, we established HEK293 and U87 cells that stably expressed IDH1-WT and IDH1-R132H and investigated the effect of glutaminase inhibition on cell proliferation with 6-diazo-5-oxo-L-norleucine (DON). We found that cell proliferation was suppressed in IDH1-R132H cells. The addition of α-KG restored cell proliferation. The metabolic features of 33 gliomas with wild type IDH1 (IDH1-WT) and with IDH1-R132H mutation were examined by global metabolome analysis using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). We showed that the 2-HG levels were highly elevated in gliomas with IDH1-R132H mutation. Intriguingly, in gliomas with IDH1-R132H, glutamine and glutamate levels were significantly reduced which implies replenishment of α-KG by glutaminolysis. Based on these results, we concluded that glutaminolysis is activated in gliomas with IDH1-R132H mutation and that development of novel therapeutic approaches targeting activated glutaminolysis is warranted.

Mantle Bouguer gravity anomaly gives density anomaly in the upper mantle. We compiled the mantle Bouguer anomaly in the Japan Trench and Arc using data of crustal structure given from explosion seismology. A profile of the gravity anomalies across the subduction zone shows a regional positive anomaly over the island arc. The profile also shows local low-density anomalies beneath the central part of the island arc and near the trench axis. A relatively positive anomaly of about 70 mgals still exists over the island arc after removing the effect of the subducting slab. We suspect missing of the low-density layers on the surface of the slab can explain the result. The low-density zone beneath the central part of the island arc relates to the zone of volcanic activity expected from petrological studies. Another low density zone relates to accretion of sediment near the trench axis.

We analyzed polychlorinated biphenyls (PCBs), dichlorodiphenyl dichloroethane and its metabolites, hexachlorocyclohexanes (HCHs), polycyclic aromatic hydrocarbons (PAHs), and hopanes, in plastic resin pellets collected from nine locations along the Portuguese coast. Concentrations of a sum of 13 PCBs were one order of magnitude higher in two major cities (Porto: 307. ng/g-pellet; Lisboa: 273. ng/g-pellet) than in the seven rural sites. Lower chlorinated congeners were more abundant in the rural sites than in the cities, suggesting atmospheric dispersion. At most of the locations, PAH concentrations (sum of 33 PAH species) were ∼100 to ∼300. ng/g-pellet; however, three orders of magnitude higher concentrations of PAHs, with a petrogenic signature, were detected at a small city (Sines). Hopanes were detected in the pellets at all locations. This study demonstrated that multiple sample locations, including locations in both urban and remote areas, are necessary for country-scale pellet watch. This research was financially supported by Mitsui and Co. Ltd., Environment Fund for their financial support (Project R11-G4-1053) and Grants-in-Aid from the Ministry of Education and Culture of Japan (Project No. 22254001). We also appreciate to be supported by Fundação para a Ciência e Tecnologia, Portugal for their financial support through the project POIZON reference PTDC/MAR/102677/2008 and fellowship reference SFRH/BD/74772/2010. published

In order to confirm engraftment of sibling-donor marrow cells or lekuemia relapse from the patient leukemic cells, DNA from nucleated cells in peripheral blood or bone-marrow fluid from patients who had received bone marrow transplantation (BMT) was examined using the MCT118 gene (D1S80) (a variable number of tandem repeats: VNTR) and 6 other genes and 9 restriction enzymes before and after BMT. In 5 of 10 patients (Case 1, 3, 4, 7, and 9) a difference between the DNA from donor cells and recipient cells was confirmed using the MCT118 gene, and engraftment of the donor marrow cells could be demonstrated. In Case 7, not only the engraftment of donor cells but also the leukemia relapse from recipient cells were confirmed using MCT118. Among the remaining 5 cases, Case 5, 8, and 10, the engraftment of donor cells was confirmed using the COLA2A1 gne (12q14.3). In Case 5, and 10, the engraftment could be detected using a gene in the CA2 locus (8g22). In Case 2, the presence of cells from the sibling was identified with the THRB gene (3p24) alone. In Case 6, the presence of cells from the donor could be confirmed using the DMD gene (Xp21.3-21.1) alone. In Case 8, the AK1 gene (9q34.1-34.2) could identified the difference between DNA from donor cells and recipient cells only, but the difference could also be detected using the COLA2A1 gene. In none of the cases, the INS gene (11p15.5) could identify the difference between the DNA from donor and recipient cells. Although only 10 cases were investigated, the findings suggest the use of first the MCT118 gene, then the COLA2A1 gene and the other genes when trying to determine engraftment of donor marrow cells or leukemia relapse after BMT.

The structure of short-chain diblock copolymers adsorbed at the interface between two immiscible liquids has been simulated using an atomistic level computer simulation. A rotational isomeric search is carried out to obtain the chain flexibility, and the equilibrium interfacial structure is studied by the Metropolis Monte Carlo procedure. The interface is characterized by number density profiles of the components comprising the simulated systems.

柴胡加竜骨牡蛎湯 (研究用エキス原末; 以下柴竜と略す) の中枢モノアミン関連物質に及ぼす影響について, マウスを用いて検討した。柴竜は50mg/kgまたは400mg/kgを経口的に単回または反復 (1日2回, 7日間) 投与した。脳の摘出, 分割は常法に従って行い, モノアミン関連物質の測定はHPLC-ECDを用いる方法で行った。主な結果は, 次の通りである。大脳皮質では, 50mg/kgの単回および反復投与でDOPAC, HVA含量の増大; 視床下部では, 50mg/kgの単回投与でNE含量の減少, 反復投与でNE含量の減少とDOPAC含量の増大; 線条体では, 50mg/kgの単回投与でDA, DOPAC, HVA, 5-HIAA含量の増大, 反復投与ではそのほかにNE, MHPG含量の増大, 400mg/kgの単回投与でNE, 5-HIAA含量の増大と反復投与でNE含量の増大; 海馬では, 50mg/kgの反復投与でMHPG含量の増大, 400mg/kgの反復投与でHVAの減少が認められた。以上のことから, 柴竜は400mg/kgよりも50mg/kg投与のほうがマウス脳内モノアミン含量への影響が強く, その効果は脳部位によって異なることが示唆される。