以健康理念出发：戴尔医学区景观设计

正戴尔医学院及附属教学医院戴尔塞顿医疗中心地处奧斯汀中部德州大学奥斯汀分校校园。占地逾6.5 hm2的医学区是市内最大的医疗卫生开发区的一部分,不仅为医学院全院师生及访客提供服务,更在校园景观中创造出一片新风貌,立下全新的生态绩效标准。戴尔医学区的景观设计过程是Sasaki及顾问团队过去2年规划工作的延续,项目团队先后在2012—2014年为大学制定了校园总体规划、医学区总体规划以及德州大学奥斯汀分校景观总体规划与设计导则。与之前的总体规划项目一样,戴尔医学区的景观设计同样以多元     

Characterization of the Oxide Scale Formed on T12 Water Wall Tube After Long-term Service in Supercritical Power Plant

Oxidation of Metals - Oxide scale control is one of the critical maintenance issues in fossil fuel power plant. Hence, the water treatment of the feed water has been changed from all-volatile...     

Small-angle X-ray scattering studies on melting and recrystallization behaviors of poly(oxyethylene) crystallites in poly(d,l-lactide)/poly(oxyethylene) blends

Direct determination of the discrete distribution for crystalline lamellar thickness has been performed for poly(d,l-lactic acid)/poly(oxyethylene) (PDLLA/PEG) blends by conducting small-angle X-ray scattering (SAXS) measurements using synchrotron radiation. The PDLLA used was an random (racemic) copolymer of bio-based poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) with the lactide monomer ratio of l:d = 50:50. It is known that PLA is miscible with PEG in the amorphous state. In the current paper, we report comprehensive results on structural analyses of PDLLA/PEG blends in the course of heating and cooling process using SAXS to elucidate the change in the thickness distribution of the lamellae. As a consequence, it was found that the distribution of the lamellar thickness moves toward the larger value (in other words, lamellar thickening) as temperature approaches the melting point. Typically, the thickness distribution was dispersed in the range of 10–20 nm at room temperature and it changed toward 40 nm in the vicinity of the melting temperature. To the best of our knowledge, this is the first report of direct determination of the discrete distribution for the crystalline lamellar thickness and their in-situ changes in the course of the lamellar thickening process. As a result, the lamellar thickening was found to occur at much lower temperature for the blend samples with 10% and 20% of PDLLA contents as compared to the PEG 100% sample. This phenomenon can be ascribed to the melting point depression owing to the miscibility between PEG and PDLLA. Thereby, thinner lamellae were melted and thicker ones appeared at much lower temperature for the blends than for the PEG 100% sample. As for the average repeating distance (long period) of the lamellar stacks, an abrupt increase similar to the critical divergence was observed (from 25 nm to 50 nm) in the heating process. Not only for the melting behavior but also in the course of recrystallization, change in the lamellar-thickness distribution was uncovered, which shows strong hysteresis depending on what temperature the sample was cooled down from.     

Change in molecular weight distribution by elution of polymers from PVA cast gel

Poly(vinyl alcohol) (PVA) cast gels with high degrees of polymerization and hydrolysis were prepared at room temperature. After sufficient exchange of the outer solvent by fresh pure water, the gel was re-dissolved in pure water at a high temperature. Using this solution, the cast gel was prepared again. This re-dissolution process was repeated again, and a third cast gel was prepared. During each swelling process after each cast-drying process, the amount of elution from the gel was measured and the molecular weight distributions of PVA in the gel as well as in the outer solvent were quantitatively evaluated. The molecular weight distribution of the eluted PVA was found to depend on that of the PVA in the gel; the average molecular weight gradually increased as the re-dissolution process was repeated, while the polydispersity indices of both the PVA from the gel and the eluted PVA decreased.     

Gene Expression over Time during Cell Transformation Due to Non-Genotoxic Carcinogen Treatment of Bhas 42 Cells

The Bhas 42 cell transformation assay (Bhas 42 CTA) is the first Organization for Economic Cooperation and Development (OECD)-certificated method used as a specific tool for the detection of the cell-transformation potential of tumor-promoting compounds, including non-genotoxic carcinogens (NGTxCs), as separate from genotoxic carcinogens. This assay offers the great advantage of enabling the phenotypic detection of oncotransformation. A key benefit of using the Bhas 42 CTA in the study of the cell-transformation mechanisms of tumor-promoting compounds, including non-genotoxic carcinogens, is that the cell-transformation potential of the chemical can be detected directly without treatment with a tumor-initiating compound since Bhas 42 cell line was established by transfecting the v-Ha-ras gene into a mouse fibroblast cloned cell line. Here, we analyzed the gene expression over time, using DNA microarrays, in Bhas 42 cells treated with the tumor-promoting compound 12-O-tetradecanoylphorbol-13-acetate (TPA), and NGTxC, with a total of three repeat experiments. This is the first paper to report on gene expression over time during the process of cell transformation with only a tumor-promoting compound. Pathways that were activated or inactivated during the process of cell transformation in the Bhas 42 cells treated with TPA were related not only directly to RAS but also to various pathways in the hallmarks of cancer.     

Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRAS^mt/SMAD4^mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRAS^mt/SMAD4^mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRAS^mt/SMAD4^mt cancer cells. These data indicate that the KRAS^mt/SMAD4^mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRAS^mt/SMAD4^mt signature.     

Self-Assembling Lectin Nano-Block Oligomers Enhance Binding Avidity to Glycans

Lectins, carbohydrate-binding proteins, are attractive biomolecules for medical and biotechnological applications. Many lectins have multiple carbohydrate recognition domains (CRDs) and strongly bind to specific glycans through multivalent binding effect. In our previous study, protein nano-building blocks (PN-blocks) were developed to construct self-assembling supramolecular nanostructures by linking two oligomeric proteins. A PN-block, WA20-foldon, constructed by fusing a dimeric four-helix bundle de novo protein WA20 to a trimeric foldon domain of T4 phage fibritin, self-assembled into several types of polyhedral nanoarchitectures in multiples of 6-mer. Another PN-block, the extender PN-block (ePN-block), constructed by tandemly joining two copies of WA20, self-assembled into cyclized and extended chain-type nanostructures. This study developed novel functional protein nano-building blocks (lectin nano-blocks) by fusing WA20 to a dimeric lectin, Agrocybe cylindracea galectin (ACG). The lectin nano-blocks self-assembled into various oligomers in multiples of 2-mer (dimer, tetramer, hexamer, octamer, etc.). The mass fractions of each oligomer were changed by the length of the linkers between WA20 and ACG. The binding avidity of the lectin nano-block oligomers to glycans was significantly increased through multivalent effects compared with that of the original ACG dimer. Lectin nano-blocks with high avidity will be useful for various applications, such as specific cell labeling.     

Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions

Metformin is a metabolic disruptor, and its efficacy and effects on metabolic profiles under different oxygen and nutrient conditions remain unclear. Therefore, the present study examined the effects of metformin on cell growth, the metabolic activities and consumption of glucose, glutamine, and pyruvate, and the intracellular ratio of nicotinamide adenine dinucleotide (NAD⁺) and reduced nicotinamide adenine dinucleotide (NADH) under normoxic (21% O₂) and hypoxic (1% O₂) conditions. The efficacy of metformin with nutrient removal from culture media was also investigated. The results obtained show that the efficacy of metformin was closely associated with cell types and environmental factors. Acute exposure to metformin had no effect on lactate production from glucose, glutamine, or pyruvate, whereas long-term exposure to metformin increased the consumption of glucose and pyruvate and the production of lactate in the culture media of HeLa and HaCaT cells as well as the metabolic activity of glucose. The NAD⁺/NADH ratio decreased during growth with metformin regardless of its efficacy. Furthermore, the inhibitory effects of metformin were enhanced in all cell lines following the removal of glucose or pyruvate from culture media. Collectively, the present results reveal that metformin efficacy may be regulated by oxygen conditions and nutrient availability, and indicate the potential of the metabolic switch induced by metformin as combinational therapy.     

Durability of radiation-sterilized polymers III. Oxidation layer determined by chemiluminescence

Chemiluminescence (CL) analysis was used for determining the oxidation layer formed by the irradiation of polypropylene for medical supplies. The depth of the oxidation layer from the surface depended on dose rate and increased with decreasing dose rate. The oxidation occurred remarkably at a region near the surface area of the film where the diffusion of oxygen is more sufficient. On the contrary, there was very little oxidation in the interior portion. The oxidation layers of polypropylene samples irradiated with electron beam showed U-shaped profiles in the cross-section of film as did as a sample irradiated with γ-rays. However, the degree of oxidation by irradiation with electron beam was very small; CL intensity at the surface area was only one-third that for the γ-irradiated samples.     

Fish intake and serum levels of organochlorines among Japanese women

This study evaluates background serum levels of selected organochlorine compounds among Japanese women of reproductive age and investigates whether lifestyle factors, especially dietary factors, may be associated with these levels. A cross-sectional study was performed on 80 Japanese women, aged 26-43 years, who complained of infertility and were confirmed not to have endometriosis. The serum levels of total toxic equivalency (TEQ), 18 polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs), 4 coplanar polychlorinated biphenyls (cPCBs), 36 ortho-substituted polychlorinated biphenyls (PCBs), and 13 chlorinated pesticides or their metabolites were measured and data were collected on the women's age, residence, occupation, body mass index (BMI), smoking and alcohol habit and 6 dietary intakes (fish, meats, rice, vegetables, fruits and dairy products). The serum median level of total TEQ was 25.1 pg TEQ/g lipid, that of PCDDs/PCDFs/cPCBs was 11.5 pmol/g lipid, that of PCBs was 0.46 nmol/g lipid, and that of total pesticides was 1.32 nmol/g lipid. The serum levels of total TEQ, PCDDs/PCDFs/cPCBs, PCBs and pesticides were positively associated with age (P for trend=0.003, 0.01, 0.005 and 0.01, respectively) and frequent fish consumption (P for trend=0.002, 0.003, 0.0003 and 0.006, respectively). Other lifestyle factors were not associated with serum organochlorine levels. The present study suggests that Japanese women who consume fish frequently in their reproductive period tend to accumulate organochlorines in their bodies.