| 2761. |
- Furuya, Hideki, et al.
(författare)
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PAI-1 is a potential transcriptional silencer that supports bladder cancer cell activity
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, acting as an inhibitor of tissue plasminogen activator and urokinase-type plasminogen activator, impacting fibrinolysis. Recent studies have revealed a pro-tumorigenic role of PAI-1 in human cancers, via the regulation of angiogenesis and tumor cell survival. In this study, immunohistochemical staining of 939 human bladder cancer specimens showed that PAI-1 expression levels correlated with tumor grade, tumor stage and overall survival. The typical subcellular localization of PAI-1 is cytoplasmic, but in approximately a quarter of the cases, PAI-1 was observed to be localized to both the tumor cell cytoplasm and the nucleus. To investigate the potential function of nuclear PAI-1 in tumor biology we applied chromatin immunoprecipitation (ChIP)-sequencing, gene expression profiling, and rapid immunoprecipitation mass spectrometry to a pair of bladder cancer cell lines. ChIP-sequencing revealed that PAI-1 can bind DNA at distal intergenic regions, suggesting a role as a transcriptional coregulator. The downregulation of PAI-1 in bladder cancer cell lines caused the upregulation of numerous genes, and the integration of ChIP-sequence and RNA-sequence data identified 57 candidate genes subject to PAI-1 regulation. Taken together, the data suggest that nuclear PAI-1 can influence gene expression programs and support malignancy.
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| 2762. |
- Gallo, Valentina, et al.
(författare)
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Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: The EPIC cohort.
- 2013
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 80:9, s. 829-838
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design. METHODS: The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality. RESULTS: Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86-0.99 per kg/m(2)); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25-0.93) with a borderline significant p value for trend across quartiles (p = 0.056). CONCLUSION: Increased prediagnostic body fat is associated with a decreased risk of ALS mortality.
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| 2763. |
- Garcia, Victor, et al.
(författare)
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Development of Training Materials for Pathologists to Provide Machine Learning Validation Data of Tumor-Infiltrating Lymphocytes in Breast Cancer
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:10, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- The High Throughput Truthing project aims to develop a dataset for validating artificial intelligence and machine learning models (AI/ML) fit for regulatory purposes. The context of this AI/ML validation dataset is the reporting of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer biopsy specimens. After completing the pilot study, we found notable variability in the sTILs estimates as well as inconsistencies and gaps in the provided training to pathologists. Using the pilot study data and an expert panel, we created custom training materials to improve pathologist annotation quality for the pivotal study. We categorized regions of interest (ROIs) based on their mean sTILs density and selected ROIs with the highest and lowest sTILs variability. In a series of eight one-hour sessions, the expert panel reviewed each ROI and provided verbal density estimates and comments on features that confounded the sTILs evaluation. We aggregated and shaped the comments to identify pitfalls and instructions to improve our training materials. From these selected ROIs, we created a training set and proficiency test set to improve pathologist training with the goal to improve data collection for the pivotal study. We are not exploring AI/ML performance in this paper. Instead, we are creating materials that will train crowd-sourced pathologists to be the reference standard in a pivotal study to create an AI/ML model validation dataset. The issues discussed here are also important for clinicians to understand about the evaluation of sTILs in clinical practice and can provide insight to developers of AI/ML models.
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| 2764. |
- Gardner, James M., 1982-, et al.
(författare)
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Electrodeposition of Nanometer-Sized Ferric Oxide Materials in Colloidal Templates for Conversion of Light to Chemical Energy
- 2011
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Ingår i: Journal of Nanomaterials. - : Hindawi Publishing Corporation. - 1687-4110 .- 1687-4129. ; 2011, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Colloidal crystal templates were prepared by gravitational sedimentation of 0.5 micron polystyrene particles onto fluorine-doped tin oxide (FTO) electrodes. Scanning electron microscopy (SEM) shows that the particles were close packed and examination of successive layers indicated a predominantly face-centered-cubic (fcc) crystal structure where the direction normal to the substrate surface corresponds to the (111) direction. Oxidation of aqueous ferrous solutions resulted in the electrodeposition of ferric oxide into the templates. Removal of the colloidal templates yielded ordered macroporous electrodes (OMEs) that were the inverse structure of the colloidal templates. Current integration during electrodeposition and cross-sectional SEM images revealed that the OMEs were about 2 mu m thick. Comparative X-ray diffraction and infrared studies of the OMEs did not match a known phase of ferric oxide but suggested a mixture of goethite and hematite. The spectroscopic properties of the OMEs were insensitive to heat treatments at 300. C. The OMEs were utilized for photoassisted electrochemical oxidation. A sustained photocurrent was observed from visible light in aqueous photoelectrochemical cells. Analysis of photocurrent action spectra revealed an indirect band gap of 1.85 eV. Addition of formate to the aqueous electrolytes resulted in an approximate doubling of the photocurrent.
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| 2765. |
- Generó, Magalí Martí, 1983-, et al.
(författare)
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Nitrogen and methanogen community composition within and among three Sphagnum dominated peatlands in Scandinavia
- 2015
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Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 81, s. 204-211
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Ombrotrophic raised bogs are nutrient poor acidic peatlands accumulating organic matter. They are widely spread on northern latitudes and are substantial sources of methane emissions to the atmosphere being of great concern from a climate change perspective. We investigated the methanogen community composition along microtopographic gradients within three bogs in Scandinavia, receiving different amounts of nitrogen precipitation. Methanogenic community analyses by terminal restriction fragment length polymorphism of the mcrA gene showed different profiles among the three sites, while no influence of the microtopographic gradients was observed. Peat temperature and dissolved organic carbon were the major edaphic variables explaining 38% of the variation of the methanogenic community diversity among the bogs. The family Methanoregulaceae (hydrogenotrophic methanogens) showed the largest relative proportion and highest activity in all three sites. Quantitative PCR of the mcrA gene and transcripts showed that the most northern site, receiving the lowest atmospheric nitrogen load, had significantly lower abundance and activity of methanogens (4.7 × 106 and 2.4 × 104 mcrA copies per gram of soil, respectively), compared to the most southern site (8.2 × 107 and 4.6 × 105 mcrA copies per gram of soil, respectively), receiving the highest nitrogen load. No patterns of the mcrA gene and transcript abundances were observed along the microtopography. The results indicated that the difference in occurrence of methanogens is mainly due to geoclimatological conditions rather than site intrinsic microtopographic variation. The study further suggests that environmental changes on the site intrinsic topography will not affect the methanogenic activity, while increasing average temperatures in Scandinavian ombrotrophic raised bogs might contribute to an increase of the methanogenic archaeal activity resulting in an increase of methane production.
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| 2766. |
- Genkinger, Jeanine M., et al.
(författare)
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Coffee, Tea, and Sugar-Sweetened Carbonated Soft Drink Intake and Pancreatic Cancer Risk : A Pooled Analysis of 14 Cohort Studies
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 21:2, s. 305-318
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. Methods: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. Results: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing >= 900 to <0 g/d; 237g approximate to 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing >= 400 to 0 g/d; 237g approximate to 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing >= 250 to 0 g/d; 355g approximate to 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). Conclusion and Impact: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.
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| 2767. |
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| 2768. |
- Gouliermis, Dimitrios A., et al.
(författare)
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Hierarchical star formation across the ring galaxy NGC 6503
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 452:4, s. 3508-3528
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed clustering analysis of the young stellar population across the star-forming ring galaxy NGC 6503, based on the deep Hubble Space Telescope photometry obtained with the Legacy ExtraGalactic UV Survey. We apply a contour-based map analysis technique and identify in the stellar surface density map 244 distinct star-forming structures at various levels of significance. These stellar complexes are found to be organized in a hierarchical fashion with 95 per cent being members of three dominant super-structures located along the star-forming ring. The size distribution of the identified structures and the correlation between their radii and numbers of stellar members show power-law behaviours, as expected from scale-free processes. The self-similar distribution of young stars is further quantified from their autocorrelation function, with a fractal dimension of similar to 1.7 for length-scales between similar to 20 pc and 2.5 kpc. The young stellar radial distribution sets the extent of the star-forming ring at radial distances between 1 and 2.5 kpc. About 60 per cent of the young stars belong to the detected stellar structures, while the remaining stars are distributed among the complexes, still inside the ring of the galaxy. The analysis of the time-dependent clustering of young populations shows a significant change from a more clustered to a more distributed behaviour in a time-scale of similar to 60 Myr. The observed hierarchy in stellar clustering is consistent with star formation being regulated by turbulence across the ring. The rotational velocity difference between the edges of the ring suggests shear as the driving mechanism for this process. Our findings reveal the interesting case of an inner ring forming stars in a hierarchical fashion.
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| 2769. |
- Grishin, Alexander M., et al.
(författare)
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Epitaxial colossal magnetoresistive/ferroelectric heterostructures on Si
- 2004
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Ingår i: Integrated Ferroelectrics. - : Informa UK Limited. - 1058-4587 .- 1607-8489. ; 67, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- We report on processing and properties of La-0.67(SrCa)(0.33)MnO3 (LSCMO) films grown by pulsed laser deposition technique on Si(001) substrates buffered with Bi4Ti3O12/CeO2/YSZ heteroepitaxial layers. X-ray diffraction shows cube-on-cube growth of epitaxial Bi4Ti3O12/CeO2/YSZ/Si heterostructure whereas the LSCMO layer grows in the diagonal-on-side manner onto the Bi4Ti3O12 (BTO) template. High resolution TEM images demonstrate sharp interfaces between the buffer layers and LSCMO film as well as rare misfit dislocations on the CeO2/YSZ interface. LSCMO film processing conditions have been optimized to get maximum temperature coefficient of resistivity TCR = 4.4% K-1 and colossal magnetoresistance (CMR) Deltarho/rho similar to 2.9% kOe(-1) @ 294 K. Almost ultimate CMR performance at room temperature has been achieved due to successive improvement of c-axis orientation of layers: full widths at half-maximum (FWHM) = 0.65, 0.58, 0.65, 1.13 and 0.18 degrees in LSCMO/BTO/CeO2/YSZ/Si stack, respectively. Characterization of electrical noise in CMR film yields Noise Equivalent Temperature Difference (NETD) as low as 1.2 muK/rootHz @ 30 Hz and 294 K.
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| 2770. |
- Grishin, Alexander M., et al.
(författare)
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Epitaxial La-0.67(Sr,Ca)(0.33)MnO3 films on Si for IR bolometer applications
- 2004
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Ingår i: Integration Of Advanced Micro-And Nanoelectronic Devices-Critical Issues And Solutions. - : Springer Science and Business Media LLC. - 155899761X ; , s. 405-410
-
Konferensbidrag (refereegranskat)abstract
- We report on processing and properties of La-0.67(Sr,Ca)(0.33)MnO3 (LSCMO) films grown by pulsed laser deposition technique on Si(001) substrates buffered with Bi4Ti3O12/CeO2/YSZ heteroepitaxial layers. X-ray diffraction shows cube-on-cube growth of epitaxial Bi4Ti3O12/CeO2/YSZ/Si heterostructure whereas the LSCMO layer grows in the "diagonal-on-side" manner onto the Bi4Ti3O12 (BTO) template. High resolution TEM images demonstrate sharp interfaces between the buffer layers and LSCMO film as well as rare misfit dislocations on the CeO2/YSZ interface. LSCMO film processing conditions have been optimized to get maximum temperature coefficient of resistivity TCR = 4.4%K-1 and colossal magnetoresistance (CMR) Deltarho/rho similar to 2.9%kOe(-1) @ 294K. Almost ultimate CMR performance at room temperature has been achieved due to successive improvement of c-axis orientation of layers: full widths at half-maximum (FWHM) 0.65, 0.58, 0.65, 1.13 and 0.18 degrees in LSCMO/BTO/CeO2/YSZ/Si stack, respectively. Characterization of electrical noise in CMR film yields noise equivalent temperature difference (NETD) as low as 1.2 muK/rootHz @ 30Hz and 294K.
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