| 71241. |
- Isvoranu, Cristina, et al.
(författare)
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Tuning the spin state of iron phthalocyanine by ligand adsorption
- 2010
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Ingår i: Journal of Physics: Condensed Matter. - : IOP Publishing. - 1361-648X .- 0953-8984. ; 22:47
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Tidskriftsartikel (refereegranskat)abstract
- The future use of single-molecule magnets in applications will require the ability to control and manipulate the spin state and magnetization of the magnets by external means. There are different approaches to this control, one being the modification of the magnets by adsorption of small ligand molecules. In this paper we use iron phthalocyanine supported by an Au(111) surface as a model compound and demonstrate, using x-ray photoelectron spectroscopy and density functional theory, that the spin state of the molecule can be tuned to different values (S similar to 0, 1/2, 1) by adsorption of ammonia, pyridine, carbon monoxide or nitric oxide on the iron ion. The interaction also leads to electronic decoupling of the iron phthalocyanine from the Au(111) support.
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| 71242. |
- Itkonen, Juha, et al.
(författare)
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Are test cases needed? Replicated comparison between exploratory and test-case-based software testing
- 2014
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Ingår i: Empirical Software Engineering. - : Springer Science and Business Media LLC. - 1573-7616 .- 1382-3256. ; 19:2, s. 303-342
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Tidskriftsartikel (refereegranskat)abstract
- Manual software testing is a widely practiced verification and validation method that is unlikely to fade away despite the advances in test automation. In the domain of manual testing, many practitioners advocate exploratory testing (ET), i.e., creative, experience-based testing without predesigned test cases, and they claim that it is more efficient than testing with detailed test cases. This paper reports a replicated experiment comparing effectiveness, efficiency, and perceived differences between ET and test-case-based testing (TCT) using 51 students as subjects, who performed manual functional testing on the jEdit text editor. Our results confirm the findings of the original study: 1) there is no difference in the defect detection effectiveness between ET and TCT, 2) ET is more efficient by requiring less design effort, and 3) TCT produces more false-positive defect reports than ET. Based on the small differences in the experimental design, we also put forward a hypothesis that the effectiveness of the TCT approach would suffer more than ET from time pressure. We also found that both approaches had distinctive issues: in TCT, the problems were related to correct abstraction levels of test cases, and the problems in ET were related to test design and logging of the test execution and results. Finally, we recognize that TCT has other benefits over ET in managing and controlling testing in large organizations.
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| 71243. |
- Ito, A., et al.
(författare)
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Cold-Season Methane Fluxes Simulated by GCP-CH4 Models
- 2023
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Ingår i: Geophysical Research Letters. - 0094-8276. ; 50:14
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Tidskriftsartikel (refereegranskat)abstract
- Cold-season methane (CH4) emissions may be poorly constrained in wetland models. We examined cold-season CH4 emissions simulated by 16 models participating in the Global Carbon Project model intercomparison and analyzed temporal and spatial patterns in simulation results using prescribed inundation data for 2000–2020. Estimated annual CH4 emissions from northern (>60°N) wetlands averaged 10.0 ± 5.5 Tg CH4 yr−1. While summer CH4 emissions were well simulated compared to in-situ flux measurement observations, the models underestimated CH4 during September to May relative to annual total (27 ± 9%, compared to 45% in observations) and substantially in the months with subzero air temperatures (5 ± 5%, compared to 27% in observations). Because of winter warming, nevertheless, the contribution of cold-season emissions was simulated to increase at 0.4 ± 0.8% decade−1. Different parameterizations of processes, for example, freezing–thawing and snow insulation, caused conspicuous variability among models, implying the necessity of model refinement.
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| 71244. |
- Ito, Akihiko, et al.
(författare)
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Soil carbon sequestration simulated in CMIP6-LUMIP models : Implications for climatic mitigation
- 2020
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- Land-use change affects both the quality and quantity of soil organic carbon (SOC) and leads to changes in ecosystem functions such as productivity and environmental regulation. Future changes in SOC are, however, highly uncertain owing to its heterogeneity and complexity. In this study, we analyzed the outputs of simulations of SOC stock by Earth system models (ESMs), most of which are participants in the Land-Use Model Intercomparison Project. Using a common protocol and the same forcing data, the ESMs simulated SOC distribution patterns and their changes during historical (1850-2014) and future (2015-2100) periods. Total SOC stock increased in many simulations over the historical period (30 ± 67 Pg C) and under future climate and land-use conditions (48 ± 32 Pg C for ssp126 and 49 ± 58 Pg C for ssp370). Land-use experiments indicated that changes in SOC attributable to land-use scenarios were modest at the global scale, in comparison with climatic and rising CO2 impacts, but they were notable in several regions. Future net soil carbon sequestration rates estimated by the ESMs were roughly 0.4‰ yr-1 (0.6 Pg C yr-1). Although there were considerable inter-model differences, the rates are still remarkable in terms of their potential for mitigation of global warming. The disparate results among ESMs imply that key parameters that control processes such as SOC residence time need to be better constrained and that more comprehensive representation of land management impacts on soils remain critical for understanding the long-term potential of soils to sequester carbon.
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| 71245. |
- Ito, Y, et al.
(författare)
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Activation of c-Src is inversely correlated with biological aggressiveness of breast carcinoma
- 2002
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 76:3, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate whether c-Src is involved in carcinogenesis and progression of breast carcinoma, we examined the expression of activated c-Src in tissue sections from surgically resected human breast specimens. First, we confirmed the specificity of the antibody against activated c-Src (Clone 28) using six cell lines established from human breast carcinomas by western blotting. As expected, activated c-Src was detected as a 60 kDa band in all cell lines tested. Immunofluorescence analysis demonstrated that the activated c-Src was mainly observed in cytoplasms of these cells. Then, we designed an immunohistochemical study with 73 human breast carcinoma tissues. Glandular epithelial and myoepithelial cells in normal mammary glands adjacent to carcinoma nests and infiltrating stromal cells were negative for activated c-Src. In contrast, 37 of the 73 breast carcinoma tested (50.7%) were positive for activated c-Src, and this positive staining was inversely correlated with Ki-67 labeling index (p <0.0001), TNM stage (p <0.0001), tumor size (p < 0.0001), and histological grade (p = 0.0002). These results strongly suggest that the activation of c-Src would be related to the progression of breast carcinomas with low aggressiveness.
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| 71246. |
- Itoh, Fumiko, et al.
(författare)
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Poor vessel formation in embryos from knock-in mice expressing ALK5 with L45 loop mutation defective in Smad activation
- 2009
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837. ; 89:7, s. 800-810
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor (TGF)-beta regulates vascular development through two type I receptors: activin receptor-like kinase (ALK) 1 and ALK5, each of which activates a different downstream Smad pathway. The endothelial cell (EC)-specific ALK1 increases EC proliferation and migration, whereas the ubiquitously expressed ALK5 inhibits both of these processes. As ALK1 requires the kinase activity of ALK5 for optimal activation, the lack of ALK5 in ECs results in defective phosphorylation of both Smad pathways on TGF-beta stimulation. To understand why TGF-beta signaling through ALK1 and ALK5 has opposing effects on ECs and whether this takes place in vivo, we carefully compared the phenotype of ALK5 knock-in (ALK5(KI/KI)) mice, in which the aspartic acid residue 266 in the L45 loop of ALK5 was replaced by an alanine residue, with the phenotypes of ALK5 knock-out (ALK5(-/-)) and wild-type mice. The ALK5(KI/KI) mice showed angiogenic defects with embryonic lethality at E10.5-11.5. Although the phenotype of the ALK5(KI/KI) mice was quite similar to that of the ALK5(-/-) mice, the hierarchical structure of blood vessels formed in the ALK5(KI/KI) embryos was more developed than that in the ALK5(-/-) mutants. Thus, the L45 loop mutation in ALK5 partially rescued the earliest vascular defects in the ALK5(-/-) embryos. This study supports our earlier observation that vascular maturation in vivo requires both TGF-beta/ALK1/BMP-Smad and TGF-beta/ALK5/activin-Smad pathways for normal vascular development. Laboratory Investigation (2009) 89, 800-810; doi:10.1038/labinvest.2009.37; published online 27 April 2009
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| 71247. |
- Itoh, Fumiko, et al.
(författare)
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Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions
- 2012
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 119:22, s. 5320-5328
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor-beta (TGF-beta) is involved in vascular formation through activin receptor-like kinase (ALK)1 and ALK5. ALK5, which is expressed ubiquitously, phosphorylates Smad2 and Smad3, whereas endothelial cell (EC)-specific ALK1 activates Smad1 and Smad5. Because ALK5 kinase activity is required for ALK1 to transduce TGF-beta signaling via Smad1/5 in ECs, ALK5 knockout (KO) mice were not able to give us the precise mechanisms by which TGF-beta/ALK5/Smad2/3 signaling is implicated in angiogenesis. To delineate the role of Smad2/3 signaling in endothelium, the Smad2 gene in Smad3 KO mice was selectively deleted in ECs using Tie2-Cre transgenic mice, termed EC-specific Smad2/3 double KO (EC-Smad2/3KO) mice. EC-Smad2/3KO embryos revealed hemorrhage leading to embryonic lethality around E12.5. EC-Smad2/3KO embryos exhibited no abnormality of vasculogenesis and angiogenesis in both the yolk sac and the whole embryo, whereas vascular maturation was incomplete because of inadequate assembly of mural cells in the vasculature. Wide gaps between ECs and mural cells could be observed in the vasculature of EC-Smad2/3KO mice because of reduced expression of N-cadherin and sphingosine-1-phosphate receptor-1 (S1PR1) in ECs from those mice. These results indicated that Smad2/3 signaling in ECs is indispensable for maintenance of vascular integrity via the fine-tuning of N-cadherin, VE-cadherin, and S1PR1 expressions in the vasculature. (Blood. 2012;119(22):5320-5328)
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| 71248. |
- Itriago, Humberto, et al.
(författare)
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Characterization of the RAD52 Gene in the Budding Yeast Naumovozyma castellii
- 2023
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Ingår i: Genes. - 2073-4425. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Several sources of DNA damage compromise the integrity and stability of the genome of every organism. Specifically, DNA double-strand breaks (DSBs) can have lethal consequences for the cell. To repair this type of DNA damage, the cells employ homology-directed repair pathways or non-homologous end joining. Homology-directed repair requires the activity of the RAD52 epistasis group of genes. Rad52 is the main recombination protein in the budding yeast Saccharomyces cerevisiae, and rad52Δ mutants have been characterized to show severe defects in DSB repair and other recombination events. Here, we identified the RAD52 gene in the budding yeast Naumovozyma castellii. Our analysis showed that the primary amino acid sequence of N. castellii Rad52 shared 70% similarity with S. cerevisiae Rad52. To characterize the gene function, we developed rad52Δ mutant strains by targeted gene replacement transformation. We found that N. castellii rad52Δ mutants showed lowered growth capacity, a moderately altered cell morphology and increased sensitivity to genotoxic agents. The decreased viability of the N. castellii rad52Δ mutants in the presence of genotoxic agents indicates that the role of the Rad52 protein in the repair of DNA damage is conserved in this species.
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| 71249. |
- Itriago, Humberto, et al.
(författare)
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The telomeric 5' end nucleotide is regulated in the budding yeast Naumovozyma castellii.
- 2022
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 50:1, s. 281-292
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Tidskriftsartikel (refereegranskat)abstract
- The junction between the double-stranded and single-stranded telomeric DNA (ds–ss junction) is fundamental in the maintenance of the telomeric chromatin, as it directs the assembly of the telomere binding proteins. In budding yeast, multiple Rap1 proteins bind the telomeric dsDNA, while ssDNA repeats are bound by the Cdc13 protein. Here, we aimed to determine, for the first time, the telomeric 5′ end nucleotide in a budding yeast. To this end, we developed a permutation-specific PCR-based method directed towards the regular 8-mer telomeric repeats in Naumovozyma castellii. We find that, in logarithmically growing cells, the 320 ± 30 bp long telomeres mainly terminate in either of two specific 5′ end permutations of the repeat, both corresponding to a terminal adenine nucleotide. Strikingly, two permutations are completely absent at the 5′ end, indicating that not all ds-ss junction structures would allow the establishment of the protective telomere chromatin cap structure. Using in vitro DNA end protection assays, we determined that binding of Rap1 and Cdc13 around the most abundant ds–ss junction ensures the protection of both 5′ ends and 3′ overhangs from exonucleolytic degradation. Our results provide mechanistic insights into telomere protection, and reveal that Rap1 and Cdc13 have complementary roles.
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| 71250. |
- Ittner, Lars M, et al.
(författare)
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Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells
- 2005
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Ingår i: Journal of Biology. - : Springer Science and Business Media LLC. - 1475-4924. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC), but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular structures are poorly understood. RESULTS: Here we reveal distinct NC contributions to both anterior and posterior mesenchymal eye structures and show that TGFbeta signaling in these cells is crucial for normal eye development. In the anterior eye, TGFbeta2 released from the lens is required for the expression of transcription factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle structures of the eye that control intraocular pressure. TGFbeta enhances Foxc1 and induces Pitx2 expression in cell cultures. As in patients carrying mutations in PITX2 and FOXC1, TGFbeta signal inactivation in NC cells leads to ocular defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the posterior eye, NC cell-specific inactivation of TGFbeta signaling results in a condition reminiscent of the human disorder persistent hyperplastic primary vitreous. As a secondary effect, retinal patterning is also disturbed in mutant mice. CONCLUSION: In the developing eye the lens acts as a TGFbeta signaling center that controls the development of eye structures derived from the NC. Defective TGFbeta signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFbeta signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.
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