949 resultados para Hot-spot –method


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This paper presents the impact of non-homogeneous deposits of dust on the performance of a PV array. The observations have been made in a 2-MW PV park in the southeast region of Spain. The results are that inhomogeneous dust leads to more significant consequences than the mere short-circuit current reduction resulting from transmittance losses. In particular, when the affected PV modules are part of a string together with other cleaned (or less dusty) ones, operation voltage losses arise. These voltage losses can be several times larger than the short-circuit ones, leading to power losses that can be much larger than what measurements suggest when the PV modules are considered separately. Significant hot-spot phenomena can also arise leading to cells exhibiting temperature differences of more than 20 degrees and thus representing a threat to the PV modules' lifetime.

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The Saccharomyces cerevisiae genome encodes four MutL homologs. Of these, MLH1 and PMS1 are known to act in the MSH2-dependent pathway that repairs DNA mismatches. We have investigated the role of MLH3 in mismatch repair. Mutations in MLH3 increased the rate of reversion of the hom3–10 allele by increasing the rate of deletion of a single T in a run of 7 Ts. Combination of mutations in MLH3 and MSH6 caused a synergistic increase in the hom3–10 reversion rate, whereas the hom3–10 reversion rate in an mlh3 msh3 double mutant was the same as in the respective single mutants. Similar results were observed when the accumulation of mutations at frameshift hot spots in the LYS2 gene was analyzed, although mutation of MLH3 did not cause the same extent of affect at every LYS2 frameshift hot spot. MLH3 interacted with MLH1 in a two-hybrid system. These data are consistent with the idea that a proportion of the repair of specific insertion/deletion mispairs by the MSH3-dependent mismatch repair pathway uses a heterodimeric MLH1-MLH3 complex in place of the MLH1-PMS1 complex.

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Vascular endothelial growth factor (VEGF) is a homodimeric member of the cystine knot family of growth factors, with limited sequence homology to platelet-derived growth factor (PDGF) and transforming growth factor β2 (TGF-β). We have determined its crystal structure at a resolution of 2.5 Å, and identified its kinase domain receptor (KDR) binding site using mutational analysis. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended. The dimerization mode of VEGF is similar to that of PDGF and very different from that of TGF-β. Mutational analysis of VEGF reveals that symmetrical binding sites for KDR are located at each pole of the VEGF homodimer. Each site contains two functional “hot spots” composed of binding determinants presented across the subunit interface. The two most important determinants are located within the largest hot spot on a short, three-stranded sheet that is conserved in PDGF and TGF-β. Functional analysis of the binding epitopes for two receptor-blocking antibodies reveal different binding determinants near each of the KDR binding hot spots.

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The variable (V) regions of immunoglobulin heavy and light chains undergo high rates of somatic mutation during the immune response. Although point mutations accumulate throughout the V regions and their immediate flanking sequences, analysis of large numbers of mutations that have arisen in vivo reveal that the triplet AGC appears to be most susceptible to mutation. We have stably transfected B cell lines with γ2a heavy chain constructs containing TAG nonsense codons in their V regions that are part of either a putative (T)AGC hot spot or a (T)AGA non-hot spot motif. Using an ELISA spot assay to detect revertants and fluctuation analysis to determine rates of mutation, the rate of reversion of the TAG nonsense codon has been determined for different motifs in different parts of the V region. In the NSO plasma cell line, the (T)AGC hot spot motif mutates at rates of ≈6 × 10−4/bp per generation and ≈3 × 10−5/bp per generation at residues 38 and 94 in the V region. At each of these locations, the (T)AGC hot spot motif is 20–30 times more likely to undergo mutation than the (T)AGA non-hot spot motif. Moreover, the AGA non-hot spot motif mutates at as high a rate as the hot spot motif when it is located adjacent to hot spot motifs, suggesting that more extended sequences influence susceptibility to mutation.

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Missense mutations within the central DNA binding region of p53 are the most prevalent mutations found in human cancer. Numerous studies indicate that ‘hot-spot’ p53 mutants (which comprise ∼30% of human p53 gene mutations) are largely devoid of transcriptional activity. However, a growing body of evidence indicates that some non-hot-spot p53 mutants retain some degree of transcriptional activity in vivo, particularly against strong p53 binding sites. We have modified a previously described yeast-based p53 functional assay to readily identify such partial loss of function p53 mutants. We demonstrate the utility of this modified p53 functional assay using a diverse panel of p53 mutants.

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High affinity antibodies are generated in mice and humans by means of somatic hypermutation (SHM) of variable (V) regions of Ig genes. Mutations with rates of 10−5–10−3 per base pair per generation, about 106-fold above normal, are targeted primarily at V-region hot spots by unknown mechanisms. We have measured mRNA expression of DNA polymerases ι, η, and ζ by using cultured Burkitt's lymphoma (BL)2 cells. These cells exhibit 5–10-fold increases in heavy-chain V-region mutations targeted only predominantly to RGYW (R = A or G, Y = C or T, W = T or A) hot spots if costimulated with T cells and IgM crosslinking, the presumed in vivo requirements for SHM. An ∼4-fold increase pol ι mRNA occurs within 12 h when cocultured with T cells and surface IgM crosslinking. Induction of pols η and ζ occur with T cells, IgM crosslinking, or both stimuli. The fidelity of pol ι was measured at RGYW hot- and non-hot-spot sequences situated at nicks, gaps, and double-strand breaks. Pol ι formed T⋅G mispairs at a frequency of 10−2, consistent with SHM-generated C to T transitions, with a 3-fold increased error rate in hot- vs. non-hot-spot sequences for the single-nucleotide overhang. The T cell and IgM crosslinking-dependent induction of pol ι at 12 h may indicate an SHM “triggering” event has occurred. However, pols ι, η, and ζ are present under all conditions, suggesting that their presence is not sufficient to generate mutations because both T cell and IgM stimuli are required for SHM induction.

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Escherichia coli possesses three SOS-inducible DNA polymerases (Pol II, IV, and V) that were recently found to participate in translesion synthesis and mutagenesis. Involvement of these polymerases appears to depend on the nature of the lesion and its local sequence context, as illustrated by the bypass of a single N-2-acetylaminofluorene adduct within the NarI mutation hot spot. Indeed, error-free bypass requires Pol V (umuDC), whereas mutagenic (−2 frameshift) bypass depends on Pol II (polB). In this paper, we show that purified DNA Pol II is able in vitro to generate the −2 frameshift bypass product observed in vivo at the NarI sites. Although the ΔpolB strain is completely defective in this mutation pathway, introduction of the polB gene on a low copy number plasmid restores the −2 frameshift pathway. In fact, modification of the relative copy number of polB versus umuDC genes results in a corresponding modification in the use of the frameshift versus error-free translesion pathways, suggesting a direct competition between Pol II and V for the bypass of the same lesion. Whether such a polymerase competition model for translesion synthesis will prove to be generally applicable remains to be confirmed.

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Previously, we reported that a 61-bp subgenomic HBV DNA sequence (designated as 15AB, nt 1855-1915) is a hot spot for genomic recombination and that a cellular protein binding to 15AB may be the putative recombinogenic protein. In the present study, we established the existence of a 15AB-like sequence in human and rat chromosomal DNA by Southern blot analysis. The 15AB-like sequence isolated from the rat chromosome demonstrated a 80.9% identity with 5'-CCAAGCTGTGCCTTGGGTGGC-3', at 1872-1892 of the hepatitis B virus genome, thought to be the essential region for recombination. Interestingly, this 15AB-like sequence also contained the pentanucleotide motifs GCTGG and CCAGC as an inverted repeat, part of the chi known hot spot for recombination in Escherichia coli. Importantly, a portion of the 15AB-like sequence is homologous (82.1%, 23/28 bp) to break point clusters of the human promyelocytic leukemia (PML) gene, characterized by a translocation [t(15;17)], and to rearranged mouse DNA for the immunoglobulin kappa light chain. Moreover, 15AB and 15AB-like sequences have striking homologies (12/15 = 80.0% and 13/15 = 86.7%, respectively) to the consensus sequence for topoisomerase II. Our present results suggest that this 15AB-like sequence in the rat genome might be a recombinogenic candidate triggering genomic instability in carcinogenesis.

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We report on the long-term X-ray monitoring of the outburst decay of the low magnetic field magnetar SGR 0418+5729 using all the available X-ray data obtained with RXTE, Swift, Chandra, and XMM-Newton observations from the discovery of the source in 2009 June up to 2012 August. The timing analysis allowed us to obtain the first measurement of the period derivative of SGR 0418+5729: ˙ P = 4(1) × 10−15 s s−1, significant at a ∼3.5σ confidence level. This leads to a surface dipolar magnetic field of Bdip 6 × 1012 G. This measurement confirms SGR 0418+5729 as the lowest magnetic field magnetar. Following the flux and spectral evolution from the beginning of the outburst up to ∼1200 days, we observe a gradual cooling of the tiny hot spot responsible for the X-ray emission, from a temperature of ∼0.9 to 0.3 keV. Simultaneously, the X-ray flux decreased by about three orders of magnitude: from about 1.4 × 10−11 to 1.2 × 10−14 erg s−1 cm−2. Deep radio, millimeter, optical, and gamma-ray observations did not detect the source counterpart, implying stringent limits on its multi-band emission, as well as constraints on the presence of a fossil disk. By modeling the magneto-thermal secular evolution of SGR 0418+5729, we infer a realistic age of ∼550 kyr, and a dipolar magnetic field at birth of ∼1014 G. The outburst characteristics suggest the presence of a thin twisted bundle with a small heated spot at its base. The bundle untwisted in the first few months following the outburst, while the hot spot decreases in temperature and size. We estimate the outburst rate of low magnetic field magnetars to be about one per year per galaxy, and we briefly discuss the consequences of such a result in several other astrophysical contexts.

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Fission track analysis was applied to the Precambrian suites of Madagascar in order to identify the lower-temperature cooling histories and their relationships to the Phanerozoic events that affected the island. Apatite ages range from 431 to 68 Ma, and zircon ages range from 452 to 238 Ma. Thermochronologically, the island can be divided into a southern, central, and northern region each with a subdivision on an east-west basis. The southern region is sharply separated from the central region by strongly contrasting apparent apatite ages over the northwest-southeast striking Ranotsara Shear Zone (RSZ). The change in apparent ages over the RSZ is indicative of later reactivation along younger brittle faults. The central region has the oldest ages of the island and has a diffuse contact to the third region northward. Along the entire western margin of the Precambrian basement initial Paleozoic exhumation was followed by heating (burial by sediments) during Jurassic and Cretaceous times. A decrease in ages along the eastern margin from 119 to 68 Ma coincides with the predicted positions of the Marion hot spot after effects of erosion are considered. On the other hand, these ages may represent progressive opening of the margin in a southward direction together with associated denudation of the rift shoulder. The eastern part of the central region has remained very stable since at least Devonian times, undergoing only long-term very slow exhumation at rates of 1–5 m/Myr.

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We have analyzed the Nd isotopic composition of both ancient seawater and detrital material from long sequences of carbonated oozes of the South Indian Ocean which are ODP Site 756 (Ninety East Ridge (-30°S), 1518 m water depth) and ODP Site 762 (Northwest Australian margin, 1360 m water depth). The measurements indicate that the epsilon-Nd changes in Indian seawater over the last 35 Ma result from changes in the oceanic circulation, large volcanic and continental weathering Nd inputs. This highlights the diverse nature of those controls and their interconnections in a small area of the ocean. These new records combined with those previously obtained at the equatorial ODP Sites 757 and 707 in the Indian Ocean (Gourlan et al., 2008, doi:10.1016/j.epsl.2007.11.054) established that the distribution of intermediate seawater epsilon-Nd was uniform over most of the Indian Ocean from 35 Ma to 10 Ma within a geographical area extending from 40°S to the equator and from -60°E to 120°E. However, the epsilon-Nd value of Indian Ocean seawater which kept an almost constant value (at about -7 to -8) from 35 to 15 Ma rose by 3 epsilon-Nd units from 15 to 10 Ma. This sharp increase has been caused by a radiogenic Nd enrichment of the water mass originating from the Pacific flowing through the Indonesian Passage. Using a two end-members model we calculated that the Nd transported to the Indian Ocean through the Indonesian Pathway was 1.7 times larger at 10 Ma than at 15 Ma. The Nd isotopic composition of ancient seawater and that of the sediment detrital component appear to be strongly correlated for some specific events. A first evidence occurs between 20 and 15 Ma with two positive spikes recorded in both epsilon-Nd signals that are clearly induced by a volcanic crisis of, most likely, the St. Paul hot-spot. A second evidence is the very large epsilon-Nd decrease recorded at ODP Sites 756 and 762 during the past 10 Ma which has never been previously observed. The synchronism between the epsilon-Nd decrease in seawater from 10 to 5 Ma and evidences of desertification in the western part of the nearly Australian continent suggests enhanced weathering inputs in this ocean from this continent as a result of climatic changes.

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The Southern Ocean (SO) plays a key role in modulating atmospheric CO2 via physical and biological processes. However, over much of the SO, biological activity is iron-limited. New in situ data from the Antarctic zone south of Africa in a region centered at -20°E - 25°E reveal a previously overlooked region of high primary production, comparable in size to the northwest African upwelling region. Here, sea ice together with enclosed icebergs is channeled by prevailing winds to the eastern boundary of the Weddell Gyre, where a sharp transition to warmer waters causes melting. This cumulative melting provides a steady source of iron, fuelling an intense phytoplankton bloom that is not fully captured by monthly satellite production estimates. These findings imply that future changes in sea-ice cover and dynamics could have a significant effect on carbon sequestration in the SO.