Microstructural evolution in coated conventionally cast Ni-based superalloys

The aim of this research project was to investigate the microstructural changes of MCrAlY coated Ni-based superalloys that are routinely used in industrial gas turbine engines for power generation. One of the main aims of the characterisation was to understand ageing time and temperature effects on the microstructural evolution so that a methodology could be developed where the characterisation of a thermally exposed microstructure can be used to estimate unknown service exposure conditions. [Continues.

data.txt

<div>Declaration of effects and linear model for time event of maj infection</div><div> FLOCK !A</div><div> ID !P</div><div> BIRTH </div><div> OP !I</div><div> LS !m-999</div><div> TIMEEVENT !m-999</div><div> TEST !A</div><div> YEAR !I</div><div> SEASON !I</div><div> FYS !A</div><div> MY !m-999</div><div> FAT !m-999</div><div> PRT !m-999</div><div> CAS !m-999</div><div> LCT !m-999</div><div> SCC !m-999</div><div> SCCS !m-999</div><div> CORLT !m-999</div><div> ESCCL !m-999</div><div> PASCL !m-999</div><div> PSELT !m-999</div><div> STACL !m-999</div><div> STHAU !m-999</div><div> STRCL !m-999</div><div> STPDG !m-999</div><div> STPUB !m-999</div><div> STPAG !m-999</div><div> BACIL !m-999</div><div> MAJINF !m-999</div><div> MININF !m-999</div><div> ALL !m-999</div><div> SCS !m-999</div><div><br></div><div>ped.txt !ALPHA !MAKE !REPEAT</div><div>fulldata_SCS.txt !NODISPLAY !MVINCLUDE !MAXIT 10000 !ASUV</div><div>STACL ALL ~ Trait.MY Trait.SCS !r Trait.FYS  Trait.ide(ID)  Trait.ID </div><div>1 2 3   # El último 3 indica que hay que especificar 3 matrices (FYS,ide(ID) y ID)</div><div>0</div><div>Trait 0 US !GFUF</div><div>1 </div><div>0     1    </div><div><br></div><div>Trait.FYS </div><div>2 0 US !GPUP</div><div>0.17</div><div>0.01    1.85</div><div>FYS 0 ID</div><div><br></div><div>Trait.ide(ID) 2 </div><div>2 0 US !GPUP</div><div>0.35</div><div>0.01   0.21</div><div>ide(ID)</div><div><br></div><div>Trait.ID 2</div><div>Trait 0 US !GPUP</div><div>0.03</div><div>1  0.09</div><div>ID</div

pedigree.txt

Pedigree used for data.tx

The ‘Monosomic’ pattern of karyotype evolution followed by most breast tumors, with endoreduplication.

<p><b>A) and B)</b> In the monosomic pattern of evolution <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Muleris1" target="_blank">[16]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Dutrillaux1" target="_blank">[17]</a>, each unbalanced translocation reduces the chromosome number by one, and leaves regions of loss of heterozygosity (LOH). <b>C)</b> Often, at some point, endoreduplication occurs, i.e. the whole chromosome complement doubles, to give a duplicated translocation and pairs of chromosome segments showing regions of loss of heterozygosity (dashed boxes). The process may then continue with more unbalanced translocations.</p

The structure of the HCC1187 genome.

<p><b>A)</b> Spectral karyotype as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Davidson1" target="_blank">[44]</a>. Chromosomes are named A-Z and a-k based on their relative sizes as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Howarth1" target="_blank">[12]</a>. Cytogenetic description of the karyotype is in Table S1 in File S2. <b>B)</b> Circos plot <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Krzywinski1" target="_blank">[45]</a> of the HCC1187 genome: Chromosome ideograms around the outside, oriented clockwise pter to qter. Moving inward, the pale grey and dark grey boxes are chromosome segments observed by array painting <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Howarth1" target="_blank">[12]</a> with their chromosome of origin indicated. Their parent of origin (light grey and dark grey) was deduced from the number of allelotypes given by PICNIC segmentation (Fig. S1 in File S1). Note that assignment of parents 1 and 2 does not transfer between chromosomes. Dark blue line, total copy number, equivalent to array CGH, from PICNIC. Red line, copy number of the minor allele; where this is zero, the genome is homozygous. Chromosome segments that share a translocation breakpoint were assumed to have the same parental origin. Inner links represent interchromosome translocations identified previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Howarth1" target="_blank">[12]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Stephens2" target="_blank">[14]</a>.</p

Summary of Mutations in HCC1187 and their timing.

a<p>Few synonymous mutations are known since they were not reported in the main survey of point mutations <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Wood1" target="_blank">[3]</a>.</p>b<p>In-frame and out-of-frame expressed fusion transcripts.</p

Point mutations on chromosome 6, and whether they occurred before or after endoreduplication.

<p><b>A)</b> Deducing the parental origin of chromosome 6 segments: the simplest explanation for the allele combinations (blue and red lines on the aCGH plot) in terms of parental origin. Both copies of chromosome 6 I (chromosome 6 fragments are designated 6 I, 6A, 6D as in ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064991#pone.0064991-Howarth1" target="_blank">[12]</a>) originate from parent 1 and the chromosome 6 segments of 6A and 6D originate from parent 2. Several small copy number steps are omitted for clarity. <b>B)</b> Sequence traces show whether mutations are on each isolated chromosome. <i>HSD17B8</i>: Chromosome 6I (2 copies) homozygous G>T mutation (black arrow); chromosome 6A and 6D, no mutation. <i>NCB5OR</i>: Chromosome 6, heterozygous mutant (black arrow). <b>C)</b> The likely evolution of the segments of chromosome 6: unbalanced translocation of one copy of chromosome 6 was followed by duplication of both chromosomes during endoreduplication. <i>HSD17B8</i> was mutated on each copy of chromosome 6I, but not on 6A or 6D, while <i>NCB5OR/CYB5R4</i> was mutated on only one copy of chromosome 6I. The pre-endoreduplication state was likely to be one normal copy of chromosome 6 with the other having a mutation in <i>HSD17B8</i> and having suffered unbalanced translocation. The <i>NCB5OR/CYB5R4</i> mutation occurred after endoreduplication.</p

Chromosome segments in HCC1187 and their most probable state before endoreduplication.

<p>Chromosome ideograms are drawn around the outside as in Fig. 2. Outer rings are array painting segments as in Fig. 2. Inner rings are chromosome segments that must have been present before endoreduplication. Coloured circles are different types of mutations, on the outer chromosome segment on which they were observed: truncating (red), non-synonymous (blue), small deletion (yellow), small duplication (black), expressed gene fusion (light blue). Mutations that were on two copies of a chromosome segment probably occurred before endoreduplication and are also shown on the inner, pre-endoreduplication genome. Dashed grey boxes on chromosome 1 and 11 indicate regions where parental origin was undetermined, because PICNIC segmentation suggested additional rearrangements had taken place.</p

Alternate Title: For the Girls

First Line: Now little Willie Newton knew his countryFirst Line of Chorus: He's doing his bit for the girlsTitle of Larger Work: Tempest and SunshineKey: B Flat Majo

Large Inverted Duplications in the Human Genome Form via a Fold-Back Mechanism

<div><p>Inverted duplications are a common type of copy number variation (CNV) in germline and somatic genomes. Large duplications that include many genes can lead to both neurodevelopmental phenotypes in children and gene amplifications in tumors. There are several models for inverted duplication formation, most of which include a dicentric chromosome intermediate followed by breakage-fusion-bridge (BFB) cycles, but the mechanisms that give rise to the inverted dicentric chromosome in most inverted duplications remain unknown. Here we have combined high-resolution array CGH, custom sequence capture, next-generation sequencing, and long-range PCR to analyze the breakpoints of 50 nonrecurrent inverted duplications in patients with intellectual disability, autism, and congenital anomalies. For half of the rearrangements in our study, we sequenced at least one breakpoint junction. Sequence analysis of breakpoint junctions reveals a normal-copy disomic spacer between inverted and non-inverted copies of the duplication. Further, short inverted sequences are present at the boundary of the disomic spacer and the inverted duplication. These data support a mechanism of inverted duplication formation whereby a chromosome with a double-strand break intrastrand pairs with itself to form a “fold-back” intermediate that, after DNA replication, produces a dicentric inverted chromosome with a disomic spacer corresponding to the site of the fold-back loop. This process can lead to inverted duplications adjacent to terminal deletions, inverted duplications juxtaposed to translocations, and inverted duplication ring chromosomes.</p></div