RESUMO
In this paper we present numerical and experimental results revealing that the mode instability threshold of highly Yb-doped, Ce/Al co-doped pedestal fibers is affected by the size of the index-increased pedestal structure surrounding the core. An alternative preparation technology for the realization of large mode area fibers with very large Al-doped silica pedestals is introduced. Three different pedestal fiber design iterations characterized by low photodarkening were manufactured and tested in counter-pumped amplifier setups. Up to 1.9â kW continuous-wave output power of near-diffraction-limited beam quality (M2 = 1.26) was achieved with an 18/200/420 µm fiber of very low NA = 0.042, limited only by the occurrence of mode instabilities.
RESUMO
Clonally related composite lymphomas of Hodgkin's lymphoma (HL) and Non-Hodgkin's lymphoma (NHL) represent models to study the multistep transformation process in tumorigenesis and the development of two distinct tumors from a shared precursor. We analyzed six such lymphomas for transforming events. The HLs were combined in two cases with follicular lymphoma (FL), and in one case each with B-cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). In the HL/FL and HL/MCL combinations, BCL2/IGH and CCND1/IGH translocations, respectively, were detected in both the HL and NHL. No mutations were found in the tumor suppressor genes FAS, NFKBIA and ATM. The HL/DLBCL case harbored clonal replacement mutations of the TP53 gene on both alleles exclusively in the DLBCL. In conclusion, we present the first examples of molecularly verified IgH-associated translocations in HL, which also show that BCL2/IGH or CCND1/IGH translocations can represent early steps in the pathogenesis of composite HL/FL or HL/MCL. The restriction of the TP53 mutations to the DLBCL in the HL/DLBCL case exemplifies a late transforming event that presumably happened in the germinal center and affected the fate of a common lymphoma precursor cell towards development of a DLBCL.
Assuntos
Transformação Celular Neoplásica/genética , Genes Supressores de Tumor , Cadeias Pesadas de Imunoglobulinas/genética , Linfoma/patologia , Mutação , Translocação Genética , Transformação Celular Neoplásica/patologia , Células Clonais , Ciclina D1/genética , Genes bcl-2 , Doença de Hodgkin/patologia , Humanos , Linfoma/etiologia , Linfoma/genética , Linfoma não Hodgkin/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
In most cases, Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin disease (HD) carry rearranged immunoglobulin (Ig) genes and thus derive from B cells. In rare cases, HRS cells originate from T cells. However, based on the unusual immunophenotype of HRS cells, often showing coexpression of markers typical for different hematopoietic lineages, and the regular detection of numerical chromosomal abnormalities, it has been speculated that HRS cells might represent cell fusions. Five cases of HD with 2 rearranged IgH alleles were analyzed for the presence of additional IgH alleles in germline configuration as a potential footprint of a cell fusion between a B and a non-B cell. Similarly, one case of T-cell-derived HD with biallelic T-cell receptor beta (TCRbeta) rearrangements was studied for the presence of unrearranged TCRbeta alleles. In none of the 6 cases was evidence for additional IgH (or TCRbeta) alleles obtained, strongly arguing against a role of cell fusion in HRS cell generation.