A novel three-colour fluorescence in situ hybridization approach for the detection of t(7;12)(q36;p13) in acute myeloid leukaemia reveals new cryptic three way translocation t(7;12;16)

© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting

Pressure and Motion of Dry Sand -- Translation of Hagen's Paper from 1852

In a remarkable paper from 1852, Gotthilf Heinrich Ludwig Hagen measured and explained two fundamental aspects of granular matter: The first effect is the saturation of pressure with depth in a static granular system confined by silo walls -- generally known as the Janssen effect. The second part of his paper describes the dynamics observed during the flow out of the container -- today often called the Beverloo law -- and forms the foundation of the hourglass theory. The following is a translation of the original German paper from 1852.Comment: 4 pages, accepted for publication in Granular Matter, original article (German) can be found under http://www.phy.duke.edu/~msperl/Janssen

t(9;11)(p21;q23) KMT2A/MLLT3

Review on t(9;11)(p21;q23), with data on clinics, and the genes involved

Validation of Non-residential Cold and Hot Water Demand Model Assumptions

AbstractExisting guidelines related to the water demand of non-residential buildings are outdated and do not cover hot water demand for the appropriate selection of hot water devices. Moreover, they generally overestimate peak demand values required for the design of an efficient and reliable water installation. Recently, a procedure was developed based on the end-use model SIMDEUM to derive design rules for peak demand values of both cold and hot water during various time steps for several types and sizes of non-residential buildings, i.e. offices, hotels and nursing homes. In this paper, the assumptions of building standardisation, on which the design rules are based, are validated. This was done with measurements of cold and hot water demands on a per second base and with surveys. The good correlation between the simulated water demand patterns and the measured patterns indicates that the basis of the design rules, the SIMDEUM simulated standardised buildings, is solid. Surveys were held to investigate whether the construction of the standardised buildings based on the dominant variable corresponds with practice. Surveys show that it is difficult to find relations to equip the standardised buildings with users and appliances. However, the validation proves that with a proper estimation of the number of users and appliances in only the dominant functional room of the standardised buildings, SIMDEUM renders a realistic cold and hot water diurnal demand pattern. Therefore, the new design rules based on these standardised buildings lead to reliable and improved designs of building installations and water heater capacity, resulting in more hygienic and economical installations

Mouse RAD54 affects DNA double-strand break repair and sister chromatid exchange

Cells can achieve error-free repair of DNA double-strand breaks (DSBs) by homologous recombination through gene conversion with or without crossover. In contrast, an alternative homology-dependent DSB repair pathway, single-strand annealing (SSA), results in deletions. In this study, we analyzed the effect of mRAD54, a gene involved in homologous recombination, on the repair of a site-specific I-SceI-induced DSB located in a repeated DNA sequence in the genome of mouse embryonic stem cells. We used six isogenic cell lines differing solely in the orientation of the repeats. The combination of the three recombination-test substrates used discriminated among SSA, intrachromatid gene conversion, and sister chromatid gene conversion. DSB repair was most efficient for the substrate that allowed recovery of SSA events. Gene conversion with crossover, indistinguishable from long tract gene conversion, preferentially involved the sister chromatid rather than the repeat on the same chromatid. Comparing DSB repair in mRAD54 wild-type and knockout cells revealed direct evidence for a role of mRAD54 in DSB repair. The substrate measuring SSA showed an increased efficiency of DSB repair in the absence of mRAD54. The substrate measuring sister chromatid gene conversion showed a decrease in gene conversion with and without crossover. Consistent with this observation, DNA damage-induced sister chromatid exchange was reduced in mRAD54-deficient cells. Our results suggest that mRAD54 promotes gene conversion with predominant use of the sister chromatid as the repair template at the expense of error-prone SSA

Validation of non-residential cold and hot water demand model assumptions

Existing guidelines related to the water demand of non-residential buildings are outdated and do not cover hot water demand for the appropriate selection of hot water devices. Moreover, they generally overestimate peak demand values required for the design of an efficient and reliable water installation. Recently, a procedure was developed based on the end-use model SIMDEUM to derive design rules for peak demand values of both cold and hot water during various time steps for several types and sizes of non-residential buildings, i.e. offices, hotels and nursing homes. In this paper, the assumptions of building standardisation, on which the design rules are based, are validated. This was done with measurements of cold and hot water demands on a per second base and with surveys. The good correlation between the simulated water demand patterns and the measured patterns indicates that the basis of the design rules, the SIMDEUM simulated standardised buildings, is solid. Surveys were held to investigate whether the construction of the standardised buildings based on the dominant variable corresponds with practice. Surveys show that it is difficult to find relations to equip the standardised buildings with users and appliances. However, the validation proves that with a proper estimation of the number of users and appliances in only the dominant functional room of the standardised buildings, SIMDEUM renders a realistic cold and hot water diurnal demand pattern. Therefore, the new design rules based on these standardised buildings lead to reliable and improved designs of building installations and water heater capacity, resulting in more hygienic and economical installations.</p