Analysis of the correlation between strength and fractal dimension of gravelly soil in debris-flow source areas

peer-reviewedParticle size distribution of gravelly soil plays a crucial role in debris flow initiation. For better understanding the mechanism of debris flow formation, two crucial mechanical property parameters of the gravelly soil are required to be studied meticulously: hydraulic conductivity and strength. With the aim of measuring the composition of the gravelly soil, 182 soil samples were taken from debris flow prone areas. With the aid of a sieve test, the particle size distribution of the samples can be obtained and analyzed. Then fractal theory was employed to compute the fractal dimension of the soil samples. By analyzing the results of sieve test (particle size distribution curves) and the results of the fractal theory calculations, the relationship between fractal dimension and particle size distribution can be explored. The results illustrate that the particle compositions of the gravelly soil tends to remain uniform as the fractal dimension increases. Moreover, as the coarse particle content increases, the fractal dimension decreases. To better understand the formation mechanism of debris flows, direct shear tests were conducted. Subsequently the experimental results were analyzed. By analysis, the following conclusions can be drawn: the soil strength decreases as the fractal dimension increases, and for soils with lower moisture content and identical dry density, a linear relationship between fractal dimension and cohesion force was identified. Moreover, cohesion force and internal friction force both decrease as the fractal dimension increases, but the internal friction angle decreases slightly while the cohesion force decreases greatly. Therefore we concluded that soil strength decreased mainly due to the reduction in cohesion force.PUBLISHEDpeer-reviewe

Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features

The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia

Structurally diverse metal coordination compounds, bearing imidodiphosphinate and diphosphinoamine ligands, as potential inhibitors of the platelet activating factor

Metal complexes bearing dichalcogenated imidodiphosphinate [ R2 P (E) NP (E) R2 ] - ligands (E = O, S, Se, Te), which act as (E,E) chelates, exhibit a remarkable variety of three-dimensional structures. A series of such complexes, namely, square-planar [ Cu (OPPh 2)(OPPh 2)N-O,O 2 ], tetrahedral [ Zn (EPPh 2)(EPPh 2)N-E,E 2 ], E = O, S, and octahedral [ Ga (OPPh2)(OPPh 2)N-O,O 3 ], were tested as potential inhibitors of either the platelet activating factor (PAF)- or thrombin-induced aggregation in both washed rabbit platelets and rabbit platelet rich plasma. For comparison, square-planar [ Ni (Ph2 P)2 N-S-CHMePh-P,P X2 ], X = Cl, Br, the corresponding metal salts of all complexes and the (OPPh2)(OPPh2)NH ligand were also investigated. Ga (O,O)3 showed the highest anti-PAF activity but did not inhibit the thrombin-related pathway, whereas Zn (S,S) 2, with also a significant PAF inhibitory effect, exhibited the highest thrombin-related inhibition. Zn (O,O)2 and Cu (O,O)2 inhibited moderately both PAF and thrombin, being more effective towards PAF. This work shows that the PAF-inhibitory action depends on the structure of the complexes studied, with the bulkier Ga (O,O)3 being the most efficient and selective inhibitor. Copyright © 2010 Alexandros B. Tsoupras et al

EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved

Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma

We recently reported a truncating deletion in the NFKBIE gene, which encodes IκB, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n 5 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%]). NFKBIE-deleted PMBL patients were more often therapy refractory (P 5 .022) and displayed inferior outcome compared with wild-Type patients (5-year survival, 59% vs 78%; P 5 .034); however, they appeared to benefit from radiotherapy (P 5 .022) and rituximab-containing regimens (P 5 .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P 5 .003) and when restricting the analysis to immunochemotherapy-Treated patients (P 5 .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL. © 2016 by The American Society of Hematology