Structure of rarefied PbGeO3 glass: a molecular dynamics study

The present contribution is dedicated to a molecular dynamics (MD) study of the structure of rarefied lead-germanate glasses of composition PbGeO3. The simulations have been performed in the constant volume regime for systems with densities of 3000, 4000, 5000 and 6285 kg/m(3), using a two-body potential (Born-Mayer repulsive forces, and Coulomb forces due to full ionic charges). The information on short-range correlations was obtained in a conventional way (from radial and angular distribution functions), while the middle-range order was studied via cation-anion ring analysis. In the paper the short and medium range order in the rarefied glasses is discussed and compared with the structure of the PbGeO3 glass in normal conditions

Improved Approximation Algorithm for <em class="EmphasisTypeItalic">k</em>-level Uncapacitated Facility Location Problem (with Penalties)

We study the k-level uncapacitated facility location problem (k-level UFL) in which clients need to be connected with paths crossing open facilities of k types (levels). In this paper we first propose an approximation algorithm that for any constant k, in polynomial time, delivers solutions of cost at most αk times OPT, where αk is an increasing function of k, with limk→∞αk=3. Our algorithm rounds a fractional solution to an extended LP formulation of the problem. The rounding builds upon the technique of iteratively rounding fractional solutions on trees (Garg, Konjevod, and Ravi SODA’98) originally used for the group Steiner tree problem. We improve the approximation ratio for k-level UFL for all k ≥ 3, in particular we obtain the ratio equal 2.02, 2.14, and 2.24 for k = 3,4, and 5. Second, we give a simple interpretation of the randomization process (Li ICALP’2011) for 1-level UFL in terms of solving an auxiliary (factor revealing) LP. Armed with this simple view point, we exercise the randomization on our algorithm for the k-level UFL. We further improve the approximation ratio for all k ≥ 3, obtaining 1.97, 2.09, and 2.19 for k = 3,4, and 5. Third, we extend our algorithm to the k-level UFL with penalties (k-level UFLWP), in which the setting is the same as k-level UFL except that the planner has the option to pay a penalty instead of connecting chosen clients.Optimizatio

Short-range order in solid and liquid KBr probed by EXAFS

Br K-edge EXAFS spectra of solid and liquid KBr have been performed and analysed using advanced techniques for data analysis (GNXAS). Structural results on solid KBr at room temperature and near melting are compared with molecular dynamics (MD) simulations and diffraction data. The first-neighbour distribution is found to be strongly asymmetric even at room temperature, as also shown by MD simulations. This confirms the existence of important anharmonic effects in solid KBr. MD simulations are in agreement with EXAFS data at room temperature. For solid KBr near melting, anharmonic effects become very important. In comparison with MD calculations, the rise of the first-neighbour peak is found to be steeper, while the foot of the first-neighbour distribution is found to be slightly shifted toward longer distances. Experimental short-range partial pair distribution functions g(BrK) and g(BrBr) are derived in liquid KBr for the first time. The first peak of the g(BrK) distribution is accurately determined and found to be in good agreement with MD simulations, confirming a slight contraction of the most probable Br-K distance in the liquid phase. The first peak of the g(BrBr) distribution, measured with less accuracy, is found to be sharper and slightly shifted to longer distances, lowering the overlap with the first-neighbour K shell

EXAFS study of glasses of the CaO–Ga2O3–GeO2 system

X-ray absorption spectroscopy (XAS) measurements for Ca3Ga2Ge3O12 and Ca3Ga2Ge4O14 glasses are presented. In particular, the extended X-ray absorption fine structure (EXAFS) spectra are analysed and local neighbourhood of Ga and Ge atoms is described in detail. The Ge/Ga atoms neighbourhood in considered glasses is compared with the data available for corresponding crystals. Performed comparative crystal-glass structural analysis confirms correlation between crystalline and glassy structures of the Ca3Ga2Ge3O12 and Ca3Ga2Ge4O14 compounds. Our results provide several new detailed data, and some general suggestions on the CaO-Ga2O3-GeO2 glass structure

Ribosomal S6 Kinase and AKT Phosphorylation as Pharmacodynamic Biomarkers in Patients With Myelodysplastic Syndrome Treated With RAD001

Protein S6K1 (S6) is downstream of mammalian target of rapamycin (mTOR), whereas protein kinase B (AKT) is upstream of mTOR. Therefore, to evaluate the pharmacodynamic effects of the mTOR inhibitor RAD001 (everolimus) in patients with myelodysplastic syndrome, S6 and AKT phosphorylation (pS6, pAKT) were measured by peripheral blood flow cytometry. As expected, RAD001 treatment produced a decrease in pS6, whereas pAKT was maintained or increased. The pS6:pAKT ratio could be useful as a biomarker of RAD001 molecular pharmacodynamic effect. Myelodysplastic syndrome (MDS) continues to cause major morbidity and mortality; thus, novel treatments are needed. The mammalian target of rapamycin (mTOR) inhibitor RAD001 (everolimus) inhibits cellular pathways important to MYC protein stability and cell growth. Pharmacodynamic biomarkers could be useful in distinguishing between (1) disease resistance that occurs even though mTOR is successfully inhibited (suggesting a need for a different treatment strategy) and (2) resistance that might respond to changes in drug dosage or schedule. This was a small phase II trial of RAD001 in patients with low- and intermediate-1-risk MDS (n = 7). Protein S6K1 (S6) is downstream of mTOR, whereas protein kinase B (AKT) is upstream of mTOR. Therefore, to evaluate the pharmacodynamic effects of RAD001, S6 and AKT phosphorylation (pS6, pAKT) were measured by peripheral blood flow cytometry. Sequential weeks of RAD001 produced a decrease in pS6, whereas pAKT was maintained or increased. There were no clinical responses despite the biomarker evidence of intended pharmacodynamic effect. The pS6:pAKT ratio could be useful as a biomarker of target inhibition by RAD001 (clinicaltrials.gov identifier: NCT00809185)

Synergistic Effect of Major Histocompatibility Complex Class I–Related Chain A and Human Leukocyte Antigen–DPB1 Mismatches in Association with Acute Graft-versus-Host Disease after Unrelated Donor Hematopoietic Stem Cell Transplantation

AbstractThe clinical relevance of mismatches at the MHC class I–related chain A (MICA) in hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated the association of MICA donor/recipient mismatch and whether there is an interaction between these and HLA-DPB1 mismatch on clinical outcomes after unrelated donor HSCT. Our study included 227 patients who underwent unrelated donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177 (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed using commercially available kits. In univariable analysis, the risk of grade II to IV acute graft-versus-host disease (GVHD) was greater for patients with MICA mismatch (hazard ratio [HR], 1.73; P = .02) than for those with HLA-DPB1 mismatch (HR, 1.62; P = .07). When MICA and HLA-DPB1 were assessed simultaneously, patients mismatched at both loci had the greatest risk (HR, 2.51; P < .01) and those mismatched at only 1 locus had somewhat greater risk (HR, 1.53; P = .12) than patients matched at both loci; this remained significant in multivariable analysis. The 100-day incidence was 66%, 45%, and 31%, respectively (P = .03). Results were similar for grade III and IV acute GVHD, with 100-day incidence 34%, 16%, and 8% (P = .01). These results are clinically pertinent to donor selection strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are at increased risk for acute GVHD

Mutation clonal burden and allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia and myelodysplastic syndromes

Next generation sequencing (NGS) has become an important tool to inform disease risk for myeloid malignancies, however data remains conflicting regarding the significance of individual mutations. We performed targeted NGS on 112 patients with AML, and 80 with MDS, who underwent allogeneic hematopoietic cell transplantation. The most common mutations in AML were TET2 (14.7%), FLT3 (12.9%), DNMT3A (12.1%), and RUNX1 (7.8%). Complex cytogenetics (HR 2.82, P = .017) and disease status (33% were associated with poor RFS (HR 3.57, P = .017; and HR 6.57, P = .003; respectively). Molecular profiling is increasingly important in the care of patients with AML and MDS. Further studies are needed to understand the molecular complexities, including the significance of clonal burden, to better inform care decisions