110 research outputs found

    Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia

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    Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), that is, a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells. Little is known regarding the impact of such genotypes in untransplanted acute myeloid leukemia (AML). For this study, NK cell phenotypes and KIR/HLA genotypes were determined in 81 AML patients who received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention (NCT01347996). We observed that presence of unlicensed NK cells impacted favorably on clinical outcome, in particular among patients harboring functional NK cells reflected by high expression of the natural cytotoxicity receptor (NCR) NKp46. Genotype analyses suggested that the clinical benefit of high NCR expression was restricted to patients with a missing ligand genotype and/or a KIR B/x genotype. These data imply that functional NK cells are significant anti-leukemic effector cells in patients with KIR/HLA genotypes that favor NK cell autoreactivity

    Positioning algorithms for cooperative networks in the presence of an unknown turn-around time

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    This paper addresses the problem of single node positioning in cooperative network using hybrid two-way time-of-arrival and time-difference-of-arrival where, the turn-around time at the target node is unknown. Considering the turn-around time as a nuisance parameter, the derived maximum likelihood estimator (MLE) brings a difficult global optimization problem due to local minima in the cost function of the MLE. To avoid drawbacks in solving the MLE, we obtain a linear two-step estimator using non-linear pre-processing which is algebraic and closed-form in each step. To compare different methods, Cramér-Rao lower bound (CRLB) is derived. Simulation results confirm that the proposed linear estimator attains the CRLB for sufficiently high signal-to-noise ratios. © 2011 IEEE

    A distributed positioning algorithm for cooperative active and passive sensors

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    The problem of positioning a target node is studied for wireless sensor networks with cooperative active and passive sensors. Two-way time-of-arrival and time-difference-of-arrival measurements made by both active and passive nodes are used to estimate the position of the target node. A maximum likelihood estimator (MLE) can be employed to solve the problem. Due to the nonlinear nature of the cost function in the MLE, an iterative search might converge to local minima which often results in large estimation errors. To avoid this drawback, we instead formulate the problem of positioning as finding the intersection of a number of convex sets derived from measurements. To obtain this intersection, we apply the projection onto convex sets approach, which is robust and can be implemented in a distributed manner. Simulations are performed to compare the performance of the MLE and the proposed method. ©2010 IEEE

    Hybrid TW-TOA/TDOA positioning algorithms for cooperative wireless networks

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    The problem of positioning an unknown target is studied for a cooperative wireless sensor network using hybrid two-way time-of-arrival and time-difference-of-arrival measurements. A maximum likelihood estimator (MLE) can be employed to solve the problem. Due to the non-linear nature of the cost function in the MLE, a numerical method, e.g., an iterative search algorithm with a good initial point, should be taken to accurately estimate the target. To avoid drawbacks in a numerical method, we instead linearize the measurements and obtain a new two-step estimator that has a closed-form solution in each step. Simulation results confirm that the proposed linear estimator can attain Cramer-Rao lower bound for sufficiently high SNR. © 2011 IEEE

    A short regulatory domain restricts glycerol transport through yeast Fps1p

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    The controlled export of solutes is crucial for cellular adaptation to hypotonic conditions. In the yeast Saccharomyces cerevisiae glycerol export is mediated by Fpslp, a member of the major intrinsic protein (MIP) family ]of channel proteins. Here we describe a short regulatory domain that restricts glycerol transport through Fpslp. This domain is required for retention of cellular glycerol under hypertonic stress and hence acquisition of osmotolerance. It is located in the N-terminal cytoplasmic extension close to the first transmembrane domain. Several residues within that domain and its precise position are critical for channel control while the proximal residues 13-215 of the N-terminal extension are not required. The sequence of the regulatory domain and its position are perfectly conserved in orthologs from other yeast species. The regulatory domain has an amphiphilic character, and structural predictions indicate that it could fold back into the membrane bilayer. Remarkably, this domain has structural similarity to the channel forming loops B and E of Fpslp and other glycerol facilitators. Intragenic second-site suppressor mutations of the sensitivity to high osmolarity conferred by truncation of the regulatory domain caused diminished glycerol transport, confirming that elevated channel activity is the cause of the osmosensitive phenotype
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