Impaired bone marrow homing of cytokine-activated CD34⁺ cells in the NOD/SCID model

The reduced engraftment potential of hematopoietic stem/progenitor cells (HSPCs) after exposure to cytokines may be related to the impaired homing ability of actively cycling cells. We tested this hypothesis by quantifying the short-term horning of human adult CD34+ cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals. We show that the loss of engraftment ability of cytokine-activated CD34+ cells is associated with a reduction in homing of colony-forming cells (CFCs) to bone marrow (BM) at 24 hours after transplantation (from median 2.8% [range, 1.9%-6.1%] to 0.3% [0.0%-0.7%]; n = 3; P < .01), coincident with an increase in CFC accumulation in the lungs (P < .01). Impaired BM homing of cytokine-activated cells was not restored by using sorted cells in G 0G1 or by inducing cell cycle arrest at the G 1/S border. Blocking Fas ligation in vivo did not increase the BM homing of cultured cells. Finally, we tested cytokine combinations or culture conditions previously reported to restore the engraftment of cultured cells but did not find that any of these was able to reverse the changes in homing behavior of cytokine-exposed cells. We suggest that these changes in homing and, as a consequence, engraftment result from the increased migratory capacity of infused activated cells, leading to the loss of selectivity of the homing process. © 2004 by The American Society of Hematology

Estimating the furrow infiltration characteristic from a single advance point

Management and control of surface irrigation, in particular furrow irrigation, is limited by spatio-temporal soil infiltration variability as well as the high cost and time associated with collecting intensive field data for estimation of the infiltration characteristics. Recent work has proposed scaling the commonly used infiltration function by using a model infiltration curve and a single advance point for every other furrow in an irrigation event. Scaling factors were calculated for a series of furrows at two sites and at four points down the length of the field (0.25 L, 0.5 L, 0.75 L and L). Differences in the value of the scaling factor with distance were found to be a function of the shape of the advance curves. It is concluded that use of points early in the advance results in a substantial loss of accuracy and should be avoided. The scaling factor was also strongly correlated with the furrow-wetted perimeter suggesting that the scaling is an appropriate way of both predicting and accommodating the effect of the hydraulic variability

Global Guidance for Local Generalization in Model Checking

SMT-based model checkers, especially IC3-style ones, are currently the most effective techniques for verification of infinite state systems. They infer global inductive invariants via local reasoning about a single step of the transition relation of a system, while employing SMT-based procedures, such as interpolation, to mitigate the limitations of local reasoning and allow for better generalization. Unfortunately, these mitigations intertwine model checking with heuristics of the underlying SMT-solver, negatively affecting stability of model checking. In this paper, we propose to tackle the limitations of locality in a systematic manner. We introduce explicit global guidance into the local reasoning performed by IC3-style algorithms. To this end, we extend the SMT-IC3 paradigm with three novel rules, designed to mitigate fundamental sources of failure that stem from locality. We instantiate these rules for the theory of Linear Integer Arithmetic and implement them on top of SPACER solver in Z3. Our empirical results show that GSPACER, SPACER extended with global guidance, is significantly more effective than both SPACER and sole global reasoning, and, furthermore, is insensitive to interpolation.Comment: Published in CAV 202

Global Guidance for Local Generalization in Model Checking

SMT-based model checkers, especially IC3-style ones, are currently the most effective techniques for verification of infinite state systems. They infer global inductive invariants via local reasoning about a single step of the transition relation of a system, while employing SMT-based procedures, such as interpolation, to mitigate the limitations of local reasoning and allow for better generalization. Unfortunately, these mitigations intertwine model checking with heuristics of the underlying SMT-solver, negatively affecting stability of model checking. In this paper, we propose to tackle the limitations of locality in a systematic manner. We introduce explicit global guidance into the local reasoning performed by IC3-style algorithms. To this end, we extend the SMT-IC3 paradigm with three novel rules, designed to mitigate fundamental sources of failure that stem from locality. We instantiate these rules for the theory of Linear Integer Arithmetic and implement them on top of Spacer solver in Z3. Our empirical results show that GSpacer, Spacer extended with global guidance, is significantly more effective than both Spacer and sole global reasoning, and, furthermore, is insensitive to interpolation

SimpleCAR: An Efficient Bug-Finding Tool Based on Approximate Reachability

We present a new safety hardware model checker SimpleCAR that serves as a reference implementation for evaluating Complementary Approximate Reachability (CAR), a new SAT-based model checking framework inspired by classical reachability analysis. The tool gives a “bottom-line” performance measure for comparing future extensions to the framework. We demonstrate the performance of SimpleCAR on challenging benchmarks from the Hardware Model Checking Competition. Our experiments indicate that SimpleCAR is particularly suited for unsafety checking, or bug-finding; it is able to solve 7 unsafe instances within 1 h that are not solvable by any other state-of-the-art techniques, including BMC and IC3/PDR, within 8 h. We also identify a bug (reports safe instead of unsafe) and 48 counterexample generation errors in the tools compared in our analysis

A Survey of Satisfiability Modulo Theory

Satisfiability modulo theory (SMT) consists in testing the satisfiability of first-order formulas over linear integer or real arithmetic, or other theories. In this survey, we explain the combination of propositional satisfiability and decision procedures for conjunctions known as DPLL(T), and the alternative "natural domain" approaches. We also cover quantifiers, Craig interpolants, polynomial arithmetic, and how SMT solvers are used in automated software analysis.Comment: Computer Algebra in Scientific Computing, Sep 2016, Bucharest, Romania. 201

MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up

Intersection and Rotation of Assumption Literals Boosts Bug-Finding

SAT-based techniques comprise the state-of-the-art in functional verification of safety-critical hardware and software, including IC3/PDR-based model checking and Bounded Model Checking (BMC). BMC is the incontrovertible best method for unsafety checking, aka bug-finding. Complementary Approximate Reachability (CAR) and IC3/PDR complement BMC for bug-finding by detecting different sets of bugs. To boost the efficiency of formal verification, we introduce heuristics involving intersection and rotation of the assumption literals used in the SAT encodings of these techniques. The heuristics generate smaller unsat cores and diverse satisfying assignments that help in faster convergence of these techniques, and have negligible runtime overhead. We detail these heuristics, incorporate them in CAR, and perform an extensive experimental evaluation of their performance, showing a 25% boost in bug-finding efficiency of CAR.We contribute a detailed analysis of the effectiveness of these heuristics: their influence on SAT-based bug-finding enables detection of different bugs from BMCbased checking. We find the new heuristics are applicable to IC3/PDR-based algorithms as well, and contribute a modified clause generalization procedure

A re-appraisal of the reliability of the 20 m multi-stage shuttle run test

This is the author's PDF version of an article published in European journal of applied physiology in 2007. The original publication is available at www.springerlink.co

The effects of childbirth on the pelvic-floor

Basically, vaginal delivery is associated with the risk of pelvic floor damage. The pelvic floor sequelae of childbirth includes anal incontinence, urinary incontinence and pelvic organ prolapse. Pathophysiology, incidence and risk factors for the development of the respective problems are reviewed. Where possible, recommendations for reducing the risk of pelvic floor damage are given