557 research outputs found

    Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL

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    We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n = 210) of our previous study. At the first 5 follow-up time points, the frequency of MRD-positive patients and the MRD levels were higher in T-ALL than in precursor-B-ALL, reflecting the more frequent occurrence of resistant disease in T-ALL. Subsequently, patients were classified according to their MRD level at time point 1 (TP1), taken at the end of induction treatment (5 weeks), and at TP2 just before the start of consolidation treatment (3 months). Patients were considered at low risk if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and TP2 were 10(-3) or higher; remaining patients were considered at intermediate risk. The relative distribution of patients with T-ALL (n = 43) over the MRD-based risk groups differed significantly from that of precursor B-ALL (n = 109). Twenty-three percent of patients with T-ALL and 46% of patients with precursor B-ALL were classified in the low-risk group (P =.01) and had a 5-year relapse-free survival (RFS) rate of 98% or greater. In contrast, 28% of patients with T-ALL were classified in the MRD-based high-risk group compared to only 11% of patients with precursor B-ALL (P =.02), and the RFS rates were 0% and 25%, respectively (P =.03). Not only was the distribution of patients with T-ALL different over the MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2 was higher in T-ALL (larger RFS gradient), and consistently higher RFS rates were found for MRD-negative T-ALL patients at the first 5 follow-up time points

    Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

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    © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe

    Theory of the c-Axis Penetration Depth in the Cuprates

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    Recent measurements of the London penetration depth tensor in the cuprates find a weak temperature dependence along the c-direction which is seemingly inconsistent with evidence for d-wave pairing deduced from in-plane measurements. We demonstrate in this paper that these disparate results are not in contradiction, but can be explained within a theory based on incoherent quasiparticle hopping between the CuO2 layers. By relating the calculated temperature dependence of the penetration depth \lambda_c(T) to the c-axis resistivity, we show how the measured ratio \lambda_c^2(0) / \lambda_c^2(T) can provide insight into the behavior of c-axis transport below Tc and the related issue of ``confinement.''Comment: 4 pages, REVTEX with psfig, 3 PostScript figures included in compressed for

    Frequency Characteristics of Visually Induced Motion Sickness

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    This article was published in the journal, Human Factors [Sage Publications / © Human Factors and Ergonomics Society.]. The definitive version is available at: http://dx.doi.org/10.1177/0018720812469046Objective: The aim of this study was to explore the frequency response of visually induced motion sickness (VIMS) for oscillating linear motion in the foreand- aft axis. Background: Simulators, virtual environments, and commercially available video games that create an illusion of self-motion are often reported to induce the symptoms seen in response to true motion. Often this human response can be the limiting factor in the acceptability and usability of such systems. Whereas motion sickness in physically moving environments is known to peak at an oscillation frequency around 0.2 Hz, it has recently been suggested that VIMS peaks at around 0.06 Hz following the proposal that the summed response of the visual and vestibular selfmotion systems is maximized at this frequency. Methods: We exposed 24 participants to random dot optical flow patterns simulating oscillating foreand- aft motion within the frequency range of 0.025 to 1.6 Hz. Before and after each 20-min exposure, VIMS was assessed with the Simulator Sickness Questionnaire. Also, a standard motion sickness scale was used to rate symptoms at 1-min intervals during each trial. Results: VIMS peaked between 0.2 and 0.4 Hz with a reducing effect at lower and higher frequencies. Conclusion: The numerical prediction of the “crossover frequency” hypothesis, and the design guidance curve previously proposed, cannot be accepted when the symptoms are purely visually induced. Application: In conditions in which stationary observers are exposed to optical flow that simulates oscillating fore-and-aft motion, frequencies around 0.2 to 0.4 Hz should be avoided
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