Modeling the clonal heterogeneity of stem cells

Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells, the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties, reflecting proliferation, apoptosis, and clonal competition. We first present closed-form expressions for the basic model which defines clonal dynamics in the presence of exogenous global disturbances. We then extend the model to include disturbances which are periodic and which may affect clones differently. Within the model framework, we propose a method to devise an optimal strategy of treatments to regulate expansion, contraction, or mutual maintenance of cells with specific properties

Selective contacts drive charge extraction in quantum dot solids via asymmetry in carrier transfer kinetics

[EN] Colloidal quantum dot solar cells achieve spectrally selective optical absorption in a thin layer of solution-processed, size-effect tuned, nanoparticles. The best devices built to date have relied heavily on drift-based transport due to the action of an electric field in a depletion region that extends throughout the thickness of the quantum dot layer. Here we study for the first time the behaviour of the best-performing class of colloidal quantum dot films in the absence of an electric field, by screening using an electrolyte. We find that the action of selective contacts on photovoltage sign and amplitude can be retained, implying that the contacts operate by kinetic preferences of charge transfer for either electrons or holes. We develop a theoretical model to explain these experimental findings. The work is the first to present a switch in the photovoltage in colloidal quantum dot solar cells by purposefully formed selective contacts, opening the way to new strategies in the engineering of colloidal quantum dot solar cells.We thank the following agencies for support of this research: Ministerio de Educacion y Ciencia under project HOPE CSD2007-00007, Generalitat Valenciana (ISIC/2012/008) and Universitat Jaume I project 12I361.01/1. EHS and KWK acknowledge the Award KUS-11-009-21, made by King Abdullah University of Science and Technology (KAUST) and the International Cooperation of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) grant funded by the Korea government Ministry of Knowledge Economy (2012T100100740).Mora-Sero, I.; Bertoluzzi, L.; González-Pedro, V.; Gimenez, S.; Fabregat-Santiago, F.; Kemp, KW.; Sargent, EH.... (2013). Selective contacts drive charge extraction in quantum dot solids via asymmetry in carrier transfer kinetics. 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Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Recent scientific debate has focused on the potential for inhaled formaldehyde to cause lymphohematopoietic cancers, particularly leukemias, in humans. The concern stems from certain epidemiology studies reporting an association, although particulars of endpoints and dosimetry are inconsistent across studies and several other studies show no such effects. Animal studies generally report neither hematotoxicity nor leukemia associated with formaldehyde inhalation, and hematotoxicity studies in humans are inconsistent. Formaldehyde's reactivity has been thought to preclude systemic exposure following inhalation, and its apparent inability to reach and affect the target tissues attacked by known leukemogens has, heretofore, led to skepticism regarding its potential to cause human lymphohematopoietic cancers. Recently, however, potential modes of action for formaldehyde leukemogenesis have been hypothesized, and it has been suggested that formaldehyde be identified as a known human leukemogen. In this article, we apply our hypothesis-based weight-of-evidence (HBWoE) approach to evaluate the large body of evidence regarding formaldehyde and leukemogenesis, attending to how human, animal, and mode-of-action results inform one another. We trace the logic of inference within and across all studies, and articulate how one could account for the suite of available observations under the various proposed hypotheses. Upon comparison of alternative proposals regarding what causal processes may have led to the array of observations as we see them, we conclude that the case fora causal association is weak and strains biological plausibility. Instead, apparent association between formaldehyde inhalation and leukemia in some human studies is better interpreted as due to chance or confounding

Single input fuzzy logic controller for unmanned underwater vehicle

This paper describes a control scheme that provides an efficient way to design a Fuzzy Logic Controller (FLC) for the unmanned underwater vehicle (UUV). The proposed method, known as the Single Input Fuzzy Logic Controller (SIFLC), reduces the conventional two-input FLC (CFLC) to a single input single output (SISO) controller. The SIFLC offers significant reduction in rule inferences and simplify the tuning of control parameters. Practically it can be easily implemented by a look-up table using a low cost microprocessor due its piecewise linear control surface. To verify its effectiveness, the control algorithm is simulated using the Marine Systems Simulator (MSS) on the Matlab/Simulink® platform. The result indicates that both the SIFLC and CFLC give identical response to the same input sets. However SIFLC requires very minimum tuning effort and its execution time is in the orders of two magnitudes less than CFLC