Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

Background: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. © 2011 Lamb et al.published_or_final_versio

Heat, Fluid, and Sample Control in Point-of-Care Diagnostics

Thesis (Ph.D.)--University of Washington, 2016-09Point-of-care diagnostics have transformed healthcare workflow, perhaps most notably in the wide-reaching impact of home pregnancy tests. Lateral flow strips are simple and inexpensive, but limited in their application to relatively simple diagnostic tasks. Nucleic acid amplification assays on the other hand are more accurate and sensitive, but currently restricted to use in well-equipped laboratories due to reliance on external supplies, power, and trained users. The Multiplexable Autonomous Disposables for Nucleic Acid Amplification Tests in Limited Resource Settings (MAD NAAT) Project, led by Paul Yager, uses instrument-free, disposable, paper-based fluidics for multiple pathogen detection with DNA/RNA. The end goal is to create a sample in, answer out isothermal nucleic acid amplification device simple enough for untrained users, with low enough cost to enable wider use of nucleic acid testing. My contributions to this project, combining to form my thesis, include advances in sample preparation for nucleic acid amplification, isothermal chemical temperature control, and fluid transport in paper microfluidics. Progress in these subject areas will help advance the development of nucleic acid tests and other advanced assays compatible with point-of-care usage

Patterns of Body Shape Diversity and Evolution in Intertidal and Subtidal Lineages of Combtooth Blennies (Blenniidae)

Abstract Marine intertidal zones can be harsher and more dynamic than bordering subtidal zones, with extreme and temporally variable turbulence, water velocity, salinity, temperature, and dissolved oxygen levels. Contrasting environmental conditions and ecological opportunities in subtidal versus intertidal habitats may generate differing patterns of morphological diversity. In this study we used phylogenetic comparative methods, measurements of body length, and two-dimensional landmarks to characterize body shape and size diversity in combtooth blennies (Ovalentaria: Blenniidae) and test for differences in morphological diversity between intertidal, subtidal, and supralittoral zones. We found that subtidal combtooth blennies have significantly higher body shape disparity and occupy a region of morphospace three times larger than intertidal lineages. The intertidal morphospace was almost entirely contained within the subtidal morphospace, showing that intertidal combtooth blennies did not evolve unique body shapes. We found no significant differences in body size disparity between tidal zones, no correlations between body shape and tidal zone or body size and tidal zone, and no body shape convergence associated with tidal zone. Our findings suggest that a subset of combtooth blenny body shapes are suitable for life in both subtidal and intertidal habitats. Many species in regions of morphospace unique to subtidal combtooth blennies exhibit distinct microhabitat use, which suggests subtidal environments promoted morphological diversification via evolutionary microhabitat transitions. In contrast, limited intertidal body shape diversity may be due to strong selective pressures that constrained body shape evolution and environmental filtering that prevented colonization of intertidal zones by certain subtidal body shapes.</jats:p

Electrical generator device including a fuel cell

[ES] La invención se refiere a una celda de combustible (1) en la que el canal de flujo de electrolito (24) está hecho de un material poroso, y a un dispositivo que incorpora dicha celda de combustible (1) y un aparato productor de hidrógeno (2) que suministra hidrógeno a La pila de combustible (1). En una realización preferida, el aparato productor de hidrógeno (2) está integrado con la celda de combustible (1) y está diseñado para generar hidrógeno que se dirige hacia la celda de combustible (1).[EN] The invention relates to a fuel cell (1) in which the electrolyte flow channel (24) is made from a porous material, and to a device incorporating said fuel cell (1) and a hydrogen-producing apparatus (2) that supplies hydrogen to the fuel cell (1). In a preferred embodiment, the hydrogen-producing apparatus (2) is integrated with the fuel cell (1) and is designed to generate hydrogen that is directed towards the fuel cell (1).Peer reviewedConsejo Superior de Investigaciones Científicas (España), University of Washington through its center for commercializationA1 Solicitud de patente con informe sobre el estado de la técnic

Electrical generator device including a fuel cell

La invención se refiere a una celda de combustible (1) en la que el canal de flujo de electrolito (24) está hecho de un material poroso, y a un dispositivo que incorpora dicha celda de combustible (1) y un aparato productor de hidrógeno (2) que suministra hidrógeno a La pila de combustible (1). En una realización preferida, el aparato productor de hidrógeno (2) está integrado con la celda de combustible (1) y está diseñado para generar hidrógeno que se dirige hacia la celda de combustible (1).Peer reviewedConsejo Superior de Investigaciones Científicas (España), University of Washington through its center for commercializationB1 Patente sin examen previ

Disposable platform for bacterial lysis and nucleic acid amplification based on a single USB-powered printed circuit board.

Recent advances in electronics and microfluidics have enabled several research groups to develop fully integrated, sample-to-result isothermal nucleic acid amplification test (NAAT) platforms for the point of care. However, high component counts and costs have limited translation of these platforms beyond the clinic to low-resource settings-including homes. Many NAATs include complex, multi-component heater electronics based on flex circuits or multiple printed circuit boards (PCBs) to support essential NAAT steps such as lysis, sample deactivation, and nucleic acid amplification. In contrast, current commercial assays for home use, such as those for pregnancy or ovulation that include electronics, typically have just one onboard PCB. This work describes a generalizable strategy to integrate all heaters and the electronics needed to control them onto a single low-cost, USB-powered PCB. We built a multiplexable disposable NAAT ("MD NAAT") platform that applies these principles, integrating small-area heaters that heat small regions to near-boiling (for pathogen lysis and deactivation) and large-area heaters (for amplification) on the same PCB. We show that both classes of heaters have high intra-board and inter-device reproducibility despite only heating a NAAT cartridge from below. We validated the small-area heaters by lysing methicillin-resistant Staphylococcus aureus (MRSA) cells and the large-area heaters by performing two types of isothermal NAATs (isothermal strand displacement amplification (iSDA) and loop-mediated isothermal amplification (LAMP)). These results demonstrate the merit of integrating NAAT heaters and control electronics onto a single printed circuit board and are a step toward translating NAATs to the home

Disposable platform for bacterial lysis and nucleic acid amplification based on a single USB-powered printed circuit board

Recent advances in electronics and microfluidics have enabled several research groups to develop fully integrated, sample-to-result isothermal nucleic acid amplification test (NAAT) platforms for the point of care. However, high component counts and costs have limited translation of these platforms beyond the clinic to low-resource settings—including homes. Many NAATs include complex, multi-component heater electronics based on flex circuits or multiple printed circuit boards (PCBs) to support essential NAAT steps such as lysis, sample deactivation, and nucleic acid amplification. In contrast, current commercial assays for home use, such as those for pregnancy or ovulation that include electronics, typically have just one onboard PCB. This work describes a generalizable strategy to integrate all heaters and the electronics needed to control them onto a single low-cost, USB-powered PCB. We built a multiplexable disposable NAAT (“MD NAAT”) platform that applies these principles, integrating small-area heaters that heat small regions to near-boiling (for pathogen lysis and deactivation) and large-area heaters (for amplification) on the same PCB. We show that both classes of heaters have high intra-board and inter-device reproducibility despite only heating a NAAT cartridge from below. We validated the small-area heaters by lysing methicillin-resistant Staphylococcus aureus (MRSA) cells and the large-area heaters by performing two types of isothermal NAATs (isothermal strand displacement amplification (iSDA) and loop-mediated isothermal amplification (LAMP)). These results demonstrate the merit of integrating NAAT heaters and control electronics onto a single printed circuit board and are a step toward translating NAATs to the home

Dispositivo generador eléctrico que incorpora una pila de combustible

[EN] The invention relates to a fuel cell (1) in which the electrolyte flow channel (24) is made from a porous material, and to a device incorporating said fuel cell (1) and a hydrogen-producing apparatus (2) that supplies hydrogen to the fuel cell (1). In a preferred embodiment, the hydrogen-producing apparatus (2) is integrated with the fuel cell (1) and is designed to generate hydrogen that is directed towards the fuel cell (1).[ES] La invención se refiere a una celda de combustible (1) en la que el canal de flujo de electrolito (24) está hecho de un material poroso, y a un dispositivo que incorpora dicha celda de combustible (1) y un aparato productor de hidrógeno (2) que suministra hidrógeno a La pila de combustible (1). En una realización preferida, el aparato productor de hidrógeno (2) está integrado con la celda de combustible (1) y está diseñado para generar hidrógeno que se dirige hacia la celda de combustible (1).Peer reviewedConsejo Superior de Investigaciones Científicas (España), University of Washington through its center for commercializationA1 Solicitud de patente con informe sobre el estado de la técnic