853 research outputs found
Investigating prostate cancer tumour-stroma interactions - clinical and biological insights from an evolutionary game
BACKGROUND: Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironment, effect tumour progression and represent a largely under appreciated therapeutic target. We use observations of primary tumor biology from prostate cancer to extrapolate a mathematical model: specifically; it has been observed that in prostate cancer three disparate cellular outcomes predominate: (i) the tumour remains well differentiated and clinically indolent - in this case the local stromal cells may act to restrain the growth of the cancer; (ii) early in its genesis the tumour acquires a highly malignant phenotype, growing rapidly and displacing the original stromal population (often referred to as small cell prostate cancer) - these less common aggressive tumours are relatively independent of the local microenvironment; and, (iii) the tumour co-opts the local stroma - taking on a classic stromagenic phenotype where interactions with the local microenvironment are critical to the cancer growth. METHODS: We present an evolutionary game theoretical construct that models the influence of tumour-stroma interactions in driving these outcomes. We consider three characteristic and distinct cellular populations: stromal cells, tumour cells that are self-reliant in terms of microenvironmental factors and tumour cells that depend on the environment for resources but can also co-opt stroma. 
RESULTS: Using evolutionary game theory we explore a number of different scenarios that elucidate the impact of tumour-stromal interactions on the dynamics of prostate cancer growth and progression and how different treatments in the metastatic setting can affect different types of tumors.
CONCLUSIONS: The tumour microenvironment plays a crucial role selecting the traits of the tumour cells that will determine prostate cancer progression. Equally important, treatments like hormone therapy affect the selection of these cancer phenotypes making it very important to understand how they impact prostate cancer’s somatic evolution
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The Persistent Southern Disadvantage in Us Early Life Mortality, 1965‒2014
Background: Recent studies of US adult mortality demonstrate a growing disadvantage among southern states. Few studies have examined long-term trends and geographic patterns in US early life (ages 1 to 24) mortality, ages at which key risk factors and causes of death are quite different than among adults. Objective: This article examines trends and variations in early life mortality rates across US states and census divisions. We assess whether those variations have changed over a 50-year time period and which causes of death contribute to contemporary geographic disparities. Methods: We calculate all-cause and cause-specific death rates using death certificate data from the Multiple Cause of Death files, combining public-use files from 1965‒2004 and restricted data with state geographic identifiers from 2005‒2014. State population (denominator) data come from US decennial censuses or intercensal estimates. Results: Results demonstrate a persistent mortality disadvantage for young people (ages 1 to 24) living in southern states over the last 50 years, particularly those located in the East South Central and West South Central divisions. Motor vehicle accidents and homicide by firearm account for most of the contemporary southern disadvantage in US early life mortality. Contribution: Our results illustrate that US children and youth living in the southern United States have long suffered from higher levels of mortality than children and youth living in other parts of the country. Our findings also suggest the contemporary southern disadvantage in US early life mortality could potentially be reduced with state-level policies designed to prevent deaths involving motor vehicles and firearms
Multimodal Imaging of Photoreceptor Structure in Choroideremia
Purpose
Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions. Methods
Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques. Results
Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina. Conclusions
Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors
Infrared chemical imaging through nondegenerate two-photon absorption in silicon-based cameras
Chemical imaging based on mid-infrared (MIR) spectroscopic contrast is an
important technique with a myriad of applications, including biomedical imaging
and environmental monitoring. Current MIR cameras, however, lack in performance
and are much less affordable compared to mature Si-based devices, which operate
in the visible and near-infrared. Here we demonstrate fast MIR chemical imaging
through non-degenerate two-photon absorption (NTA) in a standard Si-based
charge-coupled device (CCD). We show that wide-field MIR images can be obtained
at 100 ms exposure times using picosecond pulse energies of only a few fJ per
pixel through NTA directly on the CCD chip. Because this on-chip approach does
not rely on phase-matching, it is alignment-free and does not necessitate
complex post-processing of the images. We emphasize the utility of this
technique through chemically selective MIR imaging of polymers and biological
samples, including MIR videos of moving targets, physical processes and live
nematodes
Energy and spectral enhancement of femtosecond supercontinuum in a noble gas using a weak seed
We experimentally demonstrate that the use of a weak seed pulse of energy less than 0.4% of the pump results in a spectral energy enhancement that spans over 2 octaves and a total energy enhancement of more than 3 times for supercontinua generated by millijoule level femtosecond pulses in Krypton gas. Strong four-wave mixing of the pump-seed pulse interacting in the gas is observed. The spectral irradiance generated from the seeding process is sufficiently high to use white-light continuum as an alternative to conventional tunable sources of radiation for applications such as nonlinear optical spectroscopy
Photon emission correlation spectroscopy as an analytical tool for quantum defects
Photon emission correlation spectroscopy has a long history in the study of
atoms, molecules, and, more recently, solid-state quantum defects. In
solid-state systems, its most common use is as an indicator of single-photon
emission, a key property for quantum technology. However, photon correlation
data can provide a wealth of information about quantum emitters beyond their
single-photon purityinformation that can reveal details about an
emitter's electronic structure and optical dynamics that are hidden by other
spectroscopy techniques. We present a standardized framework for using photon
emission correlation spectroscopy to study quantum emitters, including
discussion of theory, data acquisition, analysis, and interpretation. We
highlight nuances and best practices regarding the commonly-used
test for single-photon emission. Finally, we illustrate
how this experimental technique can be paired with optical dynamics simulations
to formulate an electronic model for unknown quantum emitters, enabling the
design of quantum control protocols and assessment of their suitability for
quantum information science applications.Comment: 20 pages, 7 figures. Updates in version 2 include an expanded section
VI and the addition of two figures and an appendi
High-speed 2D and 3D mid-IR imaging with an InGaAs camera
Recent work on mid-infrared (MIR) detection through the process of
non-degenerate two-photon absorption (NTA) in semiconducting materials has
shown that wide-field MIR imaging can be achieved with standard Si cameras.
While this approach enables MIR imaging at high pixel densities, the low
nonlinear absorption coefficient of Si prevents fast NTA-based imaging at lower
illumination doses. Here we overcome this limitation by using InGaAs as the
photosensor. Taking advantage of the much higher nonlinear absorption
coefficient of this direct bandgap semiconductor, we demonstrate high-speed MIR
imaging up to 500 fps with under 1 ms exposure per frame, enabling 2D or 3D
mapping without pre- or post-processing of the image.Comment: 7 pages, 5 Figure
Early Detection of Ovarian Cancer with Conventional and Contrast-Enhanced Transvaginal Sonography: Recent Advances and Potential Improvements
Recently, there have been several major technical advances in the sonographic diagnosis of ovarian cancer in its early stages. These include improved assessment of tumor morphology with transvaginal sonography (TVS), and detection and characterization of tumor neovascularity with transvaginal color Doppler sonography (TV-CDS) and contrast-enhanced transvaginal sonography (CE-TVS). This paper will discuss and illustrate these improvements and describe how they enhance detection of early-stage ovarian cancer. Our initial experience with parametric mapping of CE-TVS will also be mentioned
Retroviral Interferon- α Gene Transfer Potentiates Paclitaxel against Ovarian Cancer Cells
Objective: To analyze the cytotoxic effects of paclitaxel following introduction of the retroviral interferon- α (IFN- α) gene into epithelial ovarian cancer cells.Design: Experimental molecular study.Setting: University hospital research center. Sample: Epithelial ovarian cancer cell lines OV-2774 and SKOV3. Empty vector was used as control.Methods: The cytotoxic effects of paclitaxel on ovarian cancer cells were studied prior to and after transfection with the retrovirus-mediated inteferon- α gene. RT/PCR of the interferon gene, cell survival and cell death were analyzed to assess retroviral interferon- α gene expression after transfection.Results: Paclitaxel inhibited cell growth in a dose dependent manner with half maximal inhibitory concentration (IC50) of 7.5 ng/ml. Retroviral inteferon- α gene transfer-transduced cells potentiated paclitaxel response against both ovarian cancer cell lines by 68%.Conclusion: Retrovirus-mediated IFN- α gene transfer enhanced paclitaxel cytotoxicity on ovarian cancer cells. Retroviral IFN- α gene transfer in combination with paclitaxel may have significant clinical utility for the treatment of epithelial ovarian cancers
Chaotic systems in complex phase space
This paper examines numerically the complex classical trajectories of the
kicked rotor and the double pendulum. Both of these systems exhibit a
transition to chaos, and this feature is studied in complex phase space.
Additionally, it is shown that the short-time and long-time behaviors of these
two PT-symmetric dynamical models in complex phase space exhibit strong
qualitative similarities.Comment: 22 page, 16 figure
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