119 research outputs found

    Visible Discrimination of Broadband Infrared Light by Dye-Enhanced Upconversion in Lanthanide-Doped Nanocrystals

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    Optical upconversion of near infrared light to visible light is an attractive way to capture the optical energy or optical information contained in low-energy photons that is otherwise lost to the human eye or to certain photodetectors and solar cells. Until the recent application of broadband absorbing optical antennas, upconversion efficiency in lanthanide-doped nanocrystals was limited by the weak, narrow atomic absorption of a handful of sensitizer elements. In this work, we extend the role of the optical antenna to provide false-color, visible discrimination between bands of infrared radiation. By pairing different optical antenna dyes to specific nanoparticle compositions, unique visible emission is associated with different bands of infrared excitation. In one material set, the peak emission was increased 10-fold, and the width of the spectral response was increased more than 10-fold

    Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

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    BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis

    Design of Experiments for Screening

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    The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

    Deletion of chromosome 4q predicts outcome in Stage II colon cancer patients

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    Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters to identify high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not yet been investigated for this specific group of patients. The aim of the present study was to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer

    Human Herpesvirus 8 (HHV8) Sequentially Shapes the NK Cell Repertoire during the Course of Asymptomatic Infection and Kaposi Sarcoma

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    The contribution of innate immunity to immunosurveillance of the oncogenic Human Herpes Virus 8 (HHV8) has not been studied in depth. We investigated NK cell phenotype and function in 70 HHV8-infected subjects, either asymptomatic carriers or having developed Kaposi's sarcoma (KS). Our results revealed substantial alterations of the NK cell receptor repertoire in healthy HHV8 carriers, with reduced expression of NKp30, NKp46 and CD161 receptors. In addition, down-modulation of the activating NKG2D receptor, associated with impaired NK-cell lytic capacity, was observed in patients with active KS. Resolution of KS after treatment was accompanied with restoration of NKG2D levels and NK cell activity. HHV8-latently infected endothelial cells overexpressed ligands of several NK cell receptors, including NKG2D ligands. The strong expression of NKG2D ligands by tumor cells was confirmed in situ by immunohistochemical staining of KS biopsies. However, no tumor-infiltrating NK cells were detected, suggesting a defect in NK cell homing or survival in the KS microenvironment. Among the known KS-derived immunoregulatory factors, we identified prostaglandin E2 (PGE2) as a critical element responsible for the down-modulation of NKG2D expression on resting NK cells. Moreover, PGE2 prevented up-regulation of the NKG2D and NKp30 receptors on IL-15-activated NK cells, and inhibited the IL-15-induced proliferation and survival of NK cells. Altogether, our observations are consistent with distinct immunoevasion mechanisms that allow HHV8 to escape NK cell responses stepwise, first at early stages of infection to facilitate the maintenance of viral latency, and later to promote tumor cell growth through suppression of NKG2D-mediated functions. Importantly, our results provide additional support to the use of PGE2 inhibitors as an attractive approach to treat aggressive KS, as they could restore activation and survival of tumoricidal NK cells

    An Engineering Approach to Extending Lifespan in C. elegans

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    We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways. Next, we used a modular approach to extend lifespan by combining components. Finally, we used cell- and worm-based assays to analyze changes in cell physiology and as a rapid means to evaluate whether multi-component transgenic lines were likely to have extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new framework for lifespan extension that goes beyond the constraints of the worm genome

    TOI-4010: A System of Three Large Short-Period Planets With a Massive Long-Period Companion

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    We report the confirmation of three exoplanets transiting TOI-4010 (TIC-352682207), a metal-rich K dwarf observed by TESS in Sectors 24, 25, 52, and 58. We confirm these planets with HARPS-N radial velocity observations and measure their masses with 8 - 12% precision. TOI-4010 b is a sub-Neptune (P=1.3P = 1.3 days, Rp=3.02−0.08+0.08 R⊕R_{p} = 3.02_{-0.08}^{+0.08}~R_{\oplus}, Mp=11.00−1.27+1.29 M⊕M_{p} = 11.00_{-1.27}^{+1.29}~M_{\oplus}) in the hot Neptune desert, and is one of the few such planets with known companions. Meanwhile, TOI-4010 c (P=5.4P = 5.4 days, Rp=5.93−0.12+0.11 R⊕R_{p} = 5.93_{-0.12}^{+0.11}~R_{\oplus}, Mp=20.31−2.11+2.13 M⊕M_{p} = 20.31_{-2.11}^{+2.13}~M_{\oplus}) and TOI-4010 d (P=14.7P = 14.7 days, Rp=6.18−0.14+0.15 R⊕R_{p} = 6.18_{-0.14}^{+0.15}~R_{\oplus}, Mp=38.15−3.22+3.27 M⊕M_{p} = 38.15_{-3.22}^{+3.27}~M_{\oplus}) are similarly-sized sub-Saturns on short-period orbits. Radial velocity observations also reveal a super-Jupiter-mass companion called TOI-4010 e in a long-period, eccentric orbit (P∼762P \sim 762 days and e∼0.26e \sim 0.26 based on available observations). TOI-4010 is one of the few systems with multiple short-period sub-Saturns to be discovered so far.Comment: 26 pages, 16 figures, published in A

    Complexity Theory for a New Managerial Paradigm: A Research Framework

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    In this work, we supply a theoretical framework of how organizations can embed complexity management and sustainable development into their policies and actions. The proposed framework may lead to a new management paradigm, attempting to link the main concepts of complexity theory, change management, knowledge management, sustainable development, and cybernetics. We highlight how the processes of organizational change have occurred as a result of the move to adapt to the changes in the various global and international business environments and how this transformation has led to the shift toward the present innovation economy. We also point how organizational change needs to deal with sustainability, so that the change may be consistent with present needs, without compromising the future
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