895 research outputs found

    Tuning-free controller to accurately regulate flow rates in a microfluidic network

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    We describe a control algorithm that can improve accuracy and stability of flow regulation in a microfluidic network that uses a conventional pressure pump system. The algorithm enables simultaneous and independent control of fluid flows in multiple micro-channels of a microfluidic network, but does not require any model parameters or tuning process. We investigate robustness and optimality of the proposed control algorithm and those are verified by simulations and experiments. In addition, the control algorithm is compared with a conventional PID controller to show that the proposed control algorithm resolves critical problems induced by the PID control. The capability of the control algorithm can be used not only in high-precision flow regulation in the presence of disturbance, but in some useful functions for lab-on-a-chip devices such as regulation of volumetric flow rate, interface position control of two laminar flows, valveless flow switching, droplet generation and particle manipulation. We demonstrate those functions and also suggest further potential biological applications which can be accomplished by the proposed control framework.open1142sciescopu

    β-catenin activation down-regulates cell-cell junction-related genes and induces epithelial-to-mesenchymal transition in colorectal cancers

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    WNT signaling activation in colorectal cancers (CRCs) occurs through APC inactivation or β-catenin mutations. Both processes promote β-catenin nuclear accumulation, which up-regulates epithelial-to-mesenchymal transition (EMT). We investigated β-catenin localization, transcriptome, and phenotypic differences of HCT116 cells containing a wild-type (HCT116-WT) or mutant β-catenin allele (HCT116-MT), or parental cells with both WT and mutant alleles (HCT116-P). We then analyzed β-catenin expression and associated phenotypes in CRC tissues. Wild-type β-catenin showed membranous localization, whereas mutant showed nuclear localization; both nuclear and non-nuclear localization were observed in HCT116-P. Microarray analysis revealed down-regulation of Claudin-7 and E-cadherin in HCT116-MT vs. HCT116-WT. Claudin-7 was also down-regulated in HCT116-P vs. HCT116-WT without E-cadherin dysregulation. We found that ZEB1 is a critical EMT factor for mutant β-catenin-mediated loss of E-cadherin and Claudin-7 in HCT116-P and HCT116-MT cells. We also demonstrated that E-cadherin binds to both WT and mutant β-catenin, and loss of E-cadherin releases β-catenin from the cell membrane and leads to its degradation. Alteration of Claudin-7, as well as both Claudin-7 and E-cadherin respectively caused tight junction (TJ) impairment in HCT116-P, and dual loss of TJs and adherens junctions (AJs) in HCT116-MT. TJ loss increased cell motility, and subsequent AJ loss further up-regulated that. Immunohistochemistry analysis of 101 CRCs revealed high (14.9%), low (52.5%), and undetectable (32.6%) β-catenin nuclear expression, and high β-catenin nuclear expression was significantly correlated with overall survival of CRC patients (P = 0.009). Our findings suggest that β-catenin activation induces EMT progression by modifying cell-cell junctions, and thereby contributes to CRC aggressiveness

    Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films

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    Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B+^+) and phosphorous (P+^+) ions. Different samples, prepared by varying the ion dose in the range 101410^{14} to 5 x 101510^{15} and ion energy in the range 150-350 keV, were investigated by the Raman spectroscopy, photoluminescence (PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman results from dose dependent B+^+ implanted samples show red-shifted and asymmetrically broadened Raman line-shape for B+^+ dose greater than 101410^{14} ions cm2^{-2}. The asymmetry and red shift in the Raman line-shape is explained in terms of quantum confinement of phonons in silicon nanostructures formed as a result of ion implantation. PL spectra shows size dependent visible luminescence at \sim 1.9 eV at room temperature, which confirms the presence of silicon nanostructures. Raman studies on P+^+ implanted samples were also done as a function of ion energy. The Raman results show an amorphous top SOS surface for sample implanted with 150 keV P+^+ ions of dose 5 x 101510^{15} ions cm2^{-2}. The nanostructures are formed when the P+^+ energy is increased to 350 keV by keeping the ion dose fixed. The GAXRD results show consistency with the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in SILICON(SPRINGER

    Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

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    Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

    Emergence of Bursts and Communities in Evolving Weighted Networks

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    Understanding the patterns of human dynamics and social interaction, and the way they lead to the formation of an organized and functional society are important issues especially for techno-social development. Addressing these issues of social networks has recently become possible through large scale data analysis of e.g. mobile phone call records, which has revealed the existence of modular or community structure with many links between nodes of the same community and relatively few links between nodes of different communities. The weights of links, e.g. the number of calls between two users, and the network topology are found correlated such that intra-community links are stronger compared to the weak inter-community links. This is known as Granovetter's "The strength of weak ties" hypothesis. In addition to this inhomogeneous community structure, the temporal patterns of human dynamics turn out to be inhomogeneous or bursty, characterized by the heavy tailed distribution of inter-event time between two consecutive events. In this paper, we study how the community structure and the bursty dynamics emerge together in an evolving weighted network model. The principal mechanisms behind these patterns are social interaction by cyclic closure, i.e. links to friends of friends and the focal closure, i.e. links to individuals sharing similar attributes or interests, and human dynamics by task handling process. These three mechanisms have been implemented as a network model with local attachment, global attachment, and priority-based queuing processes. By comprehensive numerical simulations we show that the interplay of these mechanisms leads to the emergence of heavy tailed inter-event time distribution and the evolution of Granovetter-type community structure. Moreover, the numerical results are found to be in qualitative agreement with empirical results from mobile phone call dataset.Comment: 9 pages, 6 figure

    Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer

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    <p>Abstract</p> <p>Background</p> <p>Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer.</p> <p>Methods</p> <p>In 146 prospectively recruited consecutive patients with clinically proven colorectal cancer, MSI carriers were identified by analysis of tumor tissue using multiplex fluorescence polymerase chain reaction (PCR) using the NCI recommended panel and classified into microsatellite instability-low (MSI-L), microsatellite instability-high (MSI-H) and microsatellite stable (MSS) groups. Immunohistochemical staining for MSH2, MSH6 and MLH1 on tissue microarrays (TMAs) was performed, and methylation of the MLH1 promoter was analyzed by quantitative methylation specific PCR (MSP). Germline mutation analysis of blood samples was performed for MSH2, MSH6 and MLH1 genes.</p> <p>Results</p> <p>Thirty-four out of the 146 colorectal cancers (CRCs, 23.2%) were MSI, including 19 MSI-H CRCs and 15 MSI-L CRCS. Negative staining for MSH2 was found in 8 CRCs, negative staining for MSH6 was found in 6 CRCs. One MSI-H CRC was negative for both MSH6 and MSH2. Seventeen CRCs stained negatively for MLH1. MLH1 promoter methylation was determined in 34 MSI CRCs. Hypermethylation of the MLH1 promoter occurred in 14 (73.7%) out of 19 MSI-H CRCs and 5 (33.3%) out of 15 MSI-L CRCs. Among the 34 MSI carriers and one MSS CRC with MLH1 negative staining, 8 had a MMR gene germline mutation, which accounted for 23.5% of all MSI colorectal cancers and 5.5% of all the colorectal cancers. Five patients harbored MSH2 germline mutations, and three patients harbored MSH6 germline mutations. None of the patients had an MLH1 mutation. Mutations were commonly located in exon 7 and 12 of MSH2 and exon 5 of MSH6. Right colonic lesions and mucinous carcinoma were not common in MSI carriers.</p> <p>Conclusion</p> <p>Our data may imply that the characteristics of HNPCC in the Chinese population are probably different from those of Western countries. Application of NCI recommended criteria may not be effective enough to identify Chinese HNPCC families. Further studies are necessary to echo or refute our results so as to make the NCI recommendation more universally applicable.</p

    Herschel images of Fomalhaut An extrasolar Kuiper belt at the height of its dynamical activity

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    Context. Fomalhaut is a young (2 ± 1 × 108 years), nearby (7.7 pc), 2 M⊙ star that is suspected to harbor an infant planetary system, interspersed with one or more belts of dusty debris. Aims. We present far-infrared images obtained with the Herschel Space Observatory with an angular resolution between 5.7′′ and 36.7′′ at wavelengths between 70 μm and 500 μm. The images show the main debris belt in great detail. Even at high spatial resolution, the belt appears smooth. The region in between the belt and the central star is not devoid of material; thermal emission is observed here as well. Also at the location of the star, excess emission is detected. We aim to construct a consistent image of the Fomalhaut system. Methods. We use a dynamical model together with radiative-transfer tools to derive the parameters of the debris disk. We include detailed models of the interaction of the dust grains with radiation, for both the radiation pressure and the temperature determination. Comparing these models to the spatially resolved temperature information contained in the images allows us to place strong constraints on the presence of grains that will be blown out of the system by radiation pressure. We use this to derive the dynamical parameters of the system. Results. The appearance of the belt points toward a remarkably active system in which dust grains are produced at a very high rate by a collisional cascade in a narrow region filled with dynamically excited planetesimals. Dust particles with sizes below the blow-out size are abundantly present. The equivalent of 2000 one-km-sized comets are destroyed every day, out of a cometary reservoir amounting to 110 Earth masses. From comparison of their scattering and thermal properties, we find evidence that the dust grains are fluffy aggregates, which indicates a cometary origin. The excess emission at the location of the star may be produced by hot dust with a range of temperatures, but may also be due to gaseous free-free emission from a stellar wind

    Frequency and predictors of miliary tuberculosis in patients with miliary pulmonary nodules in South Korea: A retrospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>Miliary pulmonary nodules are commonly caused by various infections and cancers. We sought to identify the relative frequencies of various aetiologies and the clinical and radiographic predictors of miliary tuberculosis (TB) in patients with miliary pulmonary nodules.</p> <p>Methods</p> <p>We performed a retrospective cohort study of patients who presented with micronodules occupying more than two-thirds of the lung volume, based on computed tomography (CT) of the chest, between November 2001 and April 2007, in a tertiary referral hospital in South Korea.</p> <p>Results</p> <p>We analyzed 76 patients with miliary pulmonary nodules. Their median age was 52 years and 38 (50%) were males; 18 patients (24%) had a previous or current malignancy and five (7%) had a history of TB. The most common diagnoses of miliary nodules were miliary TB (41 patients, 54%) and miliary metastasis of malignancies (20 patients, 26%). Multivariate analysis revealed that age ≤30 years, HIV infection, corticosteroid use, bronchogenic spread of lesions, and ground-glass opacities occupying >25% of total lung volume increased the probability of miliary TB. However, a history of malignancy decreased the probability of miliary TB.</p> <p>Conclusion</p> <p>Miliary TB accounted for approximately half of all causes of miliary pulmonary nodules. Young age, an immune-compromised state, and several clinical and radiographic characteristics increased the probability of miliary TB.</p
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