169 research outputs found

    A wideband linear tunable CDTA and its application in field programmable analogue array

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    This document is the Accepted Manuscript version of the following article: Hu, Z., Wang, C., Sun, J. et al. ‘A wideband linear tunable CDTA and its application in field programmable analogue array’, Analog Integrated Circuits and Signal Processing, Vol. 88 (3): 465-483, September 2016. Under embargo. Embargo end date: 6 June 2017. The final publication is available at Springer via https://link.springer.com/article/10.1007%2Fs10470-016-0772-7 © Springer Science+Business Media New York 2016In this paper, a NMOS-based wideband low power and linear tunable transconductance current differencing transconductance amplifier (CDTA) is presented. Based on the NMOS CDTA, a novel simple and easily reconfigurable configurable analogue block (CAB) is designed. Moreover, using the novel CAB, a simple and versatile butterfly-shaped FPAA structure is introduced. The FPAA consists of six identical CABs, and it could realize six order current-mode low pass filter, second order current-mode universal filter, current-mode quadrature oscillator, current-mode multi-phase oscillator and current-mode multiplier for analog signal processing. The Cadence IC Design Tools 5.1.41 post-layout simulation and measurement results are included to confirm the theory.Peer reviewedFinal Accepted Versio

    Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome

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    The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder

    Predictors of diagnostic yield in bronchoscopy: a retrospective cohort study comparing different combinations of sampling techniques

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    <p>Abstract</p> <p>Background</p> <p>The reported diagnostic yield from bronchoscopies in patients with lung cancer varies greatly. The optimal combination of sampling techniques has not been finally established.</p> <p>The objectives of this study were to find the predictors of diagnostic yield in bronchoscopy and to evaluate different combinations of sampling techniques.</p> <p>Methods</p> <p>All bronchoscopies performed on suspicion of lung malignancy in 2003 and 2004 were reviewed, and 363 patients with proven malignant lung disease were included in the study. Sampling techniques performed were biopsy, transbronchial needle aspiration (TBNA), brushing, small volume lavage (SVL), and aspiration of fluid from the entire procedure. Logistic regression analyses were adjusted for sex, age, endobronchial visibility, localization (lobe), distance from carina, and tumor size.</p> <p>Results</p> <p>The adjusted odds ratios (OR) with 95% confidence intervals (CI) for a positive diagnostic yield through all procedures were 17.0 (8.5–34.0) for endobronchial lesions, and 2.6 (1.3–5.2) for constriction/compression, compared to non-visible lesions; 3.8 (1.3–10.7) for lesions > 4 cm, 6.7 (2.1–21.8) for lesions 3–4 cm, and 2.5 (0.8–7.9) for lesions 2–3 cm compared with lesions <= 2 cm. The combined diagnostic yield of biopsy and TBNA was 83.7% for endobronchial lesions and 54.2% for the combined group without visible lesions. This was superior to either technique alone, whereas additional brushing, SVL, and aspiration did not significantly increase the diagnostic yield.</p> <p>Conclusion</p> <p>In patients with malignant lung disease, visible lesions and larger tumor size were significant predictors of higher diagnostic yield, after adjustment for sex, age, distance from carina, side and lobe. The combined diagnostic yield of biopsy and TBNA was significant higher than with either technique alone.</p

    Understanding the potential in vitro modes of action of bis(β‐diketonato) oxovanadium(IV) complexes

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    To understand the potential in vitro modes of action of bis(β-diketonato) oxovanadium(IV) complexes, nine compounds of varying functionality have been screened using a range of biological techniques. The antiproliferative activity against a range of cancerous and normal cell lines has been determined, and show these complexes are particularly sensitive against the lung carcinoma cell line, A549. Annexin V (apoptosis) and Caspase-3/7 assays were studied to confirm these complexes induce programmed cell death. While gel electrophoresis was used to determine DNA cleavage activity and production of reactive oxygen species (ROS), the Comet assay was used to determine induced genomic DNA damage. Additionally, Förster resonance energy transfer (FRET)-based DNA melting and fluorescent intercalation displacement assays have been used to determine the interaction of the complexes with double strand (DS) DNA and to establish preferential DNA base-pair binding (AT versus GC)

    Progress in particle-based multiscale and hybrid methods for flow applications

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    Cofactors are Remnants of Life\u27s Origin and Early Evolution

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    The RNA World is one of the most widely accepted hypotheses explaining the origin of the genetic system used by all organisms today. It proposes that the tripartite system of DNA, RNA, and proteins was preceded by one consisting solely of RNA, which both stored genetic information and performed the molecular functions encoded by that genetic information. Current research into a potential RNA World revolves around the catalytic properties of RNA-based enzymes, or ribozymes. Well before the discovery of ribozymes, Harold White proposed that evidence for a precursor RNA world could be found within modern proteins in the form of coenzymes, the majority of which contain nucleobases or nucleoside moieties, such as Coenzyme A and S-adenosyl methionine, or are themselves nucleotides, such as ATP and NADH (a dinucleotide). These coenzymes, White suggested, had been the catalytic active sites of ancient ribozymes, which transitioned to their current forms after the surrounding ribozyme scaffolds had been replaced by protein apoenzymes during the evolution of translation. Since its proposal four decades ago, this groundbreaking hypothesis has garnered support from several different research disciplines and motivated similar hypotheses about other classes of cofactors, most notably iron-sulfur cluster cofactors as remnants of the geochemical setting of the origin of life. Evidence from prebiotic geochemistry, ribozyme biochemistry, and evolutionary biology, increasingly supports these hypotheses. Certain coenzymes and cofactors may bridge modern biology with the past and can thus provide insights into the elusive and poorly-recorded period of the origin and early evolution of life

    Very early evolution from the perspective of microbial ecology

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    The universal ancestor at the root of the species tree of life depicts a population of organisms with a surprising degree of complexity, posessing genomes and translation systems much like that of microbial life today. As the first life forms were most likely to have been simple replicators, considerable evolutionary change must have taken place prior to the last universal common ancestor. It is often assumed that the lack of earlier branches on the tree of life is due to a prevalence of random horizontal gene transfer that obscured the delineations between lineages and hindered their divergence. Therefore, principles of microbial evolution and ecology may give us some insight into these early stages in the history of life. Here, we synthesize the current understanding of organismal and genome evolution from the perspective of microbial ecology and apply these evolutionary principles to the earliest stages of life on Earth. We focus especially on broad evolutionary modes pertaining to horizontal gene transfer, pangenome structure, and microbial mat communities

    Evaluation of the oblique fissure on lateral chest radiographs in coal workers pneumoconiosis

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    Objective: The oblique fissure separates the upper lobe from the lower lobe in the left lung and the upper lobe from the lower and middle lobes in the right lung. The aim of the present study was to compare the projection of the oblique fissure observed on lateral chest radiographs of retired coal mine workers who had coal worker's pneumoconiosis (CWP) with that of healthy men. Materials and methods: The study included 120 men divided into three groups: retired coal miner patients diagnosed with CWP (group 1), men ?38 years of age with no CWP (group 2, first control group), and men ?37 years of age with no CWP (group 3, second control group). The projection of the oblique fissure observed on lateral chest radiographs (left side) were evaluated using geometric morphometrics. Geometric morphometric analysis of each sample was performed using 11 pre-specified landmarks designated on X-ray images, using tpsDig2 software. A text file containing the landmark coordinates of the 120 samples was created, and the data in the text file was statistically analyzed using Morpheus software. Results: The projection of the oblique fissure differed significantly between the CWP patients and the control groups (p<0.05). Conclusion: We suggest that the difference in the projection of the oblique fissure between men with and without CWP was attributable to a protrusion in the fissure caused by nodules that developed in the lungs of coal miners after years of dust inhalation
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