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Farrow, Blake,Hong, Sung A,Romero, Errika C.,Lai, Bert,Coppock, Matthew B.,Deyle, Kaycie M.,Finch, Amethist S.,Stratis-Cullum, Dimitra N.,Agnew, Heather D.,Yang, Sung,Heath, James R. American Chemical Society 2013 ACS NANO Vol.7 No.10
<P>We report on a robust and sensitive approach for detecting protective antigen (PA) exotoxin from <I>Bacillus anthracis</I> in complex media. A peptide-based capture agent against PA was developed by improving a bacteria display-developed peptide into a highly selective biligand through <I>in situ</I> click screening against a large, chemically synthesized peptide library. This biligand was coupled with an electrochemical enzyme-linked immunosorbent assay utilizing nanostructured gold electrodes. The resultant assay yielded a limit of detection of PA of 170 pg/mL (2.1 pM) in buffer, with minimal sensitivity reduction in 1% serum. The powdered capture agent could be stably stored for several days at 65 °C, and the full electrochemical biosensor showed no loss of performance after extended storage at 40 °C. The engineered stability and specificity of this assay should be extendable to other cases in which biomolecular detection in demanding environments is required.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2013/ancac3.2013.7.issue-10/nn404296k/production/images/medium/nn-2013-04296k_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn404296k'>ACS Electronic Supporting Info</A></P>
Nephron-sparing management of upper tract urothelial carcinoma
Jason M. Farrow,Sean Q. Kern,Gustavo M. Gryzinski,Chandru P. Sundaram 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.4
Urothelial carcinoma of the upper urinary tract is uncommon and presents unique challenges for diagnosis and management. Nephroureterectomy has been the preferred management option, but it is associated with significant morbidity. Nephron-sparing treatments are a valuable alternative and provide similar efficacy in select cases. A PubMed literature review was performed in English language publications using the following search terms: urothelial carcinoma, upper tract, nephron-sparing, intraluminal and systemic therapy. Contemporary papers published within the last 10 years were primarily included. Where encountered, systematic reviews and meta-analyses were given priority, as were randomized controlled trials for newer treatments. Core guidelines were referenced and citations reviewed for inclusion. A summary of epidemiological data, clinical diagnosis, staging, and treatments focusing on nephron-sparing approaches to upper tract urothelial carcinoma (UTUC) are outlined. Nephron-sparing management strategies are viable options to consider in patients with favorable features of UTUC. Adjunctive therapies are being investigated but the data remains mixed. Protocol variability and dosage differences limit statistical interpretation. New mechanisms to improve treatment dwell times in the upper tracts are being designed with promising preliminary results. Studies investigating systemic therapies are ongoing but implications for nephron-sparing management are uncertain. Nephron-sparing management is an acceptable treatment modality best suited for favorable disease. More work is needed to determine if intraluminal and/or systemic therapies can further optimize treatment outcomes beyond resection alone.
Optimized entropic uncertainty for successive projective measurements
Baek, Kyunghyun,Farrow, Tristan,Son, Wonmin American Physical Society 2014 Physical review. A. Atomic, molecular, and optical Vol.89 No.3
We focus here on the uncertainty of an observable Y caused by a precise measurement of X. We illustrate the effect by analyzing the general scenario of two successive measurements of spin components X and Y. We derive an optimized entropic uncertainty limit that quantifies the necessary amount of uncertainty observed in a subsequent measurement of Y. We compare this bound to recently derived error-disturbance relations and discuss how the bound quantifies the information of successive quantum measurements.
Oglesby, Amanda G.,Farrow III, John M.,Lee, Joon-Hee,Tomaras, Andrew P.,Greenberg, E. P.,Pesci, Everett C.,Vasil, Michael L. American Society for Biochemistry and Molecular Bi 2008 The Journal of biological chemistry Vol.283 No.23
<P>In iron-replete environments, the Pseudomonas aeruginosa Fur (ferric uptake regulator) protein represses expression of two small regulatory RNAs encoded by prrF1 and prrF2. Here we describe the effects of iron and PrrF regulation on P. aeruginosa physiology. We show that PrrF represses genes encoding enzymes for the degradation of anthranilate (i.e. antABC), a precursor of the Pseudomonas quinolone signal (PQS). Under iron-limiting conditions, PQS production was greatly decreased in a DeltaprrF1,2 mutant as compared with wild type. The addition of anthranilate to the growth medium restored PQS production to the DeltaprrF1,2 mutant, indicating that its defect in PQS production is a consequence of anthranilate degradation. PA2511 was shown to encode an anthranilate-dependent activator of the ant genes and was subsequently renamed antR. AntR was not required for regulation of antA by PrrF but was required for optimal iron activation of antA. Furthermore, iron was capable of activating both antA and antR in a DeltaprrF1,2 mutant, indicating the presence of two distinct yet overlapping pathways for iron activation of antA (AntR-dependent and PrrF-dependent). Additionally, several quorum-sensing regulators, including PqsR, influenced antA expression, demonstrating that regulation of anthranilate metabolism is intimately woven into the quorum-sensing network of P. aeruginosa. Overall, our data illustrate the extensive control that both iron regulation and quorum sensing exercise in basic cellular physiology, underlining how intermediary metabolism can affect the regulation of virulence factors in P. aeruginosa.</P>
Cystic fibrosis gene therapy, novel strategies for improving long-term therapeutic efficacy
( Juliette Delhove ),( Patricia Cmielewski ),( Nigel Farrow ),( Chantelle Carpentieri ),( Alexandra Sarah Ann Mc Carron ),( Nicole Reyne ),( Nathan Rout-pitt ),( Bernadette Boog ),( Martin Donnelley ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
Background: Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) protein. CF results in airway surface dehydration and the inability to clear mucus, which leads to chronic infections, inflammation, and premature death most commonly due to respiratory failure. Gene therapy can be used to insert a correct copy of the CFTR gene into the genome to restore organ function by fixing the underlying genetic condition independent of CFTR mutation type. Lentiviruses (LV) are a promising gene therapy vehicle as they stably integrate the therapeutic gene into the genome. To achieve permanent genetic correction, we are focusing on developing vectors to improve cell targeting and specificity to overcome the current challenges of CF gene therapy. Methods: LV vectors containing reporter genes (LacZ, Luc-GFP) or epitope-tagged CFTR were developed and tested in vitro. Subsequently, each vector was administered to the nasal epithelia or lungs of CF mice or rats. Transduction efficiency, duration, localisation and CFTR function were assessed using histology, electrophysiological measurements, and in vivo bioluminescence imaging. Results: LV vectors containing reporter genes or CFTR have been shown to successfully transduce the lung and express transgenes long-term. Non-specific alveoli cells and macrophages are transduced in conjunction with a low proportion of therapeutically-relevant basal cells. Importantly, LV vector containing tagged or non-tagged CFTR produced functional correction of the nasal potential difference with tagging of CFTR having no effect on CFTR function. Conclusions: We have shown that our vector has the potential for long-term expression, and can correct CF mutation-induced electrophysiological defects. Using vector-surface engineering strategies, we now aim to overcome the current challenges of basal cell targeting, immune responses, and off-target transduction of non-therapeutic cell types. Combatting these critical obstacles will enable full and rapid progress in gene therapy treatment for this life-limiting disease.
Wise, T,Radua, J,Via, E,Cardoner, N,Abe, O,Adams, T M,Amico, F,Cheng, Y,Cole, J H,de Azevedo Marques Pé,rico, C,Dickstein, D P,Farrow, T F D,Frodl, T,Wagner, G,Gotlib, I H,Gruber, O,Ham, B J,Job Macmillan Publishers Limited, part of Springer Nat 2017 Molecular psychiatry Vol.22 No.10
<P>Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.</P>