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EUS-guided choledochoduodenostomy (EUS-CDD) with an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with malignant distal biliary obstruction (MDBO). Our aim was to assess the efficacy, safety, and outcomes in patients with MDBO who underwent EUS-CDD with an EC-LAMS. A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMSs at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 and November 2020 was undertaken. One hundred twenty patients (55% men) with a median age of 73 years (interquartile range, 17; range, 43-94) were included. The median follow-up period in 117 patients was 70 days (interquartile range, 169; range, 3-869), and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to ≤50% of original value within 14 days) was achieved in 94.8% of patients (92/97). The adverse event rate was 17.5% (n = 21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). EUS-CDD with EC-LAMSs at tertiary institutions within a regional hepatopancreatobiliary network for treatment of MDBO was effective in those where ERCP was not possible or was unsuccessful. When technical failures or adverse events occur, most patients can be managed with conservative or endoscopic therapy. [ABSTRACT FROM AUTHOR]

• A 3-D numerical model for coupled PVT and FPC system has been developed. • A close match between simulation and experiments is observed with relative error under 5% • The experiment conducted on PVT -FPC system at 30LPH showed outlet water temperature of 63–67 °C. • Thermal and electrical efficiency from the glazed PVT collector is observed to be 35% and 10.3%, respectively. • Thermal and electrical efficiency from the unglazed PVT collector is observed to be 25% and 16%, respectively. Photovoltaic Thermal (PVT) systems generate hot water and electricity simultaneously. The grade of thermal energy generated by such PVT systems is low, resulting in limited application. To overcome this challenge, the coupling of the PVT system to a secondary flat plate collector (FPC) has been explored in this work. For the system's performance estimation, a 3-D numerical model has been developed for both glazed and unglazed PVT-FPC collector. Based on the numerical model, PVT collectors have been fabricated, and each is then connected in series to a commercially available FPC collector. Experiments conducted on the fabricated PVT-FPC system showed a close match between simulation and experiments. Further, experiments conducted on the unglazed PVT – FPC collector showed a peak outlet water temperature of 60–63 °C at 30 LPH. For the unglazed PVT collector, the peak electrical and thermal efficiency of 16% and 25% is reported respectively, whereas for the FPC collector, the thermal efficiency of 35% is reported. Compared to an individual unglazed PVT collector, 17 °C higher outlet water temperature is reported for the coupled system. Similarly, for the case of glazed PVT-FPC collector, the peak outlet water temperature reported is 65–67 °C at 30 LPH with 14–15 °C higher outlet water temperature. [ABSTRACT FROM AUTHOR]

To investigate the collateral sensitivity (CS) of ABCB1-positive multidrug resistant (MDR) colorectal cancer cells to the survivin inhibitor MX106–4C and the mechanism. Biochemical assays (MTT, ATPase, drug accumulation/efflux, Western blot, RT-qPCR, immunofluorescence, flow cytometry) and bioinformatic analyses (mRNA-sequencing, reversed-phase protein array) were performed to investigate the hypersensitivity of ABCB1 overexpressing colorectal cancer cells to MX106–4C and the mechanisms. Synergism assay, long-term selection, and 3D tumor spheroid test were used to evaluate the anti-cancer efficacy of MX106–4C. MX106–4C selectively killed ABCB1-positive colorectal cancer cells, which could be reversed by an ABCB1 inhibitor, knockout of ABCB1, or loss-of-function ABCB1 mutation, indicating an ABCB1 expression and function-dependent mechanism. MX106–4C's selective toxicity was associated with cell cycle arrest and apoptosis through ABCB1-dependent survivin inhibition and activation on caspases-3/7 as well as modulation on p21-CDK4/6-pRb pathway. MX106–4C had good selectivity against ABCB1-positive colorectal cancer cells and retained this in multicellular tumor spheroids. In addition, MX106–4C could exert a synergistic anti-cancer effect with doxorubicin or re-sensitize ABCB1-positive cancer cells to doxorubicin by reducing ABCB1 expression in the cell population via long-term exposure. MX106–4C selectively kills ABCB1-positive MDR colorectal cancer cells via a novel ABCB1-dependent survivin inhibition mechanism, providing a clue for designing CS compound as an alternative strategy to overcome ABCB1-mediated colorectal cancer MDR. [Display omitted] [ABSTRACT FROM AUTHOR]

Published studies have shown that methane yield (g CH4/kg dry matter) from sheep is positively correlated with the size (volume and surface area) of the reticulo-rumen (RR) and the weight of its contents. However, the relationship between CH4 yield and RR shape has not been investigated. In this work, shape analysis has been performed on a data set of computerised tomography (CT) scans of the RR from sheep having high and low CH4 yields (n =20 and n =17, respectively). The three-dimensional geometries of the RRs were reconstructed from segmented scan data and split into three anatomical regions. An iterative fitting technique combining radial basis functions and principal component (PC) fitting was used to create a set of consistent landmarks which were then used as variables in a PC analysis to identify shape variation within the data. Significant size differences were detected for regions corresponding to the dorsal and ventral compartments between sheep with high and low CH4 yields. When the analysis was repeated after scaling the geometries to remove the effect of size, there was no significant shape variation correlating with CH4 yield. The results have demonstrated the feasibility of CT-based computational shape determination for studying the morphological characteristics of the RR and indicate that size, but not shape correlates with CH4 yield in sheep. [ABSTRACT FROM AUTHOR]

Human P-glycoprotein (P-gp) or ABCB1 is overexpressed in many cancers and has been implicated in altering the bioavailability of chemotherapeutic drugs due to their efflux, resulting in the development of chemoresistance. To elucidate the mechanistic aspects and structure-function relationships of P-gp, we previously utilized a tyrosine (Y)-enriched P-gp mutant (15Y) and demonstrated that at least 15 conserved residues in the drug-binding pocket of P-gp are responsible for optimal substrate interaction and transport. To further understand the role of these 15 residues, two new mutants were generated, namely 6Y with the substitution of six residues (F72, F303, I306, F314, F336 and L339) with Y in transmembrane domain (TMD) 1 and 9Y with nine substitutions (F732, F759, F770, F938, F942, M949, L975, F983 and F994) in TMD2. Although both the mutants were expressed at normal levels at the cell surface, the 6Y mutant failed to transport all the tested substrates except Bodipy-verapamil, whereas the 9Y mutant effluxed all tested substrates in a manner very similar to that of the wild-type protein. Further mutational analysis revealed that two second-site mutations, one in intracellular helix (ICH) 4 (F916Y) and one in the Q loop of nucleotide-binding domain (NBD) 1 (F480Y) restored the transport function of 6Y. Additional biochemical data and comparative molecular dynamics simulations of the 6Y and 6Y+F916Y mutant indicate that the Q-loop of NBD1 of P-gp communicates with the substrate-binding sites in the transmembrane region through ICH4. This is the first evidence for the existence of second-site suppressors in human P-gp that allow recovery of the loss of transport function caused by primary mutations. Further study of such mutations could facilitate mapping of the communication pathway between the substrate-binding pocket and the NBDs of P-gp and possibly other ABC drug transporters. [ABSTRACT FROM AUTHOR]

ATP-binding cassette (ABC) transporters such as ABCB1, ABCG2, and ABCC1 are the major players in drug efflux-mediated multidrug resistance (MDR), which severely affects the efficacy of chemotherapy. Several synthetic compounds block the drug transport by ABC transporters; however, they exhibit a narrow therapeutic window, and produce side effects in non-target normal tissues. Conversely, the downregulation of the expression of ABC drug transporters seems to be a promising strategy to reverse MDR in cancer cells. Several signaling pathways, such as NF-κB, STAT3, Gli, NICD, YAP/TAZ, and Nrf2 upregulate the expression of ABC drug transporters in drug-resistant cancers. Recently, natural medicinal compounds have gained importance to overcome the ABC drug-efflux pump-mediated MDR in cancer. These compounds target transcription factors and the associated signal transduction pathways, thereby downregulating the expression of ABC transporters in drug-resistant cancer cells. Several potent natural compounds have been identified as lead candidates to synergistically enhance chemotherapeutic efficacy, and a few of them are already in clinical trials. Therefore, modulation of signal transduction pathways using natural medicinal compounds for the reversal of ABC drug transporter-mediated MDR in cancer is a novel approach for improving the efficiency of the existing chemotherapeutics. In this review, we discuss the modulatory role of natural medicinal compounds on cellular signaling pathways that regulate the expression of ABC transporters in drug-resistant cancer cells. • ATP-binding cassette (ABC) transporters are the major players of multidrug resistance (MDR). • Signaling pathways upregulate the expression of ABC drug transporters in drug-resistant cancers. • Downregulation of the expression of ABC drug transporter reverses drug resistance in MDR cancer cells. • Natural medicinal compounds downregulates the expression of ABC transporters in drug-resistant cancer cells. • Natural medicinal compounds could be used as chemosensitizers to overcome ABC transporters mediated drug-resistance. [ABSTRACT FROM AUTHOR]

Cholesterol induced mechanical effects on artificial lipid bilayers are well known and have been thoroughly investigated by AFM force spectroscopy. However, dynamics of cholesterol impingement into bilayers at various cholesterol concentrations and their effects have not been clearly understood. In this paper we present, the effect of cholesterol as a function of its concentration in a simple single component dioleoylphosphatidylcholine (DOPC) bilayer. The nature of measured breakthrough forces on a bilayer with the addition of cholesterol, suggested that it is not just responsible to increase the mechanical stability but also introduces irregularities across the leaflets of the bilayer. This cholesterol induced asymmetry across the (in the inner and outer leaflets) bilayer is related to the phenomena of interleaflet coupling and is a function of cholesterol concentration probed by AFM can provide an unprecedented direction on mechanical properties of lipid membrane as it can be directly correlated to biophysical properties of a cell membrane. [ABSTRACT FROM AUTHOR]

Electrode design is investigated for electrical capacitance tomography on a 1 mm-thick 3D planar domain. Arrays of square electrodes are located on both sides of the domain, which is filled with dielectric material. Anomalies of interest are voids in the material with low dielectric constant. Simulated tomography is conducted with various electrode patterns over a range of electrode sizes in order to compare performance. The high-aspect-ratio domain requires a large finite element mesh for simulating electric fields and for defining spatial sensitivity responses of electrode pairs. Compared to the canonical 2D pipe cross-section problem, this high-aspect-ratio system requires solving the reconstruction problem on a much larger mesh and is more severely underdetermined. An efficient methodology for characterizing the sensitivity responses of various electrode pairs is developed. An image reconstruction algorithm creates binary images by sequentially composing a list of occupied cells, conditioned with a cell-to-cell energy formulation. A parametric study of four candidate electrode patterns is conducted using electrode sizes between 0.8 mm and 1.6 mm, in which each potential design is used to perform tomographic reconstruction of 100 images. A new image-error metric is proposed, which is used to evaluate each electrode design. It is found that an electrode matrix pattern on each substrate, with the patterns offset, results in lower mean image error than other candidate patterns. [ABSTRACT FROM AUTHOR]

Magnetic flux leakage based non destructive technique for detection of defect in small diameter steam generator tube is evaluated. The detect-ability of a flaw depends on the magnetic flux density passing through a specimen to be inspected. The process of magnetizing local region of the small diameter tube is complex, when the magnetizer arrangement is placed inside the tube. Bobbin coil is considered to magnetize the local region of small diameter ferromagnetic tube and a hall sensor is placed at the center of the magnetizer to sense the leakage field. ANSYS Maxwell EM V16 based Finite Element Method (FEM) and Analytical model is used to validate the proposed magnetizer arrangement. Experimental results were found to be in good agreement with both numerical and analytical results. The obtained results suggest that the performance of the proposed bobbin coil is good to inspect the small diameter tube. [ABSTRACT FROM AUTHOR]

An instrumentation technique is developed using embedded capacitive sensors to measure the thickness and evenness of coverage of a thin layer of dielectric thermal interface material (TIM) between two substrates. The technique requires an array of sensors embedded into one substrate, with an electrically conductive opposing substrate. Local capacitance measurements are sensitive to both local bond layer thickness and local voiding. We propose a means for using an array of capacitance measurements to interpret both bond layer thickness and local voiding at every sensor location. An algorithm is developed which reveals both characteristics from a single set of capacitance measurements. Experiments are conducted with thermal grease layers of different bond layer thicknesses and void distributions using a prototype system constructed on printed circuit boards. The thickness and void distribution are successfully mapped across the bond layer using the algorithm developed. The technique offers a sensing approach for in situ instrumentation of layers of thermal grease in a thermal test vehicle. [ABSTRACT FROM AUTHOR]

The ability of a diagnostic test to detect multiple pathogens simultaneously is useful to obtain meaningful information for clinical treatment and preventive measures. We report a highly sensitive and specific electrochemical biosensor assay for simultaneous detection of three gene targets using quantum dots (QDs). The targets are novel non-protein coding RNA (npcRNA) sequences of Vibrio cholerae , Salmonella sp. and Shigella sp., which cause diarrheal diseases. QDs (PbS, CdS, ZnS) were synthesized and functionalized with DNA probes that were specific to each pathogen. Electrochemical detection of QDs was performed using square wave anodic stripping voltammetry (SWASV). The QDs gave distinct peaks at 0.5 V (PbS), 0.75 V (CdS) and 1.1 V (ZnS). There was no interference in signal response when all three QDs were mixed and detected simultaneously. The detection limits of single and multiplex assays with linear targets and PCR products were in the attomolar ranges. The high assay sensitivity, in combination with specific npcRNA sequences as novel diagnostic targets, makes it a viable tool for detecting pathogens from food, environment and clinical samples. [ABSTRACT FROM AUTHOR]

Context The rate and the extent of bone remineralization at cancellous versus cortical sites after treatment of hyperthyroidism is unclear. Few studies have examined the effect of operative management of hyperthyroidism on recovery of bone mass. Objective To evaluate prospectively the bone mineral density (BMD), bone mineral content (BMC), and bone areal size at the spine, hip, and forearm before and after total thyroidectomy. Design and setting A prospective case control observational study from August 2011 to July 2014 in a single center. Participants This study evaluated 40 overt hyperthyroid patients and 31 age-matched euthyroid controls who were operative candidates. Main outcome measures Bone indices were measured at baseline and 6-month postoperatively using dual energy x-ray absorptiometry. Serum levels of alkaline phosphatase and 25-hydroxy vitamin D 3 (25OHD) were assessed. Results Baseline BMD of hyperthyroid subjects at the spine, hip, and forearm were less than euthyroid controls ( P = .001) with concomitant increases in serum alkaline phosphatase (mean ± SD, 143 ± 72 vs 72 ± 23 IU/L control; P < .001). The 25OHD level was 24.3 ± 10.6 and 26.1 ± 14.6 ng/mL in patients and controls, respectively. Among hyperthyroid patients, posttreatment BMD expressed as g/cm 2 were 0.97 ± 0.12 (vs pretreatment 0.91 ± 0.14; P = .001) at the spine, 0.87 ± 0.12 (vs pretreatment 0.80 ± 0.13; P = .001) at the hip, and 0.67 ± 0.09 (vs pretreatment 0.64 ± 0.11; P = .191) at the forearm. The percent change in BMD was greatest at spine (8.3%) followed by the hip (7.6%) and forearm (3.0%). Conclusion Operative management with total thyroidectomy improved the bone loss associated with hyperthyroidism as early as 6 months postoperatively at the hip and spine despite concomitant vitamin D deficiency. Delayed recovery of bone indices at the forearm, a cortical bone, requires further long-term evaluation. [ABSTRACT FROM AUTHOR]

A new electrical capacitance tomography (ECT) image reconstruction method, termed Sensitivity Factor Regularization (SFR), is developed. The SFR method provides an explicit formulation for solving the image reconstruction problem that performs better than other explicit methods, such as linear back-projection and Tikhonov regularization, while providing the same computational efficiency. The computational ease of the SFR method renders it an attractive option for ECT where real-time imaging is required and theoretical statistical evaluation of proposed electrode configurations may readily be performed. A statistical study is conducted using SFR image reconstructions for investigating the impact of electrode density on image quality for a symmetric ECT system characterizing a square cross-section. A larger number of smaller electrodes allows more data to be gathered for use in image reconstruction, but degrades signal-to-noise ratio in the measurements. The statistical study using SFR clearly identifies a theoretical optimum electrode density that minimizes reconstructed image error for a given level of measurement noise. [ABSTRACT FROM AUTHOR]

The existing screening systems for anti-hepatitis B virus (anti-HBV) drug discovery is time-consuming mainly due to the laborious detection system it is using. A new fluorescence based screening system for high throughput anti-HBV drug discovery was created by tagging hepatitis B surface antigen (HBsAg) with monomeric red fluorescent protein and hepatitis B virus (HBV) core protein with enhanced green fluorescent protein. The two constructs were co-transfected on to Hep3B cells and the transfection was stabilized by fluorescent activated cell sorter (FACS). The fusion proteins expressed through the secretory protein pathway as evidenced by localization with ER-Tracker and tubulin tracker. The new system has given analogues results like that of conventional enzyme-linked immunosorbent assay (ELISA). Hence it can be of very high potential for large scale drug screening systems. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Phyllanthus rheedei Wight is a plant used by Muthuvan tribes of Kerala for treating liver related diseases. Materials and methods The different extracts of Phyllanthus rheedei were analysed on cell lines were viz , PLC/PRF, Hep3B, FLCII10 and HepG2215 for its anti-HBV property. The analysis was done through ELISA, SQRT-PCR and immuno blotting. The most active extract was then divided in to fractions using HPTLC and the most active fraction was further identified. Results From the screening experiments it was shown that the ethanol extract of this plant has the maximum activity in lowering the viral markers like HBsAg, HBV Core and HBV X protein and whole virions with comparatively lesser cytotoxicity. The dose responses of this particular extract were further established. Conclusions This study concluded that the ethanol extract of Phyllanthus rheedei is very much effective in preventing the multiplication of HBV at the cellular level. This study scientifically validated the tribal claim of the use of this plant for severe liver disorders. [ABSTRACT FROM AUTHOR]

Abstract: Characterization and design of fluid–thermal transport through random porous sintered beds is critical for improving the performance of two-phase heat transport devices such as heat pipes. Two-dimensional imaging techniques are quite well developed and commonly employed for microstructure and material characterization. In this study, we employ 2D image data (thin sections) for measuring critical microstructural features of commercial wicks for use in correlation-based prediction of transport properties. We employ a stochastic characterization methodology based on the two-point autocorrelation function, and compare the predicted properties such as particle and pore diameters and permeability with those from our previously published studies, in which 3D X-ray microtomography data was employed for reconstruction. Further, we implement a reconstruction technique for reconstructing a three-dimensional stochastic equivalent structure from the thin sections. These reconstructed domains are employed for predicting effective thermal conductivity, permeability and interfacial heat transfer coefficient in single-phase flow. The current computations are found to compare well with models and correlations from the literature, as well as our previous numerical studies. Finally, we propose a new parametrized model for the design of porous materials based on the nature of the two-point autocorrelation functions. Using this model, we reconstruct sample three-dimensional microstructures, and analyze the influence of various parameters on fluid–thermal properties of interest. With advances in additive manufacturing techniques, such an approach may eventually be employed to design intricate porous structures with properties tailored to specific applications. [Copyright &y& Elsevier]

Highlights: [•] A measurement technique is developed to characterize microscale liquid–gas interfaces. [•] The interface position measurement accuracy is shown to be 1.06μm. [•] Liquid–gas interface shapes in adiabatic annular microchannel flows are mapped. [Copyright &y& Elsevier]