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Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models

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World Journal of Gastroenterology 2018年第17期24卷 1888-1900页

作者： Illona-Marie Boulete Anusha Thadi Catherine Beaufrand Viren Patwa apoorva joshi John A Foss E Priya Eddy Helene Eutamene Vaseem A Palejwala Vassilia Theodorou Kunwar Shailubhai UMR 1331 Toxalim INRA/INPT Toulouse 31555France Baruch S.Blumberg Institute DoylestownPA 18902United States Synergy Pharmaceuticals Inc. 420 Lexington AvenueNew YorkNY 10170United States

AIM To investigate the effects of plecanatide and dolcanatide on maintenance of paracellular permeability, integrity of tight junctions and on suppression of visceral hypersensitivity. METHODS Transport of fluorescein isothiocyanate(FITC)-dextran was measured to assess permeability across cell monolayers and rat colon tissues. Effects of plecanatide and dolcanatide on the integrity of tight junctions in Caco-2 and T84 monolayers and on the expression and localization of occludin and zonula occludens-1(ZO-1) were examined by immunofluorescence microscopy. Anti-nociceptive activity of these agonists was evaluated in trinitrobenzene sulfonic acid(TNBS)-induced inflammatory as well as in non-inflammatory partial restraint stress(PRS) rat models. Statistical significance between the treatment groups in the permeability studies were evaluated using unpaired *** Treatment of T84 and Caco-2 monolayers with lipopolysaccharide(LPS) rapidly increased permeability, which was effectively suppressed when monolayers were also treated with plecanatide or dolcanatide. Similarly, when T84 and Caco-2 monolayers were treated with LPS, cell surface localization of tight junction proteins occludin and ZO-1 was severely disrupted. When cell monolayers were treated with LPS in the presence of plecanatide or dolcanatide, occludin and ZO-1 were localized at the cell surface of adjoining cells, similar to that observed for vehicle treated cells. Treatment of cell monolayers with plecanatide or dolcanatide without LPS did not alter permeability, integrity of tight junctions and cell surface localization of either of the tight junction proteins. In rat visceral hypersensitivity models, both agonists suppressed the TNBS-induced increase in abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity, and both agonists also reduced colonic hypersensitivity in the PRS model. CONCLUSION Our results suggest that activation of GC-C signaling mi

关键词： Plecanatide Guanylyl cyclase-C agonists Dolcanatide Uroguanylin Preclinical cyclic guanosine monophosphate Constipation Inflammatory bowel diseases

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Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC mice

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2017年第1期8卷 47-59页

作者： Wen-Chi L Chang Shet Masih Anusha Thadi Viren Patwa apoorva joshi Harry S Cooper Vaseem A Palejwala Margie L Clapper Kunwar Shailubhai Cancer Prevention and Control Program Fox Chase Cancer Center Baruch S.Blumberg Institute Department of Pathology Fox Chase Cancer Center R and D Center Synergy Pharmaceuticals Inc.

AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC) mice with dextran sodium sulfate(DSS)-induced inflammation. METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide(0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated. Plecanatide-mediated activation of guanylate cyclase-C(GC-C) signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP) by ELISA, protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting. Ki-67, c-myc and cyclin D1 were used as markers of proliferation. Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry, respectively. Uroguanylin(UG) and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR). A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures. RESULTS Oral treatment of Apc^(+/Min-FCCC) mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid, flat and indeterminate dysplasias. This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation. Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6, IL-1 TNF), chemokines(MIP-1, IP-10) and growth factors(GCSF and GMCSF) from colon explants derived from mice with acute DSS-induced inflammation. The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues. Although GC-C expression was not altered appreciably, a statistically significant i

关键词： Guanylate cyclase-C Uroguanylin Plecanatide Inflammation Colorectal cancer

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Three-Stage Transfer Learning with AlexNet50 for MRI Image Multi-Class Classification with Optimal Learning Rate

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 155-183页

作者： Suganya Athisayamani A.Robert Singh Gyanendra Prasad joshi Woong Cho School of Computing Sastra Deemed to be UniversityThanjavur613401India Department of Computational Intelligence SRM Institute of Science and TechnologyKattankulathur603203India Department of AI and Software Engineering Kangwon National UniversitySamcheok25913Republic of Korea Department of Electronics Information and Communication EngineeringKangwon National UniversitySamcheok25913Republic of Korea

In radiology,magnetic resonance imaging(MRI)is an essential diagnostic tool that provides detailed images of a patient’s anatomical and physiological *** is particularly effective for detecting soft tissue ***,radiologists manually interpret these images,which can be labor-intensive and time-consuming due to the vast amount of *** address this challenge,machine learning,and deep learning approaches can be utilized to improve the accuracy and efficiency of anomaly detection in MRI *** manuscript presents the use of the Deep AlexNet50 model for MRI classification with discriminative learning *** are three stages for learning;in the first stage,the whole dataset is used to learn the *** the second stage,some layers of AlexNet50 are frozen with an augmented dataset,and in the third stage,AlexNet50 with an augmented dataset with the augmented *** method used three publicly available MRI classification datasets:Harvard whole brain atlas(HWBA-dataset),the School of Biomedical Engineering of Southern Medical University(SMU-dataset),and The National Institute of Neuroscience and Hospitals brain MRI dataset(NINS-dataset)for *** hyperparameter optimizers like Adam,stochastic gradient descent(SGD),Root mean square propagation(RMS prop),Adamax,and AdamW have been used to compare the performance of the learning ***-dataset registers maximum classification *** evaluated the performance of the proposed classification model using several quantitative metrics,achieving an average accuracy of 98%.

关键词： MRI tumors classification AlexNet50 transfer learning hyperparameter tuning optimizer

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Multi-Scale Dilated Convolution Network for SPECT-MPI Cardiovascular Disease Classification with Adaptive Denoising and Attenuation Correction

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 299-327页

作者： A.Robert Singh Suganya Athisayamani Gyanendra Prasad joshi Bhanu Shrestha Department of Computational Intelligence SRM Institute of Science and TechnologyKattankulathur603203Tamil NaduIndia School of Computing Sastra Deemed to be UniversityThanjavur613401Tamil NaduIndia Department of Artificial Intelligence&Software Kangwon National UniversitySamcheok25913Republic of Korea Department of Information Convergence System Graduate School of Smart ConvergenceKwangwoon UniversitySeoul01897Republic of Korea

Myocardial perfusion imaging(MPI),which uses single-photon emission computed tomography(SPECT),is a well-known estimating tool for medical diagnosis,employing the classification of images to show situations in coronary artery disease(CAD).The automatic classification of SPECT images for different techniques has achieved near-optimal accuracy when using convolutional neural networks(CNNs).This paper uses a SPECT classification framework with three steps:1)Image denoising,2)Attenuation correction,and 3)Image *** denoising is done by a U-Net architecture that ensures effective image *** correction is implemented by a convolution neural network model that can remove the attenuation that affects the feature extraction process of ***,a novel multi-scale diluted convolution(MSDC)network is *** merges the features extracted in different scales and makes the model learn the features more *** scales of filters with size 3×3 are used to extract *** three steps are compared with state-of-the-art *** proposed denoising architecture ensures a high-quality image with the highest peak signal-to-noise ratio(PSNR)value of *** proposed classification method is compared with the five different CNN models,and the proposed method ensures better classification with an accuracy of 96%,precision of 87%,sensitivity of 87%,specificity of 89%,and F1-score of 87%.To demonstrate the importance of preprocessing,the classification model was analyzed without denoising and attenuation correction.

关键词： SPECT-MPI CAD MSDC denoising attenuation correction classification

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Photometric studies of two W UMa type variables in the field of distant open cluster NGC 6866

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Research in Astronomy and Astrophysics 2016年第4期16卷 87-96页

作者： Yogesh Chandra joshi Rukmini Jagirdar Santosh joshi Aryabhatta Research Institute of Observational Sciences Manora PeakNainital 263002India Center for Advanced Study in Astronomy Osmania UniversityHyderabad 500007India

We present photometric analysis of the two W UMa type binaries identified in the field of distant open star cluster NGC 6866. Although these systems, namely ID487 and ID494, were reported by joshi et al., a detailed study of these stars has not been carried out before. The orbital periods of these stars are found to be 0.415110±0.000001 day and 0.366709±0.000004 day, respectively. Based on the photometric and infrared colors, we find their respective spectral types to be K0 and K3. The photometric light vari- ations of both stars show the O＇Connell effect which can be explained by employing a dark spot on the secondary components. The V and I band light curves are analyzed using the Wilson-Devinney （WD） code and relations given by Gazeas which yield radii and masses for the binary components of star ID487 of R1 = 1.24 ± 0.01R,R2 = 1.11 4- 0.02Re, and M1 = 1.24 ± 0.02Me, M2 = 0.96 ±0.05Me and for star ID494 of R1 = 1.22 ± 0.02Re, R2 = 0.81 4- 0.01 Re, and M1 = 1.20 4- 0.06 Me, M2 = 0.47 4- 0.01 Me.

关键词： methods: observational -- techniques: photometric -- binaries: eclipsing -- stars: fundamen-tal parameters

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Building momentum for sustainable behaviors in developing regions using Locally Managed Decentralized Circular Economy principles

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Chinese Journal of Chemical Engineering 2019年第7期27卷 1566-1571页

作者： Chandni joshi Jeffrey Seay Department of Chemical and Materials Engineering University of Kentucky

Despite the current threat from climate change,plastic collecting in the world's oceans,and the steady loss of biodiversity,the world continually fails to take action with regard to our rapidly changing ***,waiting on governments to act is no longer a viable *** change is needed and the pace of diplomacy is simply too *** governments are reactionary and taking action to solve future problems is not a priority,even as the threat of potential ecological catastrophe draws ever *** is in the hands of individuals,and it is our decisions and behaviors that will influence the future of our planet and our ability to inhabit ***,building momentum for sustainable behavior must begin with *** neoliberal approach to environmental protection posits that individuals are motivated by rational self-interest,and that economic incentives are necessary to achieve environmental ***,recent research suggests that monetary gain alone actually negatively impacts behavior,and often neglects the rural *** a result,models for projects designed to benefit the environment need more than just a monetary incentive,they must incorporate all three pillars of sustainability:environment,economy and *** approach for building momentum for sustainable behavior with regard to municipal solid waste management,particularly in the developing world,is by implementing Locally Managed Decentralized Circular Economy(LMDCE)*** contribution will describe the role behavioral economics plays in the choices made by producers and *** results of a case study on applying LMDCE principles in Uganda to manage waste plastic accumulation by conversion to fuel oil will be presented.

关键词： Pyrolysis Fuel Pollution Appropriate technology Behavioral economics Municipal solid waste

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Population I Cepheids and understanding star formation history of the Small Magellanic Cloud

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Research in Astronomy and Astrophysics 2016年第4期16卷 71-78页

作者： Yogesh Chandra joshi Auro Prasad Mohanty Santosh joshi Aryabhatta Research Institute of Observational Sciences Manora PeakNainital 263002India National Institute of Technology Rourkela 769008India

In this paper, we study the age and spatial distributions of Cepheids in the Small Magellanic Cloud （SMC） as a function of their ages using data from the OGLE III photometric catalogue. A period - age relation derived for Classical Cepheids in the Large Magellanic Cloud （LMC） has been used to find the ages of Cepheids. The age distribution of the SMC Classical Cepheids is found to have a peak at log（Age）： 8.40 ± 0.10 which suggests that a major star formation event might have occurred in the SMC about 250 4- 50 Myr ago. It is believed that this star forming burst had been triggered by close interactions of the SMC with the LMC and/or the Milky Way. A comparison of the observed spatial distributions of the Cepheids and open star clusters has also been carried out to study the star formation scenario in the SMC.

关键词： stars: Cepheids -- star type: Pop I (classical) -- galaxies: SMC -- methods: statistical

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Luminescence properties of Eu^(2+),Gd^(3+) and Pr^(3+) doped translucent Sialon phosphors

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Journal of Rare Earths 2015年第11期33卷 1142-1147页

作者： Bhupendra joshi Soo Wohn Lee Research Center for Eco Multi-Functional Nano Materials Sun Moon University

Optical properties of hot pressed Sialon ceramics doped with different rare earth oxides（REOs） i.e. Eu2O3, Gd2O3, and Pr2O3 were investigated. The α-Sialon phase was the main phase obtained after sintering as observed by X-ray diffraction（XRD）. The transparency of different samples of varying thickness measured from UV to IR region revealed that the samples were translucent in the visible region while transparent in IR region. The thin samples of 150 μm thickness had transmittance as high as 30% in the visible region. The luminescence was observed in transmittance mode to investigate the effect of sample thickness on luminescence intensity. We observed blue, yellow and red emissions in Sialon doped with Gd2O3, Eu2O3, and Pr2O3, respectively. The excitation wavelength for Gd2O3 and Pr2O3 doped samples were in UV region i.e. 280 and 270 nm, respectively, whereas, for Eu2O3 doped samples was in the blue region（460 nm）. The Eu2O3 doped Sialon having 300 μm thickness showed better white light extraction as coupled with blue LED. Moreover, the fabricated phosphor samples exhibited high hardness around 20 GPa and fracture toughness above 5 MPa·m1/2.

关键词： Sialon phosphors luminescence rare earth oxides hot pressing

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Sedimentological evidence of climate-tectonic interaction in the upper Satluj catchment of NW Himalaya

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Journal of Mountain Science 2024年第6期21卷 1978-1991页

作者： joshi Moulishree JALAL Poonam Department of Geology Kumaun UniversityNainitalUttarakhand 263001India

Quaternary valley fill deposits in the Upper Satluj Valley of NW Himalaya act as archives of changing climate-tectonic dynamics in a *** landforms help in decoding the relationship between climate and *** region is traversed by several active faults and thrusts such as the Kaurik-Chango Fault(KCF)and Sangla Detachment(SD),thereby making upper Satluj Valley tectonically *** parameters such as width of valley floor(Vfw),Normalized Steepness Index(KSn)and geomorphological evidences such as the presence of huge strath terraces,narrowing of the river valley and palaeolake deposits point towards the tectonically active nature of the *** arid,high elevation region is also climatically sensitive as it falls in a transient climatic zone which receives rainfall only during abnormal monsoon *** rainfall causes outburst floods,a common phenomenon in the area due to the blocking of headwater in the upper reaches of the Satluj *** a result,the Quaternary sequence is modified from time to *** transition from hypo concentrated deposits to channel deposits and ponding events are prominent in the depositional sequence,resulting from a response to *** studied Quaternary sediments reveal that the Trans-Himalayan region of the upper Satluj valley is affected by tectonic-climate variability,making it vulnerable to geohazards.

关键词： Himachal Pradesh Quaternary Lithofacies association Tectonics Climate

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Integrated approach for understanding spatio-temporal changes in forest resource distribution in the central Himalaya

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Journal of Forestry Research 2014年第2期25卷 281-290页

作者： A K joshi P K joshi T Chauhan Brijmohan Bairwa TERI University

Intense anthropogenic exploitation has altered distribution of forest resources. This change was analyzed using visual interpretation of satellite data of 1979, 1999 and 2009. Field and interactive social surveys were conducted to identify spatial trends in forest degradation and data were mapped on forest cover and land use maps. Perceptions of villagers were compiled in a pictorial representation to understand changes in forest resource distribution in central Himalaya from 1970 to 2010. For- ested areas were subject to degradation and isolation due to loss of con- necting forest stands. Species like Lantana camara and Eupatorium adenophorum invaded forest landscapes. Intensity of human pressure differed by forest type and elevation. An integrated approach is needed to monitor forest resource distribution and disturbance.

关键词： characterization forest central Himalaya integrated approach distribution spatio-temporal

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