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Pancreatic stellate cell: Pandora's box for pancreatic disease biology

World Journal of Gastroenterology 2017年第3期23卷 382-405页

作者： ratnakar r bynigeri Aparna Jakkampudi ramaiah Jangala Chivukula Subramanyam Mitnala Sasikala G Venkat rao D Nageshwar reddy rupjyoti Talukdar Institute of Basic Sciences Asian Healthcare FoundationHyderabad 500082India Department of Medical Gastroenterology Asian Institute of GastroenterologyHyderabad 500082India Department of Surgical Gastroenterology Asian Institute of GastroenterologyHyderabad 500082India

Pancreatic stellate cells(PSCs) were identified in the early 1980 s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC). Several pathways(e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and mi rNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma.

关键词： Pancreatic stellate cells Pancreatic fibrosis Pancreatic cancer stroma Physiological functions Pancreatic stellate cells-cancer-stromal interactions Therapeutic targets

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Geochemical studies of hybrid granite from Madugulapalli area, Eastern Dharwar Craton, Southern India: Implications for crustal mixing

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Acta Geochimica 2023年第1期42卷 9-23页

作者： Nagamma J ratnakar J Ajay kumar A Ashok Ch State Mines and Geology Department 508001 NalgondaIndia Department of Geology Osmania University500007 HyderabadIndia CSIr-National Geophysical research Institute 500007 UppalHyderabadIndia

Magma produced by melting of continental crust and mantle at the Archean-Proterozoic boundary are compositionally variable and chemical compositions provide evidence for the mixing of two sources. Understanding the composition of hybrid magma is essential for determining the comparative infl uence of crust and mantle sources during orogenesis. The hybrid granites are less documented in Indian cratons, especially less in Dharwar Craton. Here we present petrographic and whole-rock geochemical data of Madgulapalli granitic rocks situated in the NE part of the Eastern Dharwar Craton(EDC), to elucidate their petrogenesis and role in crust formation. The Madugulapalli granites(MPG) are composed chiefl y of plagioclase, quartz, and alkali feldspar with associated biotite showing alteration and inter-granular textures. Geochemically, they are metaluminous to peraluminous in nature with calc-alkaline hybrid granite. The hybrid granites exhibit both negative and positive europium anomalies;the lower rb/Sr, rb, Sr, and higher Sr/Y,(Dy/Yb)N ratios suggest that the interaction of older rocks with residual garnet source melted at high pressures. We hypothesize that hybrid granites are formed by interaction(e.g., metasomatism, mingling, or mixing) between parental magmas and pre-existing rocks with the infl uence of sanukitoid melts(heat source) in a subduction environment. The genesis of the hybrid granites demonstrates the mixing coupled with diff erentiation in the petrogeny’s residue system in a syn-collision setting followed by continental crust stability in EDC during the Neoarchean period.

关键词： Madugulapalli granite Hybrid granite Crustal mixing Subduction

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Particle Swarm Optimization Based Support Vector regression for Blind Image restoration

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Journal of Computer Science & Technology 2012年第5期27卷 989-995页

作者： ratnakar Dash Pankaj Kumar Sa Banshidhar Majhi Computer Science and Engineering Department National Institute of Technology RourkelaRourkela 769008India

This paper presents a swarm intelligence based parameter optimization of the support vector machine （SVM） for blind image restoration. In this work, SVM is used to solve a regression problem. Support vector regression （SVr） has been utilized to obtain a true mapping of images from the observed noisy blurred images. The parameters of SVr are optimized through particle swarm optimization （PSO） technique. The restoration error function has been utilized as the fitness function for PSO. The suggested scheme tries to adapt the SVM parameters depending on the type of blur and noise strength and the experimental results validate its effectiveness. The results show that the parameter optimization of the SVr model gives better performance than conventional SVr model as well as other competent schemes for blind image restoration.

关键词： image restoration support vector regression particle swarm optimization

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Hybrid, Optimal, Intelligent and Classical PV MPPT Techniques: A review

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CSEE Journal of Power and Energy Systems 2021年第1期7卷 9-33页

作者： ratnakar Babu Bollipo Suresh Mikkili Praveen Kumar Bonthagorla Department of Electrical and Electronics Engineering National Institute of Technology GoaFARMAGUDIPondaGoa 403401India

renewable energy-based solar photovoltaic(PV)generation is the best alternative for conventional energy sources because of its natural abundance and environment friendly *** power extraction from the PV system plays a critical role in increasing the efficiency of the solar power generation during partial shading conditions(PSCs).Therefore,a suitable maximum power point tracking(MPPT)technique to track the maximum power point(MPP)is of high need,even under *** paper presents an organized and concise review of MPPT techniques implemented for the PV systems in literature along with recent publications on various hardware design *** classification is done into four categories,***,intelligent,optimal,and hybrid depending on the tracking algorithm utilized to track MPP under *** uniform insolation,classical methods are highly preferred as there is only one peak in the P-V ***,under PSCs,the F-V curve exhibits multiple peaks,one global maximum power point(GMPP)and remaining are local maximum power points(LMPP’s).Under the PSCs,classical methods fail to operate at GMPP and hence there is a need for more advanced MPPT *** MPPT technique has its advantages and limits,but a streamlined MPPT is drafted in numerous parameters like sensors required,hardware implementation,cost viability,tracking speed and tracking *** study provides the advancement in this area since some parameter comparison is made at the end of every classification,which might be a prominent base-rule for picking the most gainful sort of MPPT for further research.

关键词： GMPP MPPT classification MPPT techniques partial shading conditions(PSCs) photovoltaic system

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Mineralogy and textural impact on beneficiation of goethitic ore

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矿业科学技术学报：英文版 2017年第3期27卷 445-450页

作者： Dey Shobhana Mohanta Manoj K. Singh ratnakar Mineral Processing Division CSIR-National Metallurgical Laboratory Jamshedpur 831007 India

The effect of mineralogy and texture on the beneficiation of goethitic ores from two different origins is highlighted. Sample A having 54.47% Fe with 8.57% loss of ignition(LOI) indicates the presence of vitreous and ochreous goethite, martite and microplaty hematite as the major minerals. Sample B contains 56.90% Fe with 14.4% LOI. There is a pisolithic laterite containing vitreous and ochreous goethite, quartz, kaolinitic clay and there is no hematite mineral. The liberated minerals in -150 + 100μm size class are 74% for Sample A and 37% only for Sample B which shows that the Sample A appears to be more amenable to beneficiate. A concentrate of 46.7% with 63.22% Fe could be recovered from Sample A while subjected to gravity separation followed by wet magnetic separation. The Sample B does not respond to gravity and magnetic separation due to its complex mineralogy. However, calcination of the Sample B followed by magnetic separation gives the encouraging results. Thus, anomalous behaviour of the goethite dominated ores in beneficiation is attributed to the different textural and liberation characteristic.

关键词：选矿过程矿物学织构针铁矿高岭石粘土赤铁矿湿式磁选重力分离

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Transcriptome Profiles and Gene Expression of Min6 Cells Are Altered by Pancreatic Stellate Cells

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Advances in Bioscience and Biotechnology 2018年第6期9卷 273-288页

作者： ratnakar reddy bynigeri Sasikala Mitnala ravikanth Vishnubhotla rupjyoti Talukdar Surya Satyanarayana Singh Nageshwar reddy Duvvuru Asian Healthcare Foundation Hyderabad India Asian Institute of Gastroenterology Hyderabad India Osmania University Hyderabad India

Aim: To identify the influence of pancreatic stellate cell (PSCs) secretions on gene expression profiles of Min6 cells by whole transcriptome sequencing. Methods: Pancreatic stellate cells (PSCs) were isolated from C57BL6J mice and propagated in vitro to acquire the activated phenotype. Total rNA was isolated from monocultured (MC) and PSC cocultured (CC) Min6 cells to prepare cDNA libraries, which were subjected to whole transcriptome sequencing for identifying differential expression of β-cell transcription factors (Pdx-1, rfx6 and NeuroD1) related to insulin gene transcription and GSIS related genes such as Glut2, Gck, Abcc8, Kcnj11 and L-type Ca2+ channels (Cacnb2, Cacna1c). qrT-PCr was used to validate the gene expression. GSIS of Min6 cells was examined by estimating insulin levels in response to high glucose challenge. results: Transcriptome analysis of discovery set revealed that coculture of Min6 cells with PSCs caused increased expression of β-cell specific genes (Ins1, rfx6 and NeuroD1) concomitant with decreased expression of Pdx-1, MafA and Nkx2-2. Expression of GSIS associated genes (Glut2, Gck, Abcc8, Kcnj11 and Cacnb2) was decreased in such conditions. Validation by qrT-PCr in Min6 cells cocultured with PSCs revealed increased significant expression of Ins1 (2.1 ± 0.22 folds;p ≤ 0.001), rfx6 (1.68 ± 0.23 folds;p ≤ 0.002) and NeuroD1 (0.96 ± 0.11 folds;p ≤ 0.01), accompanied by downregulation of Cacnb2 (-0.93 ± 0.57 folds;p ≤ 0.05). PSC secretions did not restore the GSIS from glucose unresponsive higher passage Min6 cells (MC: 1.33 ± 0.42;CC: 1.55 ± 0.72 pmol/mg protein;p = ns) upon high glucose stimulation. However, glucose responsive higher passage Min6 cells cocultured with PSCs presented increased insulin secretion (MC: 7.025 ± 0.64;CC: 14.84 ± 1.01 pmol/mg protein;p ≤ 0.04) concomitant with marginal increase of insulin contents. Conclusion: PSC secretions increase Ins1, rfx6 and NeuroD1 gene expression, GSIS from glucose responsive Min6 cells, b

关键词： β-Cells Gene Expression Islets Pancreatic Stellate Cells Tran-scriptome

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Tuberculosis treatment-new approach to an old problem

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Asian Pacific Journal of Tropical Medicine 2009年第1期2卷 80-82页

作者： Lakshmi Kiran Chelluri Prasad C E Murthy K J r ratnakar K S Transplant Biology & Stem Cell Global HospitalsLakdi-ka-PoolHyderabad-500004India A.P.Chest Hospital IrrumnumaHyderabad-500036India Bhagwan Mahavir Hospital & research Centre Masab TankHyderabad-500004India Global Medical Education & research Centre Global HospitalsLakdi-ka-PoolHyderabad-500004India

Chronic mycobacterium infections are major causes of disease burden of 20%in a tropical country like India. The inflammatory cascade following these bacterial infections often leads to tissue damage and perpetuates necrosis, fibrosis and the disease *** tuberculosis,multi-drug resistant tuberculosis not only affects individuals but society at *** remedial measures using various technology platforms singularly did not produce effective and appreciable reduction in global disease *** the contrary,the conventional chemotherapeutic chemical moieties have demonstrated variable pharmacogenomic expression,increased drug resistance,non compliance of strict prolonged drug regimens with debilitating side effects and contraindications. Furthermore,secreted inflammatory cytokines results in chronic infection,immune deviation,and immunopathology in the ***,identification of immune escape mechanisms leading to chronic mycobacterial infections is crucial for development of new *** review would dwell into the basic pathogenic mechanism and the newer approaches that may need to be considered for developing novel therapeutic strategies.

关键词： Tuberculosis Multi-drug resistant tuberculosis Treatment

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Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors

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Cancer Drug resistance 2019年第3期2卷 580-594页

作者： ratnakar Singh Zeeshan Fazal Sarah J.Freemantle Michael J.Spinella Department of Comparative Biosciences University of Illinois at Urbana-ChampaignUrbanaIL 61801USA The Carle Illinois College of Medicine University of Illinois at Urbana-ChampaignUrbanaIL 61801USA The Cancer Center of Illinois University of Illinois at Urbana-ChampaignUrbanaIL 61801USA

Testicular germ cell tumors(TGCTs)are a cancer pharmacology success story with a majority of patients cured even in the highly advanced and metastatic *** treatment of TGCTs is primarily due to the exquisite responsiveness of this solid tumor to cisplatin-based ***,a significant percentage of patients are,or become,refractory to cisplatin and die from progressive *** for both clinical hypersensitivity and resistance have largely remained a mystery despite the promise of applying lessons to the majority of solid tumors that are not curable in the metastatic ***,this promise has been heightened by the realization that distinct(and perhaps pharmacologically replicable)epigenetic states,rather than fixed genetic alterations,may play dominant roles in not only TGCT etiology and progression but also their curability with conventional *** this review,it discusses potential mechanisms of TGCT cisplatin sensitivity and resistance to conventional chemotherapeutics.

关键词： Testicular cancer embryonal carcinoma cisplatin resistance epigenetics testicular germ cell tumors DNA methylation p53

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Hemolysins of <i>Staphylococcus aureus</i>—An Update on Their Biology, role in Pathogenesis and as Targets for Anti-Virulence Therapy

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Advances in Infectious Diseases 2019年第2期9卷 80-104页

作者： Sireesha Divyakolu rosy Chikkala Kamaraju Suguna ratnakar Venkataraman Sritharan Department of Molecular Diagnostics & Biomarkers Global Medical Education & Research Foundation (GMERF) Hyderabad India Global Medical Education & research Foundation (GMErF) Hyderabad India Department of Molecular Diagnostics & Biomarkers Gleneagles Global Hospital & Secretary Global Medical Education & Research Foundation (GMERF) Hyderabad India

Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offe

关键词： Staphylococcus aureus Hemolysins PVL Quorum Sensing Biofilm Anti-Virulence Therapy

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Determination of genotoxic alkyl methane sulfonates and alkyl paratoluene sulfonates in lamivudine using hyphenated techniques

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Journal of Pharmaceutical Analysis 2012年第4期2卷 314-318页

作者： N.V.V.S.S.raman A.V.S.S.Prasad K.ratnakar reddy K.ramakrishna Hetero Drugs Ltd.(r&D) GITAM Institute of Science GITAM University

Two highly sensitive methods for the determination of genotoxic alkyl methane sulfonates (AMSs) and alkyl paratoluene sulfonates (APTSs) in lamivudine using hyphenated techniques have been presented. AMSs were determined by GC-MS method using GSBPINOWAX (30 m 0.25 mm 0.25 mm) column. Temperature program was set by maintaining at 100 1C initially for 3 min, then rised to 220 1C at the rate of 15 1C/min and maintained at 220 1C for 16 min. N,N-dimethyl formamide was used as diluent. APTSs were determined by LC-MS using Zorbax, rx C8, 250 mm 4.6 mm, 5 mm column as stationary phase. 0.01 M ammonium acetate is used as buffer. The mixture of buffer and methanol in 75:25 (v/v) ratio was used as mobile phase A and mixture of buffer and methanol in 5:95 (v/v) ratio was used as mobile phase B. The gradient program (T/%B) was set as 0/28, 16/50, 17/100, 23/100, 27/28 and 40/28. Both the methods were validated as per International Conference on Harmonization guidelines. Limit of quantitation was found 1.5 mg/mL for AMSs and was in the range of 1.0-1.5 mg/mL for APTSs.

关键词： Genotoxins Alkyl methane sulfonates Alkyl paratoluene sulfonates Lamivudine Hyphenated techniques

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