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Bioenhanced advanced third generation solid dispersion of tadalafil: Repurposing with improved therapy in pyelonephritis

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Asian Journal of Pharmaceutical Sciences 2017年第6期12卷 569-579页

作者： Prashant P. Mande Sagar S. Bachhav Padma v. devarajan department of Pharmaceutical Sciences and Technology Institute of Chemical Technology N. P. Marg

Tadalafil (TdL) a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN). However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid dispersion (Sd) of TdL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC) to achieve high drug loading, improved stability and rapid dissolution of TdL for enhancing bioavailability and efficacy in PN. TdLSMEC-Sd was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release Sd as a film. TdL-SMEC-Sd was evaluated for in-vivo oral bioavailability and in-vivo efficacy in lipopolysaccharide-induced PN in rats. TdL exhibited high solubility (45.6 mg/ml) in the SMEC. TdL-SMEC-Sd exhibited remarkably high TdL loading (45%w/w),exceptionally low contact angle (9°), rapid in-vitro release (t50 7.3 min), microemulsion formation(globule size ~100 nm) in aqueous dispersion, and stability as per ICH ***, dSC, and XRd confirmed high physical stability. A relative bioavailability of 350% and 150% compared to TdL and TdL-Sd without SMEC respectively, established the superiority of TdL-SMEC-Sd. A significant reduction in serum creatinine, blood urea nitrogen and nitric oxide levels in the lipopolysaccharide-induced PN confirmed the benefit of the TdL-SMECSd. The advanced third generation SMEC Sds presents the possibility of platform technology for bioenhancement of poorly water soluble drugs.

关键词： Phosphodiesterase-5 Lipopolysaccharide Kidney infection Eudragit EPO Kidney failure

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Light emission of heavily doped AlGaN structures under optical pumping

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Journal of Semiconductors 2018年第4期39卷 28-33页

作者： P. A. Bokhan N. v. Fateev I. v. Osinnykh T. v. Malin dm. E. Zakrevsky K. S. Zhuravlev Xin Wei Jian Li Lianghui Chen Rzhanov Institute of Semiconductor Physics SB RAS Novosibirsk 630090 Russia Novosibirsk State University Novosibirsk 630090 Russia Novosibirsk State Technical University Novosibirsk 630073 Russia Institute of Semiconductors Chinese Academy of Sciences Beijing 100083 China

Spectral, temporal and polarization characteristics of spontaneous and stimulated luminescence of Al0.5Ga0.5N/A1N structures grown by molecular beam epitaxy were studied at the optical pulsed pumping with 2 = 266 nm. Samples with a high degree of silicon doping were investigated. The vast majority of radiation falls on transitions within the band gap between the levels of defects. As a result, the radiation band embracing the whole visible range of more than 300 THz is observed in both spontaneous radiation and induced luminescence. In spon- taneous radiation the band has a smooth spectral intensity distribution over the wavelengths, whereas induced radi- ation has its sharp peaks corresponding to the mode structure of the planar waveguide. The measured gain of the active medium is g ≈ 70 cm 1 for a weak signal.

关键词： film optical characteristics laser material

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The Epigenome as a therapeutic target for Parkinson's disease

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Neural Regeneration Research 2016年第11期11卷 1735-1738页

作者： Shane v.Hegarty Aideen M.Sullivan Gerard W.O'Keeffe department of Anatomy and Neuroscience Biosciences InstituteUniversity College Cork

Parkinson＇s disease （Pd） is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in Pd patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in Pd. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in Pd patients, and that epigenetic modulation is a promising therapeutic approach for Pd. This ar- ticle first discusses the present evidence implicating global, and dopaminergic neuron-specific, akerations in the methylome in Pd, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase （HAT） and histone deacetylase （HdAC） enzymes that mediate this process are attractive therapeutic targets for Pd. It discusses the use of activators and/or inhibitors of HdACs and HATs in models of Pd, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for Pd, and the future research that will be required to determine and realise this therapeutic potential.

关键词： Parkinson's disease epigenetics methylation acetylation histone acetyltransferase histonedeacetyIase small molecules

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ITERATIvE ALGORITHMS FOR SYSTEM OF vARIATIONAL INCLUSIONS IN HAdAMARd MANIFOLdS

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Acta Mathematica Scientia 2022年第4期42卷 1333-1356页

作者： Qamrul Hasan ANSARI Feeroz BABU d.R.SAHU department of Mathematics Aligarh Muslim UniversityAligarh202002India department of Applied Mathematics Aligarh Muslim UniversityAligarh202002India department of Mathematics Banaras Hindu UniversityVaranasi 221005India

In this paper,we consider system of variational inclusions and its several spacial cases,namely,alternating point problems,system of variational inequalities,etc.,in the setting of Hadamard *** propose an iterative algorithm for solving system of variational inclusions and study its convergence *** special cases of the proposed algorithm and convergence result are also *** present application to constraints minimization problems for bifunctions in the setting of Hadamard *** the end,we illustrate proposed algorithms and convergence analysis by a numerical *** algorithms and convergence results of this paper either improve or extend known algorithms and convergence results from linear structure to Hadamard manifolds.

关键词： System of variational inclusions altering point problems monotone vector fields strictly pseudocontractive mappings Hadamard manifolds

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RNA-protein distance patterns in ribosomes reveal the mechanism of translational attenuation

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Science China(Life Sciences) 2014年第11期57卷 1131-1139页

作者： YU dongMei ZHANG Chao QIN PeiWu CORNISH v.Peter XU dong department of Biological Engineering University of Missouri C.S. Bond Life Science Center University of Missouri department of Computer Science University of Missouri department of Biochemistry University of Missouri

Elucidating protein translational regulation is crucial for understanding cellular function and drug development.A key molecule in protein translation is ribosome,which is a super-molecular complex extensively studied for more than a half *** structure and dynamics of ribosome complexes were resolved recently thanks to the development of X-ray crystallography,Cryo-EM,and single molecule *** studies of the ribosome have shown multiple functional states,each with a unique *** this study,we analyzed the RNA-protein distances of ribosome(2.5 Mda)complexes and compared these changes among different ribosome *** found that the RNA-protein distance is significantly correlated with the ribosomal functional ***,the analysis of RNA-protein binding distances at important functional sites can distinguish ribosomal functional states and help understand ribosome *** particular,the mechanism of translational attenuation by nascent peptides and antibiotics was revealed by the conformational changes of local functional sites.

关键词： ribosome protein translation antibiotics translocation RNA-protein interaction

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Fixed bimonthly aflibercept in nave and switched neovascular age-related macular degeneration patients:one year outcomes

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International Journal of Ophthalmology(English edition) 2016年第8期9卷 1156-1162页

作者： Alasdair N Warwick Hannah H Leaver Andrew J Lotery Srini v Goverdhan Clinical Neurosciences Research Group Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton Eye Unit University Hospital Southampton NHS Foundation Trust

AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMd) patients using bimonthly fixed dosing aflibercept ***: This was a retrospective study of 165 eyes with nv AMd started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata(PRN) ranibizumab/bevacizumab due to poor response(107 eyes), or treatment- nave( 58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity(BCvA) and central retinal thickness(CRT)from baseline were assessed using the Wilcoxon signedrank test. The proportion of patients maintaining BCvA(vA change at month 12 was +3.29 and +4.67 letters in the switched and nave aflibercept groups respectively(P vA was maintained in 95.3% of switched and 96.6% of nave patients. CRT at month 12 showed a decrease of -6.16 μm in the switched group and -35.36 μm in the nave group(P viously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6 mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections(nave group), 7.5 injections(switched group) and 4 clinic visits per ***: Fixed bimonthly aflibercept is effective in both treatment-nave and poorly responsive nv AMd patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.

关键词： age-related macular degeneration ranibizumab aflibercept anti-vascular endothelial growth factor

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Pseudopolyps in inflammatory bowel diseases: Have we learned enough?

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World Journal of Gastroenterology 2017年第9期23卷 1541-1551页

作者： dimitrios S Politis Konstantinos H Katsanos Epameinondas v Tsianos dimitrios K Christodoulou department of Gastroenterology University Hospital of IoanninaFaculty of MedicineSchool of Health SciencesUniversity of Ioannina45110 IoanninaGreece

Pseudopolyps are a well described entity in the literature and even though the exact pathogenesis of their formation is not completely understood, they are considered non-neoplastic lesions originating from the mucosa after repeated periods of inflammation and ulceration associated with excessive healing processes. Their occurrence is less common in Crohn's disease than in ulcerative colitis, and their overall prevalence ranges from 4% to 74%; moreover, they are found more often in colon but have been detected in other parts of the gastrointestinal tract as well. When their size exceeds the arbitrary point of 1.5 cm, they are classified as giant pseudopolyps. Clinical evaluation should differentiate the pseudopolyps from other polypoid lesions, such as the dysplasiaassociated mass or lesion, but this situation represents an ongoing clinical challenge. Pseudopolyps can provoke complications such as bleeding or obstruction, and their management includes medical therapy, endoscopy and surgery; however, no consensus exists about the optimal treatment approach. Patients with pseudopolyps are considered at intermediate risk for colorectal cancer and regular endoscopic monitoring is recommended. Through a review of the literature, we provide here a proposed classification of the characteristics of pseudopolyps.

关键词： Pseudopolyps Inflammatory polyps Post-inflammatory polyps Giant pseudopolyps Ulcerative colitis Inflammatory bowel disease Crohn’s disease Classification dysplasia-associated mass or lesion

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Integrated Approach of Brain disorder Analysis by Using deep Learning Based on dNA Sequence

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Computer Systems Science & Engineering 2023年第6期45卷 2447-2460页

作者： Ahmed Zohair Ibrahim P.Prakash v.Sakthivel P.Prabu Computer Sciences department College of Computer and Information SciencesPrincess Nourah Bint Abdulrahman UniversityRiyadhP.O.Box 8442811671KSA School of Computer Scence and Engineering Vellore Institute of TechnologyChennai600127India department of Computer Science CHRIST(Deemed to be University)Bangalore560029India

In order to research brain problems using MRI,PET,and CT neuroimaging,a correct understanding of brain function is *** has been considered in earlier times with the support of traditional *** learning process has also been widely considered in these genomics data processing *** this research,brain disorder illness incliding Alzheimer’s disease,Schizophrenia and Parkinson’s diseaseis is analyzed owing to misdetection of disorders in neuroimaging data examined by means fo traditional ***,deep learning approach is incorporated here for classification purpose of brain disorder with the aid of deep Belief Networks(dBN).Images are stored in a secured manner by using dNA sequence based on JPEG Zig Zag Encryption algorithm(dBNJZZ)*** suggested approach is executed and tested by using the performance metric measure such as accuracy,root mean square error,Mean absolute error and mean absolute percentage *** dBNJZZ gives better performance than previously available methods.

关键词： deep belief networks zig zag deep learning mean absolute percentage error mean absolute error root mean square error dNA genomics

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detection of Proper Motion in OQ208

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Chinese Physics Letters 2000年第4期17卷 307-309页

作者：刘祥 C.Stanghellini d.dallacasa M.Bondi Urumqi Astronomical Observatoryj National Astronomical Observatories Chinese Academy of SciencesUrumqi 830011 Istituto di Radioastronomia del CNRt Notot Italy Uhiversita di Bolognaf Italy Istituto di Radioastronomia del CNR Bolognat Italy

We report on an ongoing work aimed to detect the separation speed of the two hot-spots of the compact symmetric object *** images at 8.4 GHz taken in 6 epoches between 1994 and 1997 we obtain an estimate of 0.058±-0.038 mas/year as the relative motions between two components of the radio *** the red-shift of OQ208 I mas correspond to 1pc,thus we obtain a projected jet speed of 0.095±*** an inclination of 45°between the jets and the line of sight,we have an actual jet velocity of 0.134±0.088c and therefore the kinematic age of the source is so young of 320±210 years.

关键词： OQ epoch separation

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description of alpha-clustering of 8Be nucleus states in high-precision theoretical approach

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Chinese Physics C 2020年第12期44卷 146-157页

作者： d.M.Rodkin Yu.M.Tchuvil’sky dukhov Research Institute for Automatics 127055MoscowRussia Skobeltsyn Institute of Nuclear Physics Lomonosov Moscow State University119991 MoscowRussia

Scrupulous theoretical study of 8Be nucleus states,both clustered and non-clustered,is performed over a wide range of excitation *** quantities that characterize the degree of the alpha-clustering of these states,i.e.,spectroscopic factors,cluster form factors,and alpha-decay widths,are computed in the framework of the developed accurate ab initio *** basic properties of the 8Be spectrum,including the binding and excitation energies and the mean values of the isospin,are calculated *** the majority of instances,the results of the computation turn out to be in good agreement with the spectroscopic data.A number of predictions are made,and corresponding verification experiments are *** of the developed approach for nuclear spectroscopy are demonstrated.

关键词： nuclear clustering nuclear structure light nuclei alpha-spectroscopy ab initio computations

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