Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial Protein C-Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells.

Purpose To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid-loaded functionalized liposomes that exhibit both enhanced uptake by HRECs and superior biologic activity compared to nontargeting liposomes and free drug. Methods EPCR expression of HRECs was investigated through flow cytometry and Western blot assays. EPCR-targeting liposomes were developed by functionalizing EPCR-specific antibodies onto liposomes, and the uptake of liposomes was assessed with flow cytometry and confocal laser scanning microscopy. The therapeutic potential of EPCR-targeting liposomes was determined by loading them with prednisolone either through bilayer insertion and/or by remote loading into the aqueous core. The carrier efficacy was assessed in two ways through its ability to inhibit secretion of interleukins in cells stimulated with high glucose and angiogenesis in vitro by using an endothelial cell tube formation assay. Results HRECs express EPCR at a similar level in both human aortic and umbilic vein endothelial cells. The EPCR-targeting liposomes displayed at least a 3-fold higher uptake compared to nontargeting liposomes. This enhanced uptake was translated into superior anti-inflammatory efficacy, as the corticosteroid-loaded EPCR-targeting liposomes significantly reduced the secretion of IL-8 and IL-6 and inhibited the development of cell tube formations in contrast to nontargeting liposomes. Conclusions We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised.
A Database-Driven Website of β-Thalassemia Mutations

6 Chapter 1: Overview . 7 Chapter 2: Hemoglobin . 9 2.1: Introduction . 9 2.2: α-globin Gene Cluster . 10 2.3: β-globin Gene Cluster . 10 2.4: Structure of Globin Genes . 11 2.5: Regulation of Globin Genes . 12 Chapter 3: Hemoglobin β Gene (HBB) . 14 3.1: Introduction . 14 3.2: HBB Expression . 15 3.3: HBB Mutations . 15 Chapter 4: β-thalassemia . 22 4.1: Introduction . 22 4.2: Phenotypes of β-thalassemia . 23 4.3: Epidemiology of β-thalassemia in North America . 24 Chapter 5: Database . 25 5.1: Introduction . 25 5.2: PostgreSQL . 26 5.3: Schema . 27 Chapter 6: Web Server-Side Implementation . 31 6.1: Introduction . 31
Screening of MBL and SP-D Genes in Indian Population for SNPs and Their Association with Atopic Asthma

Abstract Mannan-binding lectin (MBL) an acute phase serum protein and surfactant protein D (SP-D) are the collectins that besides their role as innate immune molecules have been suggested to play an important role in asthma. To screen single nucleotide polymorphisms in the gene encoding MBL and SP-D in patients with atopic asthma. PCR amplification of collagen encoding region for MBL and –NH2 terminus encoding region of SP-D from DNA samples of asthmatic subjects, followed by their sequencing. In the MBL gene the SNP’s were studied in 5 controls and 20 patients in exon 1 and intron 1 of the gene. (Alleles 816 A/G, 868 C/T, 875 G/A, 884 G/A and 1011 G/A) while exon 1 of lung surfactant protein D was studied in 5 patients and 5 normal subjects. Of the five SNPs in MBL, G1011A, a novel SNP at position 1011 in the intron 1 of MBL was observed in 60% of asthma patients, while it was not observed in the controls. In case of SP-D out of the two reported SNPs (T341C and G282A in exon1 of SP-D) only T341C was observed in the present study. Present pilot study shows G allele at G1011A in MBL and C allele at T341C in SP-D to be significantly associated with atopic asthma and may serve as marker to identify individuals at risk to atopic asthma, however a greater sample size is required. Further, the present study shows Indians to be genetically distinct w.r. t. exon 1 of SP-D.
Technology, Financial Innovations and Bank Behavior in a Low Income Country

Technology has enabled banks to introduce new products that integrate markets, simplify operations and enable expansion of business at low cost, expand to new markets, take new risks and deepen their markets. Zimbabwe registered significant growth in adoption and diffusion of financial innovations over the past two decades, which coincided with a shift in the structure of credit portfolios of banks, and growth in credit as well as risk appetite. This study empirically evaluates the impact of financial innovations in influencing bank behaviour, specifically, portfolio structure risk appetite and delivery channels of banks in Zimbabwe. The study applied co-relational analysis, Fully Modified OLS and the Dynamic OLS estimation models as well as Autoregressive Granger causality approaches. Empirical results show that technology has the capacity to influence activities of banks in risk management, credit and delivery of banking service in lowincome countries. Precisely, financial innovation influences increase in credit towards previously high-risk areas, compositions of credit portfolios in banks and support growth in number of bank accounts. Causality was found to run from financial innovation to bank behaviour, and only in the long run.
Stability of Periodic Waves in Nonlocal Dispersive Equations

In this work consisting of joint projects with my advisor, Dr. Mathew Johnson, we study the existence and stability of periodic waves in equations that possess nonlocal dispersion, i.e. equations in which the dispersion relation between the temporal frequency ω and wavenumber k of a plane wave (x,t) 7→ ei(kx−ωt) is not of the form ω(k) = p(ik) where p is a polynomial. In models that involve only classical derivative operators (known as local equations), the behavior of the system at a point is influenced solely by the behavior in an arbitrarily small neighborhood. In contrast, equations involving nonlocal operators incorporate long-range interactions as well. Such operators appear in numerous applications, including water wave theory and mathematical biology. Specifically, we establish the existence and nonlinear stability of a special class of periodic bound state solutions of the Fractional Nonlinear Schrödinger Equation, where the nonlocality of the fractional Laplacian presents formidable analytical challenges and elicits the development of functional-analytic tools to complement the absence of moreunderstood techniques commonly used to analyze local equations. Further, we use numerical methods to survey the existence and spectral stability of smalland large-amplitude periodic wavetrains in Bidirectional Whitham water wave models, which implement the exact (nonlocal) dispersion relation of the incompressible Euler equations and are thus expected to better capture high-frequency phenomena than the unidirectional Whitham and Korteweg-de Vries (KdV) equations.
Genetic susceptibility to common mycobacterial diseases

Common mycobacterial diseases, including tuberculosis and leprosy, contribute to major mortality and morbidity worldwide. Despite evidence of an important role of host genetic factors in susceptibility to these infections, few compelling genetic associations have been identified with previous candidate gene and linkage approaches. This thesis investigates the genetic factors of human immunity to these mycobacterial diseases using a high-throughput approach of association testing. To assess genetic susceptibility to tuberculosis, I have conducted a genome-wide association study in the Gambian population as part of the Wellcome Trust Case Control Consortium (WTCCC). The study reveals the region flanking CADM1 as a potential susceptibility locus. Combining this study with a Ghanaian cohort further implicates two genetic loci at chromosome 18q11.2 (P = 9.2x10⁻⁹) and PARD3B (P = 1.4x10⁻⁶). For leprosy, I have performed a gene-centric association study in the New Delhi Indian population. Evidence of significant association was observed in the HLA-DRB1/DQA1 (P = 4.9x10⁻ 14 and TLR1 (P = 1.7x10⁻⁹) loci. These studies identify important genomic regions that may be involved in immunity to tuberculosis and leprosy. Further analysis revealed a significant immunogenetic overlap between tuberculosis and leprosy. This provides proof-of-principle for the subsequent aggregate analysis for mycobacterial susceptibility, which suggests that the steroid biosynthesis pathway may be important in anti-mycobacterial immunity. This thesis represents one of the largest studies to identify the genetic factors for human immunity against mycobacteria. These novel findings will further enhance vaccine and pharmaceutical efforts into prevention and treatment of these mycobacterial diseases.
Adaptation of a β-1,3-glucanase assay to microplate format

A method is described for performance of a beta-1,3-glucanase assay in microplates. The adaptation to microassay format has been made possible through the availability of heat-stable microplates. Assay samples containing beta-1,3-glucanase (cell extracts) and the substrate are mixed in 96-well, autoclavable microplates. Incubation of the enzyme-substrate mixture results in the release of reducing sugars by the action of beta-1,3-glucanase. The levels of these sugars are colorimetrically quantified through the addition of "copper reagent" and neocuproine, incubation at 100 degrees C for 10 min and the resulting reduction of Cu+2 to Cu+. A standard curve of glucose concentrations within the same plate allows for assessment of internal variance. Twenty samples can be assayed in one microplate in 1 h, compared to the 96 test tubes and 4 h needed for traditional assay methods. The net savings in reagents used with the microplate format is substantial. The measurement of optical density is performed rapidly for all of the samples, eliminating the problem of oxidization of Cu+ to Cu+2 during quantification. This method represents a significant savings in time, chemicals and cost.
Brasicystis bennetti n. gen., n. sp. (Trematoda: Didymozoidae). Parasita da Pescada (Sciaenidae) da Amazônia, Brasil

Brasicystis bennetti n. gen., n. sp. (Trematoda: Digenea: Didymozoidae) is described from a commercially important Amazonian fish called the "pescada" (Plagioscion squamosissimus). This parasite lives in the subcutaneous tissues of the mouth and opercula, and also in oval cysts attached to the gills. The presence of these helminths under the skin in these locations causes visible yellow spots because of the accumulation of large numbers of eggs. The new form is the third species of Didymozoidae to be reported from freshwater in the world, and it is caracterized as having a laterally flattened hindbody with a ventral fold anteriorly, and a single tubular testis which extends posterior to the tubular ovary The trematodes have a total length of up to 19 mm. and very small eggs (8x15 µ).
Three remarkable new moss records for South-West Asia from northern Turkey

Grimmia anomala Schimp. , Pohlia filum (Schimp.) Martensson, and Hookeria acutifolia Hook. & Grev. are noteworthy moss species reported here for the first time in South-West Asia from specimens collected in north-eastern and north-western Turkey. The diagnostic characters, habitat preferences, illustrations, and updated ranges of the treated species are given together with notes comparing them with those of related taxa.
Aging of the Autonomic Nervous System

General Aspects: Autonomic Centers and Pathways: Age-related Changes (P. Shaw, F. Ferrante, F. Amenta). The Peripheral Nerve (D. Zaccheo). Age-induced Changes in the Mammalian Autonomic and Sensory Ganglia (J.A. Vega, B. Calzada, M.E. Del Valle). Main Neurotransmitter Systems: Circulating Catecholamines and Aging (O. Kuchel and G. Kuchel). Sensory Neuropeptides and Aging (P. Geppetti). Effect of Age on the Response of Target Organs to Autonomic Neurotransmitters (J.R. Docherty). Age-Dependent Changes of Neuroeffector Mechanisms in Target Organs of the Autonomic Nervous System: Changes in the Effect of the Autonomic Nervous System on the Aging Heart (J. Roberts, D.L. Snyder, M.D. Johnson, and J. Horwitz). Influence of Age on Neuroeffector Mechanisms of the Vasculature (S.P. Duckles). The Respiratory System (C. Brink). Enteric System (R.M. Santer and D.M. Baker). Renal Autonomic Neuroeffector Mechanisms in Aging (A. Ricci). Noradrenergic Sympathetic Innervation of Lymphoid Organs during Development, Aging and in Autoimmune Disease (D.L. Bellinger, S.Y. Felten, K.D. Ackerman, D. Lorton, K.S. Madden, D.L. Felten). Autonomic Neuroeffector Mechanisms in the Reproductive and Endocrine Systems: Age-related Changes (W.L. Collier). Clinical and Therapeutic Perspectives: Age-related Disorders of the Autonomic Nervous System (P. Calabresi, L.M. Cupini, N.B. Mercuri, and G. Bernardi). Therapeutic Implications of Age-related Changes in the Autonomic Nervous System (G.A. Ford and B.B. Hoffman).
Characterisation of G protein-coupled receptor 56-signalling and its potential role in tumour progression

The adhesion G protein-coupled receptor 56 (GPR56) plays a major role in early brain development. Mutations in Gpr56 cause the developmental brain disease bilateral frontoparietal polymicrogyria (BFPP), which is recapitulated in Gpr56-/- mice. GPR56 interacts with collagen III in the brain pial basement membrane and with tissue transglutaminase (TG2) in melanoma, where it potentially acts as a tumour suppressor by antagonising TG2-related functions. In glioblastoma, however, GPR56 is highly overexpressed and might play an important role for the invasive behaviour of these cells, which could be regulated by TG2 in the tumour stroma. The main aim of this thesis was to analyse GPR56 signalling in response to TG2, thus exploring a potential link to cancer development and progression. Identifying downstream signalling pathways activated by GPR56 in response to TG2 could provide valuable information regarding potential targets for future therapeutic intervention in the context of anti-cancer therapies. In order to investigate GPR56 signalling, a cell-based assay was established that measures GPR56 activation as metalloproteinase-dependent ectodomain shedding of alkaline phosphatase-tagged amphiregulin (AP-AR) in HEK293 cells. The assay was used to demonstrate for the first time activation of GPR56 by TG2. RhoA/Rho-associated protein kinase (ROCK)are activated by GPR56, which likely requires Gα12/13 coupling to GPR56. RhoA/ROCK activity is required for the activation of a disintegrin and metalloproteinase 17 (ADAM17), the main metalloproteinase responsible for GPR56-dependent AP-AR shedding. Shedding of EGF-like ligands such as amphiregulin leads to the activation of epidermal growth factor receptors, inducing cellular responses such as cell proliferation and migration. Further investigations using different GPR56 mutants revealed that the Nterminal domain of GPR56 is required for activation by TG2. The crosslinking activity of TG2 is dispensable for GPR56 activation and the C-terminal β-barrel domains of TG2 are sufficient to stimulate GPR56 signalling. Moreover, two novel potential GPR56 ligands, TG6 and TG7, were shown to stimulate GPR56-dependent AP-AR shedding. Using confocal microscopy, GPR56-dependent internalisation of TG2 via clathrin-coated pits was demonstrated, a mechanism that is well known for agonist-activated GPCRs. Finally, the potential role of GPR56 in glioblastoma was investigated by generating stable GPR56 knockdown glioma cells. Analysis of GPR56 knockdown cells indicated that GPR56 may play a role for glioblastoma migration and invasion. These results present a novel signalling pathway activated by GPR56 in response to TG2 that is involved in cell proliferation, growth and migration, potentially providing an explanation for the supposed tumour promoting functions of GPR56 in glioblastoma.
Biochemical analysis of genetically-modified mice with learning and memory phenotypes

Recent advances in molecular genetics have enabled generation of sophisticated genetically-modified mouse models to study specific molecules and their biological function in vivo. Here, I investigated biochemical changes in two different genetically-modified mouse lines with previously described learning and memory phenotypes. Firstly, I analysed biochemical changes in a mouse line carrying a threonine to alanine point mutation at Thr286 of alpha Ca2+/calmoduline-dependent kinase II (aCaMKII), which disenables this phosphorylation site. Autophosphorylation at Thr286 switches aCaMKII into an autonomous activity mode. The T286A mutant mice displayed changes in basal phosphorylation levels. In order to study biochemical changes after activity-dependent synaptic potentiation, an in vivo long-term potentiation (LTP) approach was established and validated by assessing activity-dependent changes in phosphorylation levels of well-characterised marker molecules including synapsin I and NR2B. Both aCaMKII and pCaMKII exhibited elevated levels of autophosphorylation after LTP stimulation in hippocampal area CA1 and dentate gyrus (DG). This finding indicates that pCaMKII may compensate for the loss of autonomous aCaMKII activity in T286A mutants. Furthermore, induction of LTP triggered phosphorylation of glycogen synthase kinase 3 (GSK3) at its inhibitory site suggesting a role for GSK3 in synaptic plasticity. Secondly, I investigated a transgenic (TG) mouse line expressing the cyclin-dependent kinase (Cdk5) activator protein, p25, a protein previously linked to some aspects of Alzheimer's disease (AD). The forebrain restricted expression of p25 started postnatally and stayed constant throughout the life-span of the TG mice. The expression of p25 triggered constitutive over-activation of Cdk5 in the TG mice. The p25 TG mice displayed age-dependent hyperphosphorylation of the microtubule-associated protein tail and age-dependent alterations in the processing of amyloid precursor protein (APP). Furthermore, p25-induced over-activation of Cdk5 led to inhibition of GSK3. This negative regulation of GSK3 was lost in aged p25 TG mice and correlated with the increased tau hyperphosphorylation. The levels of tau phosphorylation in aged p25 mice were reduced after treatment with lithium, an inhibitor of GSK3. These results indicate that GSK3 directly mediates tau hyperphosphorylation, whereas Cdk5 acts indirectly via inhibitory control of GSK3.
Population genetics of selected whitebait species : Galaxias maculatus (Jenyns) and Lovettia sealii (Johnston).

Population Genetics of Selected Whitebait Species: Galaxias maculatus (Jenyns) and Lovettia sealii (Johnston). Populations of diadromous G. maculatus and anadromous L. sealii fishes have been studied for genetic variation by cellulose acetate electrophoresis. L. sealii is a small member of the family Aplochitonidae endemic to Tasmania. In contrast, G. maculatus a salmoniform fish of the Family Galaxiidae, is found throughout the southern temperate zone (Australia, New Zealand and South America). Together these species are the predominant components of Tasmanian whitebait. A significant commercial fishery for Tasmanian whitebait began in 1941 and rapidly declined after 1947 probably due to overfishing (Blackburn, 1950), until its closure in 1974. Encouraging runs of whitebait in the early 1980s prompted a major study to investigate the potential yield and present status of this resource. The lack of data regarding the genetic structure of the species prompted the following study. Eight populations of G. maculatus extending from Western Australia to New Zealand were investigated. Twenty seven samples of L. sealii representing thirteen different river populations from Tasmania were included to capture genetic data both within and between three successive spawning seasons. An analysis of the gene frequency data using Nei's genetic distance (D) and identity (I) , G-test and F-statistics indicated population substructuring in the two species. Morphometric and meristic analysis of L. sealii was also undertaken and supported the genetic data. Within G. maculatus, the Western Australian population was genetically distinct primarily based on allele frequencies observed at the ADH locus. Three genetic pools of G. maculatus were identified which have zoo-geographic implications for this species. In particular they appear to confirm the potential of marine larval dispersal between Australia and New Zealand. A clear genetic discontinuity was observed between north and south Tasmanian L. sealii primarily based on the allele frequency data at the PEPD locus. These fmdings were consistent with those of Blackburn (1950) based on differences in growth rate and pigmentation. However, many southern rivers were found to carry unique stocks. A major contributing factor to this genetic diversity is thought to be the prevailing local hydrographic conditions. The results of this study have implications for the management of the recreational whitebait fishery which has re-opened in Tasmania and possibly the commercial whitebait fishery in New Zealand which is dominated by G. maculatus.
A Survey on Website Attacks Detection And Prevention

In Web Security Applications Has Become Important As The Information Processed By Web Applications Has Become Censorious Corporations, Customers, Organizations, And Country. In Web Attacks Manage A Border Array Of Information Which Includes Financial Data, Medical Records, Social Security Numbers, Intellectual Property And National Security Data. There Many Attacks Through Which Web Based Attacks Are Believe By Security Experts To Be The Greatest And Less Understood Of All Risks All Related To Confidentiality, Availability, And Integrity. This Paper Will Introduced Website Attack And Also How To Detect And Prevent From The Attacks. Attacks Covered Are SQL Injection (SQLI), Cross Site Scripting(CSS), Cross Site Request Forgery(CSRF), Broken Access Control.
Oxygen-sensing and Mitochondrial Control of Cell Function

The cellular response to low oxygen tension (hypoxia) is orchestrated through an elegant pathway involving a number of molecular players and is well characterised in development, physiology and pathology. The hypoxia inducible factors (HIFs) comprise a family of transcription factors whose activity is responsible for mediating transcriptional responses to hypoxia and maintaining cellular oxygen homeostasis. Of particular interest, is the relationship between the HIFs and mitochondria. Mitochondria consume oxygen and generate chemical energy in the form of adenosine triphosphate (ATP). Mitochondrial function and the electron transport chain are necessary for the stabilisation of HIF-α protein in response to hypoxia and the transactivation of HIF target genes. Conversely, mitochondrial adaptation to hypoxia is controlled through a number of HIF target genes. However, the molecular relationship between the HIFs and mitochondria and vice versa is still emerging. Oxygen-dependent regulation of HIF-α protein stability is controlled by the prolyl hydroxylase domain (PHD) proteins. Using several approaches to stabilise and activate the HIFs, this thesis has explored the role of the oxygen-sensing machinery in regulating mitochondrial function. This work identifies altered subcellular localisation of the HIF-complex and PHD proteins. Additionally, manipulation of the oxygen-sensing pathway results in gross mitochondrial morphological and ultrastructural differences in addition to alterations in a number of mitochondrial parameters, including DNA maintenance, electron transport chain (ETC) protein expression, bioenergetics and autophagy. Together these data identify a novel role for members of the oxygen-sensing machinery in mitochondrial function.