Search results for: viral peptide
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 573

Search results for: viral peptide

303 Cut-Off of CMV Cobas® Taqman® (CAP/CTM Roche®) for Introduction of Ganciclovir Pre-Emptive Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Authors: B. B. S. Pereira, M. O. Souza, L. P. Zanetti, L. C. S. Oliveira, J. R. P. Moreno, M. P. Souza, V. R. Colturato, C. M. Machado

Abstract:

Background: The introduction of prophylactic or preemptive therapies has effectively decreased the CMV mortality rates after hematopoietic stem cell transplantation (HSCT). CMV antigenemia (pp65) or quantitative PCR are methods currently approved for CMV surveillance in pre-emptive strategies. Commercial assays are preferred as cut-off levels defined by in-house assays may vary among different protocols and in general show low reproducibility. Moreover, comparison of published data among different centers is only possible if international standards of quantification are included in the assays. Recently, the World Health Organization (WHO) established the first international standard for CMV detection. The real time PCR COBAS Ampliprep/ CobasTaqMan (CAP/CTM) (Roche®) was developed using the WHO standard for CMV quantification. However, the cut-off for the introduction of antiviral has not been determined yet. Methods: We conducted a retrospective study to determine: 1) the sensitivity and specificity of the new CMV CAP/CTM test in comparison with pp65 antigenemia to detect episodes of CMV infection/reactivation, and 2) the cut-off of viral load for introduction of ganciclovir (GCV). Pp65 antigenemia was performed and the corresponding plasma samples were stored at -20°C for further CMV detection by CAP/CTM. Comparison of tests was performed by kappa index. The appearance of positive antigenemia was considered the state variable to determine the cut-off of CMV viral load by ROC curve. Statistical analysis was performed using SPSS software version 19 (SPSS, Chicago, IL, USA.). Results: Thirty-eight patients were included and followed from August 2014 through May 2015. The antigenemia test detected 53 episodes of CMV infection in 34 patients (89.5%), while CAP/CTM detected 37 episodes in 33 patients (86.8%). AG and PCR results were compared in 431 samples and Kappa index was 30.9%. The median time for first AG detection was 42 (28-140) days, while CAP/CTM detected at a median of 7 days earlier (34 days, ranging from 7 to 110 days). The optimum cut-off value of CMV DNA was 34.25 IU/mL to detect positive antigenemia with 88.2% of sensibility, 100% of specificity and AUC of 0.91. This cut-off value is below the limit of detection and quantification of the equipment which is 56 IU/mL. According to CMV recurrence definition, 16 episodes of CMV recurrence were detected by antigenemia (47.1%) and 4 (12.1%) by CAP/CTM. The duration of viremia as detected by antigenemia was shorter (60.5% of the episodes lasted ≤ 7 days) in comparison to CAP/CTM (57.9% of the episodes lasting 15 days or more). This data suggests that the use of antigenemia to define the duration of GCV therapy might prompt early interruption of antiviral, which may favor CMV reactivation. The CAP/CTM PCR could possibly provide a safer information concerning the duration of GCV therapy. As prolonged treatment may increase the risk of toxicity, this hypothesis should be confirmed in prospective trials. Conclusions: Even though CAP/CTM by ROCHE showed great qualitative correlation with the antigenemia technique, the fully automated CAP/CTM did not demonstrate increased sensitivity. The cut-off value below the limit of detection and quantification may result in delayed introduction of pre-emptive therapy.

Keywords: antigenemia, CMV COBAS/TAQMAN, cytomegalovirus, antiviral cut-off

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302 Seroprevalence of Cytomegalovirus among Pregnant Women in Islamabad, Pakistan

Authors: Hassan Waseem

Abstract:

Cytomegalovirus (CMV) is ubiquitously distributed viral agent responsible for different clinical manifestations that may vary according to the immunologic status of the patient. CMV can cause morbidity and mortality among fetuses and patients with compromised immune system. A cross-sectional study was carried out in Islamabad to investigate the prevalence and risk factors associated with CMV infection among pregnant women. Blood samples of 172 pregnant women visiting Mother and Child Healthcare, Pakistan Institute of Medical Sciences (PIMS) Islamabad were taken. In present study, serum samples of the women were checked for CMV-specific IgG and IgM antibodies by enzyme linked immunosorbent assay (ELISA). Clinical, obstetrical and socio-demographical characteristics of the women were collected by using structured questionnaires. Out of 172 pregnant women included in the study, 171 (99.4%) were CMV specific IgG positive and 30 (17.4%) were found positive for CMV-IgM antibodies. The CMV has taken an endemic form in Pakistan so, routine screening of CMV among pregnant women is recommended.

Keywords: Cytomegalovirus, blood transfusion, ELISA, seroprevalence

Procedia PDF Downloads 335
301 In Vitro Antioxidant Properties of Balanites Aeqyptiaca Del Enzymatic Protein Hydrolysates

Authors: Friday A. Ogori, Ojotu M. Eke, Oneh J. Abu, Abraham T. Girgih

Abstract:

B.aeqygtiaca del (Balanites aegyptiaca del) seed protein concentrate (APC) was hydrolyzed using different enzymes such as pepsin+pancreatin (PP), Alcalase (Alca), and Flavourzyme (Flav). The Alca has higher yield (100%) when compared to PP (83.23%) and Flav (62.90%). The hydrophobic amino acid and Sulphur containing amino acid (40.19%, 7.04%) in PP hydrolysate were higher compared to Alcalase (38.92%, 6.69%), Flavourenzyme (37.43%,6.35%), and APC (39.97%, 6.95%) samples. The PP has stronger DPPH, Hydroxyl radical quenching, Ferric reducing activity, and linoleic acid peroxidation activity, followed by the protein concentrate (APC) and Alcalase (Alca), while Flavourenzyme (Flav) derived hydrolysate was least in scavenging and inhibiting radical peroxidation properties. Flavourenzyme derived hydrolysate had stronger Ferric reducing antioxidant potential and metal chelating property. The result showed that the Alcalase hydrolysate has promising peptide yield, and PP hydrolysate had excellent amino acid residues and good in-vitro antioxidant potentials and could be a preferred ingredients in the nutraceutical and functional food emerging industries.

Keywords: balanites aegyptiaca del, protein concentrate, protein hydrolysates, enzymatic hydrolysis, antioxidants

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300 A Recombinant Group a Streptococcus (GAS-2W) Strain Elicits Protective Immunity in Mice through Induction of an IFN-γ Dependent Humoral Response

Authors: Shiva Emami, Jenny Persson, Bengt Johansson Lindbom

Abstract:

Group A streptococcus (GAS) is a prevalent human pathogen, causing a wide range of infections and diseases. One of the most well-known virulence factors in GAS is M protein, a surface protein that facilitates bacterial invasion. In this study, we used a recombinant GAS strain (GAS-2W) expressing M protein containing a hyper immunogenic peptide (2W). Mice were immunized three times with heat-killed-GAS subcutaneously at three weeks intervals. Three weeks post last immunization, mice were challenged intraperitoneally with a lethal dose of live GAS. In order to investigate the impact of IFN-ƴ and antibodies in protection against GAS infection, we used a mouse model knock-out for IFN-ƴ (IFN-ƴ KO). We observed immunization with GAS-2W strain can increase protection against GAS infection in mice compared with the original GAS strain. Higher levels of antibodies against M1 protein were measured in GAS-2W-immunized mice. There was also a significant increase in IgG2c response in mice immunized with GAS2W. By using IFN-ƴ KO mice, we showed that not a high level of total IgG, but IgG2c was correlated with protection through the i.p challenge. It also emphasizes the importance of IFN-ƴ cytokine to combat GAS by isotype switching to IgG2c (which is opsonic for phagocytosis). Our data indicate the crucial role of IFN-ƴ in the protective immune response that, together with IgG2c, can induce protection against GAS.

Keywords: Group A streptococcus, IgG2c, IFN-γ, protection

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299 Potyviruses Genomic Analysis and Complete Evaluation

Authors: Narin Salehiyan, Ramin Ghasemi Shayan

Abstract:

The largest genus of plant viruses, the potyvirus, is responsible for significant crop losses. Potyviruses are aphid sent in a nonpersistent way, and some of them are likewise seed communicated. As significant microorganisms, potyviruses are substantially more examined than other plant infections having a place with different genera, and their review covers numerous parts of plant virology, like utilitarian portrayal of viral proteins, sub-atomic communication with hosts and vectors, structure, scientific classification, development, the study of disease transmission, and determination. Biotechnological utilizations of potyviruses are likewise being investigated. During this last ten years, significant advances have been made in the comprehension of the sub-atomic science of these infections and the elements of their different proteins. Potyvirus multiplication, movement, and transmission, as well as potyvirus/plant compatible interactions, including pathogenicity and symptom determinants, are updated following a general overview of the family Potyviridae and the potyviral proteins. it end the survey giving data on biotechnological uses of potyviruses.

Keywords: virology, poty, virus, genome, genetic

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298 Racial Distress in the Digital Age: A Mixed-Methods Exploration of the Effects of Social Media Exposure to Police Brutality on Black Students

Authors: Amanda M. McLeroy, Tiera Tanksley

Abstract:

The 2020 movement for Black Lives, ignited by anti-Black police brutality and exemplified by the public execution of George Floyd, underscored the dual potential of social media for political activism and perilous exposure to traumatic content for Black students. This study employs Critical Race Technology Theory (CRTT) to scrutinize algorithmic anti-blackness and its impact on Black youth's lives and educational experiences. The research investigates the consequences of vicarious exposure to police brutality on social media among Black adolescents through qualitative interviews and quantitative scale data. The findings reveal an unprecedented surge in exposure to viral police killings since 2020, resulting in profound physical, socioemotional, and educational effects on Black youth. CRTT forms the theoretical basis, challenging the notion of digital technologies as post-racial and neutral, aiming to dismantle systemic biases within digital systems. Black youth, averaging over 13 hours of daily social media use, face constant exposure to graphic images of Black individuals dying. The study connects this exposure to a range of physical, socioemotional, and mental health consequences, emphasizing the urgent need for understanding and support. The research proposes questions to explore the extent of police brutality exposure and its effects on Black youth. Qualitative interviews with high school and college students and quantitative scale data from undergraduates contribute to a nuanced understanding of the impact of police brutality exposure on Black youth. Themes of unprecedented exposure to viral police killings, physical and socioemotional effects, and educational consequences emerge from the analysis. The study uncovers how vicarious experiences of negative police encounters via social media lead to mistrust, fear, and psychosomatic symptoms among Black adolescents. Implications for educators and counselors are profound, emphasizing the cultivation of empathy, provision of mental health support, integration of media literacy education, and encouragement of activism. Recognizing family and community influences is crucial for comprehensive support. Professional development opportunities in culturally responsive teaching and trauma-informed approaches are recommended for educators. In conclusion, creating a supportive educational environment that addresses the emotional impact of social media exposure to police brutality is crucial for the well-being and development of Black adolescents. Counselors, through safe spaces and collaboration, play a vital role in supporting Black youth facing the distressing effects of social media exposure to police brutality.

Keywords: black youth, mental health, police brutality, social media

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297 The Origin, Diffusion and a Comparison of Ordinary Differential Equations Numerical Solutions Used by SIR Model in Order to Predict SARS-CoV-2 in Nordic Countries

Authors: Gleda Kutrolli, Maksi Kutrolli, Etjon Meco

Abstract:

SARS-CoV-2 virus is currently one of the most infectious pathogens for humans. It started in China at the end of 2019 and now it is spread in all over the world. The origin and diffusion of the SARS-CoV-2 epidemic, is analysed based on the discussion of viral phylogeny theory. With the aim of understanding the spread of infection in the affected countries, it is crucial to modelize the spread of the virus and simulate its activity. In this paper, the prediction of coronavirus outbreak is done by using SIR model without vital dynamics, applying different numerical technique solving ordinary differential equations (ODEs). We find out that ABM and MRT methods perform better than other techniques and that the activity of the virus will decrease in April but it never cease (for some time the activity will remain low) and the next cycle will start in the middle July 2020 for Norway and Denmark, and October 2020 for Sweden, and September for Finland.

Keywords: forecasting, ordinary differential equations, SARS-COV-2 epidemic, SIR model

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296 An Integrative Computational Pipeline for Detection of Tumor Epitopes in Cancer Patients

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

Abstract:

Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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295 Surface Active Phthalic Acid Ester Produced by a Rhizobacterial Strain

Authors: M. L. Ibrahim, A. Abdulhamid

Abstract:

A surface active molecule synthesized by a rhizobacterial strain Bacillus lentus isolated from Cajanus cajan was investigated. The bioemulsifier was extracted, purified and partially characterized using standard methods. Surface properties of the bioemulsifier were determined by studying the emulsification index, solubility test and stability studies. Partial purification of the bioemulsifier was carried out using FT-IR analysis, Silica-gel column chromatography and thin layer chromatography. GC-MS analysis was carried out to detect the composition and mass of the lipids and esters. The isolate showed an emulsifying activity of 57% and surface activity of 36mm. The stability studies revealed that the bioemulsifier had better stability at temperature of 70oC, 8% pH and 8% NaCl concentration. FT-IR indicated the bioemulsifier to contain peptide and aliphatic chain, TLC revealed the compound to be ninhydrin positive and Column chromatography showed the presence of three amino acids namely; glutamine, valine and cysteine. GC-MS indicated the lipid moiety to contain aliphatic chain ranging from C9-C16 and two major peaks of 1,2-benzenedicarboxylic acid diethyl octyl ester. Therefore, surface active agent from Bacillus lentus can be used effectively in a wide range of applications such as in MEOR and in the biosynthesis of plasticizers for industrial uses.

Keywords: Bacillus lentus, bioemulsifiers, phthalic acid ester, Rhizosphere

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294 Anterior Uveitis Caused by Infection with Cytomegalovirus and Herpes Simplex Virus Type I at Cicendo Eye Hospital Bandung

Authors: Shinta Stri Ayuda Nur Setyaningsih

Abstract:

Anterior uveitis is often triggered by viral infections such as herpes simplex virus (HSV) and cytomegalovirus (CMV). This study aims to provide an overview of the demographic and clinical characteristics of patients with anterior uveitis caused by CMV and HSV infection at PMN Cicendo Eye Hospital Bandung. This study used a retrospective observational method. Data were collected from the medical records of patients who visited the PMN Infection and Immunology Polyclinic at Cicendo Eye Hospital between February and July 2023. The results showed that anterior uveitis associated with HSV and CMV viruses often occurs in the elderly and more in women. The most common clinical symptoms are red eyes and decreased visual acuity, with a gradual onset of symptoms. Complications that often arise are cataracts and glaucoma. This study provides a deeper understanding of anterior uveitis caused by infection with HSV and CMV viruses.

Keywords: uveitis anterior, cytomegavirus, herpes simplex virus type I ELISA

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293 Antimicrobial Peptide Produced by Lactococcus garvieae with a Broad Inhibition Spectrum

Authors: Hai Chi, Ibrahim Mehmeti, Kirill Ovchinnikov, Hegle Holo, Ingolf F. Nes, Dzung B. Diep

Abstract:

By using a panel of multiple indicator strains of different bacterial species and genera, we screened a large collection of bacterial isolates (over 1800 isolates) derived from raw milk, for bacteriocin producers with broad inhibition spectra (BIS). Fourteen isolates with BIS were identified, and by 16S rDNA sequencing they were found to belong to Lactococcus garvieae (10 isolates) and Enterococcus feacalis (4 isolates). Further analysis of the ten L. garvieae isolates revealed that they were very similar, if not identical, to each other in metabolic and genetic terms: they had the same fermentation profile on different types of sugars, repetitive sequence-based PCR (rep-PCR) DNA pattern as well as they all had the same inhibition profile towards over 50 isolates of different species. The bacteriocin activity from one of the L. garvieae isolates was assessed further. The bacteriocin which was termed garvicin KS, was found to be heatstable and proteinase-labile and its inhibition spectrum contained many distantly related genera of Firmicutes, comprising most lactic acid bacteria (LAB) as well as problematic species of Bacillus, Listeria, Streptococcus and Staphylococcus and their antibiotic resistant derivatives (e.g. VRE, MRSA). Taken together, the results indicate that this is a potent bacteriocin from L. garvieae and that its very broad inhibition spectrum can be a very useful property for use in food preservation as well as in infection treatments caused by gram-positive pathogens and their antibiotic-derivatives.

Keywords: bacteriocin, lactic acid bacteria, Lactococcus garvieae, antibiotics resistance

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292 Cyclic NGR Peptide Anchored Block Co-Polymeric Nanoparticles as Dual Targeting Drug Delivery System for Solid Tumor Therapy

Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas

Abstract:

Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

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291 An Antifungal Peptide from Actinobacteria (Streptomyces Sp. TKJ2): Isolation and Partial Characterization

Authors: Abdelaziz Messis, Azzeddine Bettache, Nawel Boucherba, Said Benallaoua, Mouloud Kecha

Abstract:

Actinobacteria are of special biotechnological interest since they are known to produce chemically diverse compounds with a wide range of biological activity. This distinct clade of Gram-positve bacteria include some of the key antibiotic producers and are also sources of several bioactive compounds, established commercially a newly filamentous bacteria was recovered from Tikjda forest soil (Algeria) for its high antifungal activity against various pathogenic and phytopathogenic fungi. The nucleotide sequence of the 16S rRNA gene (1454 pb) of Streptomyces sp. TKJ2 exhibited close similarity (99 %) with other Streptomyces16S rRNA genes. Antifungal metabolite production of Streptomyces sp TKJ2 was evaluated using six different fermentation media. The extracellular products contained potent antifungal agents. Antifungal protein produced by Streptomyces sp. TKJ2 on PCA medium has been purified by ammonium sulfate precipitation, SPE column chromatography and high-performance liquid chromatography in a reverse-phase column. The UV chromatograms of the active fractions obtained at 214 nm by NanoLC-ESI-MS/MS have different molecular weights. The F20 Peptidic fraction obtained from culture filtrat of Streptomyces sp. TKJ2 precipitated at 30% of ammonium sulfate was selected for analysis by infusion ESI-MS which yielded a singly charged ion mass of 437.17 Da.

Keywords: actinobacteria, antifungal protein, chromatography, Streptomyces

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290 Synthesis and Structural Characterization of 6-Nitroindazole Derivatives

Authors: Mohamed El Moctar Abeidi

Abstract:

The indazole derivatives exhibit a wide spectrum of biological activities. They are known for their anti-tumor, antiplatelet, anti-viral, anti-microbial, anti-inflammatory, anti-leishmania and even anti-spermatogen. As part of our research on the synthesis of a number of heterocycles capable of exhibiting a biological and pharmacological property, due to our ongoing interest in the development of a simple and low-cost procedure for obtaining heterocyclic compounds that may have an interest for medicinal purposes. We present in this work the synthesis of 6-nitro-indazoles derivatives, using two different methods. the first method is the alkylation of Nitroindazole by two different alkylating agents under the conditions of solid/liquid phase transfer catalysis in N, N-dimethylformamide (DMF) in the presence of potassium carbonate (K₂CO₃) as a base, and tetra-n-butylammonium bromide (BTBA) as a catalyst. While the other method is the 1,3-dipolar cycloaddition, in this case, we have undertaken the preparation of bi-heterocyclic containing the 6-nitroindazole associate with group of isoxazoline, isoxazole or 1,2,3-Triazole under normal conditions and, under the catalytic conditions of the click chemistry we were also able to determine the structures without any ambiguity by the ¹H and ¹³C NMR.

Keywords: indazole, 6-nitroindazole, isoxazole, 1, 2, 3-Triazole

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289 Cholesterol-Lowering Effects of Lactobacillus plantarum Isolated from Northeastern Thai Fermented Vegetable Brassica juncea (L.)

Authors: T. Warinpramote, J. Sanguanjeen, P. Pholphakwaen, S. Kittisorayut, J. Kerdtubtim, S. Palachote, M. Taweechotipatr

Abstract:

Cholesterol is a type of lipid molecule which is the significant risk factor for coronary heart disease. Currently, there are many cholesterol-lowering alternative treatments especially bile salt hydrolase positive lactobacilli. BSH can cleave the peptide linkage of bile salt, which results in removal of the amino acid group from the steroid core and increases production of the new bile acid by using more cholesterol. The purpose of this study was to isolate, and screen probiotic characteristics of lactobacilli from fermented Thai foods and further investigated for their comparative BSH activity. The result showed that 2 of 81 Lactobacillus strains, JPK2-2 and JPK3-2, isolated from Brassica juncea (L.) had significantly exhibited high BSH activity. In addition, these Lactobacillus strains showed their results that the ability to tolerate acid and bile salt. Furthermore, the using of 16S rDNA sequencing for definitive microbial identifications showed that these 2 strains belong to Lactobacillus plantarum. In the future, the L. plantarum with BSH activity strains JPK2-2 and JPK3-2 may be the candidate probiotics for application in functional foods and dairy products to improve in the patient with cardiovascular diseases.

Keywords: Lactobacillus plantarum, probiotics, bile salt hydrolase, cholesterol-lowering, fermented Thai food

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288 Genotyping of G/P No Typable Group a Rotavirus Strains Revealed G2 and G9 Genotype Circulations in Moroccan Children Fully Vaccinated with Rotarix™

Authors: H. Boulahyaoui, S. Alaoui Amine, C. Loutfi, H. El Annaz, N. Touil, El M. El Fahim, S. Mrani

Abstract:

Three Moroccan children fully vaccinated with Rotarix™ have been hospitalized for Rotavirus Gastroenteritis (RVGE) in the pediatric division of the Farabi Hospital, Oujda. Rotavirus G/P genotypes could not be typed because of their delayed crossing threshold (Ct) resolute with a group A rotavirus (RVA) real time RT-PCR. These strains were adapted to cell culture. All viruses replicated and caused extensive cytopathic effects after four or five passages in MA104 cell lines. Significant improvements have been obtained in the amount of viral particles. Each virus multiplied to a high titer (7.5 TCID50/ml). VP7 and VP4 partial gene sequencing revealed distinct genotypes compared to the Rotarix(®) vaccine strain. Two strains were of G2P[4] genotype whereas the third was G9P[8] genotype. Virus isolation while labor intensive, is recommended as a second test, especially when higher sensitivity for conventional RVA genotyping RT-PCR is needed. VP7 antigenic similarities between these strains and Rotarix were determined.

Keywords: esacpe-vaccine, Morocco, Rotarix, G2P[4], G9P[8]

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287 Sitagliptin-AntiCD4 Mab Conjugated T Cell Targeting Therapy for the Effective Treatment of Type I Diabetes

Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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286 Going Viral: Constructively Aligning the Use of Digital Video to Effectively Support Faculty Development

Authors: Samuel Olugbenga King

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This review article, which is a synthesis of the relevant research literature, focuses on the capabilities of digital video to support, facilitate and enhance faculty development. Based on the literature review, faculty development (i.e., academic or educational development) requires the continued adoption of cohesive, theoretical frameworks to guide research and practice; incorporation of relevant tools from analogous fields, such as teacher professional development; systematic program evaluations; and detailed descriptions of practice to further practice and creative development. A cohesive, five-heuristic framework is subsequently outlined to inform the design and evaluation of the use of digital video, so as to address the barriers to advancing faculty development, as identified through the literature review. Alternative impact evaluation approaches are also described, while the limitations of using digital video for faculty development are highlighted. This paper is therefore conceived as one way to meaningfully leverage the educational affordances of digital video to address some lingering gaps in faculty development.

Keywords: digital video, faculty/educational development, evaluation, scholarship of teaching and learning (SoTL)

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285 Dengue Death Review: A Tool to Adjudge the Cause of Dengue Mortality and Use of the Tool for Prevention of Dengue Deaths

Authors: Gagandeep Singh Grover, Vini Mahajan, Bhagmal, Priti Thaware, Jaspreet Takkar

Abstract:

Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The state of Punjab in India shows cyclical and seasonal variation in dengue cases. The Case Fatality Rate of Dengue has ranged from 0.6 to 1.0 in the past years. The department has initiated a review of the cases that have died due to dengue in order to know the exact cause of the death in a case of dengue. The study has been undertaken to know the other associated co-morbidities and factors causing death in a case of dengue. The study used the predesigned proforma on which the records (medical and Lab) were recorded and reviewed by the expert committee of the doctors. This study has revealed that cases of dengue having co-morbidities have a longer stay in the hospital. Fluid overload and co-morbidities have been found as major factors leading to death, however, in a confirmed case of dengue hepatorenal shutdown was found to be a major cause of mortality. The data obtained will help in sensitizing the treating physicians in order to decrease the mortality due to dengue in future.

Keywords: dengue, death, morbidities, DHF, DSS

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284 Biological Activities of Flaxseed Peptides (Linusorbs)

Authors: Youn Young Shim, Ji Hye Kim, Jae Youl Cho, Martin J. T. Reaney

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Flaxseed (Linum usitatissimum L.) is gaining popularity in the food industry as a superfood due to its health-promoting properties. The flax plant synthesizes an array of biologically active cyclic peptides or linusorbs (LOs, a.k.a. cyclolinopeptides) from three or more ribosome-derived precursors. [1–9-NαC]-linusorb B3 and [1–9-NαC]-linusorb B2, suppress immunity, induce apoptosis in human epithelial cancer cell line (Calu-3) cells, and inhibit T-cell proliferation, but the mechanism of LOs action is unknown. Using gene expression analysis in nematode cultures and human cancer cell lines, we have observed that LOs exert their activity, in part, through induction of apoptosis. Specific LOs’ properties include: 1) distribution throughout the body after flaxseed consumption; 2) induce heat shock protein (HSP) 70A production as an indicator of stress and address the issue in Caenorhabditis elegans (exposure of nematode cultures to [1–9-NαC]-linusorb B3 induced a 30% increase in production of the HSP 70A protein); 3) induce apoptosis in Calu-3 cells; and 4) modulate regulatory genes in microarray analysis. These diverse activities indicate that LOs might induce apoptosis in cancer cells or act as versatile platforms to deliver a variety of biologically active molecules for cancer therapy.

Keywords: flaxseed, linusorb, cyclic peptide, orbitides, heat shock protein, apoptosis, anti-cancer

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283 Bulk Amounts of Linear and Cyclic Polypeptides on Our Hand within a Short Time

Authors: Yu Zhang, Il Kim

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Polypeptides with defined peptide sequences illustrate the power of remarkable applications in drug delivery, tissue engineering, sensing and catalysis. Especially the cyclic polypeptides, the distinctive topological architecture imparts many characteristic properties comparing to linear polypeptides. Here, a facile and highly efficient strategy for the synthesis of linear and cyclic polypeptides is reported using N-heterocyclic carbenes (NHCs)-mediated ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCA) in the presence or absence of primary amine initiator. The polymerization proceeds rapidly in a quasi-living manner, allowing access to linear and cyclic polypeptides of well-defined chain length and narrow polydispersity, as evidenced by nuclear magnetic resonance spectrum (1H NMR and 13C NMR spectra) and size exclusion chromatography (SEC) analysis. The cyclic architecture of the polypeptides was further verified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectra (MALDI-TOF MS) and electrospray ionization (ESI) mass spectra, as well as viscosity studies. This approach can also simplify workup procedures and make bulk scale synthesis possible, which thereby opens avenues for practical uses in diverse areas, opening up the new generation of polypeptide synthesis.

Keywords: α-amino acid N-carboxyanhydrides, living polymerization, polypeptides, N-heterocyclic carbenes, ring-opening polymerization

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282 Bioinformatic Study of Follicle Stimulating Hormone Receptor (FSHR) Gene in Different Buffalo Breeds

Authors: Hamid Mustafa, Adeela Ajmal, Kim EuiSoo, Noor-ul-Ain

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World wild, buffalo production is considered as most important component of food industry. Efficient buffalo production is related with reproductive performance of this species. Lack of knowledge of reproductive efficiency and its related genes in buffalo species is a major constraint for sustainable buffalo production. In this study, we performed some bioinformatics analysis on Follicle Stimulating Hormone Receptor (FSHR) gene and explored the possible relationship of this gene among different buffalo breeds and with other farm animals. We also found the evolution pattern for this gene among these species. We investigate CDS lengths, Stop codon variation, homology search, signal peptide, isoelectic point, tertiary structure, motifs and phylogenetic tree. The results of this study indicate 4 different motif in this gene, which are Activin-recp, GS motif, STYKc Protein kinase and transmembrane. The results also indicate that this gene has very close relationship with cattle, bison, sheep and goat. Multiple alignment (MA) showed high conservation of motif which indicates constancy of this gene during evolution. The results of this study can be used and applied for better understanding of this gene for better characterization of Follicle Stimulating Hormone Receptor (FSHR) gene structure in different farm animals, which would be helpful for efficient breeding plans for animal’s production.

Keywords: buffalo, FSHR gene, bioinformatics, production

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281 Modeling and Stability Analysis of Viral Propagation in Wireless Mesh Networking

Authors: Haowei Chen, Kaiqi Xiong

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This paper aims to answer how malware will propagate in Wireless Mesh Networks (WMNs) and how communication radius and distributed density of nodes affects the process of spreading. The above analysis is essential for devising network-wide strategies to counter malware. We answer these questions by developing an improved dynamical system that models malware propagation in the area where nodes were uniformly distributed. The proposed model captures both the spatial and temporal dynamics regarding the malware spreading process. Equilibrium and stability are also discussed based on the threshold of the system. If the threshold is less than one, the infected nodes disappear, and if the threshold is greater than one, the infected nodes asymptotically stabilize at the endemic equilibrium. Numerical simulations are investigated about communication radius and distributed density of nodes in WMNs, which allows us to draw various insights that can be used to guide security defense.

Keywords: Bluetooth security, malware propagation, wireless mesh networks, stability analysis

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280 Development of Chitosan/Dextran Gelatin Methacrylate Core/Shell 3D Scaffolds and Protein/Polycaprolactone Melt Electrowriting Meshes for Tissue Regeneration Applications

Authors: J. D. Cabral, E. Murray, P. Turner, E. Hewitt, A. Ali, M. McConnell

Abstract:

Worldwide demand for organ replacement and tissue regeneration is progressively increasing. Three-dimensional (3D) bioprinting, where a physical construct is produced using computer-aided design, is a promising tool to advance the tissue engineering and regenerative medicine fields. In this paper we describe two different approaches to developing 3D bioprinted constructs for use in tissue regeneration. Bioink development is critical in achieving the 3D biofabrication of functional, regenerative tissues. Hydrogels, cross-linked macromolecules that absorb large amounts of water, have received widespread interest as bioinks due to their relevant soft tissue mechanics, biocompatibility, and tunability. In turn, not only is bioink optimisation crucial, but the creation of vascularized tissues remains a key challenge for the successful fabrication of thicker, more clinically relevant bioengineered tissues. Among the various methodologies, cell-laden hydrogels are regarded as a favorable approach; and when combined with novel core/shell 3D bioprinting technology, an innovative strategy towards creating new vessel-like structures. In this work, we investigate this cell-based approach by using human umbilical endothelial cells (HUVECs) entrapped in a viscoelastic chitosan/dextran (CD)-based core hydrogel, printed simulataneously along with a gelatin methacrylate (GelMA) shell. We have expanded beyond our previously reported FDA approved, commercialised, post-surgical CD hydrogel, Chitogel®, by functionalizing it with cell adhesion and proteolytic peptides in order to promote bone marrow-derived mesenchymal stem cell (immortalized BMSC cell line, hTERT) and HUVECs growth. The biocompatibility and biodegradability of these cell lines in a 3D bioprinted construct is demonstrated. Our studies show that particular peptide combinations crosslinked within the CD hydrogel was found to increase in vitro growth of BMSCs and HUVECs by more than two-fold. These gels were then used as a core bioink combined with the more mechanically robust, UV irradiated GelMA shell bioink, to create 3D regenerative, vessel-like scaffolds with high print fidelity. As well, microporous MEW scaffolds made from milk proteins blended with PCL were found to show promising bioactivity, exhibiting a significant increase in keratinocyte (HaCaTs) and fibroblast (normal human dermal fibroblasts, NhDFs) cell migration and proliferation when compared to PCL only scaffolds. In conclusion, our studies indicate that a peptide functionalized CD hydrogel bioink reinforced with a GelMA shell is biocompatible, biodegradable, and an appropriate cell delivery vehicle in the creation of regenerative 3D constructs. In addition, a novel 3D printing technique, melt electrowriting (MEW), which allows fabrication of micrometer fibre meshes, was used to 3D print polycaprolactone (PCL) and bioactive milk protein, lactorferrin (LF) and whey protein (WP), blended scaffolds for potential skin regeneration applications. MEW milk protein/PCL scaffolds exhibited high porosity characteristics, low overall biodegradation, and rapid protein release. Human fibroblasts and keratinocyte cells were seeded on to the scaffolds. Scaffolds containing high concentrations of LF and combined proteins (LF+WP) showed improved cell viability over time as compared to PCL only scaffolds. This research highlights two scaffolds made using two different 3D printing techniques using a combination of both natural and synthetic biomaterial components in order to create regenerative constructs as potential chronic wound treatments.

Keywords: biomaterials, hydrogels, regenerative medicine, 3D bioprinting

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279 Tenofovir-Amino Acid Conjugates Act as Polymerase Substrates: Implications for Avoiding Cellular Phosphorylation in the Discovery of Nucleotide Analogs

Authors: Weijie Gu, Sergio Martinez, Hoai Nguyen, Hongtao Xu, Piet Herdewijn, Steven De Jonghe, Kalyan Das

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Nucleotide analogs are used for treating viral infections such as HIV, hepatitis B, hepatitis C, influenza, and SARS-CoV-2. To become polymerase substrates, a nucleotide analog must be phosphorylated by cellular kinases, which are rate-limiting. The goal of this study is to develop dNTP/NTP analogs directly from nucleotides. Tenofovir (TFV) analogs were synthesized by conjugating with natural or unnatural amino acids. It demonstrates that some conjugates act as dNTP analogs, and HIV-1 reverse transcriptase (RT) catalytically incorporates the TFV part as the chain terminator. X-ray structures in complex with HIV-1 RT/dsDNA showed binding of the conjugates at the polymerase active site, however, in different modes in the presence of Mg²⁺ vs. Mn²⁺ ions. The adaptability of the compounds is seemingly essential for catalytic incorporation of TFV by RT. 4d with a carboxyl sidechain demonstrated the highest incorporation. 4e showed weak incorporation and rather behaved as a dNTP-competitive inhibitor. This result advocates the feasibility of designing NTP/dNTP analogs by chemical substitutions to nucleotide analogs.

Keywords: dNTP analogs, nucleotide analogs, polymerase, tenofovir, X-ray structure

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278 Visualizing Matrix Metalloproteinase-2 Activity Using Extracellular Matrix-Immobilized Fluorescence Resonance Energy Transfer Bioprobe in Cancer Cells

Authors: Hawon Lee, Young-Pil Kim

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Visualizing matrix metalloproteinases (MMPs) activity is necessary for understanding cancer metastasis because they are implicated in cell migration and invasion by degrading the extracellular matrix (ECM). While much effort has been made to sense the MMP activity, but extracellularly long-term monitoring of MMP activity still remains challenging. Here, we report a collagen-bound fluorescent bioprobe for the detection of MMP-2 activity in the extracellular environment. This bioprobe consists of ECM-immobilized part (including collagen-bound protein) and MMP-sensing part (including peptide substrate linked with fluorescence resonance energy transfer (FRET) coupler between donor green fluorescent protein (GFP) and acceptor TAMRA dye), which was constructed through intein-mediated self-splicing conjugation. Upon being immobilized on the collagen-coated surface, this bioprobe enabled efficient long-lasting observation of MMP-2 activity in the cultured cells without affecting cell growth and viability. As a result, the FRET ratio (acceptor/donor) decreased as the MMP2 activity increased in cultured cancer cells. Furthermore, unlike wild-type MMP-2, mutated MMP-2 expression (Y580A in the hemopexin region) gave rise to lowering the secretion of MMP-2 in HeLa. Conclusively, our method is anticipated to find applications for tracing and visualizing enzyme activity.

Keywords: collagen, ECM, FRET, MMP

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277 Antigen-Presenting Cell Characteristics of Human γδ T Lymphocytes in Chronic Myeloid Leukemia

Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

Abstract:

Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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276 COVID-19 Analysis with Deep Learning Model Using Chest X-Rays Images

Authors: Uma Maheshwari V., Rajanikanth Aluvalu, Kumar Gautam

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The COVID-19 disease is a highly contagious viral infection with major worldwide health implications. The global economy suffers as a result of COVID. The spread of this pandemic disease can be slowed if positive patients are found early. COVID-19 disease prediction is beneficial for identifying patients' health problems that are at risk for COVID. Deep learning and machine learning algorithms for COVID prediction using X-rays have the potential to be extremely useful in solving the scarcity of doctors and clinicians in remote places. In this paper, a convolutional neural network (CNN) with deep layers is presented for recognizing COVID-19 patients using real-world datasets. We gathered around 6000 X-ray scan images from various sources and split them into two categories: normal and COVID-impacted. Our model examines chest X-ray images to recognize such patients. Because X-rays are commonly available and affordable, our findings show that X-ray analysis is effective in COVID diagnosis. The predictions performed well, with an average accuracy of 99% on training photographs and 88% on X-ray test images.

Keywords: deep CNN, COVID–19 analysis, feature extraction, feature map, accuracy

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275 Nanoparticles in Drug Delivery and Therapy of Alzeheimer's Disease

Authors: Nirupama Dixit, Anyaa Mittal, Neeru Sood

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Alzheimer’s disease (AD) is a progressive form of dementia, contributing to up to 70% of cases, mostly observed in elderly but is not restricted to old age. The pathophysiology of the disease is characterized by specific pathological changes in brain. The changes (i.e. accumulation of metal ions in brain, formation of extracellular β-amyloid (Aβ) peptide aggregates and tangle of hyper phosphorylated Tau protein inside neurons) damage the neuronal connections irreversibly. The current issues in improvement of life quality of Alzheimer's patient lies in the fact that the diagnosis is made at a late stage of the disease and the medications do not treat the basic causes of Alzheimer's. The targeted delivery of drug through the blood brain barrier (BBB) poses several limitations via traditional approaches for treatment. To overcome these drug delivery limitation, nanoparticles provide a promising solution. This review focuses on current strategies for efficient targeted drug delivery using nanoparticles and improving the quality of therapy provided to the patient. Nanoparticles can be used to encapsulate drug (which is generally hydrophobic) to ensure its passage to brain; they can be conjugated to metal ion chelators to reduce the metal load in neural tissue thus lowering the harmful effects of oxidative damage; can be conjugated with drug and monoclonal antibodies against BBB endogenous receptors. Finally this review covers how the nanoparticles can play a role in diagnosing the disease.

Keywords: Alzheimer's disease, β-amyloid plaques, blood brain barrier, metal chelators, nanoparticles

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274 Biosecurity Control Systems in Two Phases for Poultry Farms

Authors: M. Peña Aguilar Juan, E. Nava Galván Claudia, Pastrana Palma Alberto

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In this work was developed and implemented a thermal fogging disinfection system to counteract pathogens from poultry feces in agribusiness farms, to reduce mortality rates and increase biosafety in them. The control system consists of two phases for the conditioning of the farm during the sanitary break. In the first phase, viral and bacterial inactivation was performed by treating the stool dry cleaning, along with the development of a specialized product that foster the generation of temperatures above 55 °C in less than 24 hr, for virus inactivation. In the second phase, a process for disinfection by fogging was implemented, along with the development of a specialized disinfectant that guarantee no risk for the operators’ health or birds. As a result of this process, it was possible to minimize the level of mortality of chickens on farms from 12% to 5.49%, representing a reduction of 6.51% in the death rate, through the formula applied to the treatment of poultry litter based on oxidising agents used as antiseptics, hydrogen peroxide solutions, glacial acetic acid and EDTA in order to act on bacteria, viruses, micro bacteria and spores.

Keywords: innovation, triple helix, poultry farms, biosecurity

Procedia PDF Downloads 255