Search results for: viral clearance

Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Mudasir Gani, Rakesh Kumar Gupta, Kamlesh Bali, Abdul Rouf Wani

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The gypsy moth (Lymantria obfuscata) and tent caterpillar (Malacosoma indicum) are serious pests that attack a wide range of fruit and forest trees in Jammu & Kashmir range of North-Western Himalayas in India. Investigations were carried out to isolate and bioprospect naturally occurring nucleopolyhedroviruses (NPVs) as potent biopesticides against these pests. The biological and molecular characterization of NPV isolates from different ecosystems was conducted, and the polh, lef-8 and lef-9 genes were sequenced and subjected to phylogenetic analysis. The L. obfuscata NPV was more closely related to the L. dispar NPV, whereas M. indicum NPV was more closely related to the M. californicum NPV in the NCBI taxonomy database. Among different isolates, Bhaderwah isolates exhibited highest virus activity (LD₅₀ = 250 POBs/larvae) and speed of kill (ST₅₀ = 6.80 days) against L. obfuscata whereas Mahor isolates proved most virulent against M. indicum, with lowest LD₅₀ (257 POBs/larva) and ST₅₀ (6.80 days). The in vivo mass production for highest productivity and quality revealed that the optimum yield was obtained when 3rd instar larvae were inoculated with a viral dose of 1.44 × 105 POBs/larva and allowed to incubate for nine days for L. obfuscata. However, for M. indicum larvae, a viral dose of 2.88 × 10⁶ POBs/larva and incubation period of 10 days were found optimum. It was found that harvesting of moribund larvae yields good quality NPV. The field application of L. obfuscata NPV and M. indicum NPV against the respective host populations on apple and willow with the pre-standardized dosage of 1 × 10¹² POBs/acre reduced the larval population density up to 25-63%.

Keywords: baculoviruses, biopesticides, Lymantria obfuscata, Malacosoma indicum

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Authors: Mini P. Singh, Jagat Ram, Archit Kumar, Tripti Rungta, Jasmine Khurana, Amit Gupta, R. K. Ratho

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Introduction: Human adenovirus is the most common agent involved in viral conjunctivitis. The clinical manifestations vary with different serotypes. The identification of the circulating strains followed by phylogenetic analysis can be helpful in understanding the origin and transmission of the disease. The present study aimed to carry out molecular epidemiology of the adenovirus types in the patients with conjunctivitis presenting to the eye centre of a tertiary care hospital in North India. Materials and Methods: The conjunctival swabs were collected from 23 suspected adenoviral conjunctivitis patients between April-August, 2014 and transported in viral transport media. The samples were subjected to nested PCR targeting hexon gene of human adenovirus. The band size of 956bp was eluted and 8 representative positive samples were subjected to sequencing. The sequences were analyzed by using CLUSTALX2.1 and MEGA 5.1 software. Results: The male: female ratio was found to be 3.6:1. The mean age of presenting patients was 43.95 years (+17.2). Approximately 52.1% (12/23) of patients presented with bilateral involvement while 47.8% (11/23) with unilateral involvement of the eye. Human adenovirus DNA could be detected in 65.2% (15/23) of the patients. The phylogenetic analysis revealed presence of serotype 8 in 7 patients and serotype 4 in one patient. The serotype 8 sequences showed 99-100% identity with Tunisian, Indian and Japanese strains. The adenovirus serotype 4 strains had 100% identity with strains from Tunisia, China and USA. Conclusion: Human adenovirus was found be an important etiological agent for conjunctivitis in our set up. The phylogenetic analysis showed that the predominant circulating strains in our epidemic keratoconjunctivitis were serotypes 8 and 4.

Keywords: conjunctivitis, human adenovirus, molecular epidemiology, phylogenetics

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Authors: D. Bhowmik, Y. Tian, Q. Yin, F. Zhu

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Cyclic GMP-AMP synthase (cGAS), recognises cytoplasmic double-stranded DNA (dsDNA), indicative of bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. Viruses also have developed numerous strategies to antagonize the cGAS-STING pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that is the causative agent of Kaposi’s sarcoma and several other malignancies. To persist in the host, consequently causing diseases, KSHV must overcome the host innate immune responses, including the cGAS-STING DNA sensing pathway. We already found that ORF52 or KicGAS (KSHV inhibitor of cGAS), an abundant and basic gamma herpesvirus-conserved tegument protein, directly inhibits cGAS enzymatic activity. To better understand the mechanism, we have performed the biochemical and structural characterization of full-length KicGAS and various mutants in regarding binding to DNA. We observed that KicGAS is capable of self-association and identified the critical residues involved in the oligomerization process. We also characterized the DNA-binding of KicGAS and found that KicGAS cooperatively oligomerizes along the length of the double stranded DNA, the highly conserved basic residues at the c-terminal disordered region are crucial for DNA recognition. Deficiency in oligomerization also affects DNA binding. Thus DNA binding by KicGAS sequesters DNA and prevents it from being detected by cGAS, consequently inhibiting cGAS activation. KicGAS homologues also inhibit cGAS efficiently, suggesting inhibition of cGAS is evolutionarily conserved mechanism among gamma herpesvirus. These results highlight the important viral strategy to evade this innate immune sensor.

Keywords: Kaposi's sarcoma-associated herpesvirus, KSHV, cGAS, DNA binding, inhibition

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Authors: Juliana Lukša, Bazilė Ravoitytė, Elena Servienė, Saulius Serva

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Totiviridae L-A virus is a persistent Saccharomyces cerevisiae dsRNA virus. It encodes the major structural capsid protein Gag and Gag-Pol fusion protein, responsible for virus replication and encapsulation. These features also enable the copying of satellite dsRNAs (called M dsRNAs) encoding a secreted toxin and immunity to it (known as killer toxin). Viral capsid pore presumably functions in nucleotide uptake and viral mRNA release. During cell division, sporogenesis, and cell fusion, the virions remain intracellular and are transferred to daughter cells. By employing high throughput RNA sequencing data analysis, we describe the influence of solely L-A virus on the expression of genes in three different S. cerevisiae hosts. We provide a new perception into Totiviridae L-A virus-related transcriptional regulation, encompassing multiple bioinformatics analyses. Transcriptional responses to L-A infection were similar to those induced upon stress or availability of nutrients. It also delves into the connection between the cell metabolism and L-A virus-conferred demands to the host transcriptome by uncovering host proteins that may be associated with intact virions. To better understand the virus-host interaction, we applied differential proteomic analysis of virus particle-enriched fractions of yeast strains that harboreither complete killer system (L-A-lus and M-2 virus), M-2 depleted orvirus-free. Our analysis resulted in the identification of host proteins, associated with structural proteins of the virus (Gag and Gag-Pol). This research was funded by the European Social Fund under the No.09.3.3-LMT-K-712-19-0157“Development of Competences of Scientists, other Researchers, and Students through Practical Research Activities” measure.

Keywords: totiviridae, killer virus, proteomics, transcriptomics

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Authors: Howaida I. Abd-Alla, Amal Z. Hassan, Maha Soltan, Atef G. Hanna, Mounir M. El-Safty

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Acokanthera oblongifolia (Apocynaceae) is used for treatment of several infection diseases and is a well-known cardiac glycoside-containing plant. The infusion of their leaves is gargled to treat tonsillitis and is used medicinally to treat snakebites. The total cardiac glycosides content in the leaves was determined by referring to gitoxigenin as a reference compound. Two triterpenes, lup-20(29)-en-3β-ol (1) and oleanolic acid (2); two cardenolides, acovenoside A (3) and acobioside A (4) were isolated from the ethyl acetate extract. Their structures were determined on the basis of spectral analysis. Major constituents isolated from this species were evaluated for cytotoxicity against normal lung cell line (Wi38) and antimicrobial activities against Gram-positive (two strains) and Gram-negative bacteria (four strains), yeast-like fungi (two strains) and fungi (five strains). The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. Their viral inhibitory effects against avian influenza virus type A (AI-H5N1) and Newcastle disease virus (NDV) in specific pathogen free (SPF) embryonated chicken eggs (ECE), chicken embryo fibroblasts (CEF) and Vero cells were evaluated. The cardenolide (3) showed viral inhibitory effects against AI-H5N1 and NDV in SPF ECE. The two cardenolides isolated have shown potent cytotoxicity against Vero cells. Compound (3) showed potent anti-Gram-negative bacteria activity. These results suggested that acovenoside A might be promising for future antiviral and antimicrobial drug design.

Keywords: Acokanthera, AI-H5N1, Cardenolides, NDV, SPF-ECE, VERO, Wi38 , Microbe

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Authors: Tabassum Yasmin, Hamid Pahlevan

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HIV/Hepatitis C co-infection treatments have evolved substantially and they have similar sustained virologic response rates as those of Hepatitis C monoinfected population. There are a few studies on therapy of patients with dual genotypes, especially in HIV/Hepatic C coinfected group. Most studies portrayed case reports of dual genotype chronic Hepatitis C coinfection treatment with Sofosbuvir/Ledipasvir and Ribavirin. A 79-year-old male with a history of HIV on Truvada and Isentress had chronic Hepatitis C with 1a and 2 genotypes. The patient has a history of alcohol intake for 40 years but recently stopped drinking alcohol. He has a history of intravenous drug use in the past and currently is not using any recreational drugs. Patient has Fibro score of 0.7 with Metavir score F2 to F4. AFP is 3.2. The HCV RNA is 493,034 IU/ML. The HBV viral DNA is < 1.30 (not detected). The CD4 is 687CU/MM. The FIB 4 is 3.34 with APRI index 0.717. The HIV viral load is 101 copies/ML. MRI abdomen did not show any liver abnormality. Fixed dose Sofosbuvir/Ledipasvir was used for therapy without Ribavirin. He tolerated medication except for some minor gastrointestinal side effects like abdominal bloating. He demonstrated 100% adherence rate. Patient completed 12 weeks of therapy. HCV RNA was undetectable at 4 and 12 weeks. He achieved SVR at week 12 and subsequently had undetectable RNA for 2 years. Dual genotype prevalence in chronic hepatitis C population is rare, especially in HIV/hepatic coinfection. Our case demonstrates that dual genotypic cases can still be successfully treated with Direct Acting Antiviral agents. The newer agents for therapy for pan genotypes were not available at the time the patient was being treated. We demonstrated that dual agent therapy was still able to maintain SVR in our patient.

Keywords: HIV/Hepatitis C, SVR (sustained virologic response), DAA (direct active antiviral agents, dual genotype

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Authors: Ananya Pal, Neelakshi Sarkar, Debraj Saha, Dipanwita Das, Subhashish Kamal Guha, Bibhuti Saha, Runu Chakravarty

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Presently, tenofovir disoproxil fumurate (TDF) is the most effective anti-viral agent for the treatment of hepatitis B virus (HBV) in individuals co-infected with HIV and HBV as TDF has activity to suppress both wild-type and lamivudine (3TC)-resistant HBV. However, suboptimal response to TDF was reported in HIV-HBV co-infected individuals with prior 3TC therapy from different countries recently. The incidence of 3TC-resistant HBV strains is quite high in HIV-HBV co-infected patients experiencing long-term anti-retroviral therapy (ART) in eastern India. In spite of this risk, most of the patients with long-term 3TC treatment are continued with the same anti-viral agent in this country. Only a few have received TDF in addition to 3TC in the ART regimen since TDF has been available in India for the treatment of HIV-infected patients in 2012. In this preliminary study, we investigated the virologic and biochemical parameters among HIV-HBV co-infected patients who are non-responders to 3TC treatment during the continuation of 3TC or TDF add-on to 3TC in their ART regimen. Fifteen HIV-HBV co-infected patients who experienced long-term 3TC (mean duration months 36.87 ± 24.08 months) were identified with high HBV viremia ( > 20,000 IU/ml) or harbouring 3TC-resistant HBV. These patients receiving ART from School of Tropical Medicine Kolkata, the main ART centre in eastern India were followed-up semi-annually for next three visits. Different virologic parameters including quantification of plasma HBV load by real-time PCR, detection of hepatitis B e antigen (HBeAg) by commercial ELISA and anti-viral resistant mutations by sequencing were studied. During three follow-up among study subjects, 86%, 47%, and 43% had 3TC-mono-therapy (mean treatment-duration 41.54±18.84, 49.67±11.67, 54.17±12.37 months respectively) whereas 14%, 53%, and 57% experienced TDF in addition to 3TC (mean treatment duration 4.5±2.12, 16.56±11.06, and 23±4.07 months respectively). Mean CD4 cell-count in patients receiving 3TC was tended to be lower during third follow-up as compared to the first and the second [520.67±380.30 (1st), 454.8±196.90 (2nd), and 397.5±189.24 (3rd) cells/mm3) and similar trend was seen in patients experiencing TDF in addition to 3TC [334.5±330.218 (1st), 476.5±194.25 (2nd), and 461.17±269.89 (3rd) cells/mm3]. Serum HBV load was increased during successive follow-up of patients with 3TC-mono-therapy. Initiation of TDF lowered serum HBV-load among 3TC-non-responders at the time of second visit ( < 2,000 IU/ml), interestingly during third follow-up, mean HBV viremia increased >1 log IU/ml (mean 3.56±2.84 log IU/ml). Persistence of 3TC-resistant double and triple mutations was also observed in both the treatment regimens. Mean serum alanine aminotransferase remained elevated in these patients during this follow-up study. Persistence of high HBV viraemia and 3TC-resistant mutation in HBV during the continuation of 3TC might lead to major public health threat in India. The inclusion of TDF in the ART regimen of 3TC non-responder HIV-HBV co-infected patients showed adverse treatment response in terms of virologic and biochemical parameters. Therefore, serious attention is necessary for proper management of long-term 3TC experienced HIV-HBV co-infected patients with high HBV viraemia or 3TC-resistant HBV mutants in India.

Keywords: HBV, HIV, TDF, 3TC-resistant

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Authors: Thavasimuthu Citarasu, Mariavincent Michaelbabu, Vikram Vakharia

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The rhizome of Java grass, Cyperus rotundus was extracted different organic polar and non-polar solvents and performed the in vitro antiviral and immunostimulant activities against White Spot Syndrome Virus (WSSV) and Vibrio harveyi respectively. Based on the initial screening the ethyl acetate extract of C. rotundus was strong activities and further it was purified through silica column chromatography and the fractions were screened again for antiviral and immunostimulant activity. Among the different fractions screened against the WSSV and V. harveyi, the fractions, F-III to FV had strong activities. In order to study the in vivo influence of C. rotundus, the fractions (F-III to FV) were pooled and delivered to the F. indicus through artificial feed for 30 days. After the feeding trail the experimental and control diet fed F. indicus were challenged with virulent WSSV and studied the survival, molecular diagnosis, biochemical, haematological and immunological parameters. Surprisingly, the pooled fractions (F-III to FV) incorporated diets helped to significantly (P < 0.01) suppressed viral multiplication, showed significant (P < 0.01) differences in protein and glucose levels, improved total haemocyte count (THC), coagulase activity, significantly increased (P < =0.001) prophenol oxidase and intracellular superoxide anion production compared to the control shrimps. Based on the results, C. rotundus extracts effectively suppressed WSSV multiplication and improve the immune system in F. indicus against WSSV infection and this knowledge will helps to develop novel drugs from C. rotundus against WSSV.

Keywords: antiviral drugs, cyperus rotundus, fenneropenaeus indicus, WSSV

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Authors: Folajinmi Oluwasina, Greg Abiaziem, Moses Luke, Mobolaji Kolawole, Nancy Yibowei, Anne Taiwo

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Background: Occurrence of HIV infection has an adverse effect on the natural causes of Hepatitis B Viral (HBV) infection, faster progression of hepatic fibrosis demonstrated in patients with co-infection. This study was carried out to determine the incidence of HBV infection among HIV-positive patients, and to retrospectively evaluate laboratory characteristics of patients with HIV/HBV co-infection. Methods: A retrospective analysis of patient files for all HIV-infected cases followed-up and treated at 52 health facilities. Among HIV-infected cases, those with HBsAg positivity and HIV/Hepatitis B co-infection were determined. Socio demographic, alcohol or substance use, ART, CD4, Viral Load levels and treatment durations were retrospectively evaluated. Results: Of the 125 HIV-infected patients evaluated retrospectively, 17 (13.6%) had HBsAg positivity. Of these 17 cases were 11(64.7%) male and 6 (35.3%) female, with a mean age of 48.7 years. No patients had a history of alcohol or substance use. The mean duration of follow up was 28 months. 9 (52.9%) patients had negative HBV DNA at presentation while 8(47%) had positive HBV DNA, with normal ALT levels in all subjects. Among the 9 cases with negative HBV DNA who had no indication for the treatment of chronic hepatitis B. In five cases, treatment was commenced since HBV DNA was elevated in conjunction with low CD4. One patient in whom treatment was not indicated based on HBV DNA and CD4 levels in conjunction with the absence of AIDS defining clinical picture was currently being followed-up without treatment. Of the patients receiving HAART therapy, the average CD4 count at presentation was 278 cells/mm3 vs. 466 cells/mm3 at the end of 12 months. In three subjects with positive HBV DNA, a decrease in HBV DNA was noted after initiation of treatment. In four patients with negative DNA who received treatment, the HBV DNA negative status was found to remain, while one patient who did not receive treatment had elevated HBV DNA and decreased CD4 levels. Conclusion: It was shown that this group of patients with HIV/HBV co-infection, HAART was found to be associated with a decrease in HBV DNA in HBV DNA positive cases, absence of transition to positivity among those with negative HBV DNA, and with increased CD4 in all subjects.

Keywords: Hepatitis B, DNA, anti retroviral therapy, co-infection

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Authors: Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Dalila Gargouri, Jamel Kharrat, Abderraouf Cherif, Ahmed Bouhafa, Slim Jarboui, Mohamed Zili, Ridha Khelifa

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Background & aims: Colorectal cancer (CRC) is one of the most common malignancies throughout the world. Several risk factors, both genetic and environmental, including viral infections, have been linked to colorectal carcinogenesis. A few studies report the detection of human polyomavirus JC (JCV) DNA and transformation antigen (T-Ag) in a fraction of the colorectal tumors studied and suggest an association of this virus with CRC. In order to investigate whether such an association of JCV with CRC will hold in a different epidemiological setting, we looked for the presence of JCV DNA and T-Ag expression in a group of Tunisian CRC patients. Methods: Fresh colorectal mucosa biopsies were obtained from 17 healthy volunteers and from both colorectal tumors and adjacent normal tissues of 47 CRC patients. DNA was extracted from fresh biopsies or from formalin-fixed, paraffin-embedded tissue sections using the Invitrogen Purelink Genomic DNA mini Kit. A simple PCR and a nested PCR were used to amplify a region of the T-Ag gene. The obtained PCR products revealed a 154 bp and a 98 bp bands, respectively. Specificity was confirmed by sequencing of the PCR products. T-Ag expression was determined by immunohistochemical staining using a mouse monoclonal antibody (clone PAb416) directed against SV40 T-Ag that cross reacts with JCV T-Ag. Results: JCV DNA was found in 12 (25%) and 22 (46%) of the CRC tumors by simple PCR and by nested PCR, respectively. All paired adjacent normal mucosa biopsies were negative for viral DNA. Sequencing of the DNA amplicons obtained confirmed the authenticity of T-Ag sequences. Immunohistochemical staining showed nuclear T-Ag expression in all 22 JCV DNA- positive samples and in 3 additional tumor samples which appeared DNA-negative by PCR. Conclusions: These results suggest an association of JCV with a subpopulation of Tunisian colorectal tumors.

Keywords: colorectal cancer, immunohistochemistry, Polyomavirus JC, PCR

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human endogenous retrovirus (HERV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on HERV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", "Human endogenous retrovirus", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles chosen, studied, and analyzed. Results: In the leptomeningeal cells of MS patients, a retrovirus-like element associated with reverse transcriptase (RT) activity called multiple sclerosis-associated retroviruses (MSRV) has been identified. HERVs are expressed in the human CNS despite mechanisms to suppress their expression. External factors, especially viral infections such as influenza virus, Epstein-Barr virus, and herpes simplex virus type 1, can activate HERV gene expression. The MSRV coat protein is activated by activating TLR4 at the brain surface, particularly in oligodendroglial progenitor cells and macrophages, leading to immune cascades followed by the downregulation of myelin protein expression. The HERV-K18 envelope gene (env) acts as a superantigen and induces inflammatory responses in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HERV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of endogenous retroviruses may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human endogenous retrovirus, central nervous system, MSRV

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Authors: Marcin Szlachetka, Rafal Sochaczewski, Lukasz Grabowski

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This paper presents the results of the load simulations of main bearings in a two-stroke Diesel engine. A model of an engine lubrication system with connections of its main lubrication nodes, i.e., a connection of its main bearings in the engine block with the crankshaft, a connection of its crankpins with its connecting rod and a connection of its pin and its piston has been created for our calculations performed using the AVL EXCITE Designer. The analysis covers the loads given as a pressure distribution in a hydrodynamic oil film, a temperature distribution on the main bush surfaces for the specified radial clearance values as well as the impact of the force of gas on the minimum oil film thickness in the main bearings depending on crankshaft rotational speeds and temperatures of oil in the bearings. One of the main goals of the research has been to determine whether the minimum thickness of the oil film at which fluid friction occurs can be achieved for each value of crankshaft speed. Our model calculates different oil film parameters, i.e., its thickness, a pressure distribution there, the change in oil temperature. Additional enables an analysis of an oil temperature distribution on the surfaces of the bearing seats. It allows verifying the selected clearances in the bearings of the main engine under normal operation conditions and extremal ones that show a significant increase in temperature above the limit value. The research has been conducted for several engine crankshaft speeds ranging from 1000 rpm to 4000 rpm. The oil pressure in the bearings has ranged 2-5 bar according to engine speeds and the oil temperature has ranged 90-120 °C. The main bearing clearance has been adopted for the calculation and analysis as 0.025 mm. The oil classified as SAE 5W-30 has been used for the simulations. The paper discusses the selected research results referring to several specific operating points and different temperatures of the lubricating oil in the bearings. The received research results show that for the investigated main bearing bushes of the shaft, the results fall within the ranges of the limit values despite the increase in the oil temperature of the bearings reaching 120˚C. The fact that the bearings are loaded with the maximum pressure makes no excessive temperature rise on the bush surfaces. The oil temperature increases by 17˚C, reaching 137˚C at a speed of 4000 rpm. The minimum film thickness at which fluid friction occurs has been achieved for each of the operating points at each of the engine crankshaft speeds. Acknowledgement: This work has been realized in the cooperation with The Construction Office of WSK ‘PZL-KALISZ’ S.A.’ and is part of Grant Agreement No. POIR.01.02.00-00-0002/15 financed by the Polish National Centre for Research and Development.

Keywords: diesel engine, main bearings, opposing pistons, two-stroke

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Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.

Keywords: EBV, ATM, DNA damage, germinal center cells

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Authors: Chander Shekhar, Manoj Kumar

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Present paper deal with the discovery of the stupa’s relics which belongs to the Kushana period. These remains were found during the scientific clearance work at a mound near Brahma-SarovarThanesar, Kurukshetra. This archaeological work was done by Department of Archaeology & Museums Haryana Government. The relics of stupa show that it would have been similar to Assandh and Damekhstupa. As per-Buddhist literature, GoutamBudhha reached Thanesar. In memory of Buddh’s Journey, King Ashoka built a big Stupa at Thanesar on the bank of Sarasvati River. Chinese pilgrim Yuan Chuang also referred a Monastery and stupa near Aujas-ghatof Brahma-sarovar. It may be part of that settlement which was mentioned by Yuan Chuang.

Keywords: archaeology, stupa, buddhism, excavtoin

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Authors: Erva Akin

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– The use of copyrighted material for machine learning purposes is a challenging issue in the field of artificial intelligence (AI). While machine learning algorithms require large amounts of data to train and improve their accuracy and creativity, the use of copyrighted material without permission from the authors may infringe on their intellectual property rights. In order to overcome copyright legal hurdle against the data sharing, access and re-use of data, the use of copyrighted material for machine learning purposes may be considered permissible under certain circumstances. For example, if the copyright holder has given permission to use the data through a licensing agreement, then the use for machine learning purposes may be lawful. It is also argued that copying for non-expressive purposes that do not involve conveying expressive elements to the public, such as automated data extraction, should not be seen as infringing. The focus of such ‘copy-reliant technologies’ is on understanding language rules, styles, and syntax and no creative ideas are being used. However, the non-expressive use defense is within the framework of the fair use doctrine, which allows the use of copyrighted material for research or educational purposes. The questions arise because the fair use doctrine is not available in EU law, instead, the InfoSoc Directive provides for a rigid system of exclusive rights with a list of exceptions and limitations. One could only argue that non-expressive uses of copyrighted material for machine learning purposes do not constitute a ‘reproduction’ in the first place. Nevertheless, the use of machine learning with copyrighted material is difficult because EU copyright law applies to the mere use of the works. Two solutions can be proposed to address the problem of copyright clearance for AI training data. The first is to introduce a broad exception for text and data mining, either mandatorily or for commercial and scientific purposes, or to permit the reproduction of works for non-expressive purposes. The second is that copyright laws should permit the reproduction of works for non-expressive purposes, which opens the door to discussions regarding the transposition of the fair use principle from the US into EU law. Both solutions aim to provide more space for AI developers to operate and encourage greater freedom, which could lead to more rapid innovation in the field. The Data Governance Act presents a significant opportunity to advance these debates. Finally, issues concerning the balance of general public interests and legitimate private interests in machine learning training data must be addressed. In my opinion, it is crucial that robot-creation output should fall into the public domain. Machines depend on human creativity, innovation, and expression. To encourage technological advancement and innovation, freedom of expression and business operation must be prioritised.

Keywords: artificial intelligence, copyright, data governance, machine learning

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Authors: Zdenek Silar, Martin Dobrovolny

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This article deals with the obstacle detection on a railway crossing (clearance detection). Detection is based on the optical flow estimation and classification of the flow vectors by K-means clustering algorithm. For classification of passing vehicles is used optical flow direction determination. The optical flow estimation is based on a modified Lucas-Kanade method.

Keywords: background estimation, direction of optical flow, K-means clustering, objects detection, railway crossing monitoring, velocity vectors

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Authors: P. Mounnarath, U. Schmitz, Ch. Zhang

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Fragility analysis is an effective tool for the seismic vulnerability assessment of civil structures in the last several years. The design of the expansion joints according to various bridge design codes is almost inconsistent, and only a few studies have focused on this problem so far. In this study, the influence of the expansion joint clearances between the girder ends and the abutment backwalls on the seismic fragility assessment of continuous integral bridge frames is investigated. The gaps (ranging from 60 mm, 150 mm, 250 mm and 350 mm) are designed by following two different bridge design code specifications, namely, Caltrans and Eurocode 8-2. Five bridge models are analyzed and compared. The first bridge model serves as a reference. This model uses three-dimensional reinforced concrete fiber beam-column elements with simplified supports at both ends of the girder. The other four models also employ reinforced concrete fiber beam-column elements but include the abutment backfill stiffness and four different gap values. The nonlinear time history analysis is performed. The artificial ground motion sets, which have the peak ground accelerations (PGAs) ranging from 0.1 g to 1.0 g with an increment of 0.05 g, are taken as input. The soil-structure interaction and the P-Δ effects are also included in the analysis. The component fragility curves in terms of the curvature ductility demand to the capacity ratio of the piers and the displacement demand to the capacity ratio of the abutment sliding bearings are established and compared. The system fragility curves are then obtained by combining the component fragility curves. Our results show that in the component fragility analysis, the reference bridge model exhibits a severe vulnerability compared to that of other sophisticated bridge models for all damage states. In the system fragility analysis, the reference curves illustrate a smaller damage probability in the earlier PGA ranges for the first three damage states, they then show a higher fragility compared to other curves in the larger PGA levels. In the fourth damage state, the reference curve has the smallest vulnerability. In both the component and the system fragility analysis, the same trend is found that the bridge models with smaller clearances exhibit a smaller fragility compared to that with larger openings. However, the bridge model with a maximum clearance still induces a minimum pounding force effect.

Keywords: expansion joint clearance, fiber beam-column element, fragility assessment, time history analysis

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Authors: Sanjay Singh, Parameswara Rao Vuddanda

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The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

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Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda

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The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.

Keywords: chemokine receptors, gp120, influenza, virus restriction factors

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Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

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Authors: Sadia Imran, Zenab Naseem

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Dengue fever is one of the most alarming mosquito-borne viral diseases. Dengue virus has been distributed over the years exponentially throughout the world be it tropical or sub-tropical regions of the world, particularly in the last ten years. Changing topography, climate change in terms of erratic seasonal trends, rainfall, untimely monsoon early or late and longer or shorter incidences of either summer or winter. Globalization, frequent travel throughout the world and viral evolution has lead to more severe forms of Dengue. Global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. In recent years, Pakistan experienced a deadly outbreak of the disease. The reason could be that they have the maximum exposure outdoors. Public organizations have observed that changing climate, especially lower average summer temperature, and increased vegetation have created tropical-like conditions in the city, which are suitable for Dengue virus growth. We will conduct a time-series analysis to study the interrelationship between dengue incidence and diurnal ranges of temperature and humidity in Pakistan, Lahore being the main focus of our study. We have used annual data from 2005 to 2015. We have investigated the relationship between climatic variables and dengue incidence. We used time series analysis to describe temporal trends. The result shows rising trends of Dengue over the past 10 years along with the rise in temperature & rainfall in Lahore. Hence this seconds the popular statement that the world is suffering due to Climate change and Global warming at different levels. Disease outbreak is one of the most alarming indications of mankind heading towards destruction and we need to think of mitigating measures to control epidemic from spreading and enveloping the cities, countries and regions.

Keywords: Dengue, epidemic, globalization, climate change

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Authors: Anis Al-Yakhiri

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Introduction: The World Health Organization (WHO) classifies malignant epithelial thyroid tumors into four major groups (papillary, follicular, medullar and undifferentiated) . Papillary thyroid carcinoma (PTC) is the most common type, for about eight out of ten thyroid cancers belong to this histological type. Radioactive iodine (RAI) is considered effective for patients with total or nearly total thyroidectomy, but the beneficial effects of RAI are still controversial. War conditions forced us to study alternative methods of using radioactive iodine in the treatment of patients with PTC. Material and methods: Between January 2014 and June 2021, in Al-Yakhiri hospital, 57 Total Thyroidectomy with Radical BilateralNeckDissection (RBND) were performed, 50 for malignant disease,7 for false positive cytology.RBND involves surgical clearance of Levels II-VI. Mean age was 40.7 years old and 92% of the patients were female. 7(14%) patients had hypothyroidism which required preoperative thyroid hormone treatment. The Thyroid Stimulating Hormone- Suppression Therapy (TSH-ST) immediately started after RBND for mostpatients on the first day. It consisted in reducing the level of TSH< 0.1 mIU/L. Results: The Apron flap was used on most operations (40)80% and with lateral extensions had 10(20%). RBND involves surgical clearance of Levels II-VI performed in all operated patients, besides that, 4(8%) of them had resection of sternocleidomastoid muscle (SCM) and accessory nerve (XIn) and internal jugular vein (IJV) withclearance of Levels IB. The PTC was the most common 80.9% (38 patients from 47)by histopathological report. and 4(8%) patients of 50 had resection of sternocleidomastoid muscle (SCM) and accessory nerve (XIn) and internal jugular vein (IJV). The postoperative mortality rate not observed (0%). The postoperative morbidity rate was 22.8% (n =13).Seroma(8.7%),Hypocalcimia(7%), Wound infection(5.3%), Bleeding(1.8%). To suppress TSH and growth of any residual thyroid theTSH-ST (levothyroxine150 – 600mcg)was performed in all patients 57(100%) on the first day afterRBND. We tracked the results of treatment for two years in 30 patients with PTC, only 3 of them received radioactive iodine abroad. Biennial Recurrence rate for PTC appeared in one woman (2%), who had RAI postoperatively in the form of neck lymph nodes metastasis. Conclusion: For patients with PTC, thyroidectomy plus prophylacticRBND is a safe and efficient procedure and it results in lower recurrence rate. Postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress TSH (not less than 150mcg), decreases incidence of recurrence. Total Thyroidectomy with RBND followed by TSH-ST, in our opinion, applicable optimal treatment scheme care for this patient population.

Keywords: thyroid cancer, Yemen war, absence of radioactive iodine, neck dissection, surgery results

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Authors: M. S. Aparna, Pushparaj Shetty D.

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Nowadays social networking sites have become so popular that the producers or the sellers look for these sites as one of the best options to target the right audience to market their products. There are several tools available to monitor or analyze the social networks. Our task is to identify the right community web pages and find out the behavior analysis of the members by using these tools and formulate an appropriate strategy to market the products or services to achieve the set goals. The advertising becomes more effective when the information of the product/ services come from a known source. The strategy explores great buying influence in the audience on referral marketing. Our methodology proceeds with critical budget analysis and promotes viral influence propagation. In this context, we encompass the vital bits of budget evaluation such as the number of optimal seed nodes or primary influential users activated onset, an estimate coverage spread of nodes and maximum influence propagating distance from an initial seed to an end node. Our proposal for Buyer Prediction mathematical model arises from the urge to perform complex analysis when the probability density estimates of reliable factors are not known or difficult to calculate. Order Statistics and Buyer Prediction mapping function guarantee the selection of optimal influential users at each level. We exercise an efficient tactics of practicing community pages and user behavior to determine the product enthusiasts on social networks. Our approach is promising and should be an elementary choice when there is little or no prior knowledge on the distribution of potential buyers on social networks. In this strategy, product news propagates to influential users on or surrounding networks. By applying the same technique, a user can search friends who are capable to advise better or give referrals, if a product interests him.

Keywords: viral marketing, social network analysis, community web pages, buyer prediction, influence propagation, budget constraints

Procedia PDF Downloads 237

Authors: Karlygash Tulendieva

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Presently vaccination is the most effective method of prevention of flu and its complications. The purpose of this study was to analyze the impact of the increase of coverage of the population of South Kazakhstan region with flu vaccination and decrease of the ARVI morbidity. The analysis was performed on the data of flu vaccination of risk groups, including children under one year and pregnant women. Data on ARVI morbidity during 2010-2015 and data on vaccination were taken from the reports of the Epidemiological Surveillance Unit of Department of Consumers’ Rights Protection of South Kazakhstan region. Coverage with flu vaccination of the risk groups was annually increasing and in 2015 it reached 16% (450,000/2,800,682) from the total population. The ARVI morbidity rate in the entire population in 2010 was 2,010.4 per 100,000 of the population and decreased 3.2 times to 609.9 per 100,000 of the population in 2015. Annual growth was observed from 2010 to 2015 of specific weight of the vaccinated main risk groups: healthcare workers by 51% (from 17,331 in 2010 to 33,538 in 2015), children with chronic pulmonary and cardio-vascular diseases, immune deficiency, weak and sickly children above six months by 39% (from 63,122 in 2010 to 158,023 in 2015), adults with chronic co-morbidities by 27% (from 44,271 in 2010 to 162,595 in 2015), persons above 65 by 17% (from 10,276 in 2010 to 57,875 in 2015), and annual coverage of pregnant women on second or third trimester from 34,443 in 2010 to 37,969 in 2015. Starting from 2013 and until 2015 vaccination was performed in the region with coverage of at least 90% of children from 6 months to one year. The ARVI morbidity in this age group decreased 3.3 times from 8,687.8 per 100,000 of the population in 2010 to 2,585.8 per 100,000 of the population in 2015. Vaccination of pregnant women on 2-3 trimester was started in the region in 2012. Annual increase of vaccination coverage of pregnant women from 86.1% (34,443/40,000) in 2012 to 95% (37,969/40,000) in 2015 decreased the morbidity 1.5 times from 4,828.8 per 100,000 of population in 2012 to 3,022.7 per 100,000 of population in 2015. Following the increase of vaccination coverage of the population in South Kazakhstan region, the trend was observed of decrease of ARVI morbidity rates among the population and main risk groups, among pregnant women and children under one year.

Keywords: acute respiratory viral infections, flu, risk groups, vaccination

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Authors: Akhil Teja Kambhampati, Mark A. Hoffman

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In the realm of infectious disease research, airborne viral transmission stands as a paramount concern due to its pivotal role in propagating pathogens within densely populated regions. However, amidst this landscape, the phenomenon of hygroscopic growth within respiratory bioaerosols remains relatively underexplored. Unlike pure water aerosols, the unique composition of respiratory bioaerosols leads to varied evaporation rates and hygroscopic growth patterns, influenced by factors such as ambient humidity, temperature, and airflow. This study addresses this gap by focusing on the behaviors of single respiratory bioaerosol utilizing salinity to induce saliva-like hygroscopic behavior. By employing mass, momentum, and energy equations, the study unveils the intricate interplay between evaporation and hygroscopic growth over time. The numerical model enables temporal analysis of bioaerosol characteristics, including size, temperature, and trajectory. The analysis reveals that due to evaporation, there is a reduction in initial size, which shortens the lifetime and distance traveled. However, when hygroscopic growth begins to influence the bioaerosol size, the rate of size reduction slows significantly. The interplay between evaporation and hygroscopic growth results in bioaerosol size within the inhalation range of humans and prolongs the traveling distance. Findings procured from the analysis are crucial for understanding the spread of infectious diseases, especially in high-risk environments such as healthcare facilities and public transportation systems. By elucidating the nuanced behaviors of respiratory bioaerosols, this study seeks to inform the development of more effective preventative strategies against pathogens propagation in the air, thereby contributing to public health efforts on a global scale.

Keywords: airborne viral transmission, high-risk environments, hygroscopic growth, evaporation, numerical modeling, pathogen propagation, preventative strategies, public health, respiratory bioaerosols

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Authors: Bakytzhan Bimbetov, Abay Zhangabilov, Saule Aitbaeva, Galymzhan Meirambekov

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Mare’s milk (saumal) contains in total about 40 biological components necessary for the human body. The most significant among them are amino acids, fats, carbohydrates, enzymes (lysozyme, amylase), more minerals and vitamins which are well balanced with each other. In Kazakhstan, Company "Eurasia Invest Ltd.” produces a freeze-dried saumal in form of powder by the use of modern German innovative technology by means of evaporating at low temperature (-35°C) with an appropriate pasteurization. Research of freeze-dried biomilk for the qualitative content showed that main ingredients of freshly drown milk are being preserved. We are currently studying medical and dietary properties of freeze-dried mare's milk for diseases of the digestive system, including for nonalcoholic steatohepatitis (NASH) and liver cirrhosis (LC) viral etiology. The studied group consisted of 14 patients with NASH, and 7 patients with LC viral etiology of Class A severity degree as per Child-Pugh. Patients took freeze-dried saumal, preliminary dissolved in boiled warm water (24 g. powder per 200 ml water) 3-4 times a day for a month in conjunction with basic therapy. The results were compared to a control group (11 patients with NASH and LC) who received only basic therapy without mare’s milk. Results of preliminary research showed an improvement of subjective and objective conditions of all patients, but more significant improvement of clinical symptoms and syndromes were observed in the treatment group compared to the control one. Patients with NASH significantly over time compared to the beginning of therapy decreased asthenic and dyspeptic syndromes (p<0,01). Hepatomegaly, identified on the basis of ultrasound prior to treatment was observed in 92,8±2,4% of patients, and after combination therapy hepatomegaly the rate decreased by 14,3%, amounting to 78,5±2,8%. Patients with LC also noted the improvement of asthenic (p<0,01) and dyspeptic (p<0,05) syndromes and hemorrhagic syndrome (nosebleeds and bleeding gums when brushing your teeth, p<0,05), and jaundice. Laboratory study also showed improvement in the research group, but more significant changes were observed in the experimental group. Group of patients with NASH showed a significant improvement of index in cytolysis in conjunction with a combination therapy (p<0,05). In the control group, these indicators were also improved, but they were not statistically reliable (p>0,05). Markers of liver failure were additionally studied during the study of laboratory parameters in patients with liver cirrhosis, in particular, bilirubin, albumin and prothrombin index (PTI). Combined therapy with the use of basic treatment and mare's milk showed a significant improvement in cytolysis and bilirubin (p<0,05). In our opinion, a very important and interesting fact is that, in conjunction with basic therapy, the use of mare's milk revealed an improvement of liver function in the form of normalized PTI and albumin in patients with liver cirrhosis viral etiology. Results of this work have shown therapeutic efficiency of the use of mare's milk in complex treatment of patients with liver disease and require further in-depth study.

Keywords: liver cirrhosis, non-alcohol steatohepatitis, saumal, mare’s milk

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Authors: Yamina Boughari, Ruxandra Mihaela Botez, Florian Theel, Georges Ghazi

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Clearance of flight control laws of a civil aircraft is a long and expensive process in the Aerospace industry. Thousands of flight combinations in terms of speeds, altitudes, gross weights, centers of gravity and angles of attack have to be investigated, and proved to be safe. Nonetheless, in this method, a worst flight condition can be easily missed, and its missing would lead to a critical situation. Definitively, it would be impossible to analyze a model because of the infinite number of cases contained within its flight envelope, that might require more time, and therefore more design cost. Therefore, in industry, the technique of the flight envelope mesh is commonly used. For each point of the flight envelope, the simulation of the associated model ensures the satisfaction or not of specifications. In order to perform fast, comprehensive and effective analysis, other varying parameters models were developed by incorporating variations, or uncertainties in the nominal models, known as Linear Fractional Representation LFR models; these LFR models were able to describe the aircraft dynamics by taking into account uncertainties over the flight envelope. In this paper, the LFRs models are developed using the speeds and altitudes as varying parameters; The LFR models were built using several flying conditions expressed in terms of speeds and altitudes. The use of such a method has gained a great interest by the aeronautical companies that have seen a promising future in the modeling, and particularly in the design and certification of control laws. In this research paper, we will focus on the Cessna Citation X open loop stability analysis. The data are provided by a Research Aircraft Flight Simulator of Level D, that corresponds to the highest level flight dynamics certification; this simulator was developed by CAE Inc. and its development was based on the requirements of research at the LARCASE laboratory. The acquisition of these data was used to develop a linear model of the airplane in its longitudinal and lateral motions, and was further used to create the LFR’s models for 12 XCG /weights conditions, and thus the whole flight envelope using a friendly Graphical User Interface developed during this study. Then, the LFR’s models are analyzed using Interval Analysis method based upon Lyapunov function, and also the ‘stability and robustness analysis’ toolbox. The results were presented under the form of graphs, thus they have offered good readability, and were easily exploitable. The weakness of this method stays in a relatively long calculation, equal to about four hours for the entire flight envelope.

Keywords: flight control clearance, LFR, stability analysis, robustness analysis

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Authors: Howaida I. Abd-Alla, Omnia Kutkat, Yassmin Moatasim, Magda T. Ibrahim, Marwa A. Mostafa, Mohamed GabAllah, Mounir M. El-Safty

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Artemisia judaica (known shih-balady), Azadirachta indica and Sophora tomentosa (known yellow necklace pod) are members of available medicinal plants well-known for their traditional medical use in Egypt which suggests that they probably harbor broad-spectrum antiviral, immunostimulatory and anti-inflammatory functions. Their ethyl acetate-dichloromethane (1:1, v/v) extracts were evaluated for the potential anti-Middle East respiratory syndrome-related coronavirus (anti-MERS-CoV) activity. Their cytotoxic activity was tested in Vero-E6 cells using 3-(4,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method with minor modification. The plot of percentage cytotoxicity for each extract concentration has calculated the concentration which exhibited 50% cytotoxic concentration (TC50). A plaque reduction assay was employed using safe dose of extract to evaluate its effect on virus propagation. The highest inhibition percentage was recorded for the yellow necklace pod, followed by Shih-balady. The possible mode of action of virus inhibition was studied at three different levels viral replication, viral adsorption and virucidal activity. The necklace pod leaves have induced virucidal effects and direct effects on the replication of virus. Phytochemical investigation of the promising necklace pod led to the isolation and structure determination of nine compounds. The structure of each compound was determined by a variety of spectroscopic methods. Compounds 4-O-methyl sorbitol 1, 8-methoxy daidzin 6 and 6-methoxy apigenin-7-O-β-D-glucopyranoside 8 were isolated for the first time from the Sophora genus and the other six compounds were the first time that they were isolated from this species according to available works of literature. Generally, the highest anti-CoV 2 activity of S. tomentosa was associated with the crude ethanolic extract, indicating the possibility of synergy among the antiviral phytochemical constituents (1-9).

Keywords: coronavirus, MERS-CoV, mode of action, necklace pod, shih-balady

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Authors: Yong-Hui Zheng

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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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