Search results for: interferon alpha and beta receptor subunit 2

Authors: Sima Parvizi Omran, Rezvan Tavakoli, Mahnaz Safari, Mohammadreza Aghasadeghi, Abolfazl Fateh, Pooneh Rahimi

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Background: SARS-CoV-2, a single-stranded RNA betacoronavirus causes the global outbreak of coronavirus disease 2019 (COVID-19). Several clinical and scientific concerns are raised by this pandemic. Genetic factors can contribute to pathogenesis and disease susceptibility. There are single nucleotide polymorphisms (SNPs) in many of the genes in the immune system that affect the expression of specific genes or functions of some proteins related to immune responses against viral infections. In this study, we analyzed the impact of polymorphism in the interferon alpha and beta receptor subunit 2 (IFNAR2) and dipeptidyl peptidase 9 (Dpp9) genes and clinical parameters on the susceptibility and resistance to Coronavirus disease (COVID-19). Methods: A total of 330- SARS-CoV-2 positive patients (188 survivors and 142 nonsurvivors) were included in this study. All single-nucleotide polymorphisms (SNPs) on IFNAR2 (rs2236757) and Dpp9 (rs2109069) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In survivor patients, the frequency of the favourable genotypes of IFNAR2 SNP (rs2236757 GC) was significantly higher than in nonsurvivor patients, and also Dpp9 (rs2109069 AT) genotypes were associated with the severity of COVID-19 infection. Conclusions: This study demonstrated that the severity of COVID- 19 patients was strongly associated with clinical parameters and unfavourable IFNAR2, Dpp9 SNP genotypes. In order to establish the relationship between host genetic factors and the severity of COVID-19 infection, further studies are needed in multiple parts of the world.

Keywords: SARS-CoV-2, COVID-19, interferon alpha and beta receptor subunit 2, dipeptidyl peptidase 9, single-nucleotide polymorphisms

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Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

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In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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Authors: A. Calvin Antony, Sakthi Kumar Arul Prakash, V. R. Sanal Kumar

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In this paper a unique alpha-beta double piston 'stirling engine' is designed, manufactured and conducted laboratory test to ameliorate the efficiency of the stirling engine. The paper focuses on alpha and beta type engines, capturing their benefits and eradicating their short comings; along with the output observed from the flywheel. In this model alpha engine is kinematically with a piston cylinder arrangement which works quite like a beta engine. The piston of the new cylinder is so designed that it replicates a glued displacer and power piston as similar to that of beta engine. The bigger part of the piston is the power piston, which has a gap around it, while the smaller part of the piston is tightly fit in the cylinder and acts like the displacer piston. We observed that the alpha-beta double piston stirling engine produces 25% increase in power compare to a conventional alpha stirling engine. This working model is a pointer towards for the design and development of an alpha-beta double piston Stirling engine for industrial applications for producing electricity from the heat producing exhaust gases.

Keywords: alpha-beta double piston stirling engine , alpha stirling engine , beta double piston stirling engine , electricity from stirling engine

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Authors: Rauza Sukma Rita, Katsuya Dezaki, Yuko Maejima, Toshihiko Yada

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Oxytocin is a nine-amino acid peptide synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Oxytocin promotes contraction of the uterus during birth and milk ejection during breast feeding. Although oxytocin receptors are found predominantly in the breasts and uterus of females, many tissues and organs express oxytocin receptors, including the pituitary, heart, kidney, thymus, vascular endothelium, adipocytes, osteoblasts, adrenal gland, pancreatic islets, and many cell lines. On the other hand, in pancreatic islets, oxytocin receptors are expressed in both α-cells and β-cells with stronger expression in α- cells. However, to our knowledge there are no reports yet about the effect of oxytocin on cytosolic calcium reaction on α and β-cell. This study aims to investigate the effect of oxytocin on α-cells and β-cells and its oscillation pattern. Islet of Langerhans from wild type mice were isolated by collagenase digestion. Isolated and dissociated single cells either α-cells or β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic concentration ([Ca2+]i) in single cells were measured by fura-2 microfluorimetry. After measurement of [Ca2+]i, α-cells were identified by subsequent immunocytochemical staining using an anti-glucagon antiserum. In β-cells, the [Ca2+]i increase in response to oxytocin was observed only under 8.3 mM glucose condition, whereas in α-cells, [Ca2+]i an increase induced by oxytocin was observed in both 2.8 mM and 8.3 mM glucose. The oscillation incidence was induced more frequently in β-cells compared to α-cells. In conclusion, the present study demonstrated that oxytocin directly interacts with both α-cells and β-cells and induces increase of [Ca2+]i and its specific patterns.

Keywords: α-cells, β-cells, cytosolic calcium concentration, oscillation, oxytocin

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Authors: N. Chahmana, I. Zerroual

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The aim of our work is the contribution to the improvement of the performances of the positive plate of the lead acid battery. For that, we synthesized two varieties of PbO2 used in industry, alpha and beta PbO2 by electrochemical way starting from the not formed industrial plates. We studied the kinetics of reduction of the alpha varieties and PbO2 beta on electrode with microcavity in sulphuric medium. The electrochemical study of the powders of α and β-PbO2 was made by cyclic voltamperometry with sweeping of potential by using a traditional assembly with three electrodes. Values of the coefficient of diffusion of the proton in α and β-PbO2 are respectively equal to 0.498*10-8cm2 /s and 0.793*10-8 cm2 /s. During the cycling of the two varieties of PbO2, we obtain a clear increase in the capacity.

Keywords: lead accumulator, α and β - PbO2, synthesis, kinetics, cyclic voltametry, coefficient of diffusion

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Authors: Ghada Esheba, Fatimah Alturkistani, Arwa Obaid, Ahdab Bashehab, Moayad Alturkistani

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Introduction: Craniopharyngiomas (CPs) are rare epithelial tumors located mainly in the sellar/parasellar region. CPs have been classified histopathologically, genetically, clinically and prognostically into two distinctive subtypes: adamantinomatous and papillary variants. Aim: To examine the pattern of expression of both the β-catenin and epidermal growth factor receptor (EGFR) in surgically resected samples of adamantinomatous CP, and to asses for the possibility of using anti-EGFR in the management of ACP patients. Materials and methods: β-catenin and EGFR immunostaining was performed on paraffin-embedded tissue sections of 18 ACP cases. Result: 17 out of 18 cases (94%) of ACP exhibited strong nuclear/cytoplasmic expression of β-catenin, 15 (83%) of APC cases were positive for EGFR. Conclusion: Nuclear accumulation of β-catenin is a diagnostic hallmark of ACP. EGFR positivity in most cases of ACP could qualify the use of anti-EGFR therapy. 

Keywords: craniopharyngioma, adamantinomatous, papillary, epidermal growth factor receptor, B-catenin

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Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

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Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

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Authors: Hashaam Akhtar

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IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.

Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression

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Authors: K. Tejasri, K. Suvarna Vani, S. Prathyusha, S. Ramya

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Proteins are chained sequences of amino acids which are brought together by the peptide bonds. Many varying formations of the chains are possible due to multiple combinations of amino acids and rotation in numerous positions along the chain. Protein structure prediction is one of the crucial goals worked towards by the members of bioinformatics and theoretical chemistry backgrounds. Among the four different structure levels in proteins, we emphasize mainly the secondary level structure. Generally, the secondary protein basically comprises alpha-helix and beta-sheets. Multi-class classification problem of data with disparity is truly a challenge to overcome and has to be addressed for the beta strands. Imbalanced data distribution constitutes a couple of the classes of data having very limited training samples collated with other classes. The secondary structure data is extracted from the protein primary sequence, and the beta-strands are predicted using suitable machine learning algorithms.

Keywords: proteins, secondary structure elements, beta-sheets, beta-strands, alpha-helices, machine learning algorithms

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Authors: Bhanu Pant, Sanjay H. Upadhyay

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Titanium alloys, owing to their high specific strength coupled with excellent resistance to corrosion in many severe environments, find extensive usage in the aerospace sector. Alpha and beta lean Titanium alloys have an additional characteristic of exhibiting high toughness with an NTS/ UTS ratio greater than one down to liquid oxygen and liquid helium temperatures. The cryogenic stage of high-performance rockets utilizes cryo-fluid submerged pressurizing tanks to improve volume to mass performance factor. A superior volume-to-mass ratio is achieved for LH2-submerged pressurizing tanks as compared to those submerged in LOX. Such high-efficiency tanks for LH2 submerged application necessitate the use of difficult to process alpha type Ti5Al2.5Sn-ELI alloy, which requires close control of process parameters to develop the tanks. In the present paper, a comparison of this alpha-type cryogenic Titanium alloy has been brought out with conventional alpha-beta Ti6Al4V-ELI alloy, which is usable up to LOX temperatures. Specific challenges faced during the development of these cryogenic pressurizing tanks for a launch vehicle based on the author's experience are included in the paper on the comparatively lesser-studied alpha Ti5Al2.5Sn-ELI alloy.

Keywords: cryogenic tanks, titanium Alloys, NTS/UTS ratio, alpha and alpha-beta ELI alloys

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Authors: Roohallah Yousefi

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Introduction: In beta-thalassemia, an imbalance in the production of beta subunits of hemoglobin leads to the oxidation and deposition of excess alpha-globin chains at the cell membrane, resulting in the hemolysis of erythrocytes and a disorder of erythropoiesis. Antioxidants, such as curcumin, may promote this progression. This study aims to investigate the antioxidant effect of curcumin on hemolysate samples from patients with beta-thalassemia. Materials and methods: Pure curcumin was extracted and purified for use in studying its effect on the visual light absorbance of hemoglobin in hemolysate samples from beta-thalassemia patients compared to control samples. Changes in light absorbance at 540 and 700 nm wavelengths during exposure to curcumin were analyzed to examine the shift from oxyhemoglobin to deoxyhemoglobin. Results: Curcumin was found to dissolve rapidly and to a high degree in ethanol at 1 mg/ml, but did not dissolve in distilled water at the same concentration. The curcumin addition to the hemolysate sample of a patient with beta-thalassemia resulted in a decrease in the light absorbance of the sample at 540 nm wavelength, with minimal changes observed in the control sample. Conclusion: Curcumin deoxygenated the hemolysate samples from both the patient and control, causing hemoglobin precipitation to occur slowly. The study suggests a greater potential role for curcumin in deoxygenating hemoglobin in the hemolysate samples of beta-thalassemia patients compared to those of the normal control.

Keywords: beta-thalassemia, hemoglobin, curcumin, alpha-globin

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Authors: Shishen Xie, Yingda L. Xie

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Tuberculosis (TB) is a potentially serious infectious disease that remains a health concern. The Interferon Gamma Release Assay (IGRA) is a blood test to find out if an individual is tuberculous positive or negative. This study applies statistical analysis to the clinical data of interferon-gamma levels of seventy-three subjects who diagnosed pulmonary TB in an anti-tuberculous treatment. Data analysis is performed to determine if there is a significant decline in interferon-gamma levels for the subjects during a period of six months, and to infer if the anti-tuberculous treatment is effective.

Keywords: data analysis, interferon gamma release assay, statistical methods, tuberculosis infection

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Authors: Thiwanka Weerakkody, Lakmali Handagiripathira, Poshitha Dabare, Thisari Guruge

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The determination of gross alpha and beta activity in water is important in a wide array of environmental studies and these parameters are considered in international legislations on the quality of water. This technique is commonly applied as screening method in radioecology, environmental monitoring, industrial applications, etc. Measuring of Gross Alpha and Beta emitters by using iSolo alpha beta counting system is an adequate nuclear technique to assess radioactivity levels in natural and waste water samples due to its simplicity and low cost compared with the other methods. Twelve water samples (Six samples of commercially available bottled drinking water and six samples of industrial waste water) were measured by standard method EPA 900.0 consisting of the gas-less, firm wear based, single sample, manual iSolo alpha beta counter (Model: SOLO300G) with solid state silicon PIPS detector. Am-241 and Sr90/ Y90 calibration standards were used to calibrate the detector. The minimum detectable activities are 2.32mBq/L and 406mBq/L, for alpha and beta activity, respectively. Each of the 2L water samples was evaporated (at low heat) to a small volume and transferred into 50mm stainless steel counting planchet evenly (for homogenization) and heated by IR lamp and the constant weighted residue was obtained. Then the samples were counted for gross alpha and beta. Sample density on the planchet area was maintained below 5mg/cm. Large quantities of solid wastes sludges and waste water are generated every year due to various industries. This water can be reused for different applications. Therefore implementation of water treatment plants and measuring water quality parameters in industrial waste water discharge is very important before releasing them into the environment. This waste may contain different types of pollutants, including radioactive substances. All these measured waste water samples having gross alpha and beta activities, lower than the maximum tolerance limits for industrial waste water discharge of industrial waste in to inland surface water, that is 10-9µCi/mL and 10-8µCi/mL for gross alpha and beta respectively (National Environmental Act, No. 47 of 1980). This is according to extraordinary gazette of the democratic socialist republic of Sri Lanka in February 2008. The measured water samples were below the recommended radioactivity levels and do not pose any radiological hazard when releasing the environment. Drinking water is an essential requirement of life. All the drinking water samples were below the permissible levels of 0.5Bq/L for gross alpha activity and 1Bq/L for gross beta activity. The values have been proposed by World Health Organization in 2011; therefore the water is acceptable for consumption of humans without any further clarification with respect to their radioactivity. As these screening levels are very low, the individual dose criterion (IDC) would usually not be exceeded (0.1mSv y⁻¹). IDC is a criterion for evaluating health risks from long term exposure to radionuclides in drinking water. Recommended level of 0.1mSv/y expressed a very low level of health risk. This monitoring work will be continued further for environmental protection purposes.

Keywords: drinking water, gross alpha, gross beta, waste water

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Authors: Ali Taheri Mirghaed, Sara Ahani, Ashkan Zargar, Seyyed Morteza Hoseini

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Diseases are the major challenges in intensive aquaculture that cause significant annual losses. Antibiotic-therapy is a common way to control bacterial disease in fish, and oxytetracycline (OTC) is the only oral antibiotic in aquaculture approved FDA. OTC has been found to have negative effects on fish, such as oxidative stress and immune-suppression, thus, it is necessary to mitigate such effects. Medicinal herbs have various benefits on fish, including antioxidant, immunostimulant, and anti-microbial effects. Therefore, we hypothesized if dietary ginger meal (GM) interacts with dietary OTC by monitoring plasma protein fractions in rainbow trout. The study was conducted as a 2 × 2 factorial design, including diets containing 0 and 1% GM and 0 and 1.66 % OTC (corresponding to 100 mg/kg fish biomass per day). After ten days treating the fish (60 g individual weight) with these feeds, blood samples were taken from al treatments (n =3). Plasma was separated by centrifugation, and protein fractions were determined by electrophoresis. The results showed that OTC and GM had interaction effects on total protein (P<0.001), albumin (P<0.001), alpha-1 fraction (P=0.010), alpha-2 fraction (P=0.001), beta-2 fraction (P=0.014), and gamma fraction (P<0.001). Beta-1 fraction was significantly (P=0.030) affected by dietary GM. GM decreased plasma total protein, albumin, and beta-2 but increased beta-1 fraction. OTC significantly decreased total protein (P<0.001), albumin (P=0.001), alpha-2 fraction (P<0.001), beta-2 fraction (P=0.004), and gamma fraction (P<0.001) but had no significant effects on alpha-1 and beta-1 fractions. Dietary GM inhibited/suppressed the effects of dietary OTC on the plasma total protein and protein fractions. In conclusion, adding 1% GM to diet can mitigate the negative effects of dietary OTC on plasma proteins. Thus, GM may boost health of rainbow trout during the period of medication with OTC.

Keywords: ginger, plasma protein electrophoresis, dietary additive, rainbow trout

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Authors: Saad Khalid Niaz, Arif Mahmood Siddiqui, Afzal Haqi

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Background: Estimated prevalence of Hepatitis C in Pakistan is 5% of which 78 % are Genotype 3, in which Response to conventional interferon is reported to be 70%. Objective: To determine the efficacy of pegylated interferon 20 kDa (Unipeg) plus ribavirin (Ribazole) in HCV genotype 3 patients who relapsed to conventional interferon. Methods: This is an ongoing study of 20 enrolled patients. Pegylated interferon alfa-2a 20 kDa 180 mcg weekly with ribavirin, were administered for a period of 24 weeks. Virological Responses were measured by Qualitative HCV RNA at weeks 4, 12, 24 and 48 to determine Rapid Virological Response (RVR), Early Virological Response (EVR), End of Treatment (ETR) and Sustained Virological Response (SVR), respectively. EVR was done for those who didn’t achieve RVR. Results: Males were 12 (60%) and mean age was 38.5 ±7.62 years. Out of 20 recruited patients, all completed 4 weeks therapy; RVR was achieved in 8 (40%) patients. One patient was lost to follow up and one yet to visit at 12 weeks. From 10 patients, 8 (80%) patients achieved EVR. Out of intent-to-treat patients, 15 completed 24 weeks therapy, ETR was achieved in 14 (93%) patients and 9 patients completed post therapy follow-up, of which, 8 (89%) patients achieved SVR. Conclusion: Our interim data demonstrates that Pegylated Interferon alfa-2a 20 kDa 180 mcg (Unipeg) in combination with Ribavirin (Ribazole) has shown promising results in treating HCV Genotype 3 patients who relapsed to conventional interferon. We recommend use of Pegylated Interferon in Relapsers with Genotype 3 when financial constraints limit the use of oral antivirals.

Keywords: pegylated interferon (unipeg), hepatitis c, relapsers, Pakistan

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Authors: E. Kam, G. Karahan, H. Aslıyuksek, A. Bozkurt

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This study aims to determine the natural radioactivity levels in some foodstuffs produced in Turkey. For this purpose, 48 different foods samples were collected from different land parcels throughout the country. All samples were analyzed to designate both gross alpha and gross beta radioactivities and the radionuclides’ concentrations. The gross alpha radioactivities were measured as below 1 Bq kg^-1 in most of the samples, some of them being due to the detection limit of the counting system. The gross beta radioactivity levels ranged from 1.8 Bq kg^-1 to 453 Bq kg^-1, larger levels being observed in leguminous seeds while the highest level being in haricot bean. The concentrations of natural radionuclides in the foodstuffs were investigated by the method of gamma spectroscopy. High levels of ⁴⁰K were measured in all the samples, the highest activities being again in leguminous seeds. Low concentrations of ²³⁸U and ²²⁶Ra were found in some of the samples, which are comparable to the reported results in the literature. Based on the activity concentrations obtained in this study, average annual effective dose equivalents for the radionuclides ²²⁶Ra, ²³⁸U, and ⁴⁰K were calculated as 77.416 µSv y^-1, 0.978 µSv y^-1, and 140.55 µSv y^-1, respectively.

Keywords: foods, radioactivity, gross alpha, gross beta, annual equivalent dose, Turkey

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Saud Al Mahdi

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Traditionally,portfolio managers have been discouraged from timing the market. This means, for example, that equity managers have been forced to adhere strictly to a benchmark with static or relatively stable components, such as the SP 500 or the Russell 3000. This means that the portfolio’s exposures to all risk factors should mimic as closely as possible the corresponding exposures of the benchmark. The main risk factor, of course, is the market itself. Effectively, a long-only portfolio would be constrained to have a beta 1. More recently, however, managers have been given greater discretion to adjust their portfolio’s risk exposures (in particular, the beta of their portfolio) dynamically to match the manager’s beliefs about future performance of the risk factors themselves. This freedom translates into the manager’s ability to adjust the portfolio’s beta dynamically. These strategies have come to be known as smart beta strategies. Adjusting beta dynamically amounts to attempting to "time" the market; that is, to increase exposure when one anticipates that the market will rise, and to decrease it when one anticipates that the market will fall. Traditionally, market timing has been believed to be impossible to perform effectively and consistently. Moreover, if a majority of market participants do it, their combined actions could destabilize the market. The aim of this project is to investigate so-called smart beta strategies to determine if they really can add value, or if they are merely marketing gimmicks used to sell dubious investment strategies.

Keywords: beta, alpha, active portfolio management, trading strategies

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Authors: Karen K. Perez-Ramirez, Genevieve Dupont, Virginia Gonzalez-Velez

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Pancreatic alpha-cells participate on glucose regulation together with beta cells. They release glucagon hormone when glucose level is low to stimulate gluconeogenesis from the liver. As other excitable cells, alpha cells generate Ca2+ and metabolic oscillations when they are stimulated. It is known that the glucose level can trigger or silence this activity although it is not clear how this occurs in normal and diabetic people. In this work, we propose an electric-metabolic mathematical model implemented in Matlab to study the effect of different glucose levels on the electrical response and Ca2+ oscillations of an alpha cell. Our results show that Ca2+ oscillations appear in opposite phase with metabolic oscillations in a window of glucose values. The model also predicts a direct relationship between the level of glucose and the intracellular adenine nucleotides showing a self-regulating pathway for the alpha cell.

Keywords: Ca2+ oscillations, mathematical model, metabolic oscillations, pancreatic alpha cell

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Authors: Rayan B. M. Ameen, Ian P. Jones, Yu Lung Chiu

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Single alpha-beta colony micro-pillars have been manufactured from a polycrystalline commercial Ti-6Al-4V sample using Focused Ion Beam (FIB). Each pillar contained two alpha lamellae separated by a thin fillet of beta phase. A nano-indenter was then used to conduct uniaxial micro-compression tests on Ti alloy single crystals, using a diamond flat tip as a compression platen. By controlling the crystal orientation along the micro-pillar using Electron back scattering diffraction (EBSD) different slip systems have been selectively activated. The advantage of the micro-compression method over conventional mechanical testing techniques is the ability to localize a single crystal volume which is characterizable after deformation. By matching the stress-strain relations resulting from micro-compression experiments to TEM (Transmission Electron Microscopy) studies of slip transmission mechanisms through the α-β interfaces, some proper constitutive material parameters such as the role of these interfaces in determining yield, strain-hardening behaviour, initial dislocation density and the critical resolved shear stress are suggested.

Keywords: α/β-Ti alloy, focused ion beam, micro-mechanical test, nano-indentation, transmission electron diffraction, plastic flow

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Authors: Yonosuke Murayama

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We have developed and studied a metastable beta Ti alloy, which shows super-elasticity and low Young’s modulus according to the phase stability of its beta phase. The super-elasticity and low Young’s modulus are required in a wide range of applications in various industrial fields. For example, the metallic implant with low Young’s modulus and non-toxicity is desirable because the large difference of Young’s modulus between the human bone and the implant material may cause a stress-shielding phenomenon. We have investigated the role of Sn and Al in metastable beta Ti-Cr-Sn, Ti-Cr-Al, Ti-V-Sn, and Ti-V-Al alloys. The metastable beta Ti-Cr-Sn, Ti-Cr-Al, Ti-V-Sn, and Ti-V-Al alloys form during quenching from the beta field at high temperature. While Cr and V act as beta stabilizers, Sn and Al are considered as elements to suppress the athermal omega phase produced during quenching. The athermal omega phase degrades the properties of super-elasticity and Young’s modulus. Although Al and Sn as single elements are considered as an alpha stabilizer and neutral, respectively, Sn and Al acted also as beta stabilizers when added simultaneously with beta stabilized element of Cr or V in this experiment. The quenched microstructure of Ti-Cr-Sn, Ti-Cr-Al, Ti-V-Sn, and Ti-V-Al alloys shifts from martensitic structure to beta single-phase structure with increasing Cr or V. The Young’s modulus of Ti-Cr-Sn, Ti-Cr-Al, Ti-V-Sn, and Ti-V-Al alloys decreased and then increased with increasing Cr or V, each showing its own minimum value of Young's modulus respectively. The composition of the alloy with the minimum Young’s modulus is a near border composition where the quenched microstructure shifts from martensite to beta. The border composition of Ti-Cr-Sn and Ti-V-Sn alloys required only less amount of each beta stabilizer, Cr or V, than Ti-Cr-Al and Ti-V-Al alloys. This indicates that the effect of Sn as a beta stabilizer is stronger than Al. Sn and Al influenced the competitive relation between stress-induced martensitic transformation and slip deformation. Thus, super-elastic properties of metastable beta Ti-Cr-Sn, Ti-Cr-Al, Ti-V-Sn, and Ti-V-Al alloys varied depending on the alloyed element, Sn or Al.

Keywords: metastable beta Ti alloy, super-elasticity, low Young’s modulus, stress-induced martensitic transformation, beta stabilized element

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Authors: Bhanu Pant, Sanjay H. Upadhyay

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Frequently, the upper stage of high-performance launch vehicles utilizes cryogenic tank-submerged pressurization gas bottles with high volume-to-weight efficiency to achieve a direct gain in the satellite payload. Titanium alloys, owing to their high specific strength coupled with excellent compatibility with various fluids, are the materials of choice for these applications. Amongst the Titanium alloys, there are two alloys suitable for cryogenic applications, namely Ti6Al4V-ELI and Ti5Al2.5Sn-ELI. The two-phase alpha-beta alloy Ti6Al4V-ELI is usable up to LOX temperature of 90K, while the single-phase alpha alloy Ti5Al2.5Sn-ELI can be used down to LHe temperature of 4 K. The high-pressure gas bottles submerged in the LH2 (20K) can store more amount of gas in as compared to those submerged in LOX (90K) bottles the same volume. Thus, the use of these alpha alloy gas bottles stored at 20K gives a distinct advantage with respect to the need for a lesser number of gas bottles to store the same amount of high-pressure gas, which in turn leads to a one-to-one advantage in the payload in the satellite. The cost advantage to the tune of 15000$/ kg of weight is saved in the upper stages, and, thereby, the satellite payload gain is expected by this change. However, the processing of alpha Ti5Al2.5Sn-ELI alloy gas bottles poses challenges due to the lower forgeability of the alloy and mode of qualification for the critical severe application environment. The present paper describes the processing and challenges/ solutions during the development of these advanced gas bottles for LH2 (20K) applications.

Keywords: titanium alloys, cryogenic gas bottles, alpha titanium alloy, alpha-beta titanium alloy

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Authors: Diana G. Ramirez-Wong, Marius Ramirez, Regina Sanchez-Leija, Adriana Rugerio, R. Araceli Mauricio-Sanchez, Martin A. Hernandez-Landaverde, Arturo Carranza, John A. Pojman, Josue D. Mota-Morales, Gabriel Luna-Barcenas

Abstract:

Chitin films were prepared using alpha-chitin from shrimp shells as raw material and a simple method of precipitation-evaporation. Choline chloride: urea Deep Eutectic Solvent (DES) was used to disperse chitin and compared against hexafluoroisopropanol (HFIP). A careful analysis of the chemical and crystalline structure was followed along the synthesis of the films, revealing crystalline-phase transitions. The full conversion of alpha- to beta-, or alpha- to gamma-chitin structure were detected by XRD and NMR on the films. The synthesis of highly crystalline monophasic gamma-chitin films was achieved using a DES; whereas HFIP helps to promote the beta-phase. These results are encouraging to continue in the study of DES as good processing media to control the final properties of chitin based materials.

Keywords: chitin, deep eutectic solvent, polymorph, phase transformation

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Authors: Wen-Yu Lin, Yi-Ching Chung, Tzyy-Rong Jinn

Abstract:

It is well known that enterovirus 71 (EV71) causes recurring outbreaks of hand, foot and mouth disease (HFMD) and encephalitis leading to complications or death in young children. And, several HFMD of EV71 with high mortalities occurred in Asia countries, such as Malaysia (1997), Taiwan (1998) and China (2008). Thus, more effective antiviral drugs are needed to prevent or reduce EV71-related complications. As reported, interferon-α protects mice from lethal EV71 challenge by the modulation of innate immunity and then degrade enterovirus protease 3Cᵖʳᵒ. On the other side, pleconaril by targeting enterovirus VP1 protein and then block virus entry and attachment. Thus, the aim of this study was to evaluate the synergistic antiviral activity of interferon-α and pleconaril against enterovirus 71 infection. In a preliminary study showed that pleconaril at concentrations of 50, 100 and 300 µg/mL reduced EV71-induced CPE to 52.0 ± 2.5%, 40.2 ± 3.5% and 26.5 ± 1.5%, respectively, of that of the EV71-infected RD control cells (taken as 100%). Notably, 1000 IU/mL of interferon-α in combination with pleconaril at concentrations of 50, 100 and 300µg/mL suppressed EV71-induced CPE by 30.2 ± 3.8%, 16.5 ± 1.3% and 2.8 ± 2.0%, respectively, of that of the pleconaril alone treated with the infected RD cells. These results indicated that interferon-α 1000 IU/mL combination with pleconaril (50, 100 and 300µg/mL) inhibited EV71-induced CPE more effectively than treated with pleconaril alone in the infected RD cells.

Keywords: enterovirus 71, interferon-α, pleconaril, RD cells

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Authors: Alexander N. Savostyanov, Tatyana A. Dolgorukova, Elena A. Esipenko, Mikhail S. Zaleshin, Margherita Malanchini, Anna V. Budakova, Alexander E. Saprygin, Yulia V. Kovas

Abstract:

The present study compared spectral-power indexes and cortical topography of brain activity in a sample characterized by different levels of trait and mathematical anxiety. 52 healthy Russian-speakers (age 17-32; 30 males) participated in the study. Participants solved an error recognition task under 3 conditions: A lexical condition (simple sentences in Russian), and two numerical conditions (simple arithmetic and complicated algebraic problems). Trait and mathematical anxiety were measured using self-repot questionnaires. EEG activity was recorded simultaneously during task execution. Event-related spectral perturbations (ERSP) were used to analyze spectral-power changes in brain activity. Additionally, sLORETA was applied in order to localize the sources of brain activity. When exploring EEG activity recorded after tasks onset during lexical conditions, sLORETA revealed increased activation in frontal and left temporal cortical areas, mainly in the alpha/beta frequency ranges. When examining the EEG activity recorded after task onset during arithmetic and algebraic conditions, additional activation in delta/theta band in the right parietal cortex was observed. The ERSP plots reveled alpha/beta desynchronizations within a 500-3000 ms interval after task onset and slow-wave synchronization within an interval of 150-350 ms. Amplitudes of these intervals reflected the accuracy of error recognition, and were differently associated with the three (lexical, arithmetic and algebraic) conditions. The level of trait anxiety was positively correlated with the amplitude of alpha/beta desynchronization. The level of mathematical anxiety was negatively correlated with the amplitude of theta synchronization and of alpha/beta desynchronization. Overall, trait anxiety was related with an increase in brain activation during task execution, whereas mathematical anxiety was associated with increased inhibitory-related activity. We gratefully acknowledge the support from the №11.G34.31.0043 grant from the Government of the Russian Federation.

Keywords: anxiety, EEG, lexical and numerical error-recognition tasks, alpha/beta desynchronization

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Authors: Dwitya Elvira, Eryati Darwin

Abstract:

Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.

Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease

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Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

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HNF4a is one of the steroid hormone receptor family of transcription factors with roles in the development of the liver and the regulation of several critical metabolic pathways, such as glycolysis, drug metabolism, and apolipoproteins and blood coagulation. The transcriptional potency of HNF4a is well known due to its involvement in diabetes and other metabolic diseases. However, recently HNF4a has been discovered to be closely associated with several haematological disorders, mainly because of genetic mutations, drugs, and hepatic disorders. We review HNF4a structure and function and its role in haematological disorders. We discuss possible good therapies that are based on targeting HNF4a.

Keywords: hepatocyte nuclear factor 4 alpha, HNF4a nuclear receptor, steroid hormone receptor family of transcription factors, hematological disorders

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Authors: Richa Mardianingrum, Srie R. N. Endah

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In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate.

Keywords: anti-tuberculosis, docking, Inhibin alpha subunit, InhA, inhibition, synthesis, isonicotinohydrazide

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Authors: G. V. Novikov, V. S. Sivozhelezov, S. S. Kolesnikov, K. V. Shaitan

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The study reports about the influence of binding of orthosteric ligands as well as point mutations on the conformational dynamics of β-2-adrenoreceptor. Using molecular dynamics simulation we found that there was a little fraction of active states of the receptor in its apo (ligand free) ensemble corresponded to its constitutive activity. Analysis of MD trajectories indicated that such spontaneous activation of the receptor is accompanied by the motion in intracellular part of its alpha-helices. Thus receptor’s constitutive activity directly results from its conformational dynamics. On the other hand the binding of a full agonist resulted in a significant shift of the initial equilibrium towards its active state. Finally, the binding of the inverse agonist stabilized the receptor in its inactive state. It is likely that the binding of inverse agonists might be a universal way of constitutive activity inhibition in vivo. Our results indicate that ligand binding redistribute pre-existing conformational degrees of freedom (in accordance to the Monod-Wyman-Changeux-Model) of the receptor rather than cause induced fit in it. Therefore, the ensemble of biologically relevant receptor conformations is encoded in its spatial structure, and individual conformations from that ensemble might be used by the cell in conformity with the physiological behaviour.

Keywords: seven-transmembrane receptors, constitutive activity, activation, x-ray crystallography, principal component analysis, molecular dynamics simulation

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Authors: O. Ahmed Apampa, Yinusa, A. Jimoh

Abstract:

The aim of this study was to develop an appropriate model for predicting the compaction behavior of lateritic soils and corn cob ash (CCA) stabilized lateritic soils. This was done by first adopting an equation earlier developed for fine-grained soils and subsequent adaptation by others and extending it to modified lateritic soil through the introduction of alpha and beta parameters which are polynomial functions of the CCA binder input. The polynomial equations were determined with MATLAB R2011 curve fitting tool, while the alpha and beta parameters were determined by standard linear programming techniques using the Solver function of Microsoft Excel 2010. The model so developed was a good fit with a correlation coefficient R2 value of 0.86. The paper concludes that it is possible to determine the optimum moisture content and the maximum dry density of CCA stabilized soils from the compaction test of the unmodified soil, and recommends that this procedure is extended to other binder stabilized lateritic soils to facilitate quick decision making in roadworks.

Keywords: compaction, corn cob ash, lateritic soil, stabilization

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