Search results for: relative binding affinity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3255

Search results for: relative binding affinity

2925 Long-Term Indoor Air Monitoring for Students with Emphasis on Particulate Matter (PM2.5) Exposure

Authors: Seyedtaghi Mirmohammadi, Jamshid Yazdani, Syavash Etemadi Nejad

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One of the main indoor air parameters in classrooms is dust pollution and it depends on the particle size and exposure duration. However, there is a lake of data about the exposure level to PM2.5 concentrations in rural area classrooms. The objective of the current study was exposure assessment for PM2.5 for students in the classrooms. One year monitoring was carried out for fifteen schools by time-series sampling to evaluate the indoor air PM2.5 in the rural district of Sari city, Iran. A hygrometer and thermometer were used to measure some psychrometric parameters (temperature, relative humidity, and wind speed) and Real-Time Dust Monitor, (MicroDust Pro, Casella, UK) was used to monitor particulate matters (PM2.5) concentration. The results show the mean indoor PM2.5 concentration in the studied classrooms was 135µg/m3. The regression model indicated that a positive correlation between indoor PM2.5 concentration and relative humidity, also with distance from city center and classroom size. Meanwhile, the regression model revealed that the indoor PM2.5 concentration, the relative humidity, and dry bulb temperature was significant at 0.05, 0.035, and 0.05 levels, respectively. A statistical predictive model was obtained from multiple regressions modeling for indoor PM2.5 concentration and indoor psychrometric parameters conditions.

Keywords: classrooms, concentration, humidity, particulate matters, regression

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2924 Screening of Phytochemicals Compounds from Chasmanthera dependens and Carissa edulis as Potential Inhibitors of Carbonic Anhydrases CA II (3HS4) Receptor using a Target-Based Drug Design

Authors: Owonikoko Abayomi Dele

Abstract:

Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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2923 Fe-Doped Graphene Nanoparticles for Gas Sensing Applications

Authors: Shivani A. Singh, Pravin S. More

Abstract:

In the present inspection, we indicate the falsification of Fe-doped graphene nanoparticles by modified Hummers method. Structural and physiochemical properties of the resulting pallets were explored with the help of ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM), Photoluminescence spectroscopy (PL) for graphene sample exhibits absorption peaks ~248nm. Pure graphene shows PL peak at 348 nm. After doping of Fe with graphene the PL peak shifted from 348 nm to 332 nm. The oxidation degree, i.e. the relative amount of oxygen functional groups was estimated from the relative intensities of the oxygen related bands (ORB) in the FTIR measurements. These analyses show that this modified material can be useful for gas sensing applications and to be used in diverse areas.

Keywords: chemical doping, graphene, gas sensing, sensing

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2922 Static Simulation of Pressure and Velocity Behaviour for NACA 0006 Blade Profile of Well’s Turbine

Authors: Chetan Apurav

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In this journal the behavioural analysis of pressure and velocity has been done over the blade profile of Well’s turbine. The blade profile that has been taken into consideration is NACA 0006. The analysis has been done in Ansys Workbench under CFX module. The CAD model of the blade profile with certain dimensions has been made in CREO, and then is imported to Ansys for further analysis. The turbine model has been enclosed under a cylindrical body and has been analysed under a constant velocity of air at 5 m/s and zero relative pressure in static condition of the turbine. Further the results are represented in tabular as well as graphical form. It has been observed that the relative pressure of the blade profile has been stable throughout the radial length and hence will be suitable for practical usage.

Keywords: Well's turbine, oscillating water column, ocean engineering, wave energy, NACA 0006

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2921 Utility of Cardiac Biomarkers in Combination with Exercise Stress Testing in Patients with Suspected Ischemic Heart Disease

Authors: Rawa Delshada, Sanaa G. Hamab, Rastee D. Koyeec

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Eighty patients with suspected ischemic heart disease were enrolled in the present study. They were classified into two groups: patients with positive exercise stress test results (n=40) and control group with negative exercise stress test results (n=40). Serum concentration of troponin I, Heart-type Fatty Acid Binding Protein (H-FABP) and Ischemia Modified Albumin (IMA) were measured one hour after performing stress test. Enzyme Linked Immunosorbent Assay was used to measure both troponin I, H-FABP levels, while IMA levels were measured by albumin cobalt binding test. There was no statistically significant difference in the mean concentration of troponin I between two groups (0.75±0.55ng/ml) for patients with positive test result vs. (0.71±0.55ng/ml) for negative test result group with P>0.05. Contrary to our expectation, mean IMA level was slightly higher among control group (70.88±39.76U/ml) compared to (62.7±51.9U/ml) in positive test result group, but still with no statistically significant difference (P>0.05). Median H-FABP level was also higher among negative exercise stress testing group compared the positive one (2ng/ml vs. 1.9ng/ml respectively), but failed to reach statistically significant difference (P>0.05). When quartiles model used to explore the possible association between each study biomarkers with the others; serum H-FABP level was lowest (1.7ng/ml) in highest quartile of IMA and lowest H-FABP (1.8ng/ml) in highest quartile of troponin I but with no statistically significant association (P>0.05). Myocardial ischemia, more likely occurred after exercise stress test, is not capable of causing troponin I release. Furthermore, an increase in H-FABP and IMA levels after stress test are not reflecting myocardial ischemia. Moreover, the combination of troponin I, H-FABP and IMA after measuring their post exercise levels does not improve the diagnostic utility of exercise stress test enormously.

Keywords: cardiac biomarkers, ischemic heart disease, troponin I, ischemia modified albumin, heart-type fatty acid binding protein, exercise stress testing

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2920 Biochemical Characterization of CTX-M-15 from Enterobacter cloacae and Designing a Novel Non-β-Lactam-β-Lactamase Inhibitor

Authors: Mohammad Faheem, M. Tabish Rehman, Mohd Danishuddin, Asad U. Khan

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The worldwide dissemination of CTX-M type β-lactamases is a threat to human health. Previously, we have reported the spread of blaCTX-M-15 gene in different clinical strains of Enterobacteriaceae from the hospital settings of Aligarh in north India. In view of the varying resistance pattern against cephalosporins and other β-lactam antibiotics, we intended to understand the correlation between MICs and catalytic activity of CTX-M-15. In this study, steady-state kinetic parameters and MICs were determined on E. coli DH5α transformed with blaCTX-M-15 gene that was cloned from Enterobacter cloacae (EC-15) strain of clinical background. The effect of conventional β-lactamase inhibitors (clavulanic acid, sulbactam and tazobactam) on CTX-M-15 was also studied. We have found that tazobactam is the best among these inhibitors against CTX-M-15. The inhibition characteristic of tazobactam is defined by its very low IC50 value (6 nM), high affinity (Ki = 0.017 µM) and better acylation efficiency (k+2/K9 = 0.44 µM-1s-1). It forms an acyl-enzyme covalent complex, which is quite stable (k+3 = 0.0057 s-1). Since increasing resistance has been reported against conventional b-lactam antibiotic-inhibitor combinations, we aspire to design a non-b-lactam core containing b-lactamase inhibitor. For this, we screened ZINC database and performed molecular docking to identify a potential non-β-lactam based inhibitor (ZINC03787097). The MICs of cephalosporin antibiotics in combination with this inhibitor gave promising results. Steady-state kinetics and molecular docking studies showed that ZINC03787097 is a reversible inhibitor which binds non-covalently to the active site of the enzyme through hydrogen bonds and hydrophobic interactions. Though, it’s IC50 (180 nM) is much higher than tazobactam, it has good affinity for CTX-M-15 (Ki = 0.388 µM). This study concludes that ZINC03787097 compound can be used as seed molecule to design more efficient non-b-lactam containing b-lactamase inhibitor that could evade pre-existing bacterial resistance mechanisms.

Keywords: ESBL, non-b-lactam-b-lactamase inhibitor, bioinformatics, biomedicine

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2919 Simultaneous Targeting of MYD88 and Nur77 as an Effective Approach for the Treatment of Inflammatory Diseases

Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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2918 Frequency of Polymorphism of Mrp1/Abcc1 And Mrp2/Abcc2 in Healthy Volunteers of the Center Savannah (Colombia)

Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

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MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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2917 In-Silico Evaluation and Antihyperglycemic Potential of Leucas Cephalotes

Authors: Anjali Verma, Mahesh Pal, Veena Pande, Dalip Kumar Upreti

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The present study is carried out to explore the anti-hyperglycemic activity of Leucas cephalotes plant parts. A fruit, leaves, stems, and roots part of the Leucas cephalotes has been extracted in ethanol and have been evaluated for anti-hyperglycemic activity. The present study indicated that, ethanolic extract of fruit and leaves have shown significant α- amylase inhibitory activity with IC50 value of 92.86 ± 0.89 μg/mL and 98.09 ± 0.69 μg/mL respectively. Two known compounds β-sitosterol and lupeol were isolated from ethanolic extract of L. cephalotes leaves and were subjected to anti-hyperglycemic activity. Lupeol shows the best activity with IC50 55.73 ± 0.47 μg/mL and the results were verified by docking study of these compounds with mammalian α-amylase was carried out on its active site. It was concluded from the study that β-sitosterol and lupeol form one H-bond interactions with the active site residues either Asp212 or Thr21. The estimated free energy binding of β-sitosterol was found to be -9.47 kcal mol-1 with an estimated inhibition constant (Ki) of 558.94 nmol whereas the estimated free energy binding of lupeol was -11.73 kcal mol-1 with an estimated inhibition constant (Ki) of 476.71pmmol. The present study clearly showed that lupeol is more potent in comparison to β-sitosterol. The study indicates that L. cephalotes have significant potential to inhibit α-amylase enzyme.

Keywords: alpha-amylase, beta-sitosterol, hyperglycemia, lupeol

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2916 Improving Online Learning Engagement through a Kid-Teach-Kid Approach for High School Students during the Pandemic

Authors: Alexander Huang

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Online learning sessions have become an indispensable complement to in-classroom-learning sessions in the past two years due to the emergence of Covid-19. Due to social distance requirements, many courses and interaction-intensive sessions, ranging from music classes to debate camps, are online. However, online learning imposes a significant challenge for engaging students effectively during the learning sessions. To resolve this problem, Project PWR, a non-profit organization formed by high school students, developed an online kid-teach-kid learning environment to boost students' learning interests and further improve students’ engagement during online learning. Fundamentally, the kid-teach-kid learning model creates an affinity space to form learning groups, where like-minded peers can learn and teach their interests. The role of the teacher can also help a kid identify the instructional task and set the rules and procedures for the activities. The approach also structures initial discussions to reveal a range of ideas, similar experiences, thinking processes, language use, and lower student-to-teacher ratio, which become enriched online learning experiences for upcoming lessons. In such a manner, a kid can practice both the teacher role and the student role to accumulate experiences on how to convey ideas and questions over the online session more efficiently and effectively. In this research work, we conducted two case studies involving a 3D-Design course and a Speech and Debate course taught by high-school kids. Through Project PWR, a kid first needs to design the course syllabus based on a provided template to become a student-teacher. Then, the Project PWR academic committee evaluates the syllabus and offers comments and suggestions for changes. Upon the approval of a syllabus, an experienced and voluntarily adult mentor is assigned to interview the student-teacher and monitor the lectures' progress. Student-teachers construct a comprehensive final evaluation for their students, which they grade at the end of the course. Moreover, each course requires conducting midterm and final evaluations through a set of surveyed replies provided by students to assess the student-teacher’s performance. The uniqueness of Project PWR lies in its established kid-teach-kids affinity space. Our research results showed that Project PWR could create a closed-loop system where a student can help a teacher improve and vice versa, thus improving the overall students’ engagement. As a result, Project PWR’s approach can train teachers and students to become better online learners and give them a solid understanding of what to prepare for and what to expect from future online classes. The kid-teach-kid learning model can significantly improve students' engagement in the online courses through the Project PWR to effectively supplement the traditional teacher-centric model that the Covid-19 pandemic has impacted substantially. Project PWR enables kids to share their interests and bond with one another, making the online learning environment effective and promoting positive and effective personal online one-on-one interactions.

Keywords: kid-teach-kid, affinity space, online learning, engagement, student-teacher

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2915 Feeling, Thinking, Acting: The Role of Subjective Social Class and Social Class Identity on Emotions, Attitudes and Prosocial Behavior Towards Muslim Immigrants in Belgium

Authors: Theresa Zagers, Rita Guerra

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Most research investigating how receiving communities perceive, and experience migration has overlooked the potential role of subjective social class and social class identity in positive intergroup relations and social cohesion of migrants and host societies. The present study aimed to provide insights to understand this relationship and focused on three important features: prosocial behaviour, attitudes and emotions towards Muslim immigrants in Flanders, Belgium. Building on relative deprivation-gratification theory we examined the indirect relationships of subjective social class on prosocial behaviour/intentions, attitudes and emotions via relative deprivation (RD), as well as the moderator role of the importance of social class identity. 431 Belgian participants participated in an online survey study. Overall, our results supported the predicted indirect effect of subjective social class: the lower the subjective social class, the higher the perceptions of relative deprivation, which in turn is related to less prosocial behaviour intentions, and more negative attitudes and emotions towards immigrants. This indirect effect was, however, not moderated by the importance of social class identity. Interestingly, the direct effects of subjective social class showed a different pattern: when bypassing deprivation our results showed higher subjective social class was detrimental for intergroup relations (more negative attitudes and emotions), and that lower subjective social class was positively related to prosocial intentions for those identifying highly with their class identity. Overall, we gained valuable insights in the relationship of subjective social class and the three features of intergroup relations.

Keywords: social class, relative deprivation-gratification, prosocial behavior, attitudes, emotions, Muslim immigrants

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2914 Geometric-Morphometric Analysis of Head, Pronotum and Elytra of Brontispa Longissima Gestro in Selected Provinces of the Philippines

Authors: Ana Marie T. Acevedo

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This study was conducted to describe variations in the shapes of the elytra, head and pronotum of populations of adult Brontispa longissima (Gestro) infesting coconut farms from selected areas in the Philippines using Cluster Analysis, Relative Warp Analysis coupled with box plot and histograms and Procustean analysis. The data used in this study included shape residuals captured using the method of landmark based geometric morphometrics. Results: The results of the cluster analyses based on the average shapes of the elytra, head and pronotum shows no consistent pattern of similarity between and among five populations of B. longissima. When localized variations using Relative Warp Analysis coupled with box plot and histograms was done, the findings revealed that RWA was only successful in summarizing variations using two relative warps in the shape of the elytra where the first two warps contained 86.29% of the variations of the female and 85.48% for the males. For the head and pronotum, the first two relative warps captured less than 50% of the overall variation. Looking at the shapes of the frequency histograms, all were found to follow a unimodal distribution. The box plots reveal no consistent results. Among the three characters studied only the elytra were more robust and reliable compared to head and pronotum and then Tandag differ from the rest of the other over-lapping populations. On the other hand, Procustean Analyses revealed that elytra were more spread in the posterior region both in male and female. The coordinates in head and pronotum were evenly distributed. In the overlapping consensus configurations show that variability was exaggerated in the right side of the elytra and the posterior parts of the head and pronotum. Results also showed expansion among females while compression among males in elytra. For males, expansion are localized in the posterior part of the elytra, For the head, results showed asymmetry in the distribution of expansion areas where expansion are observed in the right postero-lateral aspect of the female head. Conclusion: The overall results may imply that they might belong to one operational taxonomic unit or ecotype or biotype. Geography might not be the factor responsible for the differentiation of the populations of B. longissima.

Keywords: cluster analysis, relative warp analysis, procrustean analysis, environmental parameters

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2913 SARS-CoV-2: Prediction of Critical Charged Amino Acid Mutations

Authors: Atlal El-Assaad

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Viruses change with time through mutations and result in new variants that may persist or disappear. A Mutation refers to an actual change in the virus genetic sequence, and a variant is a viral genome that may contain one or more mutations. Critical mutations may cause the virus to be more transmissible, with high disease severity, and more vulnerable to diagnostics, therapeutics, and vaccines. Thus, variants carrying such mutations may increase the risk to human health and are considered variants of concern (VOC). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the contagious in humans, positive-sense single-stranded RNA virus that caused coronavirus disease 2019 (COVID-19) - has been studied thoroughly, and several variants were revealed across the world with their corresponding mutations. SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins, but prior study and vaccines development focused on genetic mutations in the S protein due to its vital role in allowing the virus to attach and fuse with the membrane of a host cell. Specifically, subunit S1 catalyzes attachment, whereas subunit S2 mediates fusion. In this perspective, we studied all charged amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 in a crystal structure and assessed the effect of different mutations. We generated all missense mutants of SARS-CoV-2 protein amino acids (AAs) within the SARS-CoV-2:CC12.1 complex model. To generate the family of mutants in each complex, we mutated every charged amino acid with all other charged amino acids (Lysine (K), Arginine (R), Glutamic Acid (E), and Aspartic Acid (D)) and studied the new binding of the complex after each mutation. We applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations to determine the effect of each mutation on binding. After analyzing our data, we identified charged amino acids keys for binding. Furthermore, we validated those findings against published experimental genetic data. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants found worldwide.

Keywords: SARS-CoV-2, variant, ionic amino acid, protein-protein interactions, missense mutation, AESOP

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2912 Dissatisfaction as a Cause of Social Uprisings: An Empirical Analysis Utilizing the Social Uprisings Composite Indicator

Authors: Sondos Shaheen

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This paper employs a newly constructed composite indicator of social uprisings (SUCI) to analyze the causes of their occurrence. This empirical study is based on an unbalanced panel of 45 countries over the period of 1982–2007. The paper’s contribution to the literature is distinguishing between the causes of violent and nonviolent uprisings. The analysis shows that that certain variables have a significant impact on both violent and nonviolent uprisings in terms of relative SUCI values, for example, ethnic fractionalization and mountainous terrain. Nevertheless, differences between the causes of violent and nonviolent uprisings can be found. For example, life dissatisfaction is related to nonviolent social uprisings, but when life dissatisfaction is accompanied by democratic dissatisfaction, violent social uprisings are more likely.

Keywords: social uprisings, relative deprivation, dissatisfaction, mobilization, anti-government movements, causes

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2911 PointNetLK-OBB: A Point Cloud Registration Algorithm with High Accuracy

Authors: Wenhao Lan, Ning Li, Qiang Tong

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To improve the registration accuracy of a source point cloud and template point cloud when the initial relative deflection angle is too large, a PointNetLK algorithm combined with an oriented bounding box (PointNetLK-OBB) is proposed. In this algorithm, the OBB of a 3D point cloud is used to represent the macro feature of source and template point clouds. Under the guidance of the iterative closest point algorithm, the OBB of the source and template point clouds is aligned, and a mirror symmetry effect is produced between them. According to the fitting degree of the source and template point clouds, the mirror symmetry plane is detected, and the optimal rotation and translation of the source point cloud is obtained to complete the 3D point cloud registration task. To verify the effectiveness of the proposed algorithm, a comparative experiment was performed using the publicly available ModelNet40 dataset. The experimental results demonstrate that, compared with PointNetLK, PointNetLK-OBB improves the registration accuracy of the source and template point clouds when the initial relative deflection angle is too large, and the sensitivity of the initial relative position between the source point cloud and template point cloud is reduced. The primary contribution of this paper is the use of PointNetLK to avoid the non-convex problem of traditional point cloud registration and leveraging the regularity of the OBB to avoid the local optimization problem in the PointNetLK context.

Keywords: mirror symmetry, oriented bounding box, point cloud registration, PointNetLK-OBB

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2910 Sensing Mechanism of Nano-Toxic Ions Using Quartz Crystal Microbalance

Authors: Chanho Park, Juneseok You, Kuewhan Jang, Sungsoo Na

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Detection technique of nanotoxic materials is strongly imperative, because nano-toxic materials can harmfully influence human health and environment as their engineering applications are growing rapidly in recent years. In present work, we report the DNA immobilized quartz crystal microbalance (QCM) based sensor for detection of nano-toxic materials such as silver ions, Hg2+ etc. by using functionalization of quartz crystal with a target-specific DNA. Since the mass of a target material is comparable to that of an atom, the mass change caused by target binding to DNA on the quartz crystal is so small that it is practically difficult to detect the ions at low concentrations. In our study, we have demonstrated fast and in situ detection of nanotoxic materials using quartz crystal microbalance. We report the label-free and highly sensitive detection of silver ion for present case, which is a typical nano-toxic material by using QCM and silver-specific DNA. The detection is based on the measurement of frequency shift of Quartz crystal from constitution of the cytosine-Ag+-cytosine binding. It is shown that the silver-specific DNA measured frequency shift by QCM enables the capturing of silver ions below 100pM. The results suggest that DNA-based detection opens a new avenue for the development of a practical water-testing sensor.

Keywords: nano-toxic ions, quartz crystal microbalance, frequency shift, target-specific DNA

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2909 Development of Metal-Organic Frameworks-Type Hybrid Functionalized Materials for Selective Uranium Extraction

Authors: Damien Rinsant, Eugen Andreiadis, Michael Carboni, Daniel Meyer

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Different types of materials have been developed for the solid/liquid uranium extraction processes, such as functionalized organic polymers, hybrid silica or inorganic adsorbents. In general, these materials exhibit a moderate affinity for uranyl ions and poor selectivity against impurities like iron, vanadium or molybdenum. Moreover, the structural organization deficiency of these materials generates ion diffusion issues inside the material. Therefore, the aim of our study is to developed efficient and organized materials, stable in the acid media encountered in uranium extraction processes. Metal organic frameworks (MOFs) are hybrid crystalline materials consisting of an inorganic part (cluster or metal ions) and tailored organic linkers connected via coordination bonds. These hierarchical materials have exceptional surface area, thermal stability and a large variety of tunable structures. However, due to the reversibility of constitutive coordination bonds, MOFs have moderate stability in strongly complexing or acidic media. Only few of them are known to be stable in aqueous media and only one example is described in strong acidic media. However, these conditions are very often encountered in the environmental pollution remediation of mine wastewaters. To tackle the challenge of developing MOFs adapted for uranium extraction from acid mine waters, we have investigated the stability of several materials. To ensure a good stability we have synthetized and characterized different materials based on highly coordinated metal clusters, such as LnOFs and Zirconium based materials. Among the latter, the UiO family shows a great stability in sulfuric acid media even in the presence of 1.4 M sodium sulfate at pH 2. However, the stability in phosphoric media is reduced due to the high affinity between zirconium and phosphate ligand. Based on these results, we have developed a tertiary amine functionalized MOF denoted UiO-68-NMe2 particularly adapted for the extraction of anionic uranyl (VI) sulfate complexes mainly present in the acid mine solutions. The adsorption capacity of the material has been determined upon varying total sulfate concentration, contact time and uranium concentration. The extraction tests put in evidence different phenomena due to the complexity of the extraction media and the interaction between the MOF and sulfate anion. Finally, the extraction mechanisms and the interaction between uranyl and the MOF structure have been investigated. The functionalized material UiO-68-NMe2 has been characterized in the presence and absence of uranium by FT-IR, UV and Raman techniques. Moreover, the stability of the protonated amino functionalized MOF has been evaluated. The synthesis, characterization and evaluation of this type of hybrid material, particularly adapted for uranium extraction in sulfuric acid media by an anionic exchange mechanism, paved the way for the development of metal organic frameworks functionalized by different other chelating motifs, such as bifunctional ligands showing an enhanced affinity and selectivity for uranium in acid and complexing media. Work in this direction is currently in progress.

Keywords: extraction, MOF, ligand, uranium

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2908 Evaluation in Vitro and in Silico of Pleurotus ostreatus Capacity to Decrease the Amount of Low-Density Polyethylene Microplastics Present in Water Sample from the Middle Basin of the Magdalena River, Colombia

Authors: Loren S. Bernal., Catalina Castillo, Carel E. Carvajal, José F. Ibla

Abstract:

Plastic pollution, specifically microplastics, has become a significant issue in aquatic ecosystems worldwide. The large amount of plastic waste carried by water tributaries has resulted in the accumulation of microplastics in water bodies. The polymer aging process caused by environmental influences such as photodegradation and chemical degradation of additives leads to polymer embrittlement and properties change that require degradation or reduction procedures in rivers. However, there is a lack of such procedures for freshwater entities that develop over extended periods. The aim of this study is evaluate the potential of Pleurotus ostreatus a fungus, in reducing lowdensity polyethylene microplastics present in freshwater samples collected from the middle basin of the Magdalena River in Colombia. The study aims to evaluate this process both in vitro and in silico by identifying the growth capacity of Pleurotus ostreatus in the presence of microplastics and identifying the most likely interactions of Pleurotus ostreatus enzymes and their affinity energies. The study follows an engineering development methodology applied on an experimental basis. The in vitro evaluation protocol applied in this study focused on the growth capacity of Pleurotus ostreatus on microplastics using enzymatic inducers. In terms of in silico evaluation, molecular simulations were conducted using the Autodock 1.5.7 program to calculate interaction energies. The molecular dynamics were evaluated by using the myPresto Portal and GROMACS program to calculate radius of gyration and Energies.The results of the study showed that Pleurotus ostreatus has the potential to degrade low-density polyethylene microplastics. The in vitro evaluation revealed the adherence of Pleurotus ostreatus to LDPE using scanning electron microscopy. The best results were obtained with enzymatic inducers as a MnSO4 generating the activation of laccase or manganese peroxidase enzymes in the degradation process. The in silico modelling demonstrated that Pleurotus ostreatus was able to interact with the microplastics present in LDPE, showing affinity energies in molecular docking and molecular dynamics shown a minimum energy and the representative radius of gyration between each enzyme and its substract. The study contributes to the development of bioremediation processes for the removal of microplastics from freshwater sources using the fungus Pleurotus ostreatus. The in silico study provides insights into the affinity energies of Pleurotus ostreatus microplastic degrading enzymes and their interaction with low-density polyethylene. The study demonstrated that Pleurotus ostreatus can interact with LDPE microplastics, making it a good agent for the development of bioremediation processes that aid in the recovery of freshwater sources. The results of the study suggested that bioremediation could be a promising approach to reduce microplastics in freshwater systems.

Keywords: bioremediation, in silico modelling, microplastics, Pleurotus ostreatus

Procedia PDF Downloads 90
2907 Time and Kinematics of Moving Bodies

Authors: Muhammad Omer Farooq Saeed

Abstract:

The purpose of the proposal is to find out what time actually is! And to understand the natural phenomenon of the behavior of time and light corresponding to the motion of the bodies at relatively high speeds. The utmost concern of the paper is to deal with the possible demerits in the equations of relativity, thereby providing some valuable extensions in those equations and concepts. The idea used develops the most basic conception of the relative motion of the body with respect to space and a real understanding of time and the variation of energy of the body in different frames of reference. The results show the development of a completely new understanding of time, relative motion and energy, along with some extensions in the equations of special relativity most importantly the time dilation and the mass-energy relationship that will explain all frames of a body, all in one go. The proposal also raises serious questions on the validity of the “Principle of Equivalence” on which the General Relativity is based, most importantly a serious case of the bending light that eventually goes against its own governing concepts of space-time being proposed in the theory. The results also predict the existence of a completely new field that explains the fact just how and why bodies acquire energy in space-time. This field explains the production of gravitational waves based on time. All in all, this proposal challenges the formulas and conceptions of Special and General Relativity, respectively.

Keywords: time, relative motion, energy, speed, frame of reference, photon, curvature, space-time, time –differentials

Procedia PDF Downloads 47
2906 Comfort Sensor Using Fuzzy Logic and Arduino

Authors: Samuel John, S. Sharanya

Abstract:

Automation has become an important part of our life. It has been used to control home entertainment systems, changing the ambience of rooms for different events etc. One of the main parameters to control in a smart home is the atmospheric comfort. Atmospheric comfort mainly includes temperature and relative humidity. In homes, the desired temperature of different rooms varies from 20 °C to 25 °C and relative humidity is around 50%. However, it varies widely. Hence, automated measurement of these parameters to ensure comfort assumes significance. To achieve this, a fuzzy logic controller using Arduino was developed using MATLAB. Arduino is an open source hardware consisting of a 24 pin ATMEGA chip (atmega328), 14 digital input /output pins and an inbuilt ADC. It runs on 5v and 3.3v power supported by a board voltage regulator. Some of the digital pins in Aruduino provide PWM (pulse width modulation) signals, which can be used in different applications. The Arduino platform provides an integrated development environment, which includes support for c, c++ and java programming languages. In the present work, soft sensor was introduced in this system that can indirectly measure temperature and humidity and can be used for processing several measurements these to ensure comfort. The Sugeno method (output variables are functions or singleton/constant, more suitable for implementing on microcontrollers) was used in the soft sensor in MATLAB and then interfaced to the Arduino, which is again interfaced to the temperature and humidity sensor DHT11. The temperature-humidity sensor DHT11 acts as the sensing element in this system. Further, a capacitive humidity sensor and a thermistor were also used to support the measurement of temperature and relative humidity of the surrounding to provide a digital signal on the data pin. The comfort sensor developed was able to measure temperature and relative humidity correctly. The comfort percentage was calculated and accordingly the temperature in the room was controlled. This system was placed in different rooms of the house to ensure that it modifies the comfort values depending on temperature and relative humidity of the environment. Compared to the existing comfort control sensors, this system was found to provide an accurate comfort percentage. Depending on the comfort percentage, the air conditioners and the coolers in the room were controlled. The main highlight of the project is its cost efficiency.

Keywords: arduino, DHT11, soft sensor, sugeno

Procedia PDF Downloads 283
2905 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

Abstract:

This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

Procedia PDF Downloads 264
2904 Energy Service Companies as a Facilitator for Implementation of Energy-Environment Conventions

Authors: Bahareh Arghand

Abstract:

The establishment of rules and regulations for more effective energy-environment interactions are essential to achieving sustainable development. Sustainable development requires mechanisms that can promote compliance in energy-environment conventions. There are many binding agreements and non-binding instruments at regional and international levels on energy and the environment. These conventions try to decrease conflicts of interest between energy, environment and economic by legal principles and practical mechanisms. The major core of conventions is their implementations because the poor implementation and enforcement power affect their success. In this regard, the main goal of this study is proposing the effective implementation mechanisms. Energy service companies' (ESCOs) activities can improve energy efficiency and decrease the environmental degradations. Therefore, it can be proposed and assessed the merit mechanism of ESCO performance as a facilitator to implement energy-environment conventions. An assessment of ESCO performance, including its potentials, problems, and limitations, as a facilitator for effective implementation of the energy-environment convention, is included. This study is oriented towards effective development and application of laws and the function of ESCOs as appropriate economic instruments and facilitator for implementation of energy-environment conventions. The resulting system of close cooperation between the energy-environment conventions and ESCOs is geared toward advancing environmental protection and economic factors by the transfer of environmentally-sound technologies that meet sustainable development objectives.

Keywords: energy-environment conventions, energy service company, facilitator mechanism, sustainable development

Procedia PDF Downloads 153
2903 Proteomic Analysis of Cytoplasmic Antigen from Brucella canis to Characterize Immunogenic Proteins Responded with Naturally Infected Dogs

Authors: J. J. Lee, S. R. Sung, E. J. Yum, S. C. Kim, B. H. Hyun, M. Her, H. S. Lee

Abstract:

Canine brucellosis is a critical problem in dogs leading to reproductive diseases which are mainly caused by Brucella canis. There are, nonetheless, not clear symptoms so that it may go unnoticed in most of the cases. Serodiagnosis for canine brucellosis has not been confirmed. Moreover, it has substantial difficulties due to broad cross-reactivity between the rough cell wall antigens of B. canis and heterospecific antibodies present in normal, uninfected dogs. Thus, this study was conducted to characterize the immunogenic proteins in cytoplasmic antigen (CPAg) of B. canis, which defined the antigenic sensitivity of the humoral antibody responses to B. canis-infected dogs. In analysis of B. canis CPAg, first, we extracted and purified the cytoplasmic proteins from cultured B. canis by hot-saline inactivation, ultrafiltration, sonication, and ultracentrifugation step by step according to the sonicated antigen extract method. For characterization of this antigen, we checked the sort and range of each protein on SDS-PAGE and verified the immunogenic proteins leading to reaction with antisera of B. canis-infected dogs. Selected immunodominant proteins were identified using MALDI-MS/MS. As a result, in an immunoproteomic assay, several polypeptides in CPAg on one or two-dimensional electrophoresis (DE) were specifically reacted to antisera from B. canis-infected dogs but not from non-infected dogs. The polypeptides with approximate 150, 80, 60, 52, 33, 26, 17, 15, 13, 11 kDa on 1-DE were dominantly recognized by antisera from B. canis-infected dogs. In the immunoblot profiles on 2-DE, ten immunodominant proteins in CPAg were detected with antisera of infected dogs between pI 3.5-6.5 at approximate 35 to 10 KDa, without any nonspecific reaction with sera in non-infected dogs. Ten immunodominant proteins identified by MALDI-MS/MS were identified as superoxide dismutase, bacteroferritin, amino acid ABC transporter substrate-binding protein, extracellular solute-binding protein family3, transaldolase, 26kDa periplasmic immunogenic protein, Rhizopine-binding protein, enoyl-CoA hydratase, arginase and type1 glyceraldehyde-3-phosphate dehydrogenase. Most of these proteins were determined by their cytoplasmic or periplasmic localization with metabolism and transporter functions. Consequently, this study discovered and identified the prominent immunogenic proteins in B. canis CPAg, highlighting that those antigenic proteins may accomplish a specific serodiagnosis for canine brucellosis. Furthermore, we will evaluate those immunodominant proteins for applying to the advanced diagnostic methods with high specificity and accuracy.

Keywords: Brucella canis, Canine brucellosis, cytoplasmic antigen, immunogenic proteins

Procedia PDF Downloads 126
2902 Accelerated Molecular Simulation: A Convolution Approach

Authors: Jannes Quer, Amir Niknejad, Marcus Weber

Abstract:

Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be ”steared” out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind ”stearing” is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.

Keywords: extrapolation, Eyring-Kramers, metastability, multilevel sampling

Procedia PDF Downloads 303
2901 Molecular Characterization of Functional Domain (LRR) of TLR9 Genes in Malnad Gidda Cattle and Their Comparison to Cross Breed Cattle

Authors: Ananthakrishna L. R., Ramesh D., Kumar Wodeyar, Kotresh A. M., Gururaj P. M.

Abstract:

Malnad Gidda is the indigenous recognized cattle breed of Shivamogga District of Karnataka state, India is known for its disease resistance to many of the infectious diseases. There are 25 LRR (Leucine Rich Repeats) identified in bovine (Bos indicus) TLR9. The amino acid sequence of LRR is deduced to nucleotide sequence in BLASTx bioinformatic online tools. LRR2 to LRR10 are involved in pathogen recognition and binding in human TLR9 which showed a higher degree of nucleotide variations with respect to disease resistance to various pathogens. Hence, primers were designed to amplify the flanking sequences of LRR2 to LRR10, to discover the nucleotide variations if any, in Malnad Gidda breed of Cattle which is associated with disease resistance. The DNA isolated from peripheral blood mononuclear cells of ten Malnad Gidda cattle. A desired and specific amplification product of 0.8 kb was obtained at an annealing temperature of 56.6ᵒC. All the PCR products were sequenced on both sides by gene-specific primers. The sequences were compared with TLR9 sequence of cross breed cattle obtained from NCBI data bank. The sequence analysis between Malnad Gidda and crossbreed cattle revealed no nucleotide variations in the region LRR2 to LRR9 which shows the conserved in pathogen binding domain (LRR) of TLR9.

Keywords: leucine rich repeats, Malnad Gidda, cross breed, TLR9

Procedia PDF Downloads 198
2900 Design of Liquid Crystal Based Interface to Study the Interaction of Gram Negative Bacterial Endotoxin with Milk Protein Lactoferrin

Authors: Dibyendu Das, Santanu Kumar Pal

Abstract:

Milk protein lactoferrin (Lf) exhibits potent antibacterial activity due to its interaction with Gram-negative bacterial cell membrane component, lipopolysaccharide (LPS). This paper represents fabrication of new Liquid crystals (LCs) based biosensors to explore the interaction between Lf and LPS. LPS self-assembled at aqueous/LCs interface and orients interfacial nematic 4-cyano-4’- pentylbiphenyl (5CB) LCs in a homeotropic fashion (exhibiting dark optical image under polarized optical microscope). Interestingly, on the exposure of Lf on LPS decorated aqueous/LCs interface, an optical image of LCs changed from dark to bright indicating an ordering alteration of interfacial LCs from homeotropic to tilted/planar state. The ordering transition reflects strong binding between Lf and interfacial LPS that, in turn, perturbs the orientation of LCs. With the help of epifluorescence microscopy, we further affirmed the interfacial LPS-Lf binding event by imaging the presence of FITC tagged Lf at the LPS laden aqueous/LCs interface. Finally, we have investigated the conformational behavior of Lf in solution as well as in the presence of LPS using Circular Dichroism (CD) spectroscopy and further reconfirmed with Vibrational Circular Dichroism (VCD) spectroscopy where we found that Lf undergoes alpha-helix to random coil-like structure in the presence of LPS. As a whole the entire results described in this paper establish a robust approach to envisage the interaction between LPS and Lf through the ordering transitions of LCs at aqueous/LCs interface.

Keywords: endotoxin, interface, lactoferrin, lipopolysaccharide

Procedia PDF Downloads 243
2899 Validation of the Formula for Air Attenuation Coefficient for Acoustic Scale Models

Authors: Katarzyna Baruch, Agata Szelag, Aleksandra Majchrzak, Tadeusz Kamisinski

Abstract:

Methodology of measurement of sound absorption coefficient in scaled models is based on the ISO 354 standard. The measurement is realised indirectly - the coefficient is calculated from the reverberation time of an empty chamber as well as a chamber with an inserted sample. It is crucial to maintain the atmospheric conditions stable during both measurements. Possible differences may be amended basing on the formulas for atmospheric attenuation coefficient α given in ISO 9613-1. Model studies require scaling particular factors in compliance with specified characteristic numbers. For absorption coefficient measurement, these are for example: frequency range or the value of attenuation coefficient m. Thanks to the possibilities of modern electroacoustic transducers, it is no longer a problem to scale the frequencies which have to be proportionally higher. However, it may be problematic to reduce values of the attenuation coefficient. It is practically obtained by drying the air down to a defined relative humidity. Despite the change of frequency range and relative humidity of the air, ISO 9613-1 standard still allows the calculation of the amendment for little differences of the atmospheric conditions in the chamber during measurements. The paper discusses a number of theoretical analyses and experimental measurements performed in order to obtain consistency between the values of attenuation coefficient calculated from the formulas given in the standard and by measurement. The authors performed measurements of reverberation time in a chamber made in a 1/8 scale in a corresponding frequency range, i.e. 800 Hz - 40 kHz and in different values of the relative air humidity (40% 5%). Based on the measurements, empirical values of attenuation coefficient were calculated and compared with theoretical ones. In general, the values correspond with each other, but for high frequencies and low values of relative air humidity the differences are significant. Those discrepancies may directly influence the values of measured sound absorption coefficient and cause errors. Therefore, the authors made an effort to determine an amendment minimizing described inaccuracy.

Keywords: air absorption correction, attenuation coefficient, dimensional analysis, model study, scaled modelling

Procedia PDF Downloads 401
2898 Relevance of the Variation in the Angulation of Palatal Throat Form to the Orientation of the Occlusal Plane- A Cephalometric Study

Authors: Sanath Kumar Shetty, Sanya Sinha, K. Kamalakanth Shenoy

Abstract:

The posterior reference for the ala tragal line is a cause of confusion, with different authors suggesting different locations as to the superior, middle or inferior part of the tragus. This study was conducted on 200 subjects to evaluate if any correlation exists between the variation of angulation of palatal throat form and the relative parallelism of occlusal plane to ala-tragal line at different tragal levels. A Custom made Occlusal Plane Analyzer was used to check the parallelism between the ala-tragal line and occlusal plane. A lateral cephalogram was shot for each subject to measure the angulation of the palatal throat form. Fisher’s exact test was used to evaluate the correlation between the angulation of the palatal throat form and the relative parallelism of occlusal plane to the ala tragal line. Also, a classification was formulated for the palatal throat form, based on confidence interval. From the results of the study, the inferior part, middle part and superior part of the tragus were seen as the reference points in 49.5%, 32% and 18.5% of the subjects respectively. Class I palatal throat form (41degree-50 degree), Class II palatal throat form (below 41 degree) and Class III palatal throat form (above 50 degree) were seen in 42%, 43% and 15% of the subjects respectively. It was also concluded that there is no significant correlation between the variation in the angulations of the palatal throat form and the relative parallelism of occlusal plane to the ala-tragal line.

Keywords: Ala-Tragal line, occlusal plane, palatal throat form, cephalometry

Procedia PDF Downloads 288
2897 Distinct Antiviral Pathway for ZFP36-Like Family Members Against Flavivirus Infection

Authors: Ren-Jye Lin, Li-Hsiung Lin, Bing-Cheng Liu, Ching-Len Liao

Abstract:

The human zinc finger protein 36-like protein family, containing zinc finger protein 36-like 1 (ZFP36L1) and zinc finger protein 36-like 2 (ZFP36L2), belongs to CCCH-type zinc-finger protein identified as an RNA-binding protein that participates in controlling posttranscriptional regulation via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 showed potent antiviral activity against flavivirus Infection by both 5´-3´ XRN1 and 3´-5´RNA-exosome RNA decay pathways (Journal of Virology 2022 Jan 12;96(1): e0166521). However, another zinc finger protein 36-like protein member, ZFP36L2, in the host defense response against flaviviruses has yet to be addressed. Here, we also demonstrate that ZFP36L2 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L2 reduced JEV and DENV infection, and ZFP36L2 knockdown significantly promoted viral replication. Distinct from the antiviral mechanism of ZFP36L1, ZFP36L2 inhibits flavivirus infection by only a 5´-3´ XRN1-mediated RNA decay pathway but not the 3´-5´RNA-exosome RNA decay pathway. Human ZFP36L1 and ZFP36L2 can restrict flavivirus replication by directly binding and destabilizing viral RNA. Thus, for the first time, human zinc finger protein 36-like family members, ZFP36L1 and ZFP36L2, are identified as host antiviral factors that can bind and degrade flavivirus viral RNA by diverse antiviral mechanisms.

Keywords: ZFP36L1, ZFP36L2, 5'-3' exonuclease XRN1, antiviral mechansim

Procedia PDF Downloads 55
2896 The Role of Glutamine-Rich Region of Candida Albicans Tec1p in Mediating Morphological Transition and Invasive Growth

Authors: W. Abu Rayyan, A. Singh, A. M. Al-Jaafreh, W. Abu Dayyih, M. Bustami, S. Salem, N. Seder, K. Schröppel

Abstract:

Hyphal growth and the transcriptional regulation to the host environment are key issues during the pathogenesis of C. albicans. Tec1p is the C. albicans homolog of a TEA transcription factor family, which share a conserved DNA-binding TEA domain in their N-terminal. In order to define a structure-function relationship of the C. albicans Tec1p protein, we constructed several mutations on the N terminal, C terminal or in the TEA binding domain itself by homologous recombination technology. The modifications in the open reading frame of TEC1 were tested for reconstitution of the morphogenetic development of the tec1/tec1 mutant strain CaAS12. Mutation in the TEA consensus sequence did not confer transition to hyphae whereas the reconstitution of the full-length Tec1p has reconstituted hyphal development. A deletion in one of glutamine-rich regions either in the Tec1p N-terminal or the C-terminal in regions of 53-212 or 637–744 aa, respectively, did not restore morphological development in mutant CaAS12 strain. Whereas, the reconstitution with Tec1p mutants other than the glutamate-rich region has restored the morphogenetic switch. Additionally, the deletion of the glutamine-rich region has attenuated the invasive growth and the heat shock resistance of C. albicans. In conclusion, we show that a glutamine-rich region of Tec1p is essential for the hyphal development and mediating adaptation to the host environment of C. albicans.

Keywords: Candida albicans, morphogenetic development, TEA domain, hyphal formation, TEC1

Procedia PDF Downloads 128