Search results for: inverse docking

Authors: Haowen Xi

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We propose and solve exactly a class of non-linear generalization of the Black-Scholes process of stochastic differential equations describing price bubble and crashes dynamics. As a result of nonlinear positive feedback, the faster-than-exponential price positive growth (bubble forming) and negative price growth (crash forming) are found to be the power-law finite-time singularity in which bubbles and crashes price formation ending at finite critical time tc. While most literature on the market bubble and crash process focuses on the nonlinear positive feedback mechanism aspect, very few studies concern the noise level on the same process. The present work adds to the market bubble and crashes literature by studying the external sources noise influence on the critical time tc of the bubble forming and crashes forming. Two main results will be discussed: (1) the analytical expression of expected value of the critical time is found and unexpected critical slowing down due to the coupling external noise is predicted; (2) numerical simulations of the nonlinear stochastic equation is presented, and the probability distribution of Prob(tc) is found to be the inverse gamma function.

Keywords: bubble, crash, finite-time-singular, numerical simulation, price dynamics, stochastic differential equations

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Mandira Mishra, Mark Allen

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This meta-analysis explored whether rejection sensitivity relates to facets of romantic relationships. A comprehensive literature search identified 60 studies (147 effect sizes; 16,955 participants) that met inclusion criteria. Data were analysed using inverse-variance weighted random effects meta-analysis. Mean effect sizes from 21 meta-analyses provided evidence that more rejection sensitive individuals report lower levels of relationship satisfaction and relationship closeness, lower levels of perceived partner satisfaction, a greater likelihood of intimate partner violence (perpetration and victimization), higher levels of relationship concerns and relationship conflict, and higher levels of jealousy and self-silencing behaviours. There was also some evidence that rejection sensitive individuals are more likely to engage in risky sexual behaviour and are more prone to sexual compulsivity. There was no evidence of publication bias and various levels of heterogeneity in computed averages. Random effects meta-regression identified participant age and sex as important moderators of pooled mean effects. These findings provide a foundation for the theoretical development of rejection sensitivity in romantic relationships and should be of interest to relationship and marriage counsellors and other relationship professionals.

Keywords: intimate partner violence, relationship satisfaction, commitment, sexual orientation, risky sexual behaviour

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Authors: J. F. Viljoen, Catherine Foxcroft

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Expert sight readers rely on their ability to recognize patterns in scores, their inner hearing and prediction skills in order to perform complex sight reading exercises. They also have the ability to observe deviations from expected patterns in musical scores. This increases the “Eye-hand span” (reading ahead of the point of playing) in order to process the elements in the score. The study aims to investigate the gaze patterns of expert and non-expert sight readers focusing on key and time signatures. 20 musicians were tasked with playing 12 sight reading examples composed for one hand and five examples composed for two hands to be performed on a piano keyboard. These examples were composed in different keys and time signatures and included accidentals and changes of time signature to test this theory. Results showed that the experts fixate more and for longer on key and time signatures as well as deviations in examples for two hands than the non-expert group. The inverse was true for the examples for one hand, where expert sight readers showed fewer and shorter fixations on key and time signatures as well as deviations. This seems to suggest that experts focus more on the key and time signatures as well as deviations in complex scores to facilitate sight reading. The examples written for one appeared to be too easy for the expert sight readers, compromising gaze patterns.

Keywords: cognition, eye tracking, musical notation, sight reading

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Authors: M. Eckert, M. Oliveira, A. Bettencourt Ribeiro

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The intensive use of natural aggregate, near the towns, associated to the increase of the global population, leads to its depletion and increases the transport distances. The uncontrolled deposition of construction and demolition waste in landfills and city outskirts, causes pollution and take up space for noblest purposes. The main problem of recycled aggregate lies in its high water absorption, what is due to the porosity of the materials which constitute this type of aggregate. When the aggregates are dry, water flows from the inside to the engaging cement paste matrix, and when they are saturated an inverse process occurs. This water flow breaks the aggregate-cement paste bonds and the greater water concentration, in the inter-facial transition zone, degrades the concrete properties in its fresh and hardened state. Based on the water absorption over time, it was optimized an staged mixing method, to regulate the said flow and manufacture recycled aggregate concrete with levels of work-ability, strength and shrinkage equivalent to those of conventional concrete.The physical, mechanical and geometrical properties of the aggregates where related to the properties of concrete in its fresh and hardened state. Three types of commercial recycled aggregates and two types of natural aggregates where evaluated. Six compositions with different percentages of recycled coarse aggregate where tested.

Keywords: recycled aggregate, water absorption, interfacial transition zone, compressive-strength, shrinkage

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Authors: Abdelghani May

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This paper reports on experimental investigations concerning the underlying reasons for the anisotropic behavior observed during the cyclic loading of AA2017 aluminum alloy. Initially, we quantified the evolution of fatigue damage resulting from controlled proportional cyclic loadings along the axial and shear directions. Our primary objective at this stage was to verify the anisotropic mechanical behavior recently observed. To accomplish this, we utilized various models of fatigue damage quantification and conducted a comparative study of the obtained results. Our analysis confirmed the anisotropic nature of the material under investigation. In the subsequent step, we performed microstructural investigations aimed at understanding the origins of the anisotropic mechanical behavior. To this end, we utilized scanning electron microscopy to examine the phases and precipitates in both the transversal and longitudinal sections. Our findings indicate that the structure and morphology of these entities are responsible for the anisotropic behavior observed in the aluminum alloy. Furthermore, results obtained from Kikuchi diagrams, pole figures, and inverse pole figures have corroborated these conclusions. These findings demonstrate significant differences in the crystallographic texture of the material.

Keywords: microstructural investigation, fatigue damage quantification, anisotropic behavior, AA2017 aluminum alloy, cyclic loading, crystallographic texture, scanning electron microscopy

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Authors: Ms Azam Najafkouchak, David Todem, Dorothy Pathak, Pramod Pathak, Joseph Gardiner

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Propensity score (PS) methods have recently become the standard analysis as a tool for the causal inference in the observational studies where exposure is not randomly assigned, thus, confounding can impact the estimation of treatment effect on the outcome. For the binary outcome, the effect of treatment on the outcome can be estimated by odds ratios, relative risks, and risk differences. However, using the different PS methods may give you a different estimation of the treatment effect on the outcome. Several methods of PS analyses have been used mainly, include matching, inverse probability of weighting, stratification, and covariate adjusted on PS. Due to the dangers of discretizing continuous variables (exposure, covariates), the focus of this paper will be on how the variation in cut-points or boundaries will affect the average treatment effect (ATE) utilizing the stratification of PS method. Therefore, we are trying to avoid choosing arbitrary cut-points, instead, we continuously discretize the PS and accumulate information across all cut-points for inferences. We will use Monte Carlo simulation to evaluate ATE, focusing on two PS methods, stratification and covariate adjusted on PS. We will then show how this can be observed based on the analyses of the data from a case-control study of breast cancer, the Polish Women’s Health Study.

Keywords: average treatment effect, propensity score, stratification, covariate adjusted, monte Calro estimation, breast cancer, case_control study

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Authors: Sajid Shah, Yoshimitsu Uemura, Katsuki Kusakabe

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Sol-gel derived hydrophobic silica membranes with pore sizes less than 1 nm are quite attractive for gas separation in a wide range of temperatures. A nano-structured hydrophobic membrane was prepared by sol-gel technique on a porous α–Al₂O₃ tubular support with yttria stabilized zirconia (YSZ) as an intermediate layer. Bistriethoxysilylethane (BTESE) derived sol was modified by adding phenyltriethoxysilylethane (PhTES) as an organic template. Six times dip coated modified silica membrane having a thickness of about 782 nm was characterized by field emission scanning electron microscopy. Thermogravimetric analysis, together along contact angle and Fourier transform infrared spectroscopy, showed that hydrophobic properties were improved by increasing the PhTES content. The contact angle of water droplet increased from 37° for pure to 111.5° for the modified membrane. The permeance of single gas H₂ was higher than H₂:CO₂ ratio of 75:25 binary feed mixtures. However, the permeance of H₂ for 60:40 H₂:CO₂ was found lower than single and binary mixture 75:25 H₂:CO₂. The binary selectivity values for 75:25 H₂:CO₂ were 24.75, 44, and 57, respectively. Selectivity had an inverse relation with PhTES content. Hydrophobicity properties were improved by increasing PhTES content in the silica matrix. The system exhibits proper three layers adhesion or integration, and smoothness. Membrane system suitable in steam environment and high-temperature separation. It was concluded that the hydrophobic silica membrane is highly promising for the separation of H₂/CO₂ mixture from various H₂-containing process streams.

Keywords: gas separation, hydrophobic properties, silica membrane, sol–gel method

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Authors: M. Benothman, M. Stear, S. Mitchel, O. Abuargob, R. Vijayan, Sateesh Kumar

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Parasitic gastroenteritis caused by gastrointestinal nematodes (GIN) is a serious pathological complication in lambs. The dispersion pattern of GIN influences their transmission dynamics. There is no proper study on this aspect in Scottish Blackface lambs in Scotland. This study undertaken on 758 naturally infected, weaned, straight bred Scottish Blackface lambs in high land pasture in East Scotland extending over three months (August, September and October) in a year, and for three successive years demonstrated that the distribution of faecal egg counts (FEC) followed negative binomial distribution, with the exception of a few samples. The inverse index of dispersion (k) ranged between 0.19 ± 0.51 and 1.09 ± 0.08. Expression of low k values resulting from aggregation in a few individuals, suggested that a small proportion of animals with heavy parasitic influx significantly influenced the level of pasture contamination and parasite transmission. There was no discernible trend in the mean faecal egg count (FEC) and mean herbage larval population (HLP) in different months and in different years. Teladorsagia was the highest pasture contaminant (85.14±14.30 L3/kdh) followed by Nematodirus (53.00±13.96), Ostertagia (28.21±10.18) and Cooperia (11.43±5.55). The results of this study would be useful in instituting gastrointestinal nematode control strategies for sheep in cool temperate agro-ecological zones.

Keywords: blackface lamb, faecal egg count, Gastrointestinal nematodes, herbage larval population, Scotland

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Authors: Muhammad Ajmal, Muhammad Siddiq, Nurettin Sahiner

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We prepared poly(methacrylic acid-co-acrylonitrile) (p(MAc-co-AN)) microgels by inverse suspension polymerization, and converted the nitrile groups into amidoxime groups to obtain more hydrophilic amidoximated poly(methacrylic acid-co-acrylonitile) (amid-p(MAc-co-AN)) microgels. Amid-microgels were used as microreactors for in situ synthesis of copper and cobalt nanoparticles. Cu (II) and Co (II) ions were loaded into microgels from their aqueous metal salt solutions and then converted to corresponding metal nanoparticle (MNP) by treating the loaded metal ions with sodium borohydride (NaBH4). The characterization of the prepared microgels and microgel metal nanoparticle composites was carried out by SEM, TEM and TG analysis. The amounts of metal nanoparticles within microgels were estimated by AAS measurements by dissolving the MNP entrapped within microgels by concentrated HCl acid treatment. Catalytic performances of the prepared amid-p(MAc-co-AN)-M (M: Cu, Co) microgel composites were investigated by using them as catalyst for the degradation of cationic and anionic organic dyes such as eosin Y (EY), methylene blue (MB) and methyl Orange (MO), and for the reduction of nitro aromatic pollutants like 2-nitrophenol (2-NP) and 4-nitrophenol (4-NP) to their corresponding amino phenols. Here, we also report for the first time, the simultaneous degradation/reduction of MB, EY, and 4-NP by amid-p(MAc-co-AN)-Cu microgel composites. Different parameters affecting the reduction rates such as metal types, amount of catalysts, temperature and the amount of reducing agent were investigated.

Keywords: microgels, nanoparticles, catalyst, pollutants

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Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

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The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

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Authors: André C. Silva, Débora N. Sousa, Elenice M. S. Silva, Thales P. Fontes, Raphael S. Tomaz

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Starches are widely used as depressant in froth flotation operations in Brazil due to their efficiency, increasing the selectivity in the inverse flotation of quartz depressing iron ore. Starches market have been growing and improving in recent years, leading to better products attending the requirements of the mineral industry. The major source of starch used for iron ore is corn starch, which needs to be gelatinized with sodium hydroxide (NaOH) prior to use. This stage has a direct impact on industrials costs, once the lowest consumption of NaOH in gelatinization provides better control of the pH in the froth flotation and reduces the amount of electrolytes present in the pulp. In order to evaluate the gelatinization degree of different starches and flour were subjected to the addiction of NaOH and temperature variation experiments. Samples of starch (corn, cassava, HIPIX 100, HIPIX 101 and HIPIX 102 commercialized by Ingredion) and flour (cassava and potato) were tested. The starch samples were characterized through Scanning Electronic Microscopy and the amylose content were determined through spectrometry, swelling and solubility tests. The gelatinization was carried out through titration with NaOH, keeping the solution temperature constant at 40 ^oC. At the end of the tests, the optimal amount of NaOH consumed to gelatinize the starch or flour from different botanical sources was established and a correlation between the content of amylopectin in the starch and the starch/NaOH ratio needed for its gelatinization.

Keywords: froth flotation, gelatinization, sodium hydroxide, starches and flours

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Authors: Petr Gurný

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One of the most important tasks in the risk management is the correct determination of probability of default (PD) of particular financial subjects. In this paper a possibility of determination of financial institution’s PD according to the credit-scoring models is discussed. The paper is divided into the two parts. The first part is devoted to the estimation of the three different models (based on the linear discriminant analysis, logit regression and probit regression) from the sample of almost three hundred US commercial banks. Afterwards these models are compared and verified on the control sample with the view to choose the best one. The second part of the paper is aimed at the application of the chosen model on the portfolio of three key Czech banks to estimate their present financial stability. However, it is not less important to be able to estimate the evolution of PD in the future. For this reason, the second task in this paper is to estimate the probability distribution of the future PD for the Czech banks. So, there are sampled randomly the values of particular indicators and estimated the PDs’ distribution, while it’s assumed that the indicators are distributed according to the multidimensional subordinated Lévy model (Variance Gamma model and Normal Inverse Gaussian model, particularly). Although the obtained results show that all banks are relatively healthy, there is still high chance that “a financial crisis” will occur, at least in terms of probability. This is indicated by estimation of the various quantiles in the estimated distributions. Finally, it should be noted that the applicability of the estimated model (with respect to the used data) is limited to the recessionary phase of the financial market.

Keywords: credit-scoring models, multidimensional subordinated Lévy model, probability of default

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Authors: Yosra Ben Mhamed

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Most previous research that investigates the importance of earnings volatility for a firm’s value has focused on the effects of earnings volatility on the cost of capital. Many study illustrate that earnings volatility can reduce the firm’s value by enhancing the cost of capital. However, a few recent studies directly examine the relation between earnings volatility and subsequent earnings levels. In our study, we further explore the role of volatility in forecasting. Our study makes two primary contributions to the literature. First, taking into account the level of current firm’s performance, we provide causal theory to the link between volatility and earnings predictability. Nevertheless, previous studies testing the linearity of this relationship have not mentioned any underlying theory. Secondly, our study contributes to the vast body of fundamental analysis research that identifies a set of variables that improve valuation, by showing that earnings volatility affects the estimation of future earnings. Projections of earnings are used by valuation research and practice to derive estimates of firm value. Since we want to examine the impact of volatility on earnings predictability, we sort the sample into three portfolios according to the level of their earnings volatility in ascending order. For each quintile, we present the predictability coefficient. In a second test, each of these portfolios is, then, sorted into three further quintiles based on their level of current earnings. These yield nine quintiles. So we can observe whether volatility strongly predicts decreases on earnings predictability only for highest quintile of earnings. In general, we find that earnings volatility has an inverse relationship with earnings predictability. Our results also show that the sensibility of earnings predictability to ex-ante volatility is more pronounced among profitability firms. The findings are most consistent with overinvestment and persistence explanations.

Keywords: earnings volatility, earnings predictability, earnings persistence, current profitability

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Authors: Ayse Cagil Kandemir, Derya Erdem, Markus Niederberger, Ralph Spolenak

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Dip Pen nanolithography (DPN), which is a tip based method, serves a novel approach to produce nano and micro-scaled patterns due to its high resolution and pattern flexibility. It is introduced as a new constructive scanning probe lithography (SPL) technique. DPN delivers materials in the form of an ink by using the tip of a cantilever as pen and substrate as paper in order to form surface architectures. First studies rely on delivery of small organic molecules on gold substrate in ambient conditions. As time passes different inks such as; polymers, colloidal particles, oligonucleotides, metallic salts were examined on a variety of surfaces. Discovery of DPN also enabled patterning with multiple inks by using multiple cantilevers for the first time in SPL history. Specifically, polymer inks, which constitute a flexible matrix for various materials, can have a potential in MEMS, NEMS and drug delivery applications. In our study, it is aimed to construct polymer patterns using DPN by studying wetting behavior of polymer on semiconductor, metal and polymer surfaces. The optimum viscosity range of polymer and effect of environmental conditions such as humidity and temperature are examined. It is observed that there is an inverse relation with ink viscosity and depletion time. This study also yields the optimal writing conditions to produce consistent patterns with DPN. It is shown that written dot sizes increase with dwell time, indicating that the examined writing conditions yield repeatable patterns.

Keywords: dip pen nanolithography, polymer, surface patterning, surface science

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Authors: Karthika Chandran, Pulkit Prakash, Amitabh Das, Santhosh P. N.

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Rare earth orthoferrites (RFeO₃) exhibit interesting and useful magnetic properties like multiferroicity, magnetodielectric coupling, spin reorientation (SR) and exchange bias. B site doped RFeO₃ are attracting attention due to the complex and tuneable magnetic transitions. In this work, 45% Mn-doped HoFeO₃ polycrystalline sample (HoFe₀.₅₅Mn₀.₄₅O₃) was synthesized by a solid-state reaction method. The magnetic structure and transitions were studied by magnetization measurements and neutron powder diffraction methods. The neutron diffraction patterns were taken at 13 different temperatures from 7°K to 300°K (7°K and 25°K to 300°K in 25°K intervals). The Rietveld refinement was carried out by using a FULLPROF suite. The magnetic space groups and the irreducible representations were obtained by SARAh module. The room temperature neutron diffraction refinement results indicate that the sample crystallizes in an orthorhombic perovskite structure with Pnma space group with lattice parameters a = 5.6626(3) Ǻ, b = 7.5241(3) Ǻ and c = 5.2704(2) Ǻ. The temperature dependent magnetization (M-T) studies indicate the presence of two magnetic transitions in the system ( TN Fe/Mn~330°K and TSR Fe/Mn ~290°K). The inverse susceptibility vs. temperature curve shows a linear behavior above 330°K. The Curie-Weiss fit in this region gives negative Curie constant (-34.9°K) indicating the antiferromagnetic nature of the transition. The neutron diffraction refinement results indicate the presence of mixed magnetic phases Γ₄(AₓFᵧG

Keywords: neutron powder diffraction, rare earth orthoferrites, Rietveld analysis, spin reorientation

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Authors: Mariel L. Alonzo, Patricia Mae T. Chi, Juliana Patrice P. Mayormita, Sanjana A. Sorio

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Compassion fade proposes an inverse relationship between the magnitude of stimuli to elicited compassion. This phenomenon is viewed within a framework that integrates a 3-Act Compassion structure with Latané and Darley’s Unresponsive Bystander Model and Prospect Theory of Decision-making under risk. Students (N=211) from Ateneo de Davao were sampled to examine the effects of mass perception (increasing number of needy persons) and intertemporal choice (soon versus later) on volunteering behavior. Collegiate classes in their natural setting were randomly assigned to five different treatment groups and were presented with audiovisual presentations featuring an increasing number of needy persons. The students were deceived to believe that two hypothetical feeding programs for Marawi refugees, taking place in 1 month and 6 months, were in need of volunteers for its preparatory phase. Results show a statistically significant (p=0.000; p=0.013) non-linear trend consistently for both feeding programs. There was a decrease in volunteered time means as identifiable victims increased from 0-47 and an increase as it progressed towards 267 non-identifiable victims. Highest interest was expressed for the 0 needy people shown and least for 47. The 0 hours volunteered was consistently the mode and median in all treatments. There was no statistically significant temporal discounting effect.

Keywords: compassion, group perception, identifiable victim, intertemporal choice, prosocial behavior, unresponsive bystander

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Maryam Nabati, Mahmood Moosazadeh, Ehsan Soroosh, Hanieh Shiraj, Mahnaneh Gholami, Ali Ghaemian

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Background: Reported effects of obesity on the extent of angiographic coronary artery disease(CAD) have beeninconsistent. The present study aimed to investigate the relationships between the indices of obesity and otheranthropometric markers with the extent of CAD. Methods: This study was conducted on 1008 consecutive patients who underwent coronary angiography. Bodymass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) wereseparately calculated for each patient. Extent, severity, and complexity of CAD were determined by the Gensini andSYNTAX scores. Results: According to the results, there was a significant inverse correlation between the SYNTAX score with BMI(r = − 0.110; P < 0.001), WC (r = − 0.074; P = 0.018), and WHtR (r = − 0.089; P = 0.005). Furthermore, a significant inversecorrelation was observed between the Gensini score with BMI (r = − 0.090; P = 0.004) and WHtR (r = − 0.065; P =0.041). However, the results of multivariate linear regression analysis did not show any association between theSYNTAX and Gensini scores with the indices of obesity and overweight. On the other hand, the patients with anunhealthy WC had a higher prevalence of diabetes mellitus (DM) (P = 0.004) and hypertension (HTN) (P < 0.001) compared to the patients with healthy values. Coexistence of HTN and DM was more prevalent in subjects with anunhealthy WC and WHR compared to that in those with healthy values (P = 0.002 and P = 0.032, respectively). Conclusion: It seems that the anthropometric indices of obesity are not the predictors of the angiographic severityof CAD. However, they are associated with an increased risk of cardiovascular risk factors and higher risk profile.

Keywords: body mass index, BMI, coronary artery disease, waist circumference

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Authors: Owonikoko Abayomi Dele

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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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Authors: Alla Levina, Sergey Taranov

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The classical approach to the providing noise immunity and integrity of information that process in computing devices and communication channels is to use linear codes. Linear codes have fast and efficient algorithms of encoding and decoding information, but this codes concentrate their detect and correct abilities in certain error configurations. To protect against any configuration of errors at predetermined probability can robust codes. This is accomplished by the use of perfect nonlinear and almost perfect nonlinear functions to calculate the code redundancy. The paper presents the error-correcting coding scheme using biorthogonal wavelet transform. Wavelet transform applied in various fields of science. Some of the wavelet applications are cleaning of signal from noise, data compression, spectral analysis of the signal components. The article suggests methods for constructing linear codes based on wavelet decomposition. For developed constructions we build generator and check matrix that contain the scaling function coefficients of wavelet. Based on linear wavelet codes we develop robust codes that provide uniform protection against all errors. In article we propose two constructions of robust code. The first class of robust code is based on multiplicative inverse in finite field. In the second robust code construction the redundancy part is a cube of information part. Also, this paper investigates the characteristics of proposed robust and linear codes.

Keywords: robust code, linear code, wavelet decomposition, scaling function, error masking probability

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Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

Procedia PDF Downloads 149

Authors: Yang Zheng, Wei Sun

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This paper describes a new approach which can be used to interpret the experimental creep deformation data obtained from miniaturized thin plate bending specimen test to the corresponding uniaxial data based on an inversed application of the reference stress method. The geometry of the thin plate is fully defined by the span of the support, l, the width, b, and the thickness, d. Firstly, analytical solutions for the steady-state, load-line creep deformation rate of the thin plates for a Norton’s power law under plane stress (b → 0) and plane strain (b → ∞) conditions were obtained, from which it can be seen that the load-line deformation rate of the thin plate under plane-stress conditions is much higher than that under the plane-strain conditions. Since analytical solution is not available for the plates with random b-values, finite element (FE) analyses are used to obtain the solutions. Based on the FE results obtained for various b/l ratios and creep exponent, n, as well as the analytical solutions under plane stress and plane strain conditions, an approximate, numerical solutions for the deformation rate are obtained by curve fitting. Using these solutions, a reference stress method is utilised to establish the conversion relationships between the applied load and the equivalent uniaxial stress and between the creep deformations of thin plate and the equivalent uniaxial creep strains. Finally, the accuracy of the empirical solution was assessed by using a set of “theoretical” experimental data.

Keywords: bending, creep, thin plate, materials engineering

Procedia PDF Downloads 457

Authors: Xia Huo

Abstract:

Children are more vulnerable to environmental toxicants compared to adults, and their developing immune system is among the most sensitive targets regarding toxicity of environmental toxicants. Studies have found that exposure to environmental toxicants is associated with impaired immune function in children, but only a few studies have focused on the relationship between environmental toxicant exposure and vaccine antibody potency and immunoglobulin (Ig) levels in children. These studies investigated the associations of exposure to polychlorinated biphenyls (PCBs), perfluorinated compounds (PFCs), heavy metals (Pb, Cd, As, Hg) and PM2.5 with the serum-specific antibody concentrations and Ig levels against different vaccines, such as anti-Hib, tetanus, diphtheria toxoid, and analyze the possible mechanisms underlying exposure-related alterations of antibody titers and Ig levels against different vaccines. Results suggest that exposure to these toxicants is generally associated with decreased potency of antibodies produced from childhood immunizations and an overall deficiency in the protection the vaccines provide. Toxicant exposure is associated with vaccination failure and decreased antibody titers, and increased risk of immune-related diseases in children by altering specific immunoglobulin levels. Age, sex, nutritional status, and co-exposure may influence the effects of toxicants on the immune function in children. Epidemiological evidence suggests that exposure-induced changes to humoral immunerelated tissue/cells/molecules response to vaccines may have predominant roles in the inverse associations between antibody responsiveness to vaccines and environmental toxicants. These results help us to conduct better immunization policies for children under environmental toxicant burden.

Keywords: environmental toxicants, immunotoxicity, vaccination, antibodies, children's health

Procedia PDF Downloads 32

Authors: Mahadzirah Mohamad, Morliyati Mohammad, Nor Azman Mat Ali, Zainudin Awang

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Globally, youth substance abuse has been identified as the problem that causes substantial damage not only to individuals, but also to families and communities. In addition, substance abuse youths have become unproductive resources that would play lesser roles in the nation’s development. The increasing trend of substance abuse among youths has raised a lot of concern among various quarters in Malaysia. It has also been reported that Malay youths are the majority group involved in substance abuse. However, it was noted that life satisfaction had been found to be an important mitigating factor that addressed substance abuse. The objectives of the study were twofold: firstly, to ascertain the effect of life satisfaction on substance abuse among Malay youth. Secondly, to identify the role of delinquency on the relationship between life satisfaction and substance abuse. This study adopted a cross-sectional research design. Self-administered questionnaires were distributed to 500 Malay youths at the youth programmes using a two-step sampling technique: area sampling and systematic sampling. The research hypotheses were tested using Structural Equation Modelling. The findings of the study revealed that there is no significance relationship between life satisfaction and substance abuse. There is a significant inverse relationship between life satisfaction and delinquency. Moreover, delinquency has a positive significant influence on substance abuse. The use of Bootstrapping analysis proved that delinquency plays a full mediating role in the relationship between life satisfaction and substance abuse. This study suggested that life satisfaction has no effect on youth substance abuse. In order to reduce substance abuse, efforts should be undertaken to reduce delinquency behaviour by increasing youth life satisfaction.

Keywords: delinquency, life satisfaction, substance abuse, youth

Procedia PDF Downloads 330

Authors: Jovana Bogojeski, Dusan Cocic, Nenad Jankovic, Angelina Petrovic

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Kinetically-inert transition metal complexes, such as Rh(III) and Os(III) complexes, attract increasing attention as leading scaffolds for the development of potential pharmacological agents due to their inertness and stability. Therefore, we have designed and fully characterized a few novel rhodium(III) and osmium(III) complexes with a tridentate nitrogen−donor chelate system. For some complexes, the crystal X-ray structure analysis was performed. Reactivity of the newly synthesized complexes towards small biomolecules, such as L-methionine (L-Met), guanosine-5’-monophosphate (5’-GMP), and glutathione (GSH) has been examined. Also, the reactivity of these complexes towards the DNA/RNA (Ribonucleic acid) duplexes was investigated. Obtained results show that the newly synthesized complexes exhibit good affinity towards the studied ligands. Results also show that the complexes react faster with the RNA duplex than with the DNA and that in the DNA duplex reaction is faster with 15mer GG than with the 22mer GG. The UV-Vis (Ultraviolet-visible spectroscopy) is absorption spectroscopy, and the EB (Ethidium bromide) displacement studies were used to examine the interaction of these complexes with CT-DNA and BSA (Bovine serum albumin). All studied complex showed good interaction ability with both the DNA and BSA. Furthermore, the DFT (Density-functional theory) calculation and docking studies were performed. The impact of the metal complex on the cytotoxicity was tested by MTT assay (a colorimetric assay for assessing cell metabolic activity) on HCT-116 lines (human colon cancer cell line). In addition, all these tests were repeated in the presence of several water-soluble biologically active ionic liquids. Attained results indicate that the ionic liquids increase the activity of the investigated complexes. All obtained results in this study imply that the introduction of different spectator ligand can be used to improve the reactivity of rhodium(III) and osmium(III) complexes. Finally, these results indicate that the examined complexes show reactivity characteristics needed for potential anti-tumor agents, with possible targets being both the DNA and proteins. Every new contribution in this field is highly warranted due to the current lack of clinically used Metallo-based alternatives to cisplatin.

Keywords: biomolecules, ionic liquids, osmium(III), rhodium(III)

Procedia PDF Downloads 129

Authors: Isaac Laryea

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Underwater remote-operated vehicles (ROVs) are highly useful in aquatic research and underwater operations. Unfortunately, unsteady and unpredictable conditions underwater make it difficult for underwater vehicles to maintain a steady attitude during motion. Existing underwater vehicles make use of multiple thrusters positioned at specific positions on their frame to maintain a certain pose. This study proposes an alternate way of maintaining a steady attitude during horizontal motion at low speeds by making use of a thrust vector-controlled propulsion system. The study began by carrying out some preliminary calculations to get an idea of a suitable shape and form factor. Flow simulations were carried out to ensure that enough thrust could be generated to move the system. Using the Lagrangian approach, a mathematical system was developed for the ROV, and this model was used to design a control system. A PID controller was selected for the control system. However, after tuning, it was realized that a PD controller satisfied the design specifications. The designed control system produced an overshoot of 6.72%, with a settling time of 0.192s. To achieve the effect of thrust vectoring, an inverse kinematics synthesis was carried out to determine what angle the actuators need to move to. After building the system, intermittent angular displacements of 10°, 15°, and 20° were given during bench testing, and the response of the control system as well as the servo motor angle was plotted. The final design was able to move in water but was not able to handle large angular displacements as a result of the small angle approximation used in the mathematical model.

Keywords: PID control, thrust vectoring, parallel manipulators, ROV, underwater, attitude control

Procedia PDF Downloads 49

Authors: Q. Toufeeq, R. Kauser, U. R. Jamil, N. Sohaib

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Foundation design of a structure needs soil investigation to avoid failures due to settlements. This soil investigation is expensive and time-consuming. Developments of new residential societies involve huge leveling of large sites that is accompanied by heavy land filling. Poor practices of land fill for deep depths cause differential settlements and consolidations of underneath soil that sometimes result in the collapse of structures. The extent of filling remains unknown to the individual developer unless soil investigation is carried out. Soil investigation cannot be performed on each available site due to involved costs. However, fair estimate of bearing capacity can be made if such tests are already done in the surrounding areas. The geotechnical guidance maps can provide a fair assessment of soil properties. Previously, GIS-based approaches have been used to develop maps using extrapolation and interpolations techniques for bearing capacities, underground recharge, soil classification, geological hazards, landslide hazards, socio-economic, and soil liquefaction mapping. Standard penetration test (SPT) data of surrounding sites were already available. Google Earth is used for digitization of collected data. Few points were considered for data calibration and validation. Resultant Geographic information system (GIS)-based guidance maps are helpful to anticipate the bearing capacity in the real estate industry.

Keywords: bearing capacity, soil classification, geographical information system, inverse distance weighted, radial basis function

Procedia PDF Downloads 114

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

Abstract:

There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

Procedia PDF Downloads 214

Authors: Nia McRae, Robert Wright, Ghalib Bello

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Introduction: Postpartum depression is a prevalent mood disorder that is detrimental to the mental and physical health of mothers and their newborns. Lead (Pb) is a toxic metal that is associated with hormonal imbalance and mental impairments. The hormone changes that accompany pregnancy and childbirth may be exacerbated by Pb and increase new mothers’ susceptibility to postpartum depression. To the best of the author’s knowledge, this is the only study that investigates the association between prenatal Pb exposure and postpartum depression. Identifying risk factors can contribute to improved prevention and treatment strategies for postpartum depression. Methods: Data was derived from the Programming Research in Obesity, Growth, Environment and Social Stress (PROGRESS) study which is an ongoing longitudinal birth cohort. Postpartum depression was identified by a score of 13 or above on the 10-Item Edinburg Postnatal Depression Scale (EPDS) 6-months and 12-months postpartum. Pb was measured in the blood (BPb) in the second and third trimester and in the tibia and patella 1-month postpartum. Quantile regression models were used to assess the relationship between BPb and postpartum depression. Results: BPb in the second trimester was negatively associated with the 80th percentile of depression 6-months postpartum (β: -0.26; 95% CI: -0.51, -0.01). No significant association was found between BPb in the third trimester and depression 6-months postpartum. BPb in the third trimester exhibited an inverse relationship with the 60th percentile (β: -0.23; 95% CI: -0.41, -0.06), 70th percentile (β: -0.31; 95% CI: -0.52, -0.10), and 90th percentile of depression 12-months postpartum (β: -0.36; 95% CI: -0.69, -0.03). There was no significant association between BPb in the second trimester and depression 12-months postpartum. Bone Pb concentrations were not significantly associated with postpartum depression. Conclusion: The negative association between BPb and postpartum depression may support research which demonstrates lead is a nontherapeutic stimulant. Further research is needed to verify these results and identify effect modifiers.

Keywords: depression, lead, postpartum, prenatal

Procedia PDF Downloads 202