Search results for: receptor activator of nuclear factor kappa-B ligand
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6620

Search results for: receptor activator of nuclear factor kappa-B ligand

4100 Conjugated Chitosan-Carboxymethyl-5-Fluorouracil Nanoparticles for Skin Delivery

Authors: Mazita Mohd Diah, Anton V. Dolzhenko, Tin Wui Wong

Abstract:

Nanoparticles, being small with a large specific surface area, increase solubility, enhance bioavailability, improve controlled release and enable precision targeting of the entrapped compounds. In this study, chitosan as polymeric permeation enhancer was conjugated to a polar pro-drug, carboxymethyl-5-fluorouracil (CMFU) to increase the skin drug permeation. Chitosan-CMFU conjugate was synthesized using chemical conjugation process through succinate linker. It was then transformed into nanoparticles via spray drying method. The conjugation was elucidated using Fourier Transform Infrared and Proton Nuclear Magnetic Resonance techniques. The nanoparticle size, size distribution, zeta potential, drug content, skin permeation and retention profiles were characterized. The conjugation was denoted using 1H NMR by new peaks at signal δ = 4.184 ppm (singlet, 2H for CH2) and 7.676-7.688 ppm (doublet, 1H for C6) attributed to CMFU in chitosan-CMFU NMR spectrum. The nanoparticles had profiles of particle size: 93.97 ±35.11 nm, polydispersity index: 0.40 ± 0.14, zeta potential: +18.25 ±2.95 mV and drug content: 6.20 ± 1.98 % w/w. Almost 80 % w/w CMFU in the form of nanoparticles permeated through the skin in 24 hours and close to 50 % w/w permeation occurred in first 1-2 hours. Without conjugation to chitosan and nanoparticulation, less than 40 % w/w CMFU permeated through the skin in 24 hours. The skin drug retention likewise was higher with chitosan-CMFU nanoparticles (15.34 ± 5.82 % w/w) than CMFU (2.24 ± 0.57 % w/w). CMFU, through conjugation with chitosan permeation enhancer and processed in nanogeometry, had its skin permeation and retention degree promoted.

Keywords: carboxymethyl-5-fluorouracil, chitosan, conjugate, skin permeation, skin retention

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4099 Enhanced Functional Production of a Crucial Biomolecule Human Serum Albumin in Escherichia coli

Authors: Ashima Sharma

Abstract:

Human Serum Albumin (HSA)- one of the most demanded therapeutic proteins with immense biotechnological applications- is a large multidomain protein containing 17 disulfide bonds. The current source of HSA is human blood plasma which is a limited and unsafe source. Thus, there exists an indispensable need to promote non-animal derived recombinant HSA (rHSA) production. Escherichia coli is one of the most convenient hosts which had contributed to the production of more than 30% of the FDA approved recombinant pharmaceuticals. It grows rapidly and reaches high cell density using inexpensive and simple substrates. E. coli derived recombinant products have more economic potential as fermentation processes are cheaper compared to the other expression hosts. The major bottleneck in exploiting E. coli as a host for a disulfide-rich multidomain protein is the formation of aggregates of overexpressed protein. The majority of the expressed HSA forms inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA from inclusion bodies is not preferred because it is difficult to obtain a large multidomain disulfide bond rich protein like rHSA in its functional native form. Purification is tedious, time-consuming, laborious and expensive. Because of such limitations, the E. coli host system was neglected for rHSA production for the past few decades despite its numerous advantages. In the present work, we have exploited the capabilities of E. coli as a host for the enhanced functional production of rHSA (~60% of the total expressed rHSA in the soluble fraction). Parameters like intracellular environment, temperature, induction type, duration of induction, cell lysis conditions etc. which play an important role in enhancing the level of production of the desired protein in its native form in vivo have been optimized. We have studied the effect of assistance of different types of exogenously employed chaperone systems on the functional expression of rHSA in the E. coli host system. Different aspects of cell growth parameters during the production of rHSA in presence and absence of molecular chaperones in E. coli have also been studied. Upon overcoming the difficulties to produce functional rHSA in E. coli, it has been possible to produce significant levels of functional protein through engineering the biological system of protein folding in the cell, the E. coli-derived rHSA has been purified to homogeneity. Its detailed physicochemical characterization has been performed by monitoring its conformational properties, secondary and tertiary structure elements, surface properties, ligand binding properties, stability issues etc. These parameters of the recombinant protein have been compared with the naturally occurring protein from the human source. The outcome of the comparison reveals that the recombinant protein resembles exactly the same as the natural one. Hence, we propose that the E. coli-derived rHSA is an ideal biosimilar for human blood plasma-derived serum albumin. Therefore, in the present study, we have introduced and promoted the E. coli- derived rHSA as an alternative to the preparation from a human source, pHSA.

Keywords: recombinant human serum albumin, Escherichia coli, biosimilar, chaperone assisted protein folding

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4098 Novel Correlations for P-Substituted Phenols in NMR Spectroscopy

Authors: Khodzhaberdi Allaberdiev

Abstract:

Substituted phenols are widely used for the synthesis of advanced polycondensation polymers. In terms of the structure regularity and practical value of obtained polymers are of special interest the p-substituted phenols. The lanthanide induced shifts (LIS) of the aromatic ring and the OH protons by addition Eu(fod)3 to various p-substituted phenols in CDCL3 solvent were measured Nuclear Magnetic Resonance spectroscopy. A linear relationship has been observed between the LIS of protons (∆=δcomplex –δsubstrate) and Eu(fod)3/substrate molar ratios. The LIS protons of the investigated phenols decreases in the following order: ОН > ortho > meta. The LIS of these protons also depends on both steric and electronic effects of p-substituents. The effect on the LIS of protons steric hindrance of substituents by way of example p-substituted alkyl phenols was studied. Alkyl phenols exhibit pronounced europium- induced shifts, their sensitivity increasing in the order: CH3 > C2H5 > sym-C5H11 > tert-C5H11 > tert-C4H9, i.e. in parallel with decreasing steric hindrance. The influence steric hindrance p-substituents of phenols on the LIS of protons in sequence following decreases: OH> meta >ortho. Contrary to the expectations, it is found that the LIS of the ortho protons an excellent linear correlation with meta-substituent constants, σm for 14 p-substituted phenols: ∆H2, 6=8.165-9.896 σm (r2=0,999). Moreover, a linear correlation between the LIS of the ortho protons and ionization constants, РКa of p-substituted phenols has been revealed. Similarly, the linear relationships for the LIS of the meta and the OH protons were obtained. Use the LIS of the phenolic hydroxyl groups for linear relationships is necessary with care, because of the signal broadening of the OH protons. New constants may be determinate with unusual case by this approach.

Keywords: novel correlations, NMR spectroscopy, phenols, shift reagent

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4097 Coping Strategies Used by Persons with Spinal Cord Injury: A Rehabilitation Hospital Based Qualitative Study

Authors: P. W. G. D. P. Samarasekara, S. M. K. S. Seneviratne, D. Munidasa, S. S. Williams

Abstract:

Sustaining a spinal cord injury (SCI) causes severe disruption of all aspects of a person’s life, resulting in the difficult process of coping with the distressing effects of paralysis affecting their ability to lead a meaningful life. These persons are hospitalized in the acute stage of injury and subsequently for rehabilitation and the treatment of complications. The purpose of this study was to explore coping strategies used by persons with SCI during their rehabilitation period. A qualitative study was conducted among persons with SCI, undergoing rehabilitation at the Rheumatology and Rehabilitation Hospitals, Ragama and Digana Sri Lanka. Twelve participants were selected purposively to represent both males and females, with cervical, thoracic or lumbar levels of injuries due to traumatic and non-traumatic causes as well as from different socioeconomic backgrounds. Informed consent was taken from the participants. In-depth interviews were conducted using an interview guide to collect data. Probes were used to get more information and to encourage participants. Interviews were audio taped and transcribed verbatim. Qualitative content analysis was conducted. Ethical approval for this study was obtained from the Ethics Review Committee, Faculty of Medicine, University of Kelaniya. Five themes were identified in the content analysis: social support, religious beliefs, determination, acceptance and making comparisons. Participants indicated that the support from their family members had been an essential factor in coping, after sustaining an SCI and they expressed the importance of emotional support from family members during their rehabilitation. Many participants had a strong belief towards the God, who had a personal interest in their lives, played an important role in their ability to cope with the injury. They believed that what happens to them in this life results from their actions in previous lives. They expressed that determination was essential as a factor that helps them cope with their injury. They indicated their focus on the positive aspects of the life and accepted the disability. They made comparisons to other persons who were worse off than them to help lift them out of unpleasant experience. Even some of the most severely injured and disabled participants presented evidence of using this coping strategy. Identification of coping strategies used by persons with SCI will help nurses and other health-care professionals in reinforcing the most effective coping strategies among persons with SCI. The findings recommend that engagement coping positively influences psychosocial adaptation.

Keywords: content analysis, coping strategies, rehabilitation, spinal cord injury

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4096 Guidance for Strengthening Ethics of Entrepreneurs in Information and Communication Technology Professional

Authors: Routsukol Sunalai

Abstract:

The objectives of this paper were to study current problem of ethics of entrepreneurs in information and communication technology professional, and to build their awareness of ethics, which would be useful as guidance for strengthening professional ethics among them. The study employed quantitative research method in order to analyze relationships or differences found in each ethics factor and report in statistics. The sample of this paper was 300 information technology users of Rajabhat Universities in Bangkok. The findings revealed that the ethics factors which gained the highest and high level of opinion included possessing principles of righteousness, having trust in themselves and others, and respecting different opinions of others and accepting the fact that people of different opinions.

Keywords: communication, ethics, information, entrepreneurs

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4095 Investigation of Mesoporous Silicon Carbonization Process

Authors: N. I. Kargin, G. K. Safaraliev, A. S. Gusev, A. O. Sultanov, N. V. Siglovaya, S. M. Ryndya, A. A. Timofeev

Abstract:

In this paper, an experimental and theoretical study of the processes of mesoporous silicon carbonization during the formation of buffer layers for the subsequent epitaxy of 3C-SiC films and related wide-band-gap semiconductors is performed. Experimental samples were obtained by the method of chemical vapor deposition and investigated by scanning electron microscopy. Analytic expressions were obtained for the effective diffusion factor and carbon atoms diffusion length in a porous system. The proposed model takes into account the processes of Knudsen diffusion, coagulation and overgrowing of pores during the formation of a silicon carbide layer.

Keywords: silicon carbide, porous silicon, carbonization, electrochemical etching, diffusion

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4094 A Review of Existing Turnover Intention Theories

Authors: Pauline E. Ngo-Henha

Abstract:

Existing turnover intention theories are reviewed in this paper. This review was conducted with the help of the search keyword “turnover intention theories” in Google Scholar during the month of July 2017. These theories include: The Theory of Organizational Equilibrium (TOE), Social Exchange Theory, Job Embeddedness Theory, Herzberg’s Two-Factor Theory, the Resource-Based View, Equity Theory, Human Capital Theory, and the Expectancy Theory. One of the limitations of this review paper is that data were only collected from Google Scholar where many papers were sometimes not freely accessible. However, this paper attempts to contribute to the research in clarifying the distinction between theories and models in the context of turnover intention.

Keywords: Literature Review, Theory, Turnover, Turnover intention

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4093 A Pilot Study on the Development and Validation of an Instrument to Evaluate Inpatient Beliefs, Expectations and Attitudes toward Reflexology (IBEAR)-16

Authors: Samuel Attias, Elad Schiff, Zahi Arnon, Eran Ben-Arye, Yael Keshet, Ibrahim Matter, Boker Lital Keinan

Abstract:

Background: Despite the extensive use of manual therapies, reflexology in particular, no validated tools have been developed to evaluate patients' beliefs, attitudes and expectations regarding reflexology. Such tools however are essential to improve the results of the reflexology treatment, by better adjusting it to the patients' attitudes and expectations. The tool also enables assessing correlations with clinical results of interventional studies using reflexology. Methods: The IBEAR (Inpatient Beliefs, Expectations and Attitudes toward Reflexology) tool contains 25 questions (8 demographic and 17 specifically addressing reflexology), and was constructed in several stages: brainstorming by a multidisciplinary team of experts; evaluation of each of the proposed questions by the experts' team; and assessment of the experts' degree of agreement per each question, based on a Likert 1-7 scale (1 – don't agree at all; 7 – agree completely). Cronbach's Alpha was computed to evaluate the questionnaire's reliability while the Factor analysis test was used for further validation (228 patients). The questionnaire was tested and re-tested (48h) on a group of 199 patients to assure clarity and reliability, using the Pearson coefficient and the Kappa test. It was modified based on these results into its final form. Results: After its construction, the IBEAR questionnaire passed the expert group's preliminary consensus, evaluation of the questions' clarity (from 5.1 to 7.0), inner validation (from 5.5 to 7) and structural validation (from 5.5 to 6.75). Factor analysis pointed to two content worlds in a division into 4 questions discussing attitudes and expectations versus 5 questions on belief and attitudes. Of the 221 questionnaires collected, a Cronbach's Alpha coefficient was calculated on nine questions relating to beliefs, expectations, and attitudes regarding reflexology. This measure stood at 0.716 (satisfactory reliability). At the Test-Retest stage, 199 research participants filled in the questionnaire a second time. The Pearson coefficient for all questions ranged between 0.73 and 0.94 (good to excellent reliability). As for dichotomic answers, Kappa scores ranged between 0.66 and 1.0 (mediocre to high). One of the questions was removed from the IBEAR following questionnaire validation. Conclusions: The present study provides evidence that the proposed IBEAR-16 questionnaire is a valid and reliable tool for the characterization of potential reflexology patients and may be effectively used in settings which include the evaluation of inpatients' beliefs, expectations, and attitudes toward reflexology.

Keywords: reflexology, attitude, expectation, belief, CAM, inpatient

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4092 Online Estimation of Clutch Drag Torque in Wet Dual Clutch Transmission Based on Recursive Least Squares

Authors: Hongkui Li, Tongli Lu , Jianwu Zhang

Abstract:

This paper focuses on developing an estimation method of clutch drag torque in wet DCT. The modelling of clutch drag torque is investigated. As the main factor affecting the clutch drag torque, dynamic viscosity of oil is discussed. The paper proposes an estimation method of clutch drag torque based on recursive least squares by utilizing the dynamic equations of gear shifting synchronization process. The results demonstrate that the estimation method has good accuracy and efficiency.

Keywords: clutch drag torque, wet DCT, dynamic viscosity, recursive least squares

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4091 Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

Abstract:

MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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4090 On Improving Breast Cancer Prediction Using GRNN-CP

Authors: Kefaya Qaddoum

Abstract:

The aim of this study is to predict breast cancer and to construct a supportive model that will stimulate a more reliable prediction as a factor that is fundamental for public health. In this study, we utilize general regression neural networks (GRNN) to replace the normal predictions with prediction periods to achieve a reasonable percentage of confidence. The mechanism employed here utilises a machine learning system called conformal prediction (CP), in order to assign consistent confidence measures to predictions, which are combined with GRNN. We apply the resulting algorithm to the problem of breast cancer diagnosis. The results show that the prediction constructed by this method is reasonable and could be useful in practice.

Keywords: neural network, conformal prediction, cancer classification, regression

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4089 Electrical Characterization of Hg/n-bulk GaN Schottky Diode

Authors: B. Nabil, O. Zahir, R. Abdelaziz

Abstract:

We present the results of electrical characterizations current-voltage and capacity-voltage implementation of a method of making a Schottky diode on bulk gallium nitride doped n. We made temporary Schottky contact of Mercury (Hg) and an ohmic contact of silver (Ag), the electrical characterizations current-voltage (I-V) and capacitance-voltage (C-V) allows us to determine the difference parameters of our structure (Hg /n-GaN) as the barrier height (ΦB), the ideality factor (n), the series resistor (Rs), the voltage distribution (Vd), the doping of the substrate (Nd) and density of interface states (Nss).

Keywords: Bulk Gallium nitride, electrical characterization, Schottky diode, series resistance, substrate doping

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4088 Structural Equation Modelling Based Approach to Integrate Customers and Suppliers with Internal Practices for Lean Manufacturing Implementation in the Indian Context

Authors: Protik Basu, Indranil Ghosh, Pranab K. Dan

Abstract:

Lean management is an integrated socio-technical system to bring about a competitive state in an organization. The purpose of this paper is to explore and integrate the role of customers and suppliers with the internal practices of the Indian manufacturing industries towards successful implementation of lean manufacturing (LM). An extensive literature survey is carried out. An attempt is made to build an exhaustive list of all the input manifests related to customers, suppliers and internal practices necessary for LM implementation, coupled with a similar exhaustive list of the benefits accrued from its successful implementation. A structural model is thus conceptualized, which is empirically validated based on the data from the Indian manufacturing sector. With the current impetus on developing the industrial sector, the Government of India recently introduced the Lean Manufacturing Competitiveness Scheme that aims to increase competitiveness with the help of lean concepts. There is a huge scope to enrich the Indian industries with the lean benefits, the implementation status being quite low. Hardly any survey-based empirical study in India has been found to integrate customers and suppliers with the internal processes towards successful LM implementation. This empirical research is thus carried out in the Indian manufacturing industries. The basic steps of the research methodology followed in this research are the identification of input and output manifest variables and latent constructs, model proposition and hypotheses development, development of survey instrument, sampling and data collection and model validation (exploratory factor analysis, confirmatory factor analysis, and structural equation modeling). The analysis reveals six key input constructs and three output constructs, indicating that these constructs should act in unison to maximize the benefits of implementing lean. The structural model presented in this paper may be treated as a guide to integrating customers and suppliers with internal practices to successfully implement lean. Integrating customers and suppliers with internal practices into a unified, coherent manufacturing system will lead to an optimum utilization of resources. This work is one of the very first researches to have a survey-based empirical analysis of the role of customers, suppliers and internal practices of the Indian manufacturing sector towards an effective lean implementation.

Keywords: customer management, internal manufacturing practices, lean benefits, lean implementation, lean manufacturing, structural model, supplier management

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4087 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells

Authors: S. Pradhan, D. Pradhan, G. Tripathy

Abstract:

Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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4086 Designing of Multi-Epitope Peptide Vaccines for Fasciolosis (Fasciola gigantica) using Immune Epitope and Analysis Resource (IEDB) Server

Authors: Supanan Chansap, Werachon Cheukamud, Pornanan Kueakhai, Narin Changklungmoa

Abstract:

Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future.

Keywords: fasciola gigantica, Immunoinformatic tools, multi-epitope, Vaccine

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4085 Poverty: The Risk to Children’s Mental Health

Authors: Steven Walker

Abstract:

This paper assesses recent data on the prevalence of poverty among children and young people diagnosed with mental health problems. The paper will demonstrate that the current hierarchy of risk factors for developing mental health problems needs adjusting to place poverty among the highest risk factors. Globally poverty is calculated to keep rising especially among less developed countries, and the post-Covid 19 economic recession in developed countries is set to rise. The experience of young people enduring Pandemic isolation is already being quantified and is expected to increase referrals for specialist intervention. Searches on several medical/psychological/social databases using keywords: poverty, children, mental illness were undertaken between 2018 and 2021. Worldwide, 700 million people still live in extreme poverty, half of whom are children. Children are physically and mentally disproportionately affected. Children who grow up impoverished lack the basic necessities they need to survive and thrive. 150 million children have been plunged into multidimensional poverty due to COVID-19. The poorest children are twice as likely to die in childhood than their wealthier peers. For those growing up in humanitarian crises such as Ukraine, the risks of deprivation and exclusion are magnified. In the world’s richest countries, one in seven children still live in poverty. Currently, one in four children in the European Union are at risk of falling into poverty. In Europe the impact of Brexit on the UK economy is predicted to reduce GDP by 5% in 2021 with a corresponding rise in poverty. According to the global charity Oxfam wealth inequality impacts levels of child abuse and affects women and girls worse and is a contributory factor in the risk of developing childhood mental illness. In the UK 2000 Foodbanks have opened since 2010, handing out 2 million food parcels annually, where there are currently 4 million children officially living in poverty. This research demonstrates that there is a strong association between families’ socio-economic circumstances and the chances that their children will experience mental illness. Evidence of this association is found repeatedly across developed countries. The paper will conclude by arguing that psychologists, psychiatrists, psychotherapists, social workers and CAMHS specialists need to place more importance on this critical socio-economic variable when assessing referred children and also advocate for political priorities in governments to reduce poverty and lower the risk of childhood mental illness.

Keywords: poverty, resilience, risk factor, socio economic, susceptibility

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4084 The Differential Impacts of Shame and Guilt on Father Involvement in Families with Special Needs Children

Authors: Lo Kai Chung

Abstract:

Fathers in the family of disabled children play a crucial role in fostering child development. Previous studies addressing emotions of father involvement in rearing children with special needs have been rare. With reference to the cultural orientation and masculine idea of Chinese fathers, shame and guilt are probable causal emotions that affect fathers’ psycho-behavioral reactions and, thus, father involvement. Based on the findings of our earlier qualitative studies, the current study aims to develop and validate a multi-item scale of guilt or shame and explore their relations with and fatherhood in families with children with special needs. A model is proposed to understand the roles that shame and guilt play in affecting fathers’ involvement in their family system. The severity and type of the child’s special needs are regarded as independent variables affecting the father’s emotional responses – shame and guilt. It is hypothesized that shame and guilt, under the influence of masculinity, lead to avoidance and compensation, respectively, which subsequently decrease and increase father involvement with children with special needs. A cross-sectional online questionnaire survey of fathers with children with special needs recruited by convenience sampling was conducted. Potential participants were reached by bulk emails, related groups on the Internet and education/social services providers. Totally 537 valid sets of online questionnaires were collected from fathers of children with special needs. EFA on the items pool of shame and guilt was performed, resulting in an x-item single-factor solution and y-item single-factor solution, respectively. Further path model analysis revealed that shame and guilt, under the influence of masculinity, showed differential avoidance and compensation responses and resulted in a decrease and increase in father involvement with special needs children. Demographic and key confounding variables were controlled in the analysis. The shame and guilt scales developed show good psychometric properties. Furthermore, they showed significant differential impacts, under the influence of masculinity, on avoidance and compensation behaviours, consequently resulting in a decrease/increase in father involvement in the expected directions. The findings have important theoretical and practical implications. At the community and policy level, the findings inform the design of strategies for strengthening the role of men in families with special needs children.

Keywords: emotions, father involvement, guilt, shame, special needs

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4083 Differentiation of Drug Stereoisomers by Their Stereostructure-Selective Membrane Interactions as One of Pharmacological Mechanisms

Authors: Maki Mizogami, Hironori Tsuchiya, Yoshiroh Hayabuchi, Kenji Shigemi

Abstract:

Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.

Keywords: chiral membrane, differentiation, drug stereoisomer, enantioselective membrane interaction

Procedia PDF Downloads 218
4082 Components of Emotional Intelligence in Iranian Entrepreneurs

Authors: Farzaneh Noori

Abstract:

Entrepreneurs face different sort of difficulties especially with customers, organizations and employees. Emotional intelligence which is the ability to understand and control the emotions is an important factor to help entrepreneurs end up challenges to the result they prefer. Thus, it is assumed that entrepreneurs especially those who have passed the first challenging years of starting a new business, have high emotional intelligence. In this study the Iranian established entrepreneurs have been surveyed. According to Iran Gem 2014 report the percentage of established entrepreneur in Iran is 10.92%. So by using Cochran sample formula (1%) 96 Iranian established entrepreneurs have been selected and Emotional intelligence appraisal questionnaire distributed to them. The SPSS19 result shows high emotional intelligence in Iranian established entrepreneurs.

Keywords: emotional intelligence, emotional intelligence appraisal questionnaire, entrepreneurs, Iran

Procedia PDF Downloads 438
4081 Potentiality of Litchi-Fodder Based Agroforestry System in Bangladesh

Authors: M. R. Zaman, M. S. Bari, M. Kajal

Abstract:

A field experiment was conducted at the Agroforestry and Environment Research Field, Hajee Mohammad Danesh Science and Technology University, Dinajpur during 2013 to investigate the potentiality of three napier fodder varieties under Litchi orchard. The experiment was consisted of 2 factors RCBD with 3 replications. Among the two factors, factor A was two production systems; S1= Litchi + fodder and S2 = Fodder (sole crop); another factor B was three napier varieties: V1= BARI Napier -1 (Bazra), V2= BARI Napier - 2 (Arusha) and V3= BARI Napier -3 (Hybrid). The experimental results revealed that there were significant variation among the varieties in terms of leaf growth and yield. The maximum number of leaf plant -1 was recorded in variety Bazra (V1) whereas the minimum number was recorded in hybrid variety (V3).Significantly the highest (13.75, 14.53 and14.84 tha-1 at 1st, 2nd and 3rd harvest respectively) yield was also recorded in variety Bazra whereas the lowest (5.89, 6.36 and 9.11 tha-1 at 1st, 2nd v and 3rd harvest respectively) yield was in hybrid variety. Again, in case of production systems, there were also significant differences between the two production systems were founded. The maximum number of leaf plant -1 was recorded under Litchi based AGF system (T1) whereas the minimum was recorded in open condition (T2). Similarly, significantly the highest (12.00, 12.35 and 13.31 tha-1 at 1st, 2nd and 3rd harvest respectively) yield of napier was recorded under Litchi based AGF system where as the lowest (9.73, 10.47 and 11.66 tha-1 at 1st, 2nd and 3rd harvest respectively) yield was recorded in open condition i.e. napier in sole cropping. Furthermore, the interaction effect of napier variety and production systems were also gave significant deviation result in terms of growth and yield. The maximum number of leaf plant -1 was recorded under Litchi based AGF systems with Bazra variety whereas the minimum was recorded in open condition with hybrid variety. The highest yield (14.42, 16.14 and 16.15 tha-1 at 1st, 2nd and 3rd harvest respectively) of napier was found under Litchi based AGF systems with Bazra variety. Significantly the lowest (5.33, 5.79 and 8.48 tha-1 at 1st, 2nd and 3rd harvest respectively) yield was found in open condition i.e. sole cropping with hybrid variety. In case of the quality perspective, the highest nutritive value (DM, ASH, CP, CF, EE, and NFE) was found in Bazra (V1) and the lowest value was found in hybrid variety (V3). Therefore, the suitability of napier production under Litchi based AGF system may be ranked as Bazra > Arusha > Hybrid variety. Finally, the economic analysis showed that maximum BCR (5.20) was found in the Litchi based AGF systems over sole cropping (BCR=4.38). From the findings of the taken investigation, it may be concluded that the cultivation of Bazra napier varieties in the floor of Litchi orchard ensures higher revenue to the farmers compared to its sole cropping.

Keywords: potentiality, Litchi, fodder, agroforestry

Procedia PDF Downloads 319
4080 Implications of Agricultural Subsidies Since Green Revolution: A Case Study of Indian Punjab

Authors: Kriti Jain, Sucha Singh Gill

Abstract:

Subsidies have been a major part of agricultural policies around the world, and more extensively since the green revolution in developing countries, for the sake of attaining higher agricultural productivity and achieving food security. But entrenched subsidies lead to distorted incentives and promote inefficiencies in the agricultural sector, threatening the viability of these very subsidies and sustainability of the agricultural production systems, posing a threat to the livelihood of farmers and laborers dependent on it. This paper analyzes the economic and ecological sustainability implications of prolonged input and output subsidies in agriculture by studying the case of Indian Punjab, an agriculturally developed state responsible for ensuring food security in the country when it was facing a major food crisis. The paper focuses specifically on the environmentally unsustainable cropping pattern changes as a result of Minimum Support Price (MSP) and assured procurement and on the resource use efficiency and cost implications of power subsidy for irrigation in Punjab. The study is based on an analysis of both secondary and primary data sources. Using secondary data, a time series analysis was done to capture the changes in Punjab’s cropping pattern, water table depth, fertilizer consumption, and electrification of agriculture. This has been done to examine the role of price and output support adopted to encourage the adoption of green revolution technology in changing the cropping structure of the state, resulting in increased input use intensities (especially groundwater and fertilizers), which harms the ecological balance and decreases factor productivity. Evaluation of electrification of Punjab agriculture helped evaluate the trend in electricity productivity of agriculture and how free power imposed further pressure on the extant agricultural ecosystem. Using data collected from a primary survey of 320 farmers in Punjab, the extent of wasteful application of groundwater irrigation, water productivity of output, electricity usage, and cost of irrigation driven electricity subsidy to the exchequer were estimated for the dominant cropping pattern amongst farmers. The main findings of the study revealed how because of a subsidy has driven agricultural framework, Punjab has lost area under agro climatically suitable and staple crops and moved towards a paddy-wheat cropping system, that is gnawing away the state’s natural resources like water table has been declining at a significant rate of 25 cms per year since 1975-76, and excessive and imbalanced fertilizer usage has led to declining soil fertility in the state. With electricity-driven tubewells as the major source of irrigation within a regime of free electricity and water-intensive crop cultivation, there is both wasteful application of irrigation water and electricity in the cultivation of paddy crops, burning an unproductive hole in the exchequer’s pocket. There is limited access to both agricultural extension services and water-conserving technology, along with policy imbalance, keeping farmers in an intensive and unsustainable production system. Punjab agriculture is witnessing diminishing returns to factor, which under the business-as-usual scenario, will soon enter the phase of negative returns to factor.

Keywords: cropping pattern, electrification, subsidy, sustainability

Procedia PDF Downloads 183
4079 Study the Effects of Increasing Unsaturation in Palm Oil and Incorporation of Carbon Nanotubes on Resinous Properties

Authors: Muhammad R. Islam, Mohammad Dalour H. Beg, Saidatul S. Jamari

Abstract:

Considering palm oil as non-drying oil owing to its low iodine value, an attempt was taken to increase the unsaturation in the fatty acid chains of palm oil for the preparation of alkyds. To increase the unsaturation in the palm oil, sulphuric acid (SA) and para-toluene sulphonic acid (PTSA) was used prior to alcoholysis for the dehydration process. The iodine number of the oil samples was checked for the unsaturation measurement by Wijs method. Alkyd resin was prepared using the dehydrated palm oil by following alcoholysis and esterification reaction. To improve the film properties 0.5 wt% multi-wall carbon nano tubes (MWCNTs) were used to manufacture polymeric film. The properties of the resins were characterized by various physico-chemical properties such as density, viscosity, iodine value, acid value, saponification value, etc. Structural elucidation was confirmed by Fourier transform of infrared spectroscopy and proton nuclear magnetic resonance; surfaces of the cured films were observed by scanning electron microscopy. In addition, pencil hardness and chemical resistivity was also measured by using standard methods. The effect of enhancement of the unsaturation in the fatty acid chain found significant and motivational. The resin prepared with dehydrated palm oil showed improved properties regarding hardness and chemical resistivity testing. The incorporation of MWCNTs enhanced the thermal stability and hardness of the films as well.

Keywords: alkyd resin, nano-coatings, dehydration, palm oil

Procedia PDF Downloads 307
4078 Impact of Zeolite NaY Synthesized from Kaolin on the Properties of Pyrolytic Oil Derived from Used Tire

Authors: Julius Ilawe Osayi, Peter Osifo

Abstract:

Solid waste disposal, such as used tires is a global challenge as well as energy crisis due to rising energy demand amidst price uncertainty and depleting fossil fuel reserves. Therefore, the effectiveness of pyrolysis as a disposal method that can transform used tires into liquid fuel and other end-products has made the process attractive to researchers. Although used tires have been converted to liquid fuel using pyrolysis, there is the need to improve on the liquid fuel properties. Hence, this paper reports the investigation of zeolite NaY synthesized from kaolin, a locally abundant soil material in the Benin metropolis as a suitable catalyst and its effect on the properties of pyrolytic oil produced from used tires. The pyrolysis process was conducted for a range of 1 to 10 wt.% of catalyst concentration to used tire at a temperature of 600 oC, a heating rate of 15oC/min and particle size of 6mm. Although no significant increase in pyrolytic oil yield was observed compared to the previously investigated non-catalytic pyrolysis of a used tire. However, the Fourier transform infrared (FTIR), Nuclear Magnetic Resonance (NMR); and Gas chromatography-mass spectrometry (GC-MS) characterization results revealed the pyrolytic oil to possess an improved physicochemical and fuel properties alongside valuable industrial chemical species. This confirms the possibility of transforming kaolin into a catalyst suitable for improved fuel properties of the liquid fraction obtainable from thermal cracking of hydrocarbon materials.

Keywords: catalytic pyrolysis, fossil fuel, kaolin, pyrolytic oil, used tyres, Zeolite NaY

Procedia PDF Downloads 175
4077 Dancing with Perfectionism and Emotional Inhibition on the Ground of Disordered Eating Behaviors: Investigating Emotion Regulation Difficulties as Mediating Factor

Authors: Merve Denizci Nazligul

Abstract:

Dancers seem to have much higher risk levels for the development of eating disorders, compared to non-dancing counterparts. In a remarkably competitive nature of dance environment, perfectionism and emotion regulation difficulties become inevitable risk factors. Moreover, early maladaptive schemas are associated with various eating disorders. In the current study, it was aimed to investigate the mediating role of difficulties with emotion regulation on the relationship between perfectionism and disordered eating behaviors, as well as on the relationship between early maladaptive schemas and disordered eating behaviors. A total of 70 volunteer dancers (n = 47 women, n = 23 men) were recruited in the study (M age = 25.91, SD = 8.9, range 19–63) from the university teams or private clubs in Turkey. The sample included various types of dancers (n = 26 ballets or ballerinas, n =32 Latin, n = 10 tango, n = 2 hiphop). The mean dancing hour per week was 11.09 (SD = 7.09) within a range of 1-30 hours. The participants filled a questionnaire set including demographic information form, Dutch Eating Behavior Questionnaire, Multidimensional Perfectionism Scale, three subscales (Emotional Inhibition, Unrelenting Standards-Hypercriticalness, Approval Seeking-Recognition Seeking) from Young Schema Questionnaire-Short Form-3 and Difficulties in Emotion Regulation Scale. The mediation hypotheses were tested using the PROCESS macro in SPSS. The findings revealed that emotion regulation difficulties significantly mediated the relationship between three distinct subtypes of perfectionism and emotional eating. The results of the Sobel test suggested that there were significant indirect effects of self-oriented perfectionism (b = .06, 95% CI = .0084, .1739), other-oriented perfectionism (b = .15, 95% CI = .0136, .4185), and socially prescribed perfectionism (b = .09, 95% CI = .0104, .2344) on emotional eating through difficulties with emotion regulation. Moreover, emotion regulation difficulties significantly mediated the relationship between emotional inhibition and emotional eating (F(1,68) = 4.67, R2 = .06, p < .05). These results seem to provide some evidence that perfectionism might become a risk factor for disordered eating behaviors when dancers are not able to regulate their emotions. Further, gaining an understanding of how inhibition of emotions leads to inverse effects on eating behavior may be important to develop intervention strategies to manage their disordered eating patterns in risk groups. The present study may also support the importance of using unified protocols for transdiagnostic approaches which focus on identifying, accepting, prompting to express maladaptive emotions and appraisals.

Keywords: dancers, disordered eating, emotion regulation difficulties, perfectionism

Procedia PDF Downloads 140
4076 Modelling Sudden Deaths from Myocardial Infarction and Stroke

Authors: Y. S. Yusoff, G. Streftaris, H. R Waters

Abstract:

Death within 30 days is an important factor to be looked into, as there is a significant risk of deaths immediately following or soon after, Myocardial Infarction (MI) or stroke. In this paper, we will model the deaths within 30 days following a Myocardial Infarction (MI) or stroke in the UK. We will see how the probabilities of sudden deaths from MI or stroke have changed over the period 1981-2000. We will model the sudden deaths using a Generalized Linear Model (GLM), fitted using the R statistical package, under a Binomial distribution for the number of sudden deaths. We parameterize our model using the extensive and detailed data from the Framingham Heart Study, adjusted to match UK rates. The results show that there is a reduction for the sudden deaths following a MI over time but no significant improvement for sudden deaths following a stroke.

Keywords: sudden deaths, myocardial infarction, stroke, ischemic heart disease

Procedia PDF Downloads 284
4075 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 198
4074 Vascular Targeted Photodynamic Therapy Monitored by Real-Time Laser Speckle Imaging

Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

Abstract:

Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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4073 Efficacy and Safety of COVID-19 Vaccination in Patients with Multiple Sclerosis: Looking Forward to Post-COVID-19

Authors: Achiron Anat, Mathilda Mandel, Mayust Sue, Achiron Reuven, Gurevich Michael

Abstract:

Introduction: As coronavirus disease 2019 (COVID-19) vaccination is currently spreading around the world, it is of importance to assess the ability of multiple sclerosis (MS) patients to mount an appropriate immune response to the vaccine in the context of disease-modifying treatments (DMT’s). Objectives: Evaluate immunity generated following COVID-19 vaccination in MS patients, and assess factors contributing to protective humoral and cellular immune responses in MS patients vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus infection. Methods: Review our recent data related to (1) the safety of PfizerBNT162b2 COVID-19 mRNA vaccine in adult MS patients; (2) the humoral post-vaccination SARS-CoV2 IgG response in MS vaccinees using anti-spike protein-based serology; and (3) the cellular immune response of memory B-cells specific for SARS-CoV-2 receptor-binding domain (RBD) and memory T-cells secreting IFN-g and/or IL-2 in response to SARS-CoV2 peptides using ELISpot/Fluorospot assays in MS patients either untreated or under treatment with fingolimod, cladribine, or ocrelizumab; (4) covariate parameters related to mounting protective immune responses. Results: COVID-19 vaccine proved safe in MS patients, and the adverse event profile was mainly characterised by pain at the injection site, fatigue, and headache. Not any increased risk of relapse activity was noted and the rate of patients with acute relapse was comparable to the relapse rate in non-vaccinated patients during the corresponding follow-up period. A mild increase in the rate of adverse events was noted in younger MS patients, among patients with lower disability, and in patients treated with DMTs. Following COVID-19 vaccination protective humoral immune response was significantly decreased in fingolimod- and ocrelizumab- treated MS patients. SARS-CoV2 specific B-cell and T-cell cellular responses were respectively decreased. Untreated MS patients and patients treated with cladribine demonstrated protective humoral and cellular immune responses, similar to healthy vaccinated subjects. Conclusions: COVID-19 BNT162b2 vaccine proved as safe for MS patients. No increased risk of relapse activity was noted post-vaccination. Although COVID-19 vaccination is new, accumulated data demonstrate differences in immune responses under various DMT’s. This knowledge can help to construct appropriate COVID-19 vaccine guidelines to ensure proper immune responses for MS patients.

Keywords: covid-19, vaccination, multiple sclerosis, IgG

Procedia PDF Downloads 135
4072 Hard Sludge Formation and Consolidation in Pressurized Water Reactor Steam Generators: An Experimental Study

Authors: R. Fernandez-Saavedra, M. B. Gomez-Mancebo, D. Gomez-Briceno

Abstract:

The gradual corrosion of PWR (Pressurized Water Reactor) feedwater, condensate and drain systems results in the inevitable liberation of corrosion products, principally metallic oxides, to the secondary circuit. In addition, other contaminants and impurities are introduced into the makeup water, auxiliary feedwater and by condenser leaks. All these compounds circulating in the secondary flow can eventually be transported to steam generators and be transformed into deposits on their surfaces. Deposits that accumulate on the tube sheet are known as sludge piles and when they consolidate and harden become into hard sludge. Hard sludge is especially detrimental because it favors tube deformation or denting at the top of tube sheet and further stress corrosion cracking (SCC). These failures affect the efficiency of nuclear power plants. In a recent work, a model for the formation and consolidation of hard sludge has been formulated, highlighting the influence of aluminum and silicon compounds in the initial formation of hard sludge. In this work, an experimental study has been performed in order to get a deeper understanding of the behavior of Al and Si species in hard sludge formation and consolidation. For this purpose, the key components of hard sludge (magnetite, aluminum and/or silicon sources) have been isothermally autoclaved in representative secondary circuit conditions during one week, and the resulting products have been chemically and structurally characterized by XRF and XRD techniques, respectively.

Keywords: consolidation, hard sludge, secondary circuit, steam generator

Procedia PDF Downloads 187
4071 Improving the Academic Performance of Students: Management Role of Head Teachers as a Key Contributing Factor

Authors: Dominic Winston Kaku

Abstract:

The academic performance of students is an area of great concern in education to the various stakeholders of education. This is because the academic performance of students is widely used as a measure of the success of the educational process. There are several factors, such as school-related factors, teachers related factors, pupils or students’ factors, and many others determining their academic performance. It appears that the management role of head teachers as a determining factor of pupils’ academic achievement is not much investigated. The management role of head teachers is an essential element in the educational process that has a huge influence on students’ academic performance. The aim of the research was to examine the management role of head teachers in improving the academic performance of students. The study employed a descriptive survey and was conducted among Junior High Schools in the Ellembelle District of the Western Region of Ghana. The respondents for the study were mainly all the head teachers, teachers, and some selected basic school pupils (JHS) in four-selected public basic schools in the Ellembelle district in the Western part of Ghana. A questionnaire was used to collect primary data from a sampling size of 252 persons, including 226 JHS pupils, all JHS teachers, and head teachers of all four selected schools. Descriptive statistics, specifically frequencies, percentages, pie charts, bar charts, means, and standard deviation, were used to analyse the data, and that formed the basis of the presentation of findings. The study discovered that planning academic activities, fostering relationships between the school and the community, supervising lessons, staff motivation, and punishing students who go wrong are some of the activities the head teachers participate in to help improve students’ academic performance. The academic performance of students is an area of great concern in education to the various stakeholders of education. This is because the academic performance of students is widely used as a measure of the success of the educational process. There are several factors, such as school-related factors, teachers related factors, pupils or students’ factors, and many others determining their academic performance. It appears that the management role of head teachers as a determining factor of pupils’ academic achievement is not much investigated. The management role of head teachers is an essential element in the educational process that has a huge influence on students’ academic performance. The aim of the research was to examine the management role of head teachers in improving the academic performance of students. The study employed a descriptive survey and was conducted among Junior High Schools in the Ellembelle District of the Western Region of Ghana. The respondents for the study were mainly all the head teachers, teachers, and some selected basic school pupils (JHS) in four-selected public basic schools in the Ellembelle district in the Western part of Ghana. A questionnaire was used to collect primary data from a sampling size of 252 persons, including 226 JHS pupils, all JHS teachers, and head teachers of all four selected schools. Descriptive statistics, specifically frequencies, percentages, pie charts, bar charts, means, and standard deviation, were used to analyse the data, and that formed the basis of the presentation of findings. The study discovered that planning academic activities, fostering relationships between the school and the community, supervising lessons, staff motivation, and punishing students who go wrong are some of the activities the head teachers participate in to help improve students’ academic performance.

Keywords: supervision, head teacher, academic performance, planning, motivation, relationships

Procedia PDF Downloads 63