Search results for: functional mutations
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3133

Search results for: functional mutations

3013 Computational Prediction of the Effect of S477N Mutation on the RBD Binding Affinity and Structural Characteristic, A Molecular Dynamics Study

Authors: Mohammad Hossein Modarressi, Mozhgan Mondeali, Khabat Barkhordari, Ali Etemadi

Abstract:

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant concerns worldwide due to its catastrophic effects on public health. The SARS-CoV-2 infection is initiated with the binding of the receptor-binding domain (RBD) in its spike protein to the ACE2 receptor in the host cell membrane. Due to the error-prone entity of the viral RNA-dependent polymerase complex, the virus genome, including the coding region for the RBD, acquires new mutations, leading to the appearance of multiple variants. These variants can potentially impact transmission, virulence, antigenicity and evasive immune properties. S477N mutation located in the RBD has been observed in the SARS-CoV-2 omicron (B.1.1. 529) variant. In this study, we investigated the consequences of S477N mutation at the molecular level using computational approaches such as molecular dynamics simulation, protein-protein interaction analysis, immunoinformatics and free energy computation. We showed that displacement of Ser with Asn increases the stability of the spike protein and its affinity to ACE2 and thus increases the transmission potential of the virus. This mutation changes the folding and secondary structure of the spike protein. Also, it reduces antibody neutralization, raising concern about re-infection, vaccine breakthrough and therapeutic values.

Keywords: S477N, COVID-19, molecular dynamic, SARS-COV2 mutations

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3012 Automotive Quality Engineering: A Roadmap for Functional Safety

Authors: Hugo d’Albert, Udo Lindemann

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The number of automotive electronic systems that allow realizing new functions, like driver assistance systems, has been increasing extremely in the last decade. Although they bring several benefits, their malfunctions can lead to severe consequences, such as personal injury of road users. Functional safety is an approach to identify these critical malfunctions and arrange technical systems that include only tolerable risk. This approach is– in comparison with other technical areas– relatively new in the automotive sector. For a long time, the automotive systems have based on mechanical components and approved principles, like robust design. With a growing number of electric and electronic components in the modern cars and realizing by software of the system functions, the need for new standards and methods to assure the functional safety has arisen. This paper described the current state of engineering for safety in automotive sector and discusses new directions to meet the challenges of the future.

Keywords: automotive systems, functional safety, quality engineering, quality management

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3011 Update on Epithelial Ovarian Cancer (EOC), Types, Origin, Molecular Pathogenesis, and Biomarkers

Authors: Salina Yahya Saddick

Abstract:

Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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3010 Phenotypic and Genotypic Diagnosis of Gaucher Disease in Algeria

Authors: S. Hallal, Z. Chami, A. Hadji-Lehtihet, S. Sokhal-Boudella, A. Berhoune, L. Yargui

Abstract:

Gaucher disease is the most common lysosomal storage in our population, it is due to a deficiency of β –glucosidase acid. The enzyme deficiency causes a pathological accumulation of undegraded substrate in lysosomes. This metabolic overload is responsible for a multisystemic disease with hepatosplenomegaly, anemia, thrombocytopenia, and bone involvement. Neurological involvement is rare. The laboratory diagnosis of Gaucher disease consists of phenotypic diagnosis by determining the enzymatic activity of β - glucosidase by fluorimetric method, a study by genotypic diagnosis in the GBA gene, limiting the search recurrent mutations (N370S, L444P, 84 GG); PCR followed by an enzymatic digestion. Abnormal profiles were verified by sequencing. Monitoring of treated patients is provided by the determination of chitotriosidase. Our experience spaning a period of 6 years (2007-2014) has enabled us to diagnose 78 patients out of a total of 328 requests from the various departments of pediatrics, internal medicine, neurology. Genotypic diagnosis focused on the entire family of 9 children treated at pediatric CHU Mustapha, which help define the clinical form; or 5 of them had type III disease, carrying the L444P mutation in the homozygous state. Three others were composite (N370/L444P) (N370S/other unintended mutation in our study), and only in one family no recurrent mutation has been found. This molecular study permits screening of heterozygous essential for genetic counseling.

Keywords: Gaucher disease, mutations, N370S, L444P

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3009 The Effect of Physical and Functional Structure on Citizens` Social Behavior: Case Study of Valiasr Crossroads, Tehran, Iran

Authors: Seyedeh Samaneh Hosseini Yousefi

Abstract:

Space does not play role just in mentioning the place or locations. It also takes part in people attendance and social structures. Urban space is of substantial aspects of city which is a public sphere for free and unlimited appearance of citizens. Along with such appearances and regarding physical, environmental and functional conditions, different personal and social behaviors can be seen and analyzed toward people. The main principle of an urban space is including social relations and communications. In this survey, urban space has been referred to one in which physical, environmental and functional attractions cause pause and staying of people. Surveys have shown that urban designers have discussed about place more than architects or planners. With attention to mutual relations between urban space, society and civilization, proper policy making and planning are essential due to achieving an ideal urban space. The survey has been decided to analyze the effect of functional and physical structure of urban spaces on citizens' social behaviors. Hence, Valiasr crossroads, Tehran identified public space, has been selected in which analytic-descriptive method utilized. To test the accuracy of assumptions, statistical test has been accomplished by SPSS. Findings have shown that functional structure affects social behaviors, relations, integration and participation more than physical structure does.

Keywords: citizens' social behavior, functional structure, physical structure, urban space

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3008 Time-Dependent Density Functional Theory of an Oscillating Electron Density around a Nanoparticle

Authors: Nilay K. Doshi

Abstract:

A theoretical probe describing the excited energy states of the electron density surrounding a nanoparticle (NP) is presented. An electromagnetic (EM) wave interacts with a NP much smaller than the incident wavelength. The plasmon that oscillates locally around the NP comprises of excited conduction electrons. The system is based on the Jellium model of a cluster of metal atoms. Hohenberg-Kohn (HK) equations and the variational Kohn-Sham (SK) scheme have been used to obtain the NP electron density in the ground state. Furthermore, a time-dependent density functional (TDDFT) theory is used to treat the excited states in a density functional theory (DFT) framework. The non-interacting fermionic kinetic energy is shown to be a functional of the electron density. The time dependent potential is written as the sum of the nucleic potential and the incoming EM field. This view of the quantum oscillation of the electron density is a part of the localized surface plasmon resonance.

Keywords: electron density, energy, electromagnetic, DFT, TDDFT, plasmon, resonance

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3007 On the Homology Modeling, Structural Function Relationship and Binding Site Prediction of Human Alsin Protein

Authors: Y. Ruchi, A. Prerna, S. Deepshikha

Abstract:

Amyotrophic lateral sclerosis (ALS), also known as “Lou Gehrig’s disease”. It is a neurodegenerative disease associated with degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord characterized by distal muscle weakness, atrophy, normal sensation, pyramidal signs and progressive muscular paralysis reflecting. ALS2 is a juvenile autosomal recessive disorder, slowly progressive, that maps to chromosome 2q33 and is associated with mutations in the alsin gene, a putative GTPase regulator. In this paper we have done homology modeling of alsin2 protein using multiple templates (3KCI_A, 4LIM_A, 402W_A, 4D9S_A, and 4DNV_A) designed using the Prime program in Schrödinger software. Further modeled structure is used to identify effective binding sites on the basis of structural and physical properties using sitemap program in Schrödinger software, structural and function analysis is done by using Prosite and ExPASy server that gives insight into conserved domains and motifs that can be used for protein classification. This paper summarizes the structural, functional and binding site property of alsin2 protein. These binding sites can be potential drug target sites and can be used for docking studies.

Keywords: ALS, binding site, homology modeling, neuronal degeneration

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3006 English Complex Aspectuality: A Functional Approach

Authors: Cunyu Zhang

Abstract:

Based on Systemic Functional Linguistics, this paper aims to explore the complex aspectuality system of English. This study shows that the complex aspectuality is classified into complex viewpoint aspect which refers to the homogeneous or heterogeneous ways continuously viewing on the same situation by the speaker and complex situation aspect which is the combined configuration of the internal time schemata of situation. Through viewpoint shifting and repeating, the complex viewpoint aspect is formed in two combination ways. Complex situation aspect is combined by the way of hypotactic verbal complex and the limitation of participant and circumstance in a clause.

Keywords: aspect series, complex situation aspect, complex viewpoint aspect, systemic functional linguistics

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3005 Functional Properties of Sunflower Protein Concentrates Extracted Using Different Anti-greening Agents - Low-Fat Whipping Cream Preparation

Authors: Tamer M. El-Messery

Abstract:

By-products from sunflower oil extraction, such as sunflower cakes, are rich sources of proteins with desirable functional properties for the food industry. However, challenges such as sensory drawbacks and the presence of phenolic compounds have hindered their widespread use. In this study, sunflower protein concentrates were obtained from sunflower cakes using different ant-greening solvents (ascorbic acid (ASC) and N-acetylcysteine (NAC)), and their functional properties were evaluated. The color of extracted proteins ranged from dark green to yellow, where the using of ASC and NAC agents enhanced the color. The protein concentrates exhibited high solubility (>70%) and antioxidant activity, with hydrophobicity influencing emulsifying activity. Emulsions prepared with these proteins showed stability and microencapsulation efficiency. Incorporation of protein concentrates into low-fat whipping cream formulations increased overrun and affected color characteristics. Rheological studies demonstrated pseudoplastic behavior in whipped cream, influenced by shear rates and protein content. Overall, sunflower protein isolates showed promising functional properties, indicating their potential as valuable ingredients in food formulations.

Keywords: functional properties, sunflower protein concentrates, antioxidant capacity, ant-greening agents, low-fat whipping cream

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3004 The Estimation of Human Vital Signs Complexity

Authors: L. Bikulciene, E. Venskaityte, G. Jarusevicius

Abstract:

Non-stationary and nonlinear signals generated by living complex systems defy traditional mechanistic approaches, which are based on homeostasis. Previous our studies have shown that the evaluation of the interactions of physiological signals by using special analysis methods is suitable for observation of physiological processes. It is demonstrated the possibility of using deep physiological model, based interpretation of the changes of the human body’s functional states combined with an application of the analytical method based on matrix theory for the physiological signals analysis, which was applied on high risk cardiac patients. It is shown that evaluation of cardiac signals interactions show peculiar for each individual functional changes at the onset of hemodynamic restoration procedure. Therefore we suggest that the alterations of functional state of the body, after patients overcome surgery can be complemented by the data received from the suggested approach of the evaluation of functional variables interactions.

Keywords: cardiac diseases, complex systems theory, ECG analysis, matrix analysis

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3003 Study of Functional Relevant Conformational Mobility of β-2 Adrenoreceptor by Means of Molecular Dynamics Simulation

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

Abstract:

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

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

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3002 Allelic Diversity of Productive, Reproductive and Fertility Traits Genes of Buffalo and Cattle

Authors: M. Moaeen-ud-Din, G. Bilal, M. Yaqoob

Abstract:

Identification of genes of importance regarding production traits in buffalo is impaired by a paucity of genomic resources. Choice to fill this gap is to exploit data available for cow. The cross-species application of comparative genomics tools is potential gear to investigate the buffalo genome. However, this is dependent on nucleotide sequences similarity. In this study gene diversity between buffalo and cattle was determined by using 86 gene orthologues. There was about 3% difference in all genes in term of nucleotide diversity; and 0.267±0.134 in amino acids indicating the possibility for successfully using cross-species strategies for genomic studies. There were significantly higher non synonymous substitutions both in cattle and buffalo however, there was similar difference in term of dN – dS (4.414 vs 4.745) in buffalo and cattle respectively. Higher rate of non-synonymous substitutions at similar level in buffalo and cattle indicated a similar positive selection pressure. Results for relative rate test were assessed with the chi-squared test. There was no significance difference on unique mutations between cattle and buffalo lineages at synonymous sites. However, there was a significance difference on unique mutations for non synonymous sites indicating ongoing mutagenic process that generates substitutional mutation at approximately the same rate at silent sites. Moreover, despite of common ancestry, our results indicate a different divergent time among genes of cattle and buffalo. This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae.

Keywords: buffalo, cattle, gene diversity, molecular evolution

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3001 The Mediating Role of Bank Image in Customer Satisfaction Building

Authors: H. Emari, Z. Emari

Abstract:

The main objective of this research was to determine the dimensions of service quality in the banking industry of Iran. For this purpose, the study empirically examined the European perspective suggesting that service quality consists of three dimensions, technical, functional and image. This research is an applied research and its strategy is casual strategy. A standard questionnaire was used for collecting the data. 287 customers of Melli Bank of Northwest were selected through cluster sampling and were studied. The results from a banking service sample revealed that the overall service quality is influenced more by a consumer’s perception of technical quality than functional quality. Accordingly, the Gronroos model is a more appropriate representation of service quality than the American perspective with its limited concentration on the dimension of functional quality in the banking industry of Iran. So, knowing the key dimensions of the quality of services in this industry and planning for their improvement can increase the satisfaction of customers and productivity of this industry.

Keywords: technical quality, functional quality, banking, image, mediating role

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3000 Effect of Dehydration Methods of the Proximate Composition, Mineral Content and Functional Properties of Starch Flour Extracted from Maize

Authors: Olakunle M. Makanjuola, Adebola Ajayi

Abstract:

Effect of the dehydrated method on proximate, functional and mineral properties of corn starch was evaluated. The study was carried and to determine the proximate, functional and mineral properties of corn starch produced using three different drying methods namely (sun) (oven) and (cabinet) drying methods. The corn starch was obtained by cleaning, steeping, milling, sieving, dewatering and drying corn starch was evaluated for proximate composition, functional properties, and mineral properties to determine the nutritional properties, moisture, crude protein, crude fat, ash, and carbohydrate were in the range of 9.35 to 12.16, 6.5 to 10.78 1.08 to 2.5, 1.08 to 2.5, 4.0 to 5.2, 69.58 to 75.8% respectively. Bulk density range between 0.610g/dm3 to 0.718 g/dm3, water, and oil absorption capacities range between 116.5 to 117.25 and 113.8 to 117.25 ml/g respectively. Swelling powder had value varying from 1.401 to 1.544g/g respectively. The results indicate that the cabinet method had the best result item of the quality attribute.

Keywords: starch flour, maize, dehydration, cabinet dryer

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2999 A Proposal for Developing a Post Occupancy Evaluation Sustainability Assessment Tool for Refurbished Historic Government Buildings

Authors: Hasnizan Aksah, Adi Irfan Che Ani

Abstract:

Refurbished historic government buildings should perform as intended to support the organization’s goals that enhance occupant satisfaction. However, these buildings may have issues associated with functional performance evaluation. The aim of this study is to develop a Post Occupancy Evaluation (POE) sustainability assessment tool for functional performance evaluation of refurbished historic government buildings. Developing an assessment tool requires a strategic methodology for a logical and cohesive tool that incorporating relevant theories and practical experiences. In this study, mixed method approaches use to collect all necessary data to achieve the objectives of this study. The design of sampling involves are interviews and survey questionnaires to relevant professionals in order to evaluate the criteria and problem encircled in functional performance evaluation. Then, the involvement of expert panels is required in establishing the assessment tool. During the process of investigation on the functional performance criteria, it was discovered that is seen to be critical in aspects of comfort, safety, and services. The proposed assessment tool has a significant role in providing opportunities for the improvement of building performance especially on functional performance for the future historic government building refurbishment project. It is hoped that the tool developed from this study will give benefits to related professionals, public agencies, local municipality, and relevant interested parties in historic building management.

Keywords: refurbished historic government buildings, functional performance, Post Occupancy Evaluation, sustainability

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2998 Preferred Left-Handed Conformation of Glycyls at Pathogenic Sites

Authors: Purva Mishra, Rajesh Potlia, Kuljeet Singh Sandhu

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The role of glycyl residues in the protein structure has lingered within the research community for the last several decades. Glycyl residue is the only amino acid that is achiral due to the lack of a side chain and can, therefore, exhibit Ramachandran conformations that are disallowed for L-amino acids. The structural and functional significance of glycyl residues with L-disallowed conformation, however, remains obscure. Through statistical analysis of various datasets, we found that the glycyls with L-disallowed conformations are over-represented at disease-associated sites and tend to be evolutionarily conserved. The mutations of L-disallowed glycyls tend to destabilize the native conformation, reduce protein solubility, and promote inter-molecular aggregations. We uncovered a structural motif referred to as “β-crescent” formed around the L-disallowed glycyl, which prevents β-sheet aggregation by disrupting the alternating pattern of β-pleats. The L-disallowed conformation of glycyls also holds predictive power to infer the pathogenic missense variants. Altogether, our observations highlight that the L-disallowed conformation of glycyls is selected to facilitate native folding and prevent inter-molecular aggregations. The findings may also have implications for designing more stable proteins and prioritizing the genetic lesions implicated in diseases.

Keywords: Ramachandran plot, β-sheet, protein stability, protein aggregation

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2997 Design and in Slico Study of the Truncated Spike-M-N SARS-CoV-2 as a Novel Effective Vaccine Candidate

Authors: Aghasadeghi MR., Bahramali G., Sadat SM., Sadeghi SA., Yousefi M., Khodaei K., Ghorbani M., Sadat Larijani M.

Abstract:

Background:The emerging COVID-19 pandemic is a serious concernfor the public health worldwide. Despite the many mutations in the virus genome, it is important to find an effective vaccine against viral mutations. Therefore, in current study, we aimed at immunoinformatic evaluation of the virus proteins immunogenicity to design a preventive vaccine candidate, which could elicit humoral and cellular immune responses as well. Methods:Three antigenic regions are included;Spike, Membrane, and Nucleocapsid amino acid sequences were obtained, and possible fusion proteins were assessed andcompared by immunogenicity, structural features, and population coverage. The best fusion protein was also evaluated for MHC-I and MHC-II T-cell epitopes and the linear and conformational B-cell epitopes. Results: Among the four predicted models, the truncated Spike protein in fusion with M and N proteins is composed of 24 highly immunogenic human MHC class I and 29 MHC class II, along with 14 B-cell linear and 61 discontinues epitopes. Also, the selected protein has high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. Conclusion: The data indicate that the truncated Spike-M-N SARS-CoV-2form which could be potential targets of neutralizing antibodies. The protein also has the ability to stimulate humoral and cellular immunity. The in silico study provided the fusion protein as a potential preventive vaccine candidate for further in vivo evaluation.

Keywords: SARS-CoV-2, immunoinformatic, protein, vaccine

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2996 Disturbance Observer-Based Predictive Functional Critical Control of a Table Drive System

Authors: Toshiyuki Satoh, Hiroki Hara, Naoki Saito, Jun-ya Nagase, Norihiko Saga

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This paper addresses a control system design for a table drive system based on the disturbance observer (DOB)-based predictive functional critical control (PFCC). To empower the previously developed DOB-based PFC to handle constraints on controlled outputs, we propose to take a critical control approach. To this end, we derive the transfer function representation of the PFC controller, and yield a detailed design procedure. The effectiveness of the proposed method is confirmed through an experimental evaluation.

Keywords: critical control, disturbance observer, mechatronics, motion control, predictive functional control, table drive systems

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2995 The Development of an Automated Computational Workflow to Prioritize Potential Resistance Variants in HIV Integrase Subtype C

Authors: Keaghan Brown

Abstract:

The prioritization of drug resistance mutations impacting protein folding or protein-drug and protein-DNA interactions within macromolecular systems is critical to the success of treatment regimens. With a continual increase in computational tools to assess these impacts, the need for scalability and reproducibility became an essential component of computational analysis and experimental research. Here it introduce a bioinformatics pipeline that combines several structural analysis tools in a simplified workflow, by optimizing the present computational hardware and software to automatically ease the flow of data transformations. Utilizing preestablished software tools, it was possible to develop a pipeline with a set of pre-defined functions that will automate mutation introduction into the HIV-1 Integrase protein structure, calculate the gain and loss of polar interactions and calculate the change in energy of protein fold. Additionally, an automated molecular dynamics analysis was implemented which reduces the constant need for user input and output management. The resulting pipeline, Automated Mutation Introduction and Analysis (AMIA) is an open source set of scripts designed to introduce and analyse the effects of mutations on the static protein structure as well as the results of the multi-conformational states from molecular dynamic simulations. The workflow allows the user to visualize all outputs in a user friendly manner thereby successfully enabling the prioritization of variant systems for experimental validation.

Keywords: automated workflow, variant prioritization, drug resistance, HIV Integrase

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2994 Refractory T-Cell Prolymphocytic Leukemia with JAK3 Mutation: In Vitro and Clinical Synergy of Tofacitinib and Ruxolitinib

Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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2993 Functional Performance Needs of Individuals with Intellectual and Developmental Disabilities

Authors: Noor Taleb Ismael, Areej Abd Al Kareem Al Titi, Ala'a Fayez Jaber

Abstract:

Objectives: To investigate self-perceived functional performance among adults with IDD who are Jordanian residential care and rehabilitation centers residents. Also, to investigate their functional abilities (i.e., motor, and cognitive). In addition, to determine the motor and cognitive predictors of their functional performance. Methods: The study utilized a cross-sectional descriptive design; the sample included 180 individuals with IDD (90 males and 90 females) aged 18 to 75 years. The inclusion criteria encompassed: 1) Adults with a confirmed IDD by their physician’s professional and 2) residents in Jordanian Residential Care and Rehabilitation Centers affiliated with the Jordanian Ministry of Social Development. The exclusion criteria were: 1) bedridden or totally dependent on their care providers; 2) who had an accident or acquired neurological conditions. Researchers conducted semi-structured interviews to complete the outcome measures that include the Canadian Occupational Performance Measure (COPM), the Functional Independence Measure (FIM), the Montreal Cognitive Assessment (MoCA), the Mini-Mental Status Examination (MMSE), and the sociodemographic questionnaire. Data analyses consisted of descriptive statistics, analysis of frequencies, correlation, and regression analyses. Result: Individuals with IDD showed low functional performance in all daily life areas, including self-care, productivity, and leisure; there was severe cognitive impairment and poor independence and functional performance. (COPM Performance M= 1.433, SD±.57021, COPM Satisfaction M= 1.31, SD±.54, FIM M= 3.673, SD± 1.7918). Two predictive models were validated for the COPM performance and FIM total scores. First, significant predictors of high self-perceived functional performance on COPM were high scores on FIM Motor sub scores, FIM cognitive sub scores, young age, and having a high school educational level (R2=0.603, p=0.012). Second, significant predictors of high functional capacity on FIM were a high score on the COPM performance subscale, a high MMSE score, and having a cerebral palsy (CP) diagnosis (R2=0.671, p<0.001). Conclusions: Evaluating functional performance and associated factors is important in rehabilitation to provide better services and improve health and QoL for individuals with IDD. This study suggested conducting future studies targeting integrated individuals with IDD who live with their families in the communities.

Keywords: functional performance, intellectual and developmental disabilty, cognitive abilities, motor abilities

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2992 Effect of Thermal Pretreatment on Functional Properties of Chicken Protein Hydrolysate

Authors: Nutnicha Wongpadungkiat, Suwit Siriwatanayotin, Aluck Thipayarat, Punchira Vongsawasdi, Chotika Viriyarattanasak

Abstract:

Chicken products are major export product of Thailand. With a dramatically increasing consumption of chicken product in the world, there are abundant wastes from chicken meat processing industry. Recently, much research in the development of value-added products from chicken meat industry has focused on the production of protein hydrolysate, utilized as food ingredients for human diet and animal feed. The present study aimed to determine the effect of thermal pre-treatment on functional properties of chicken protein hydrolysate. Chicken breasts were heated at 40, 60, 80 and 100ºC prior to hydrolysis by Alcalase at 60ºC, pH 8 for 4 hr. The hydrolysate was freeze-dried, and subsequently used for assessment of its functional properties molecular weight by gel electrophoresis (SDS-PAGE). The obtained results show that increasing the pre-treatment temperature increased oil holding capacity and emulsion stability while decreasing antioxidant activity and water holding capacity. The SDS-PAGE analysis showed the evidence of protein aggregation in the hydrolysate treated at the higher pre-treatment temperature. These results suggest the connection between molecular weight of the hydrolysate and its functional properties.

Keywords: chicken protein hydrolysate, enzymatic hydrolysis, thermal pretreatment, functional properties

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2991 Functional Foods and Their Health Benefits with an Emphasis on Probiotics

Authors: Tanu Malik, Eusebe Gnonlonfoun, Eudes L. Anihouvi

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The rise of nutrition-related diseases, increase of health care cost, and the social perception that food could directly affect health have naturally created an environment conducive to the development of foods and beverages with an asserted health benefit. Consumer habits have turned considerably healthier in recent years and led to the demand for fortified and enhanced foods that could adequately provide health benefits beyond necessary nutrients for humans when they are consumed as part of the diet and regularly. These trends have developed a global market for functional foods, that grows annually and undoubtedly requires to be diversified. Product development appears thus as a key research priority for both the food industry and science sectors. The health benefits of these functional foods are summarized in two possible ways: either indirectly as a desired result of biogenic effect or through the direct interaction of ingested live microorganisms with the host (probiotic effect). This paper reviews functional foods and their beneficial health effects with a key focus on probiotics for the possible expansion of their use by the food industry in order to develop non-dairy based probiotics foods. Likewise, it reveals the need for more researches oriented towards an accurate understanding of the possible interaction between probiotic strains and the matrix and, on the other hand, the interaction between probiotic strains and some enzymes used during food manufacturing.

Keywords: functional foods, food industry, health benefits, probiotics

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2990 Factors Predicting Symptom Cluster Functional Status and Quality of Life of Chronic Obstructive Pulmonary Disease Patients

Authors: D. Supaporn, B. Julaluk

Abstract:

The purposes of this study were to study symptom cluster, functional status and quality of life of patients with chronic obstructive pulmonary disease (COPD), and to examine factors related to and predicting symptom cluster, functional status and quality of life of COPD patients. The sample was 180 COPD patients multi-stage random sampling from 4 hospitals in the eastern region, Thailand. The research instruments were 8 questionnaires and recorded forms measuring personal and illness data, co-morbidity, physical and psychological symptom, health status perception, social support, and regimen adherence, functional status and quality of life. Spearman rank and Pearson correlation coefficient, exploratory factors analysis and standard multiple regression were used to analyzed data. The findings revealed that two symptom clusters were generated: physical symptom cluster including dyspnea, fatigue and insomnia; and, psychological symptom cluster including anxiety and depression. Scores of physical symptom cluster was at moderate level while that of psychological symptom cluster was at low level. Scores on functional status, social support and overall regimen adherence were at good level whereas scores on quality of life and health status perception were at moderate level. Disease severity was positively related to physical symptom cluster, psychological symptom cluster and quality of life, and was negatively related to functional status at a moderate level (rs = .512, .509, .588 and -.611, respectively). Co-morbidity was positively related to physical symptom cluster and psychological symptom cluster at a low level (r = .179 and .176, respectively). Regimen adherence was negatively related to quality of life and psychological symptom cluster at a low level (r=-.277 and -.309, respectively), and was positively related to functional status at a moderate level (r=.331). Health status perception was negatively related to physical symptom cluster, psychological symptom cluster and quality of life at a moderate to high level (r = -.567, -.640 and -.721, respectively) and was positively related to functional status at a high level (r = .732). Social support was positively related to functional status (r=.235) and was negatively related to quality of life at a low level (r=-.178). Physical symptom cluster was negatively related to functional status (r= -.490) and was positively related to quality of life at a moderate level (r=.566). Psychological symptom cluster was negatively related to functional status and was positively related to quality of life at a moderate level (r= -.566 and .559, respectively). Disease severity, co-morbidity and health status perception could predict 40.2% of the variance of physical symptom cluster. Disease severity, co-morbidity, regimen adherence and health status perception could predict 49.8% of the variance of psychological symptom cluster. Co-morbidity, regimen adherence and health status perception could predict 65.0% of the variance of functional status. Disease severity, health status perception and physical symptom cluster could predict 60.0% of the variance of quality of life in COPD patients. The results of this study can be used for enhancing quality of life of COPD patients.

Keywords: chronic obstructive pulmonary disease, functional status, quality of life, symptom cluster

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2989 Searching for an Effective Marketing in the Food Supplement Industry in Japan

Authors: Michiko Miyamoto

Abstract:

The market for "functional foods" and "foods with functional claims" that are effective in maintaining and improving health, has expanded year by year due to the entry of major food and beverage manufacturers following the introduction of the specified health food system in 1991 in Japan. To bring health claims related products or services to the market, it is necessary to let consumers to learn about these products or services; an effective marketing through advertising are important. This research proposes a framework for an effective advertisement medium for the food supplement industry by using survey data of 2,500 people.

Keywords: functional foods, dietary supplements, marketing strategy, structural equation modeling

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2988 Psycholinguistic Analysis on Stuttering Treatment through Systemic Functional Grammar in Tom Hooper’s The King’s Speech

Authors: Nurvita Wijayanti

Abstract:

The movie titled The King’s Speech is based on a true story telling an English king suffers from stuttering and how he gets the treatment from the therapist, so that he can reduce the high frequency on stuttering. The treatment uses the unique approach implying the linguistic principles. This study shows how the language works significantly in order to treat the stuttering sufferer using psychological approach. Therefore, the linguistic study is done to analyze the treatment activity. Halliday’s Systemic Functional Grammar is used as the main approach in this study along with qualitative descriptive method. The study finds that the therapist though using the orthodox approach applies the psycholinguistic method to overcome the king’s stuttering.

Keywords: psycholinguistics, stuttering, systemic functional grammar, treatment

Procedia PDF Downloads 252
2987 RNA Expression Analysis of Mycobacterial Methyltransferases Genes in Different Resistant Strains of Mycobacterium Tuberculosis

Authors: Seyed Davar Siadat, Samira Tarashi, Abolfazl Fateh, Arfa Moshiri

Abstract:

Background: The global health issue of tuberculosis (TB) still affects patients in every country. TB control may not be as effective as it should be, especially when resistant strains are involved. In this regard, mycobacterial MTases play a major role in tuberculosis, but the mechanisms underlying their function have yet to be fully deciphered. Methods: Five resistant isolates of M.tb were accumulated. As a reference strain, M.tb H37Rv (ATCC 27249) was used. For this analysis, seven putative mycobacterial MTase genes (Rv0645c, Rv1694, Rv2966c, Rv3919c, Rv2756c, Rv1988, and Rv3263), as well as Rv1392 as SAM synthase, were selected. Comparing mutations and expression levels of MTases in different strains was accomplished by PCR-sequencing and qRT-PCR. The relative expression levels of these genes were calculated using the 2 -ΔΔCt method. Results: The Rv3919c gene (T to G in codon 341) and Rv1392 gene (G to A in codon 97) were the only mutations found in the INHR strain. In all sensitive and resistant isolates, Rv0645c, Rv3263, Rv2756c, and Rv2966c were overexpressed. However, the expression of Rv1988 and Rv3919c decreased in the sensitive strains, whereas the expression of Rv1694 increased. There was also a decreased expression of Rv1392 in the INHR isolate. Conclusion: The presence of mycobacterial MTases as well as resistance to antibiotics were found to be correlated in M.tb strains. Undoubtedly, there are some MTases that are associated with the virulence process. It is necessary to conduct additional studies to fully explore the impact of mycobacterial MTases within specific strains of M.tb to develop novel diagnostic and treatment strategies.

Keywords: mycobacterium tuberculosis, drug resistance, methyltransferases, s-adenosylmethionine

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2986 Prey-Stage Preference, Functional Response, and Mutual Interference of Amblyseius swirskii Anthias-Henriot on Frankliniella occidentalis Priesner

Authors: Marjan Heidarian Dehkordi, Hossein Allahyari, Bruce Parker, Reza Talaee-Hassanlouei

Abstract:

The Western flower thrips, Frankliniella occidentalis Priesner (Thysanoptera: Thripidae), is a significant pest of many economically important crops. This study evaluated the functional responses, prey-stage preferences and mutual interference of Amblyseius swirskii Anthias-Henriot (Acari: Phytoseiidae) with F. occidentalis as the host under laboratory conditions. The predator species showed no prey stage preference for either prey 1st or 2nd instar. Logistic regression analysis suggested Type II (convex) functional response for the predator species. Consequently, the per capita searching efficiency decreased significantly from 1.2425 to -7.4987 as predator densities increased from 2 to 8. The findings from this study could help select better biological control agents for effective control of F. occidentalis and other pests in vegetable production.

Keywords: biological control, functional responses, mutual interference, prey-stage preferences

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2985 Ab Initio Studies of Structural and Thermal Properties of Aluminum Alloys

Authors: M. Saadi, S. E. H. Abaidia, M. Y. Mokeddem.

Abstract:

We present the results of a systematic and comparative study of the bulk, the structural properties, and phonon calculations of aluminum alloys using several exchange–correlations functional theory (DFT) with different plane-wave basis pseudo potential techniques. Density functional theory implemented by the Vienna Ab Initio Simulation Package (VASP) technique is applied to calculate the bulk and the structural properties of several structures. The calculations were performed for within several exchange–correlation functional and pseudo pententials available in this code (local density approximation (LDA), generalized gradient approximation (GGA), projector augmented wave (PAW)). The lattice dynamic code “PHON” developed by Dario Alfè was used to calculate some thermodynamics properties and phonon dispersion relation frequency distribution of Aluminium alloys using the VASP LDA PAW and GGA PAW results. The bulk and structural properties of the calculated structures were compared to different experimental and calculated works.

Keywords: DFT, exchange-correlation functional, LDA, GGA, pseudopotential, PAW, VASP, PHON, phonon dispersion

Procedia PDF Downloads 487
2984 The Impact of P108L Genetic Variant on Calcium Release and Malignant Hyperthermia Susceptibility

Authors: Mohammed Althobiti, Patrick Booms, Dorota Fiszer, Philip Hopkins

Abstract:

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. MH results from anaesthetics induced breakdown of calcium homeostasis. RYR1 and CACN1AS mutations represent the aetiology in ~70% of the MH population. Previous studies indicate that up to 25% of MH patients carry no variants in these genes. Therefore, the aim of this study is to investigate the relationships between MH susceptibility and genes encoding skeletal muscle Ca2+ channels as well as accessory proteins. The JSRP, encoding JP-45, was previously sequenced and novel genetic variants were identified. The variant p.P108L (c.323C > T) was identified in exon 4 and encodes a change from a proline at amino acid 108 to leucine residue. The variant P108L was detected in two patients out of 50 with 4% frequency in the sample population. The alignment of DNA sequences in different species indicates highly conserved proline sequences involved in the substitution of the P108L variant. In this study, the variant P108L co-segregates with the SNP p.V92A (c.275T > C) at the same exon, both variants being inherited in the same two patients only. This indicates that the two variants may represent a haplotype. Therefore, a set of single nucleotide polymorphisms and statistical analysis will be used to investigate the effects of haplotypes on MH susceptibility. Furthermore, investigating the effect of the P108L variant in combination with RYR1 mutations or other genetic variants in other genes as a combination of two or more genetic variants, haplotypes may then provide stronger genetic evidence indicating that JSRP1 is associated with MH susceptibility. In conclusion, these preliminary results lend a potential modifier role of the variant P108L in JSRP1 in MH susceptibility and further investigations are suggested to confirm these results.

Keywords: JSRP1, malignant hyperthermia, RyR1, skeletal muscle

Procedia PDF Downloads 335