Search results for: gene expression programming (GEP

Authors: Saeideh Salimpour, Sophie-Charlotte Viaux, Ahmed Azab, Mohammed Fazle Baki

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The Facility Layout Problem (FLP) is key to the efficient and cost-effective operation of a system. This paper presents a hybrid heuristic- and mathematical-programming-based approach that divides the problem conceptually into those of clustering and sequencing. First, clusters of vertically aligned facilities are formed, which are later on sequenced horizontally. The developed methodology provides promising results in comparison to its counterparts in the literature by minimizing the inter-distances for facilities which have more interactions amongst each other and aims at placing the facilities with more interactions at the centroid of the shop.

Keywords: clustering-sequencing approach, mathematical modeling, optimization, unequal facility layout problem

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Authors: Pedro Acevedo, Carlos Díaz, Mónica Vázquez, Joel Durán

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This paper describes the design of a pulse generator based on the Programmable System-on-Chip (PSoC) module. In this module, using programmable logic is possible to implement different pulses which are required for ultrasonic applications, either in a single channel or multiple channels. This module can operate with programmable frequencies from 3-74 MHz; its programming may be versatile covering a wide range of ultrasonic applications. It is ideal for low-power ultrasonic applications where PZT or PVDF transducers are used.

Keywords: PSoC, pulse generator, PVDF, ultrasonic transducer

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Authors: Yena Lee, Vassilis M. Charitopoulos, Karthik Thyagarajan, Ian Morris, Jose M. Pinto, Lazaros G. Papageorgiou

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With globalisation, the need to have better coordination of production and distribution decisions has become increasingly important for industrial gas companies in order to remain competitive in the marketplace. In this work, we investigate a problem that integrates production, inventory, and routing decisions in a liquid oxygen supply chain. The oxygen supply chain consists of production facilities, external third-party suppliers, and multiple customers, including hospitals and industrial customers. The product produced by the plants or sourced from the competitors, i.e., third-party suppliers, is distributed by a fleet of heterogenous vehicles to satisfy customer demands. The objective is to minimise the total operating cost involving production, third-party, and transportation costs. The key decisions for production include production and inventory levels and product amount from third-party suppliers. In contrast, the distribution decisions involve customer allocation, delivery timing, delivery amount, and vehicle routing. The optimisation of the coordinated production, inventory, and routing decisions is a challenging problem, especially when dealing with large-size problems. Thus, we present a two-stage procedure to solve the integrated problem efficiently. First, the problem is formulated as a mixed-integer linear programming (MILP) model by simplifying the routing component. The solution from the first-stage MILP model yields the optimal customer allocation, production and inventory levels, and delivery timing and amount. Then, we fix the previous decisions and solve a detailed routing. In the second stage, we propose a column generation scheme to address the computational complexity of the resulting detailed routing problem. A case study considering a real-life oxygen supply chain in the UK is presented to illustrate the capability of the proposed models and solution method. Furthermore, a comparison of the solutions from the proposed approach with the corresponding solutions provided by existing metaheuristic techniques (e.g., guided local search and tabu search algorithms) is presented to evaluate the efficiency.

Keywords: production planning, inventory routing, column generation, mixed-integer linear programming

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Authors: Neha Bhadauria, Indu Gaur, Shilpi Shilpi, Susmita Goswami, Prabir K. Paul

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The aerial surface of plants colonized by Human Enteric Pathogens ()has been implicated in outbreaks of enteric diseases in humans. Practice of organic farming primarily using animal dung as manure and sewage water for irrigation are the most significant source of enteric pathogens on the surface of leaves, fruits and vegetables. The present work aims to have an insight into the molecular mechanism of interaction of Human Enteric Pathogens or their metabolites with cell wall receptors in plants. Tomato plants grown under aseptic conditions at 12 hours L/D photoperiod, 25±1°C and 75% RH were inoculated individually with S. fonticola and K. pneumonia. The leaves from treated plants were sampled after 24 and 48 hours of incubation. The cell wall and cytoplasmic proteins were extracted and isocratically separated on 1D SDS-PAGE. The sampled leaves were also subjected to formaldehyde treatment prior to isolation of cytoplasmic proteins to study protein-protein interactions induced by Human Enteric Pathogens. Protein bands extracted from the gel were subjected to MALDI-TOF-TOF MS analysis. The foremost interaction of Human Enteric Pathogens on the plant surface was found to be cell wall bound receptors which possibly set ups a wave a critical protein-protein interaction in cytoplasm. The study revealed the expression and suppression of specific cytoplasmic and cell wall-bound proteins, some of them being important components of signaling pathways. The results also demonstrated HEP induced rearrangement of signaling pathways which possibly are crucial for adaptation of these pathogens to plant surface. At the end of the study, it can be concluded that controlling the over-expression or suppression of these specific proteins rearrange the signaling pathway thus reduces the outbreaks of food-borne illness.

Keywords: cytoplasmic protein, cell wall-bound protein, Human Enteric Pathogen (HEP), protein-protein interaction

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Authors: Tramuta Clara, Masotti Chiara, Pitti Monica, Adriano Daniela, Battistini Roberta, Serraca Laura, Decastelli Lucia

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Oysters are considered filter organisms, and their raw consumption may increase health risks for consumers: it is often associated with outbreaks of gastroenteritis or enteric illnesses. Most of these foodborne diseases are caused by Vibrio strains, enteric pathogens also involved in the diffusion of genetic determinants of antibiotic resistance and their entrance along the food chain. The European Food Safety Authority (EFSA), during the European Union report on antimicrobial resistance in 2017, focused the attention about the role of food as a possible carrier of antibiotic-resistant bacteria or antibiotic-resistance genes that determine health risks for humans. This study wants to determine antibiotic resistance and antibiotic-resistance genes in Vibrio spp. isolated from Crassostrea gigas oysters collected in the Golfo della Spezia (Liguria, Italy). A total of 47 Vibrio spp. strains were isolated (ISO21872-2:2017) during the summer of 2021 from oysters of Crassostrea gigas. The strains were identified by MALDI-TOF (Bruker, Germany) mass spectrometry and tested for antibiotic susceptibility using a broth microdiluition method (ISO20776-1:2019) using Sensititre EUVSEC plates (Thermo-Fisher Scientific) to obtain the Minimum Inhibitory Concentration (MIC). The strains were tested with PCR-based biomolecular methods, according to previous works, to define the presence of 23 resistance genes of the main classes of antibiotics used in human and veterinary medicine: tet (B), tet (C), tet (D), tet (A), tet (E), tet (G ), tet (K), tet (L), tet (M), tet (O), tet (S) (tetracycline resistance); blaCTX-M, blaTEM, blaOXA, blaSHV (β-lactam resistance); mcr-1 and mcr-2 (colistin resistance); qnrA, qnrB, and qnrS (quinolone resistance); sul1, sul2 and sul3 (sulfonamide resistance). Six different species have been identified: V. alginolyticus 34% (n=16), V. harveyi 28% (n=13), V. fortis 15% (n=7), V. pelagius 8% (n=4), V. parahaemolyticus 11% (n=5) e V. chagasii 4% (n=2). The PCR assays showed the presence of the blaTEM gene on 40% of the strains (n=19). All the other genes were not detected, except for a V. alginolyticus positive for anrS gene. The broth microdiluition method results showed an high level of resistance for ciprofloxacin (62%; n=29), ampicillin (47%; n=22), and colistin (49%; n=23). Furthermore, 32% (n=15) of strains can be considered multiresistant bacteria for the simultaneous presence of resistance for three different antibiotic classes. Susceptibility towards meropenem, azithromycin, gentamicin, ceftazidime, cefotaxime, chloramphenicol, tetracycline and sulphamethoxazole reached 100%. The Vibrio species identified in this study are widespread in marine environments and can cause gastrointerstinal infections after the ingestion of raw fish products and bivalve molluscs. The level of resistance to antibiotics such as ampicillin, ciprofloxacin and colistin can be connected to anthropic factors (industrial, agricultural and domestic wastes) that promote the spread of resistance to these antibiotics. It can be also observed a strong correlation between phenotypic (resistant MIC) and genotypic (positive blaTEM gene) resistance for ampicillin on the same strains, probably due to the transfer of genetic material between bacterial strains. Consumption of raw bivalve molluscs can represent a risk for consumers heath due to the potentially presence of foodborne pathogens, highly resistant to different antibiotics and source of transferable antibiotic-resistant genes.

Keywords: vibrio species, blaTEM genes, antimicrobial resistance, PCR

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Authors: Nurulhikma Md Isa, Intan Elya Suka, Nur Farhana Roslan, Chew Bee Lynn

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The evolutionarily conserved N-end rule pathway marks proteins for degradation by the Ubiquitin Proteosome System (UPS) based on the nature of their N-terminal residue. Proteins with a destabilizing N-terminal residue undergo a series of condition-dependent N-terminal modifications, resulting in their ubiquitination and degradation. Intensive research has been carried out in Arabidopsis previously. The group VII Ethylene Response Factor (ERFs) transcription factors are the first N-end rule pathway substrates found in Arabidopsis and their role in regulating oxygen sensing. ERFs also function as central hubs for the perception of gaseous signals in plants and control different plant developmental including germination, stomatal aperture, hypocotyl elongation and stress responses. However, nothing is known about the role of this pathway during fruit development and ripening aspect. The plant model system Arabidopsis cannot represent fleshy fruit model system therefore tomato is the best model plant to study. PROTEOLYSIS6 (PRT6) is an E3 ubiquitin ligase of the N-end rule pathway. Two homologs of PRT6 sequences have been identified in tomato genome database using the PRT6 protein sequence from model plant Arabidopsis thaliana. Homology search against Ensemble Plant database (tomato) showed Solyc09g010830.2 is the best hit with highest score of 1143, e-value of 0.0 and 61.3% identity compare to the second hit Solyc10g084760.1. Further homology search was done using NCBI Blast database to validate the data. The result showed best gene hit was XP_010325853.1 of uncharacterized protein LOC101255129 (Solanum lycopersicum) with highest score of 1601, e-value 0.0 and 48% identity. Both Solyc09g010830.2 and uncharacterized protein LOC101255129 were genes located at chromosome 9. Further validation was carried out using BLASTP program between these two sequences (Solyc09g010830.2 and uncharacterized protein LOC101255129) to investigate whether they were the same proteins represent PRT6 in tomato. Results showed that both proteins have 100 % identity, indicates that they were the same gene represents PRT6 in tomato. In addition, we used two different RNAi constructs that were driven under 35S and Polygalacturonase (PG) promoters to study the function of PRT6 during tomato developmental stages and ripening processes.

Keywords: ERFs, PRT6, tomato, ubiquitin

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Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat

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We hypothesized that rexinoids such as bexarotene, a selective retinoid X receptor α (RXRα) agonist, may be beneficial for preventing mortality due to inflammation associated with increased expression/activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). Therefore, we investigated effects of bexarotene on the changes in circulating protein levels of iNOS (an index for systemic iNOS expression), myeloperoxidase (MPO) (an index for systemic inflammation), and lactate dehydrogenase (LDH) (an index for systemic tissue injury) in LPS-induced systemic inflammation model resulting in septic shock in rats. Rats were injected with saline (4 ml/kg; i.p.), LPS (10 mg/kg; i.p.), dimethylsulphoxide (4 ml/kg, 0.1%; s.c.) at time 0. Mean arterial blood pressure and heart rate were measured using a tail-cuff device. Bexarotene (0.03, 0.1, 0.3, and 1 mg/kg; s.c.) was administered to separate groups of rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and blood was collected for measurement of serum iNOS, MPO, and LDH protein levels. Blood pressure decreased by 31 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. Bexarotene at 0.3 and 1 mg/kg doses caused 20% mortality 4 h after LPS injection. In the LPS-treated rats, serum iNOS, MPO, and LDH protein levels were increased. Bexarotene only at 0.1 mg/kg dose prevented the LPS-induced hypotension and increased in iNOS, MPO, and LDH protein levels. These data are consistent with the view that a decrease in systemic iNOS levels contributes to the beneficial effect of bexarotene to prevent the hypotension associated with inflammation and tissue injury during rat endotoxemia. [This work was financially supported by The Scientific and Technological Research Council of Turkey (SBAG-109S121)].

Keywords: bexarotene, inflammation, iNOS, lipopolisaccharide, RXRa

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Authors: Abdul Basit Kiani

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Web technologies are growing rapidly in the current era with the increasing development of the web, various novel web technologies emerged to web applications, compared to HTML. JavaScript is the language that provided a dynamic web site which actively interacts with users. The JavaScript language supports the Model View Controller (MVC) architecture that maintains a readable code and clearly separates parts of the program code. Our research is focused on the comparison of the popular JavaScript frameworks; Angular JS, Django, Node JS, Laravel. These frameworks are rely on MVC. In this paper, we will discuss the merits and demerits of each framework, the influence on the application speed, testing methods, for example, JS applications, and methods to advance code security.

Keywords: java script, react, nodejs, htmlcsss

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Authors: Mohd Ali Abbas Zaidi, Meenu Sachdeva, Jonaki Sen

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In the vertebrate embryo, the forebrain anlagen develops from the anterior-most region of the neural tube which is the precursor of the central nervous system (CNS). The roof plate located at the dorsal midline region of the forebrain anlagen, acts as a source of several secreted molecules involved in patterning and morphogenesis of the forebrain. One such key morphogenetic event is the invagination of the forebrain roof plate which results in separation of the single forebrain vesicle into two cerebral hemispheres. Retinoic acid (RA) signaling plays a key role in this process. Blocking RA signaling at the dorsal forebrain midline inhibits dorsal invagination and results in the absence of certain key features of this region, such as thinning of the neuroepithelium and a lowering of cell proliferation. At present we are investigating the possibility of other signaling pathways acting in concert with RA signaling to regulate this process. We have focused on BMP signaling, which we found to be active in a mutually exclusive domain to that of RA signaling within the roof plate. We have also observed that there is a change in BMP signaling activity on modulation of RA signaling indicating an antagonistic relationship between the two. Moreover, constitutive activation of BMP signaling seems to completely inhibit thinning and partially affect invagination, leaving the lowering of cell proliferation in the midline unaffected. We are employing in-silico modeling as well as molecular manipulations to investigate the relative contribution if any, of regional differences in rates of cell proliferation and thinning of the neuroepithelium towards the process of invagination. We have found expression of certain cell adhesion molecules in forebrain roof-plate whose mRNA localization across the thickness of neuroepithelium is influenced by Bmp and RA signaling, giving regional rigidity to roof plate and assisting invagination. We also found expression of certain cytoskeleton modifiers in a localized small domains in invaginating forebrain roof plate suggesting that midline invagination is under control of many factors.

Keywords: bone morphogenetic signaling, cytoskeleton, cell adhesion molecules, forebrain roof plate, retinoic acid signaling

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Authors: Ethel E. Phiri, Lionel Hartzenberg, Percy Chimwamuromba, Emmanuel Nepolo, Jens Kossmann, James R. Lloyd

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Orphan crops are underresearched and underutilized food plant species that have not been categorized as major food crops, but have the potential to be economically and agronomically significant. They have been documented to have the ability to tolerate extreme environmental conditions. However, limited research has been conducted to uncover their potential as food crop species. The New Partnership for Africa’s Development (NEPAD) has classified Marama bean, Tylosema esculentum, as an orphan crop. The plant is one of the 101 African orphan crops that must have their genomes sequenced, assembled, and annotated in the foreseeable future. Marama bean is a perennial leguminous plant that primarily grows in poor, arid soils in southern Africa. The plants produce large tubers that can weigh as much as 200kg. While the foliage provides fodder, the tuber is carbohydrate rich and is a staple food source for rural communities in Namibia. Also, the edible seeds are protein- and oil-rich. Marama Bean plants respond rapidly to increased temperatures and severe water scarcity without extreme consequences. Advances in molecular biology and biotechnology have made it possible to effectively transfer technologies between model- and major crops to orphan crops. In this research, the aim was to assemble the first transcriptomic analysis of Marama Bean RNA-sequence data. Many model plant species have had their genomes sequenced and their transcriptomes assembled. Therefore the availability of transcriptome data for a non-model crop plant species will allow for gene identification and comparisons between various species. The data has been sequenced using the Ilumina Hiseq 2500 sequencing platform. Data analysis is underway. In essence, this research will eventually evaluate the potential use of Marama Bean as a crop species to improve its value in agronomy. data for a non-model crop plant species will allow for gene identification and comparisons between various species. The data has been sequenced using the Ilumina Hiseq 2500 sequencing platform. Data analysis is underway. In essence, this researc will eventually evaluate the potential use of Marama bean as a crop species to improve its value in agronomy.

Keywords: 101 African orphan crops, RNA-Seq, Tylosema esculentum, underutilised crop plants

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Authors: Lívia Pimentel Sant'ana Dourado, Raquel Das Neves Almeida, Luís Henrique Costa Corrêa Neto, Nayara Soares, Kelly Grace Magalhães

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Introduction: Obesity and high-fat diet intake have a crucial impact on immune cells and inflammatory profile, highlighting an emerging realization that obesity is an inflammatory disease. In the present work, we aimed to characterize the role of caspase-1/11 and NLRP3 inflammasome in the establishment of mice obesity and modulation of inflammatory lipid metabolism induced by high fat diet intake. Methods and results: Wild type, caspase-1/11 and NLRP3 knockout mice were fed with standard fat diet (SFD) or high fat diet (HFD) for 90 days. The weight of animals was measured weekly to monitor the weight gain. After 90 days, the blood, peritoneal lavage cells, heart and liver were collected from mice studied here. Cytokines were measured in serum by ELISA and analyzed in spectrophotometry. Lipid antigen presentation molecule CD1d expression, reactive oxygen species (ROS) generation and lipid droplets biogenesis were analyzed in cells from mice peritoneal cavity by flow cytometry. Liver histopathology was performed for morphological evaluation of the organ. The absence of caspase-1/11, but not NLRP3, in mice fed with HFD favored the mice weight gain, increased liver size, induced development of hepatic steatosis and IL-12 secretion in mice compared to mice fed with SFD. In addition, caspase-1/11 knockout mice fed with HFD presented an increased CD1d molecule expression, as well as higher levels of lipid droplets biogenesis and ROS generation compared to wild type mice also fed with HFD. Conclusion: Our data suggest that caspase-1/11 knockout mice have greater susceptibility to obesity as well as increased activation of lipid metabolism and inflammatory markers.

Keywords: caspase 1, caspase 11, inflamassome, obesity, lipids

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Authors: Mrinal Kanti Bhowmik, Debanjana Debnath Jr., Debotosh Bhattacharjee

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A facial expression is undeniably the human manners. It is a significant channel for human communication and can be applied to extract emotional features accurately. People in pain often show variations in facial expressions that are readily observable to others. A core of actions is likely to occur or to increase in intensity when people are in pain. To illustrate the changes in the facial appearance, a system known as Facial Action Coding System (FACS) is pioneered by Ekman and Friesen for human observers. According to Prkachin and Solomon, a set of such actions carries the bulk of information about pain. Thus, the Prkachin and Solomon pain intensity (PSPI) metric is defined. So, it is very important to notice that facial expressions, being a behavioral source in communication media, provide an important opening into the issues of non-verbal communication in pain. People express their pain in many ways, and this pain behavior is the basis on which most inferences about pain are drawn in clinical and research settings. Hence, to understand the roles of different pain behaviors, it is essential to study the properties. For the past several years, the studies are concentrated on the properties of one specific form of pain behavior i.e. facial expression. This paper represents a comprehensive study on pain assessment that can model and estimate the intensity of pain that the patient is suffering. It also reviews the historical background of different pain assessment techniques in the context of painful expressions. Different approaches incorporate FACS from psychological views and a pain intensity score using the PSPI metric in pain estimation. This paper investigates in depth analysis of different approaches used in pain estimation and presents different observations found from each technique. It also offers a brief study on different distinguishing features of real and fake pain. Therefore, the necessity of the study lies in the emerging fields of painful face assessment in clinical settings.

Keywords: facial action coding system (FACS), pain, pain behavior, Prkachin and Solomon pain intensity (PSPI)

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Authors: Zeynep Sener, Mehtap Dursun

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Supplier evaluation and selection is one of the most important components of an effective supply chain management system. Due to the expanding competition in healthcare, selecting the right medical device suppliers offers great potential for increasing quality while decreasing costs. This paper proposes a fuzzy decision making approach for medical supplier selection. A real-world medical device supplier selection problem is presented to illustrate the application of the proposed decision methodology.

Keywords: fuzzy decision making, fuzzy multiple objective programming, medical supply chain, supplier selection

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Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Sammani Danwawu Abdullahi

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Vertex Enumeration Algorithms explore the methods and procedures of generating the vertices of general polyhedra formed by system of equations or inequalities. These problems of enumerating the extreme points (vertices) of general polyhedra are shown to be NP-Hard. This lead to exploring how to count the vertices of general polyhedra without listing them. This is also shown to be #P-Complete. Some fully polynomial randomized approximation schemes (fpras) of counting the vertices of some special classes of polyhedra associated with Down-Sets, Independent Sets, 2-Knapsack problems and 2 x n transportation problems are presented together with some discovered open problems.

Keywords: counting with uncertainties, mathematical programming, optimization, vertex enumeration

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Authors: Abdulmajid Mukhtar Afat

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This paper aims at introducing finite automata theory, the different ways to describe regular languages and create a program to implement the subset construction algorithms to convert nondeterministic finite automata (NFA) to deterministic finite automata (DFA). This program is written in c++ programming language. The program reads FA 5tuples from text file and then classifies it into either DFA or NFA. For DFA, the program will read the string w and decide whether it is acceptable or not. If accepted, the program will save the tracking path and point it out. On the other hand, when the automation is NFA, the program will change the Automation to DFA so that it is easy to track and it can decide whether the w exists in the regular language or not.

Keywords: finite automata, subset construction, DFA, NFA

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Authors: Jiraporn Rojtinnakorn

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ICAM-2 (intercellular adhesion molecule 2) or CD102 (Cluster of Differentiation 102) is type I trans-membrane glycoproteins, composing 2-9 immunoglobulin-like C2-type domains. ICAM-2 plays the particular role in immune response and cell surveillance. It is concerned in innate and specific immunity, cell survival signal, apoptosis, and anticancer. EST clone of ICAM-2, from P. gigas blood cell EST libraries, showed high identity to human ICAM-2 (92%) with conserve region of ICAM N-terminal domain and part of Ig superfamily. Gene and protein of ICAM-2 has been founded in mammals. This is the first report of ICAM-2 in fish.

Keywords: ICAM-2, CD102, Pangasianodon gigas, antitumor

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Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: D. Hammad, D. P. Tonge

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Rheumatoid arthritis (RA) is a disabling and common autoimmune disease during which the body's immune system attacks healthy tissues. This results in complicated and long-lasting actions being carried out by the immune system, which typically only occurs when the immune system encounters a foreign object. In the case of RA, the disease affects millions of people and causes joint inflammation, ultimately leading to the destruction of cartilage and bone. Interestingly, the disease mechanism still remains unclear. It is likely that RA occurs as a result of a complex interplay of genetic and environmental factors including an imbalance in the microorganism population inside our body. The human microbiome or microbiota is an extensive community of microorganisms in and on the bodies of animals, which comprises bacteria, fungi, viruses, and protozoa. Recently, the development of molecular techniques to characterize entire bacterial communities has renewed interest in the involvement of the microbiome in the development and progression of RA. We believe that an imbalance in some of the specific bacterial species in the gut, mouth and other sites may lead to atopobiosis; the translocation of these organisms into the blood, and that this may lead to changes in immune system status. The aim of this study was, therefore, to characterize the microbiome of RA serum samples in comparison to healthy control subjects using 16S rRNA gene amplification and sequencing. Serum samples were obtained from healthy control volunteers and from patients with RA both prior to, and following treatment. The bacterial community present in each sample was identified utilizing V4 region 16S rRNA amplification and sequencing. Bacterial identification, to the lowest taxonomic rank, was performed using a range of bioinformatics tools. Significantly, the proportions of the Lachnospiraceae, Ruminococcaceae, and Halmonadaceae families were significantly increased in the serum of RA patients compared with healthy control serum. Furthermore, the abundance of Bacteroides and Lachnospiraceae nk4a136_group, Lachnospiraceae_UGC-001, RuminococcaceaeUCG-014, Rumnococcus-1, and Shewanella was also raised in the serum of RA patients relative to healthy control serum. These data support the notion of a blood microbiome and reveal RA-associated changes that may have significant implications for biomarker development and may present much-needed opportunities for novel therapeutic development.

Keywords: blood microbiome, gut and oral bacteria, Rheumatoid arthritis, 16S rRNA gene sequencing

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Authors: Rada Somkhuean, Sa-aat Niwitpong, Suparat Niwitpong

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This paper presents the generalized p-values for testing the difference between two future population means when the variances are unknown, in both cases for when the variances are equal and unequal. We also derive a closed form expression of the upper bound of the proposed generalized p-value.

Keywords: generalized p-value, two future population means, upper bound, variances

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Authors: K. M. Anusha, R. Krishnaveni

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Crossing a decade of the 21st century, the paradigm of human resources can be seen evolving with the strategic gene induced into it. There seems to be a radical shift descending as the corporate sector calls on its HR team to become strategic rather than administrative. This transferal eventually requires the metrics employed by these HR teams not to be just operationally reactive but to be aligned to an evidence-based strategic thinking. Realizing the growing need for a prescriptive metric model for effective HR analytics, this study has designed a conceptual framework for a basic metric model that can assist IT-HRM professionals to transition to a practice of evidence-based decision-making to enhance organizational performance.

Keywords: metric model, evidence based HR, HR analytics, strategic HR practices, IT sector

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Authors: J. Fernandez de Canete

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Object-oriented modeling is spreading in the current simulation of physiological systems through the use of the individual components of the model and its interconnections to define the underlying dynamic equations. In this paper, we describe the use of both the SIMSCAPE and MODELICA simulation environments in the object-oriented modeling of the closed-loop cardiovascular system. The performance of the controlled system was analyzed by simulation in light of the existing hypothesis and validation tests previously performed with physiological data. The described approach represents a valuable tool in the teaching of physiology for graduate medical students.

Keywords: object-oriented modeling, SIMSCAPE simulation language, MODELICA simulation language, cardiovascular system

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Authors: Madhulika Pathak, Polani Seshagiri, Vani Venkatappa

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Blastocyst hatching is an indispensable process for successful implantation. One of the major reasons for implantation failure in IVF clinic is poor quality of embryo, which are not development/hatching-competent. Therefore, attempts are required to develop or enhance the culture system with a molecule recapitulating the autocrine/paracrine factors containing the environment of in-vivo endometrial milieu. We have tried to explore the functional molecules involved in the hamster hatching phenomenon. Blastocyst hatching is governed by several molecules that are entwined and regulate this process, among which cytokines are known to be expressed and are still least explored. Two of such cytokines we have used for our study are IL-1β and its natural antagonist IL-1ra to understand the functional dynamics of cytokines involved in the hatching process. Using hamster, an intriguing experimental model for hatching behavior, we have shown the mRNA (qPCR) and protein (ICC) expression of IL-1β, IL-1ra and IL-1 receptor type 1 throughout all the stages of morula, blastocyst and hatched blastocyst. Post-asserting the expression, the functional role is shown by supplementation studies, where IL-1β supplementation showed enhancement in hatching level (IL-1β treated: 84.1 ± 4.2% vs control: 63.7 ± 3.1 %, N=11), further confirmed by the diminishing effect of IL-1ra on hatching rate (IL-1ra treated: 27.5 ± 11.1% vs control: 67.9 ± 3.1%). The exogenous supplementation of IL-1ra decreased the survival rate of embryos and affected the viability in dose-dependent manner, establishing the importance of IL-1β in blastocyst cell survival. Previously, the cathepsin L and B were established as the proteases that were involved in the hamster hatching process. The inducing effect of IL-1β was correlated with enhanced mRNA level, as analyzed by qPCR, for both CAT L (by 1.9 ± 0.5 fold) and CAT B (by 3.5 ± 0.1) fold which was diminished in presence of IL-1ra (Cat L by 88 percent and Cat B by 94 percent. Moreover, using a specific fluorescent substrate-based assay kit, the enzymatic activity of these proteases was found to be increased in presence of IL-1β (Cat L by 2.1 ± 0.1 fold and CAT B by 2.3 ± 0.7 fold) and was curtailed in presence of IL-1ra. These observations provide functional insights with respect to the involvement of cytokines in the hatching process. This has implications in understanding the hatching biology and improving the embryo development quality in IVF clinics.

Keywords: Blastocyst, Cytokines, Hatching, Interleukin

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Authors: Joulié Aurélien, Jourdain Elsa, Bailly Xavier, Gasqui Patrick, Yang Elise, Leblond Agnès, Rousset Elodie, Sidi-Boumedine Karim

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Q fever is a worldwide zoonosis caused by the gram-negative obligate intracellular bacterium Coxiella burnetii. Following the recent outbreaks in the Netherlands, a hyper virulent clone was found to be the cause of severe human cases of Q fever. In livestock, Q fever clinical manifestations are mainly abortions. Although the abortion rates differ between ruminant species, C. burnetii’s virulence remains understudied, especially in enzootic areas. In this study, the infectious potential of three C. burnetii isolates collected from French farms of small ruminants were compared to the reference strain Nine Mile (in phase II and in an intermediate phase) using an in vivo (CD1 mice) model. Mice were challenged with 105 live bacteria discriminated by propidium monoazide-qPCR targeting the icd-gene. After footpad inoculation, spleen and popliteal lymph node were harvested at 10 days post-inoculation (p.i). The strain invasiveness in spleen and popliteal nodes was assessed by qPCR assays targeting the icd-gene. Preliminary results showed that the avirulent strains (in phase 2) failed to pass the popliteal barrier and then to colonize the spleen. This model allowed a significant differentiation between strain’s invasiveness on biological host and therefore identifying distinct virulence profiles. In view of these results, we plan to go further by testing fifteen additional C. burnetii isolates from French farms of sheep, goat and cattle by using the above-mentioned in vivo model. All 15 strains display distant MLVA (multiple-locus variable-number of tandem repeat analysis) genotypic profiles. Five of the fifteen isolates will bee also tested in vitro on ovine and bovine macrophage cells. Cells and supernatants will be harvested at day1, day2, day3 and day6 p.i to assess in vitro multiplication kinetics of strains. In conclusion, our findings might help the implementation of surveillance of virulent strains and ultimately allow adapting prophylaxis measures in livestock farms.

Keywords: Q fever, invasiveness, ruminant, virulence

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Hussaini Garba Mohammed

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Background/Significance: The lack of data gathering is affecting NGOs world-wide in general to have good data information about educational and health related issues among communities in any country and around the world. For example, HIV/AIDS smoking (Tuberculosis diseases) and COVID-19 virus carriers is becoming a serious public health problem, especially among old men and women. But there is no full details data survey assessment from communities, villages, and rural area in some countries to show the percentage of victims and patients, especial with this world COVID-19 virus among the people. These data are essential to inform programming targets, strategies, and priorities in getting good information about data gathering in any society.

Keywords: reliable information, data assessment, data mining, data communication

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Authors: Vaclav Sadilek, Miroslav Vorechovsky

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The paper deals with the classical fiber bundle model of equal load sharing, sometimes referred to as the Daniels' bundle or the democratic bundle. Daniels formulated a multidimensional integral and also a recursive formula for evaluation of the strength cumulative distribution function. This paper describes three algorithms for evaluation of the recursive formula and also their implementations with source codes in high-level programming language Python. A comparison of the algorithms are provided with respect to execution time. Analysis of orders of magnitudes of addends in the recursion is also provided.

Keywords: equal load sharing, mpmath, python, strength of Daniels' bundle

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Authors: Hadas Hirsch

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Clothing is aimed at concealing and revealing the body, protecting it, and manifesting religious, political, and social declarations. The material and symbolic meanings of clothing and its raw materials are evaluated through the context of their social, cultural, and religious systems. The raw materials for clothing that were frequent and familiar in the 7th century Arab Peninsula were wool, leather, cotton, and some kinds of silk. The spread of the Muslim empire and the intersections with other religions and cultures enable the trickling of new raw materials that were unknown to Muslims or unaccepted. The sources for this research are hadith collections that discuss in details various kinds of textiles and their origin, together with a legal explanation that permits or prohibits its use. The paper will describe and analyze this discussion by contextualizing it in social, religious, and cultural reality that creates a structure of socio-religious dependency. The aim is not to identify, catalogue, and technically analyze fabrics but to reveal their role in Muslims’ life as a means of creating dependency for the community and setting borders inside and outside. The analysis is built upon a scale that starts with the most recommended raw materials, then comes the permitted ones and, in the end, the prohibited raw materials. This mapping will provide an insight into the ways textiles, as a cultural medium, help to shape and redefine identities and, at the same time, enable a sphere for creative expression within socio-cultural and religious limits and context. To sum up, hadith literature has the main role is characterizing Muslim clothing, from garments to textiles and colors, including multiple variations and contradicting aspects. The Muslim style of clothing and, in particular, textiles is a manifestation of the socio-religious structure of dependency that creates differentiated Muslim identity together with subdivision of gendered groups. Some other aspects are the tension between authenticity and imitation and the jurists’ pragmatic and practice attitude that enables an individual sphere of expression within the limits of jurisprudence.

Keywords: Hadith, jurisprudence, medieval Islam, material culture

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Authors: Awais Asif

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This article investigates fixed point theorems of Chatterjea type F-contraction in the setting of F-metric space. We relax the conditions of F-contraction and define modified F-contraction for two mappings. The study provides fixed point results for both single-valued and multivalued mappings. The results are further extended to common fixed point theorems for two mappings. Moreover, to discuss the applicability of our results, an application is provided, which shows the role of our results in finding the solution to functional equations in dynamic programming. Our results generalize and extend the existing results in the literature.

Keywords: Chatterjea type F-contraction, F-cauchy sequence, F-convergent, multi valued mappings

Procedia PDF Downloads 131