Search results for: human transmembrane transporter proteins

Authors: Kanchan Yadav, Ai-Chuan Chou, Rajesh Kumar Ulaganathan, Hua-De Gao, Hsien-Ming Lee, Chien-Yuan Pan, Yit-Tsong Chen

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Optogenetics is an innovative technology now widely adopted by researchers in different fields of the biological sciences. However, due to the weak tissue penetration capability of the short wavelengths used to activate light-sensitive proteins, an invasive light guide has been used in animal studies for photoexcitation of target tissues. Upconverting nanoparticles (UCNPs), which transform near-infrared (NIR) light to short-wavelength emissions, can help address this issue. To improve optogenetic performance, we enhance the target selectivity for optogenetic controls by specifically conjugating the UCNPs with light-sensitive proteins at a molecular level, which shortens the distance as well as enhances the efficiency of energy transfer. We tagged V5 and Lumio epitopes to the extracellular N-terminal of channelrhodopsin-2 with an mCherry conjugated at the intracellular C-terminal (VL-ChR2m) and then bound NeutrAvidin-functionalized UCNPs (NAv-UCNPs) to the VL-ChR2m via a biotinylated antibody against V5 (bV5-Ab). We observed an apparent energy transfer from the excited UCNP (donor) to the bound VL-ChR2m (receptor) by measuring emission-intensity changes at the donor-receptor complex. The successful patch-clamp electrophysiological test and an intracellular Ca2+ elevation observed in the designed UCNP-ChR2 system under optogenetic manipulation confirmed the practical employment of UCNP-assisted NIR-optogenetic functionality. This work represents a significant step toward improving therapeutic optogenetics.

Keywords: Channelrhodopsin-2, near infrared, optogenetics, upconverting nanoparticles

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Authors: Ibraheem Husain, Abul Kalam Najmi, Karishma Chester

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First-in-human (FIH) studies are a critical step in clinical development of any molecule that has shown therapeutic promise in preclinical evaluations, since preclinical research and safety studies into clinical development is a crucial step for successful development of monoclonal antibodies for guidance in pharmaceutical industry for the treatment of human diseases. Therefore, comparison between USFDA and nine pharmacologically guided approaches (PGA) (simple allometry, maximum life span potential, brain weight, rule of exponent (ROE), two species methods and one species methods) were made to determine maximum recommended starting dose (MRSD) for first in human clinical trials using four drugs namely Denosumab, Bevacizumab, Anakinra and Omalizumab. In our study, the predicted pharmacokinetic (pk) parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The study indicated that the clearance and volume of distribution of antibodies can be predicted with reasonable accuracy in human and a good estimate of first human dose can be obtained from the predicted human clearance and volume of distribution. A pictorial method evaluation chart was also developed based on fold errors for simultaneous evaluation of various methods.

Keywords: clinical pharmacology (CPH), clinical research (CRE), clinical trials (CTR), maximum recommended starting dose (MRSD), clearance and volume of distribution

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Authors: Orsolya Horvath, Laszlo Deres, Krisztian Eros, Katalin Ordog, Tamas Habon, Balazs Sumegi, Kalman Toth, Robert Halmosi

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Introduction: Oxidative stress induces an imbalance in mitochondrial fusion and fission processes, finally leading to cell death. The two antioxidant molecules, BGP-15 and L2286 have beneficial effects on mitochondrial functions and on cellular oxidative stress response. In this work, we studied the effects of these compounds on the processes of mitochondrial quality control. Methods: We used H9c2 cardiomyoblast and isolated neonatal rat cardiomyocytes (NRCM) for the experiments. The concentration of stressors and antioxidants was beforehand determined with MTT test. We applied 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) in 125 µM, 400 µM and 800 µM concentrations for 4 and 8 hours on H9c2 cells. H₂O₂ was applied in 150 µM and 300 µM concentration for 0.5 and 4 hours on both models. L2286 was administered in 10 µM, while BGP-15 in 50 µM doses. Cellular levels of the key proteins playing role in mitochondrial dynamics were measured in Western blot samples. For the analysis of mitochondrial network dynamics, we applied electron microscopy and immunocytochemistry. Results: Due to MNNG treatment the level of fusion proteins (OPA1, MFN2) decreased, while the level of fission protein DRP1 elevated markedly. The levels of fusion proteins OPA1 and MNF2 increased in the L2286 and BGP-15 treated groups. During the 8 hour treatment period, the level of DRP1 also increased in the treated cells (p < 0.05). In the H₂O₂ stressed cells, administration of L2286 increased the level of OPA1 in both H9c2 and NRCM models. MFN2 levels in isolated neonatal rat cardiomyocytes raised considerably due to BGP-15 treatment (p < 0.05). L2286 administration decreased the DRP1 level in H9c2 cells (p < 0.05). We observed that the H₂O₂-induced mitochondrial fragmentation could be decreased by L2286 treatment. Conclusion: Our results indicated that the PARP-inhibitor L2286 has beneficial effect on mitochondrial dynamics during oxidative stress scenario, and also in the case of directly induced DNA damage. We could make the similar conclusions in case of BGP-15 administration, which, via reducing ROS accumulation, propagates fusion processes, this way aids preserving cellular viability. Funding: GINOP-2.3.2-15-2016-00049; GINOP-2.3.2-15-2016-00048; GINOP-2.3.3-15-2016-00025; EFOP-3.6.1-16-2016-00004; ÚNKP-17-4-I-PTE-209

Keywords: H9c2, mitochondrial dynamics, neonatal rat cardiomyocytes, oxidative stress

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Authors: Albina V. Moskvicheva, Gevorg G. Kazarian, Anna R. Valeeva, Marina A. Efimova, Malik N. Mukminov, Eduard A. Shuralev, Rustam Kh. Ravilov, Kamil S. Khaertynov

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Improving the early diagnosis of tuberculosis and solving a number of problems associated with the differential diagnosis of Mycobacterium bovis infection, nonspecific tuberculin reactions caused by sensitization of the body by non-tuberculosis mycobacteria, is urgent. The filtrates and extracts of M. bovis cell surface components are promising antigens with diagnostic potential. The purpose of this study was to isolate and characterize antigenic proteins and determine the dominant M. bovis antigens recognized by the humoral immune system. The mycobacterial cells were homogenized on FastPrep-24. Gel-filtration chromatography was used to fractionate the lysates of cell surface component extracts and proteins isolated from M. bovis culture supernatant. The separated fractions were analyzed using two-dimensional gel electrophoresis followed by determination of antigen serological activity using immunoblot with specific hyperimmune rabbit blood serum. As a result of electrophoretic separation of components by molecular weight, 23 antigen fractions were obtained. Analysis of densitograms showed that the fractions contained two zones of antigens with pronounced serological activity, corresponding to molecular weights of 28 and 21 kDa. The high serological activity of the 28 kDa antigen was established by immunoblot using hyperimmune blood sera. Separated and characterized by M. bovis specific antigen with a molecular weight of 28 kDa was added to the collection of specific marker antigens for M. bovis.

Keywords: antigen, gel-filtration chromatography, immunoblot, Mycobacterium bovis

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Authors: A. T. Omarova, G. N. Nakipova

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This article discusses the principles of object-oriented human capital development using the technology program. Also the article includes priorities of the strategy of industrial-innovative development of Kazakhstan in conditions of integration activity into the world community. The article shows the tasks of human resource management in the implementation of industrial and innovation development, particularities of Kazakhstan's theory of management staff, as well as due to the specificity of the Kazakhstan authorities. In the article, we have considered the factors which are affecting the people in the organization and also have considered mechanisms of HRM within organization in the conditions of innovative development in Kazakhstan.

Keywords: programming, management of human resources, innovation, investment, innovation process, HRD model, innovative development, integration, management, transformation, economic potential, competitiveness

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Authors: Eli Maikoto Agison

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The relevance of enhancing human resource development in entrepreneurship for economic growth and development cannot be overemphasized since no country can grow and developed economically above its citizenry. Africa for example and Nigeria in particular is lagging behind in terms of economic growth and development when compared with other developed countries of the world like China, Japan, Singapore, USA etc. The reason is not farfetched from these developed countries efforts in enhancing human resource development in entrepreneurship education. For Nigeria to attain this height of development, this paper discusses the meaning of human resource development in entrepreneurship as the framework for helping employees develop their personal and organizational skills knowledge and abilities as this includes employee training, career development and performance management to enable an organization achieve a set goal. While entrepreneurship education is seen as an aspect of education that is geared towards self-reliance, some of the challenges faced in the enhancement of human resource development in Nigeria include inadequate training and re-training of instructors of entrepreneurship in higher education. Insufficient funding to higher education were discussed and recommendations to include adequate funding, training and re-training of instructors of higher education be enhanced as some of the ways forward.

Keywords: economic development, economic growth, entrepreneurship education, human resource development

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Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

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Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis, were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands cannabinol and cannabidiol were obtained from PubChem. After a necessary process of the obtained files, AutoDock Vina was used to performing molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: Bo-Wei Song, Yun-Jung Lee

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This paper presents an intention interface and controller for a wire-driven heavy object lifting system that assists the operator with moving a heavy object. The handler is designed to allow a comfortable working posture for the operator. Plus, as a human assistive system, the operator is involved in the control loop, where a fuzzy control system is used to consider the human control characteristics. The effectiveness and performance of the proposed system are proved by experiments.

Keywords: fuzzy controller, handler design, heavy object lifting system, human-assistive device, human-in-the-loop system

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Authors: Yaowen Sheng, Jiuxian Liu

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In order to analyze the pedestrian bridge dynamic characteristics and degree of comfortability, the finite element method and live load time history method is used to calculate the dynamic response of the bridge. The example bridge’s dynamic characteristics and degree of human comfortability need to be analyzed. The project background is a three-way intersection. The intersection has three side blocks. An intersection bridge is designed to help people cross the streets. The finite element model of the bridge is established by the Midas/Civil software, and the analysis of the model is done. The strength, stiffness, and stability checks are also completed. Apart from the static analysis of the bridge, the dynamic analysis of the bridge is also completed to avoid the problems resulted from vibrations. The results show that the pedestrian bridge has different dynamic characteristics compared to other normal bridges. The degree of human comfortability satisfies the requirements of Chinese and British specifications. The live load time history method can be used to calculate the dynamic response of the bridge.

Keywords: pedestrian bridge, steel box girder, human-induced vibration, finite element analysis, degree of human comfortability

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Authors: Sofia Papadimitriou

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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.

Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score

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Authors: Mohammed Sabbah, Prospero Di Pierro, Raffaele Porta

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Protein-based edible films and coatings have attracted an increasing interest in recent years since they might be used to protect pharmaceuticals or improve the shelf life of different food products. Among them, several plant proteins represent an abundant, inexpensive and renewable raw source. These natural biopolymers are used as film forming agents, being able to form intermolecular linkages by various interactions. However, without the addition of a plasticizing agent, many biomaterials are brittle and, consequently, very difficult to be manipulated. Plasticizers are generally small and non-volatile organic additives used to increase film extensibility and reduce its crystallinity, brittleness and water vapor permeability. Plasticizers normally act by decreasing the intermolecular forces along the polymer chains, thus reducing the relative number of polymer-polymer contacts, producing a decrease in cohesion and tensile strength and thereby increasing film flexibility allowing its deformation without rupture. The most commonly studied plasticizers are polyols, like glycerol (GLY) and some mono or oligosaccharides. In particular, GLY not only increases film extensibility but also migrates inside the film network often causing the loss of desirable mechanical properties of the material. Therefore, replacing GLY with a different plasticizer might help to improve film characteristics allowing potential industrial applications. To improve film properties, it seemed of interest to test as plasticizers some cationic small molecules like polyamines (PAs). Putrescine, spermidine (SPD), and spermine are PAs widely distributed in nature and of particular interest for their biological activities that may have some beneficial health effects. Since PAs contains amino instead of hydroxyl functional groups, they are able to trigger ionic interactions with negatively charged proteins. Bitter vetch (Vicia ervilia; BV) is an ancient grain legume crop, originated in the Mediterranean region, which can be found today in many countries around the world. This annual Vicia genus shows several favorable features, being their seeds a cheap and abundant protein source. The main objectives of this study were to investigate the effect of different concentrations of SPD on the mechanical and permeability properties of films prepared with native or heat denatured BV proteins in the presence of different concentrations of SPD and/or GLY. Therefore, a BV seed protein concentrate (BVPC), containing about 77% proteins, was used to prepare film forming solutions (FFSs), whereas GLY and SPD were added as film plasticizers, either singly or in combination, at various concentrations. Since a primary plasticizer is generally defined as a molecule that when added to a material makes it softer, more flexible and easier to be processed, our findings lead to consider SPD as a possible primary plasticizer of protein-based films. In fact, the addition of millimolar concentrations of SPD to BVPC FFS allowed obtaining handleable biomaterials with improved properties. Moreover, SPD can be also considered as a secondary plasticizer, namely an 'extender', because of its ability even to enhance the plasticizing performance of GLY. In conclusion, our studies indicate that innovative edible protein-based films and coatings can be obtained by using PAs as new plasticizers.

Keywords: edible films, glycerol, plasticizers, polyamines, spermidine

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Authors: Omid Kalatpour, Mohammadreza Ajdari

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This article studied the possible causes of human error-induced incidents in the petrochemical industry maintenance activities by using Human Factors Analysis and Classification System (HFACS). The purpose of the study was anticipating and identifying these causes and proposing corrective and preventive actions. Maintenance department in a petrochemical company was selected for research. A checklist of human error-induced incidents was developed based on four HFACS main levels and nineteen sub-groups. Hierarchical task analysis (HTA) technique was used to identify maintenance activities and tasks. The main causes of possible incidents were identified by checklist and recorded. Corrective and preventive actions were defined depending on priority. Analyzing the worksheets of 444 activities in four levels of HFACS showed 37.6% of the causes were at the level of unsafe actions, 27.5% at the level of unsafe supervision, 20.9% at the level of preconditions for unsafe acts and 14% of the causes were at the level of organizational effects. The HFACS sub-groups showed errors (24.36%) inadequate supervision (14.89%) and violations (13.26%) with the most frequency. According to findings of this study, increasing the training effectiveness of operators and supervision improvement respectively are the most important measures in decreasing the human error-induced incidents in petrochemical industry maintenance.

Keywords: human error, petrochemical industry, maintenance, HFACS

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Authors: Mulata Haile Nega, Derebew Fikadu Berhe, Vera Ribeiro Marques

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There is no epidemiologic data on this gene polymorphism in several countries. Therefore, this study aimed to assess the genotype and allele frequencies of the gene variant in three countries. This study involved healthy individuals from Colombia, Mozambique, and Portugal. Genomic DNA was isolated from blood samples using the Qiamp DNA Extraction Kit (Qiagen). The isolated DNA was genotyped using Polymerase Chain Reaction (PCR) - Restriction Fragment Length Polymorphism. Microstat and GraphPad quick cal software were used for the Chi-square test and evaluation of Hardy-Weinberg equilibrium, respectively. A total of 181 individuals’ blood sample was analyzed. Overall, TT (74.0%) genotype was the highest, and CC (7.8%) was the lowest. Country wise genotypic frequencies were Colombia 47(70.2%) TT, 12(17.9%) TC and 8(11.9%) CC; Mozambique 47(88.7%) TT, 5(9.4%) TC, and 1(1.9%) CC; and Portugal 40(65.6%) TT, 16(26.2%) TC, and 5(8.2%) CC. The reference (T) allele was highest among Mozambicans (93.4%) compared to Colombians (79.1%) and Portuguese (78.7%). Mozambicans showed statistically significant genotypic and allelic frequency differences compared to Colombians (p<0.01) and Portuguese (p <0.01). Overall and country-wise, the CC genotype was less frequent and relatively high for Colombians and Portuguese populations. This finding may imply statins risk-benefit variability associated with CC genotype among these populations that needs further understanding.

Keywords: c.521T>C, polymorphism, SLCO1B1, SNP, statins

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Authors: Hafiza Javaria Ashraf, Xinghong Wang, Zhanghong Shi, Youming Hou

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Insect’s innate immunity depends on a variety of defense responses for the recognition of invading pathogens. Pathogen recognition involves particular proteins known as pattern recognition receptors (PRRs). These PRRs interact with pathogen-associated molecular patterns (PAMPs) present on the surface of pathogens to distinguish between self and non-self. C-type lectins (CTLs) belong to a superfamily of PPRs which involved in insect immunity and defense mechanism. Rhynchophorus ferrugineus Olivier is a devastating pest of Palm cultivations in China. Although studies on R. ferrugineus immune mechanism and host defense have conducted, however, the role of CTL in immune responses of R. ferrugineus remains elusive. Here, we report RfCTL, which is a secreted protein containing a single-CRD domain. The open reading frame (ORF) of CTL is 226 bp, which encodes a putative protein of 168 amino acids. Transcript expression analysis revealed that RfCTL highly expressed in immune-related tissues, i.e., hemolymph and fat body. The abundance of RfCTL in the gut and fat body dramatically increased upon Staphylococcus aureus and Escherichia coli bacterial challenges, suggesting a role in defense against gram-positive and gram-negative bacterial infection. Taken together, we inferred that RfCTL might be involved in the immune defense of R. ferrugineus and established a solid foundation for future studies on R. ferrugineus CTL domain proteins for better understanding of insect immunity.

Keywords: biological invasion, c-type lectin, insect immunity, Rhynchophorus ferrugineus Oliver

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Authors: Alkhathlan Mansour

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Current research aims at achieving the organizational development in the educational institutions in the governorate of Al-Kharj through the human performance technology (HPT) model that is named; “The Intellectual Model to improve human performance”. To achieve the goal of this research, it tools -that it is consisting of targeted questionnaires to research sample numbered (120)- have been set up. This sample is represented in; department managers in Prince Sattam Bin Abdulaziz University (50), educational supervisors in the Department of Education (40), school administrators in the governorate (30), and the views of education experts through personal interviews in the proposal to achieve organizational development through the intellectual model to improve human performance. Among the most important research results is that there are many obstacles prevent the organizational development in the educational institutions, so the research suggested a model to achieve organizational development through human performance technologies, as well as the researcher recommended through the results of his research that the administrators have to take into account the justice in the distribution of incentives to employees of educational institutions and training leaders in educational institutions on organizational development strategies and working on the preparation of experts of organizational development in the educational institutions to develop the necessary policies and procedures of each institution.

Keywords: human performance, development, education, organizational

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Authors: Philip Tachin

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Despite the positive contributions that religion has impacted human society, religious discrimination and violence also have been growing globally with extreme negative effects on human life and social relationships. Believers in religious extremism are motivated by a sense of exhibiting true religious piety in which case they do not only withhold their practical benevolence from those who do not belong to their faith but they even seek the elimination of other adherents from human existence. This phenomenon has a very high magnitude in Nigeria over the years, which deserves more research for the purpose of finding sustainable solutions to the problem. Calvin believed that true religious piety must, among other things, be categorized in personal and corporate positive social actions that esteem human needs irrespective of ethnic, ideological and belief differences. It is therefore appropriate to pose the following questions: Should true religious piety be seen in terms of how the actions of adherents positively impact human society? Could Calvin’s idea on this issue be very significant and helpful in the context of the Nigerian situation? In answering these questions, this research will limit its investigation to Calvin’s Institutes and some of his Commentaries. The goal of this research is to offer an instructive orientation to the readers that will help in building a more tolerable, peaceful, and a free and virtuous society.

Keywords: Calvin, human good, religious piety, virtuous society

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Authors: Arubi Thompson Abari

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Globally, a writer is absolutely necessary to the society, for he mirrors and projects the society, grumbles and protects against the ills that hinders its development. A writer is committed to the language, social-cultural, political and economic factors that determine the sustenance of human dignity in the society. In this 21st century. The literary artist holds literature as a tool for the restoration and sustenance of human dignity. In Nigeria, literature is politically committed because colonialism gives birth to the modern Nigerian literature. Literature thus was regarded as one of the greatest weapons against colonialism in Nigeria. Nigerian literature is aimed at the restoration and sustenance of the dignity of Nigerians in the 21st century. A literary writer is a member of the society and his sensibility is conditioned by the socio-political situations around him. A writer cannot be excused from the task of regeneration and restoration of his past lost glorious days that must be done. This academic paper therefore showcases the efficacy of literature in bringing about the sustenance of human dignity in the 21st century. Consequently, the paper in its introduction clarifies some vital concepts. It discusses the forms of literature, portrays the ability and capability of literature as a tool for the sustenance of human dignity globally, and makes useful recommendations for the growth of knowledge in the 21st century and beyond.

Keywords: literature, sustenance, human dignity, 21st century

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Authors: Ahmed Alkarimi, Kevin Welham

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Organic mixed mode monolithic columns were fabricated from; glycidyl methacrylate-co-ethylene dimethacrylate-co-stearyl methacrylate, using glycidyl methacrylate and stearyl methacrylate as co monomers representing 30% and 70% respectively of the liquid volume with ethylene dimethacrylate crosslinker and 2,2-dimethoxy-2-phenylacetophenone as the free radical initiator. The monomers were mixed with a binary porogenic solvent, comprising propan-1-ol, and methanol (0.825 mL each). The monolith was formed by photo polymerization (365 nm) inside a borosilicate glass tube (1.5 mm ID and 3 mm OD x 50 mm length). The monolith was observed to have formed correctly by optical examination and generated reasonable backpressure, approximately 650 psi at a flow rate of 0.2 mL min⁻¹ 50:50 acetonitrile: water. The morphological properties of the monolithic columns were investigated using scanning electron microscopy images, and Brunauer-Emmett-Teller analysis, the results showed that the monolith was formed properly with 19.98 ± 0.01 mm² surface area, 0.0205 ± 0.01 cm³ g⁻¹ pore volume and 6.93 ± 0.01 nm average pore size. The polymer monolith formed was further investigated using proton nuclear magnetic resonance, and Fourier transform infrared spectroscopy. The monolithic columns were investigated using high-performance liquid chromatography to test their ability to separate different samples with a range of properties. The columns displayed both hydrophobic/hydrophilic and hydrophobic/ion exchange interactions with the compounds tested indicating that true mixed mode separations. The mixed mode monolithic columns exhibited significant separation of proteins.

Keywords: LC separation, proteins separation, monolithic column, mixed mode

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Authors: Shirin Ghasemi

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The structure of Asadi’s poem in Garshasb-Nameh coordinates with the structure of human psyche based on Jung’s perspective. The poetic stories of Asadi in Garshasb-Nameh is contrasted to human psyche according to Jung’s view in psychology which indicated the similarity of poetic structure of stories of Garshasb-Nameh to analytical psychology of Jung. In fact, by studying the stories of this collection the reader travels with him and finds it consistent with the human psyche. To demonstrate this, the story of Jamshid marriage with Kuhrang’s daughter and the story of Garshasb marriage with King’s daughter are selected. These two stories illustrate the poetic structure and the human psyche based on Jung’s analytical psychology perspective.

Keywords: Asadi Tusi, Garshasb-Nameh, Jung, analytical psychology

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Authors: Marie-Laure Mimoun-Sorel

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Scholars concerned with the destiny of human species point out that our future will not only depend on progress made in technology and sciences but above all it will depend on human progress understood as quality of being. Teachers are significant force in developing a knowledgeable, creative, productive and democratic society. The values that underpin their profession are integrity, respect and responsibility. Therefore, being a teacher in the context of the 21st century requires embracing a Transdisciplinary Attitude which is about venturing within, between, across and beyond disciplines in order to bring forth quality of being in every learning process. In this article, the Transdisciplinary Attitude is defined and its benefits are shown through examples of Transdisciplinary inquiries in an Australian school. Finally, the conclusion invites to reflect on quality of teaching in regard to the development of individual autonomy, community participation and awareness of belonging to the human species.

Keywords: human progress, quality of being, quality of teaching, transdisciplinary attitude in education

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Authors: T. N. Girish, B. E. Pradeep, Ravi Parkash

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Insects from tropical wet or dry seasons are likely to cope starvation stress through seasonal phenotypic plasticity in energy metabolites. Accordingly, we analyzed such plastic changes in Zaprionus indianus flies reared under wet or dry season-specific conditions; and also after adult acclimation at 32℃ for 1 to 6 days; and to low (40% RH) or high (70% RH) humidity. Both thermal or humidity acclimation revealed significant accumulation of body lipids for wet season flies but low humidity acclimation did not change the level of body lipids in dry season flies. Developmental and adult acclimation showed sex specific differences i.e., starvation resistance and body lipids were higher in the males of dry season but in females of wet season. We found seasonal and sex specific differences in the relative level for body lipids at death; and in the rates of accumulation or utilization of energy metabolites (body lipids, carbohydrates and proteins). Body lipids constitute the preferred energy source under starvation for flies of both the seasons. However, utilization of carbohydrates (~20% to 30%) and proteins (~20% to 25%) was evident only in dry season flies. Higher starvation resistance after thermal or humidity acclimation is achieved by increased accumulation of lipids. Adult acclimation of wet or dry season flies revealed plastic changes in mean daily fecundity despite reduction in fecundity under starvation. Thus, thermal or humidity induced plastic responses in body lipids support starvation resistance under wet or dry seasons.

Keywords: heat or humidity acclimation, plastic changes in body lipids and starvation resistance, tropical drosophilid, Wet- or Dry seasons, Zaprionus indianus

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Authors: Athari Farhani

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Abstract The existence of space debris is a direct implication of human activities in outer space. The amount of orbital debris resulting from human exploration and use of outer space has been steadily increasing in the history of human exploration and use of outer space, so that space debris in the responsibility of the launching state. Space debris not only hs a direct impact on environmentalpollution but can also harm and endanger the safety of human life. Despite the legal provisions governing the exploration and use of outer space, both international space law and liability convention, however, these legal provisions are only basic prinsiples, so that further thought or effort are needed, such as new international legal instruments to regulate the existence of space debris. The method used in this research is normative juridical with an approach to written legal regulation, especially international agreements related to space law.

Keywords: state’s responsibility, space debris, outerspace, international law

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Authors: Mohammed Abdulridha Hamdan

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To face the water crisis, understanding the role of human activities on nutrient concentrations in aquatic ecosystems needs more investigations to compare to extensively studies which have been carried out to understand these impacts on the water quality of different aquatic ecosystems. We hypothesized human activates on the catchments of Tigris river may change nutrient concentrations in water along the river. The results showed that phosphate concentration differed significantly among the studied sites due to distributed human activities, while nitrate concentration did not. Phosphate and nitrate concentrations were not affected by water temperature. We concluded that human activities on the surrounding landscapes could be more essential sources for nutrients of aquatic ecosystems than role of ongoing climate warming. Despite the role of warming in driving nutrients availability in aquatic ecosystems, our findings suggest to take the different activities on the surrounding catchments into account in the studies caring about the trophic status classification of aquatic ecosystems.

Keywords: nitrate, phosphate, anthropogenic, warming

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Authors: Chitra Rajagopal, Indra Deo Kumar, Ila Chauhan, Ruchi Joshi, Binoy Bhargavan

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Reliability and safety are essential for the success of mission-critical and safety-critical defense systems. Humans are part of the entire life cycle of defense systems development and deployment. The majority of industrial accidents or disasters are attributed to human errors. Therefore, considerations of human performance and human reliability are critical in all complex systems, including defense systems. Defense systems are operating from the ground, naval and aerial platforms in diverse conditions impose unique physical and psychological challenges to the human operators. Some of the safety and mission-critical defense systems with human-machine interactions are fighter planes, submarines, warships, combat vehicles, aerial and naval platforms based missiles, etc. Human roles and responsibilities are also going through a transition due to the infusion of artificial intelligence and cyber technologies. Human operators, not accustomed to such challenges, are more likely to commit errors, which may lead to accidents or loss events. In such a scenario, it is imperative to understand the human factors in defense systems for better systems performance, safety, and cost-effectiveness. A case study using Task Analysis (TA) based methodology for assessment and reduction of human errors in the Air and Missile Defense System in the context of emerging technologies were presented. Action-oriented task analysis techniques such as Hierarchical Task Analysis (HTA) and Operator Action Event Tree (OAET) along with Critical Action and Decision Event Tree (CADET) for cognitive task analysis was used. Human factors assessment based on the task analysis helps in realizing safe and reliable defense systems. These techniques helped in the identification of human errors during different phases of Air and Missile Defence operations, leading to meet the requirement of a safe, reliable and cost-effective mission.

Keywords: defence systems, reliability, risk, safety

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Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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Authors: C. Flynn, Q. Yuan, C. Reinhardt

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.

Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration

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Authors: Sengly Sroy, Elodie Arnaud, Adrien Servent, Sokneang In, Sylvie Avallone

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In Cambodia, fish plays an important role for local community in term of food habits, preference and contribution to several nutritional intakes. Consumed on a daily basis, fishes and their derivatives products are good sources of proteins, essential fatty acids and fat-soluble vitamins. They mainly obtain from the Tonle Sap Lake but, during the last decade, the fish population decreased drastically due to climate change and human activities as well. Contamination by agricultural residues and heavy metals were identified. However, fishes are currently used in several nutrition programs for children and pregnant women to improve their nutritional status. The aim of our work was to characterize the nutritional profile and contamination of 10 fish species consumed near the Tonle Sap Lake with a special attention to fatty acid and fat-soluble vitamin profiles. Fish samples were analyzed for their nutritional profiles (AOAC methods for macronutrients and micronutrients), their lipid content (Folch modified method), their Fatty acid (FAME method), their vitamin A (HPLC) and their heavy metals (ICP-MS). The total lipid contents ranged from 1.43 to 10.00% according to fish species. Lipid profile was mainly dominated by saturated fat (from 47.95 to 57.32%) but some fish species were particularly rich in ω-3 and ω-6 especially eicosapentaenoic acid EPA (3.05%) and docosahexaenoic acid DHA (2.82%). The more the fishes were fats, the more they contained vitamin A, DHA and EPA. Vitamin A is particularly abundant in small fishes (250.10 μg RE/100 g) compare to big ones (13.77 μg RE/100 g) because they are consumed as a whole with their organs (liver) and head. However, the contents of heavy metal in some species are higher than the maximum permitted level (MPL) from codex alimentarius, especially Mn. The results obtained provided important information on the most interesting fish in term of human nutrition and the potential risk of contaminants. The fatty acids are important for child development and pregnant women. These data are useful for supply chain stakeholders and the people in charge of nutrition program.

Keywords: fat-soluble vitamin, fatty acid, freshwater fish, lipid content, Tonle Sap Lake

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Authors: M. Kosandi, V. Susanti, N. I. Subono, E. Kartini

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This paper discusses the risk of glorification trap in combating human trafficking, as it is shown in the case of Indonesia. Based on a research on Indonesian combat against trafficking in 2017-2018, this paper shows the tendency of misinterpretation and misapplication of the Indonesian anti-trafficking law into misusing the law for glorification, to create an image of certain extent of achievement in combating human trafficking. The objective of this paper is to explain the persistent occurrence of human trafficking crimes despite the significant progress of anti-trafficking efforts of Indonesian government. The research was conducted in 2017-2018 by qualitative approach through observation, depth interviews, discourse analysis, and document study, applying the three-dimensional model for analyzing human trafficking in the source country. This paper argues that the drive for glorification of achievement in the combat against trafficking has trapped Indonesian government in the loop of misinterpretation, misapplication, and misuse of the anti-trafficking law. In return, the so-called crime against humanity remains high and tends to increase in Indonesia.

Keywords: human trafficking, anti-trafficking policy, transnational crime, source country, glorification trap

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Authors: Ni Zhenyu

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A human settlement is defined as the social activities, social relationships and lifestyles generated within a certain territory, which is also relatively independent territorial living space and domain composed of common people. Along with the advancement of technology and the development of society, the idea, presented in traditional research, that human settlements are deemed as substantial organic integrity with strong autonomy, are more often challenged nowadays. Spatial form of human settlements is one of the most outstanding external expressions with its subjectivity and autonomy, nevertheless, the projections of social, economic activities on certain territories are even more significant. What exactly is the relationship between human beings and the spatial form of the settlements where they live in? a question worth thinking over has been raised, that if a new view, a spatial anthropological one , can be constructed to review and respond to spatial form of human settlements based on research theories and methods of cultural anthropology within the profession of architecture. This article interprets how the typical spatial form of human settlements in the basin area of Bac Giang Province is formed under the collective impacts of local social order, land use condition, topographic features, and social contracts. A particular case of the settlement in Sizhai Village, City of Zhuji, Zhejiang Province is chosen to study for research purpose. Spatial form of human settlements are interpreted as a modeled integrity affected corporately by dominant economy, social patterns, key symbol marks and core values, etc.. Spatial form of human settlements, being a structured existence, is a materialized, behavioral, and social space; it can be considered as a place where human beings realize their behaviors and a path on which the continuity of their behaviors are kept, also for social practice a territory where currant social structure and social relationships are maintained, strengthened and rebuilt. This article aims to break the boundary of understanding that spatial form of human settlements is pure physical space, furthermore, endeavors to highlight the autonomy status of human beings, focusing on their relationships with certain territories, their interpersonal relationships, man-earth relationships and the state of existence of human beings, elaborating the deeper connotation behind spatial form of human settlements.

Keywords: spatial anthropology, human settlement, spatial pattern, spatial structure

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