Search results for: cellular targeting

Authors: Sohaib Z. Khan, Farrukh Mustahsan, Essam R. I. Mahmoud, S. H. Masood

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Materials or structures that contract laterally on the application of a compressive load and vice versa are said to be Auxetic materials which exhibit Negative Poisson’s Ratio (NPR). Numerous auxetic structures are proposed in the literature. One of the most studied periodic auxetic structure is the re-entrant honeycomb model. In this paper, a modified re-entrant model is proposed to enhance the auxetic behavior. The paper aimed to investigate the elastic behaviour of the proposed model to improve Young’s modulus and NPR by evaluating the analytical model. Finite Element Analysis (FEA) is also conducted to support the analytical results. A significant increment in Young’s modulus and NPR can be achieved in one of the two orthogonal directions of the loading at the cost of compromising these values in other direction. The proposed modification resulted in lower relative densities when compared to the existing re-entrant honeycomb structure. A trade-off in the elastic properties in one direction at low relative density makes the proposed model suitable for uni-direction applications where higher stiffness and NPR is required, and strength to weight ratio is important.

Keywords: 2D model, auxetic materials, re-entrant honeycomb, negative Poisson's ratio

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Authors: Chao Wu

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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Lukas Stiburek, Jana Cesnekova, Josef Houstek, Jiri Zeman

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Cellular function depends on mitochondrial function and integrity that is therefore maintained by several classes of proteins possessing chaperone and/or proteolytic activities. In this work, we focused on characterization of LACE1 (lactation elevated 1) function in mitochondrial protein homeostasis maintenance. LACE1 is the human homologue of yeast mitochondrial Afg1 ATPase, a member of SEC18-NSF, PAS1, CDC48-VCP, TBP family. Yeast Afg1 was shown to be involved in mitochondrial complex IV biogenesis, and based on its similarity with CDC48 (p97/VCP) it was suggested to facilitate extraction of polytopic membrane proteins. Here we show that LACE1, which is a mitochondrial integral membrane protein, exists as part of three complexes of approx. 140, 400 and 500 kDa and is essential for maintenance of fused mitochondrial reticulum and lamellar cristae morphology. Using affinity purification of LACE1-FLAG expressed in LACE1 knockdown background we show that the protein physically interacts with mitochondrial inner membrane protease YME1L. We further show that human LACE1 exhibits significant pro-apoptotic activity and that the protein is required for normal function of the mitochondrial respiratory chain. Thus, our work establishes LACE1 as a novel factor with the crucial role in mitochondrial homeostasis maintenance.

Keywords: LACE1, mitochondria, apoptosis, protease

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Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu

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Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.

Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer

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Authors: Musoke Ivan, Birungi Racheal

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The construction trend is characterized by increased use of modern methods yet traditional methods are cheaper in terms of costs, in addition to the benefits it offers to the construction sector, like providing more jobs that could have been worked with the intensive machines. The purpose of this research was to assess the influence of using Traditional methods of construction (TMC) on the costs and quality of building structures and determine the different ways. Traditional methods of construction (TMC) can be applicable and integrated into the construction trend, and propose ways how this can be a success. The study adopted a quantitative method approach targeting various construction professionals like Architects, Quantity surveyors, Engineers, and Construction Managers. Questionnaires and analyses of literature were used to obtain research data and findings. Simple random sampling was used to select 40 construction professionals to which questionnaires were administered. The data was then analyzed using Microsoft Excel. The findings of the research indicate that Traditional methods of construction (TMCs) in Uganda are cheaper in terms of costs, but the quality is still low. This is attributed to a lack of skilled labour and efficient supervision while undertaking tasks leading to low quality. The study identifies strategies that would improve Traditional methods of construction (TMC), which include the employment of skilled manpower and effective supervision. It also identifies the need by stakeholders like the government, clients, and professionals to appreciate Traditional methods of construction (TMCs) and allow for a levelled ground for Traditional Methods of Construction and Modern methods of construction (MMCs).

Keywords: traditional methods of construction, integration, cost, quality

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Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

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In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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Authors: Rui Liu, Pengyu Cui, Nan Jiang

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At present, there is much research on the application of centralized management and cross-integration application of basic geographic information. However, the idea of information integration and sharing between land, sea, and air navigation targets is not deeply applied into the research of navigation information service, especially in the information expression. Targeting at this problem, the paper carries out works about the expression pattern of navigation electronic map for ground vehicles under air and land united navigation mechanism. At first, with the support from multi-source information fusion of GIS vector data, RS data, GPS data, etc., an air and land united information expression pattern is designed aiming at specific navigation task of emergency rescue in the earthquake. And then, the characteristics and specifications of the united expression of air and land navigation information under the constraints of map load are summarized and transferred into expression rules in the rule bank. At last, the related navigation experiment is implemented to evaluate the effect of the expression pattern. The experiment selects evaluation factors of the navigation task accomplishment time and the navigation error rate as the main index, and make comparisons with the traditional single information expression pattern. To sum up, the research improved the theory of navigation electronic map and laid a certain foundation for the design and realization of united navigation system in the aspect of real-time navigation information delivery.

Keywords: navigation electronic map, united navigation, multi-element expression pattern, multi-source information fusion

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Authors: Lavinia Ruta, Ileana Farcasanu

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The yeast surface display (YSD) technique enables the expression of proteins on yeast cell surfaces, facilitating the identification and isolation of proteins with targeted binding properties, such as nanobodies. Nanobodies, derived from camelid species, are single-domain antibody fragments renowned for their high affinity and specificity towards target proteins, making them valuable in research and potentially in therapeutics. Their advantages include a compact size (~15 kDa), robust stability, and the ability to target challenging epitopes. The project endeavors to establish and validate a platform for producing Green Fluorescent Protein (GFP) and mCherry nanobodies using the yeast surface display method. mCherry, a prevalent red fluorescent protein sourced from coral species, is commonly utilized as a genetic marker in biological studies due to its vibrant red fluorescence. The GFP-nanobody, a single variable domain of heavy-chain antibodies (VHH), exhibits specific binding to GFP, offering a potent means for isolating and engineering fluorescent protein fusions across various biological research domains. Both GFP and mCherry nanobodies find specific utility in cellular imaging and protein analysis applications.

Keywords: YSD, nanobodies, GFP, Saccharomyces cerevisiae

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Authors: Nusret Mesut Sahin

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Hrant Dink, a prominent Turkish-Armenian journalist, and editor-in-chief of the bilingual Turkish-Armenian newspaper Agos was assassinated in Istanbul on January 19th, 2007 by a nationalist extremist, Ogun Samast. Dink had been voicing the atrocities against the Armenians between 1915 and 1922 during the Ottoman rule, and his comments on the issue appeared in the Turkish media many times before his assassination. It has been argued that the suffocating atmosphere created by the Turkish news media targeting Mr. Dink made him a target of an extremist Turkish juvenile. This study analyzes the media news to understand and explain why Hrant Dink became the target of a nationalist extremist. In this research, content analysis of news articles (N= 170) is conducted to identify whether there is a link between hate speech against Hrant Dink in the Turkish media and his assassination. The content of the newspaper articles is categorized and coded according to the hate language being used. The analysis suggested that Turkish media paved the way for Dink’s assassination. Hate speech against Hrant Dink on the media had risen gradually before the assassination. The study also found that the number of news stories covering hate speech and racist discourse against non-Muslim citizens of Turkey also increased dramatically before the assassination. Therefore, hate speech against minorities in media narratives and news reports should be monitored, and political figures or leaders of social groups who are targeted by some media outlets should be protected.

Keywords: Hrant Dink, assassination, Turkish Armenian journalist, media

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Authors: Annika J. Meyer, Tom Piechotta

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Unmanned Aerial Vehicles (UAVs) have increasingly become vital tools in various applications, including surveillance, search and rescue, and environmental monitoring. One common approach to ensure redundant communication systems when flying beyond visual line of sight is for UAVs to employ multiple mobile data modems by different providers. Although widely adopted, this approach suffers from several drawbacks, such as high costs, added weight and potential increases in signal interference. In light of these challenges, this paper proposes a communication framework intermeshing mobile networks and LoRa (Long Range) technology—a low-power, long-range communication protocol. LoRaWAN (Long Range Wide Area Network) is commonly used in Internet of Things applications, relying on stationary gateways and Internet connectivity. This paper, however, utilizes the underlying LoRa protocol, taking advantage of the protocol’s low power and long-range capabilities while ensuring efficiency and reliability. Conducted in collaboration with the Potsdam Fire Department, the implementation of mobile network technology in combination with the LoRa protocol in small UAVs (take-off weight < 0.4 kg), specifically designed for search and rescue and area monitoring missions, is explored. This research aims to test the viability of LoRa as an additional redundant communication system during UAV flights as well as its intermeshing with the primary, mobile network-based controller. The methodology focuses on direct UAV-to-UAV and UAV-to-ground communications, employing different spreading factors optimized for specific operational scenarios—short-range for UAV-to-UAV interactions and long-range for UAV-to-ground commands. This explored use case also dramatically reduces one of the major drawbacks of LoRa communication systems, as a line of sight between the modules is necessary for reliable data transfer. Something that UAVs are uniquely suited to provide, especially when deployed as a swarm. Additionally, swarm deployment may enable UAVs that have lost contact with their primary network to reestablish their connection through another, better-situated UAV. The experimental setup involves multiple phases of testing, starting with controlled environments to assess basic communication capabilities and gradually advancing to complex scenarios involving multiple UAVs. Such a staged approach allows for meticulous adjustment of parameters and optimization of the communication protocols to ensure reliability and effectiveness. Furthermore, due to the close partnership with the Fire Department, the real-world applicability of the communication system is assured. The expected outcomes of this paper include a detailed analysis of LoRa's performance as a communication tool for UAVs, focusing on aspects such as signal integrity, range, and reliability under different environmental conditions. Additionally, the paper seeks to demonstrate the cost-effectiveness and operational efficiency of using a single type of communication technology that reduces UAV payload and power consumption. By shifting from traditional cellular network communications to a more robust and versatile cellular and LoRa-based system, this research has the potential to significantly enhance UAV capabilities, especially in critical applications where reliability is paramount. The success of this paper could pave the way for broader adoption of LoRa in UAV communications, setting a new standard for UAV operational communication frameworks.

Keywords: LoRa communication protocol, mobile network communication, UAV communication systems, search and rescue operations

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Authors: Olivier de Backer, Alexis Khelfi, Olivier Svensek, Axelle Nolmans, Dominique Desnoeck

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The SMC5-SMC6 complex helps replication and repair of DNA double-strand breaks. Nse1, Nse3 and Nse4 are non-SMC components of the complex in which Nse3 stimulates the E3 ubiquitin ligase activity of Nse1 and is required for recruiting the complex on DNA. In most eukaryotes, Nse3 is a single protein, but in eutherians (placental mammals), it belongs to a large family of proteins called MAGE (Melanoma antigen) that share a conserved domain of about 200 aa known as MHD (Mage homology domain). MAGE assembles specific RING and HECT ubiquitin ligases and determines new substrates for ubiquitination. The MHD is required for the interaction with the cognate E3 ligase. Some MAGEs (referred to as Type I) are exclusively expressed in germ cells of the testis but are often expressed ectopically in cancer cells as the result of epigenetic modifications. The 12 MAGE-A genes belong to this category. Serval MAGE-A proteins could promote tumorigenesis by targeting tumor suppressor proteins (including p53) for ubiquitination and degradation. We showed that depletion of MAGE-A proteins in melanoma cells results in impaired DNA damage response and increased double-strand breaks after exposure to camptothecin. Moreover, it was shown that other actors of the DNA Damage Response were impacted when cells were depleted of MAGEA proteins.

Keywords: DNA damage response, melanoma, camptothecin, new role, MAGEA

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Authors: Nicolas Haber

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The study addresses the conceptual design of Product-Service Systems (PSSs) as a means of innovating solutions with the aim of reducing the environmental load of conventional product based solutions. Functional approaches targeting PSS solutions are developed in instinctive methods within the constraints of the setting in which they are conceived. Adopting morphological matrices in designing PSS concepts allows a thorough understanding of the settings, stakeholders, and functional requirements. Additionally, such a methodology is robust and adaptable to product-oriented, use-oriented and result-oriented systems. The research is based on a functional decomposition of the task in a similar way as in product design; while extended to include service components, providers, and receivers, while assessing the adaptability and homogeneity of the selected components and actors. A use-oriented concept is presented via a practical case study at an agricultural boom-sprayer manufacturer to demonstrate the effectiveness of the morphological approach to justify its viability. Additionally, a life cycle analysis is carried out in order to evaluate the environmental advantages inherited in a PSS solution versus a conventional solution. In light of the applications presented, the morphological approach appears to be a valid and generic tactic to conceiving integrated solutions whilst capturing the interrelations between the actors and elements of an integrated product-service system.

Keywords: conceptual design, design for sustainability, functional decomposition, product-service systems

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Richard White, Anne Drabble, Maureen O’Neill

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The University of the Sunshine Coast (USC) offers secondary school students in the final two years of school (Years 11 and 12, 16 – 18 years of age) an opportunity to participate in a program which provides an accelerated pathway to tertiary studies. Whilst still at secondary school, the students undertake two first year university subjects that are required subjects in USC undergraduate degree programs. The program is called Integrated Learning Pathway (ILP) and offers a range of disciplines, including business, design, drama, education, and engineering. Between 2010 and 2014, 38% of secondary students who participated in an ILP program commenced undergraduate studies at USC following completion of secondary school studies. The research reported here considers “before and after” literacy and numeracy competencies of students to determine what impact participation in the ILP program has had on their academic skills. Qualitative and quantitative data has been gathered via numeracy and literacy testing of the students, and a survey asking the students to self-evaluate their numeracy and literacy skills, and reflect on their views of these academic skills. The research will enable improved targeting of teaching strategies so that students will acquire not only course-specific learning outcomes but also collateral academic skills. This enhancement of academic skills will improve undergraduate experience and improve student retention.

Keywords: academic skills enhancement, accelerated pathways, improved teaching, student retention

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Authors: Antonio Breda d’Azevedo

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Regularity has often been present in the form of regular polyhedra or tessellations; classical examples are the nine regular polyhedra consisting of the five Platonic solids (regular convex polyhedra) and the four Kleper-Poinsot polyhedra. These polytopes can be seen as regular maps. Maps are cellular embeddings of graphs (with possibly multiple edges, loops or dangling edges) on compact connected (closed) surfaces with or without boundary. The n-dimensional abstract polytopes, particularly the regular ones, have gained popularity over recent years. The main focus of research has been their symmetries and regularity. Planification of polyhedra helps its spatial construction, yet it destroys its symmetries. To our knowledge there is no “planification” for n-dimensional polytopes. However we show that it is possible to make a “surfacification” of the n-dimensional polytope, that is, it is possible to construct a restrictedly-marked map representation of the abstract polytope on some surface that describes its combinatorial structures as well as all of its symmetries. We also show that there are infinitely many ways to do this; yet there is one that is more natural that describes reflections on the sides ((n−1)-faces) of n-simplices with reflections on the sides of n-polygons. We illustrate this construction with the 4-tetrahedron (a regular 4-polytope with automorphism group of size 120) and the 4-cube (a regular 4-polytope with automorphism group of size 384).

Keywords: abstract polytope, automorphism group, N-simplicies, symmetry

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Authors: Janneth Gonzalez, Marco Avila, George Barreto

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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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Authors: Ali Fuad Ashour

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Introduction: Contrary to the common belief that physical training for multiple sclerosis (MS) patients might exacerbate fatigue and provoke other symptoms of the illness, it is now widely accepted that exercise can be actually beneficial in terms of activities of daily living, reduced fatigue, and improved quality of life. The aim of this study was to assess the attitude of MS patients toward exercise. Methodology: 112 MS patients who were recruited from the local community participated in this study. We utilised a self-developed questionnaire targeting attitudes and perceptions of MS patients towards physical exercise. The questionnaire was piloted and tested for validity and reliability. Results: Before being diagnosed with MS, 49.9% of our MS patients’ respondents used to engage in different types of physical activities and sports, namely aerobics/walking (35.3%), stretching exercise (18.7%), and strengthening exercise (11.4%). After being diagnosed with MS, 40.8% of our sample showed determination to remain physically active. The interest in sports activities was consistent after the diagnoses with MS and included aerobics/walking (33.8%), stretching exercise (22.6%), and strengthening exercise (19.7%). Discussion: The Kuwaiti respondents thought that lack of encouragement was the main reason for them not exercise. Aptly put, if they try to exercise, they will be discouraged by the loved ones lest the worse happens. On the other side, British patients are generally aware of the benefits of physical and mental health-promoting activities; they can seek help from a wide range of professionals and are more actively involved in the management of their condition. It is therefore important that the benefits of physical activity are promoted among MS patients, and that attitude towards MS and MS patients is changed through education.

Keywords: perception, multiple sclerosis, exercise, physical training

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Authors: Atena Naeimi, Mehri-Sadat Ekrami-Kakhki

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Fe3O4 is one of the important magnetic oxides with spinel structure; it has exhibited unique electric and magnetic properties based on the electron transfer between Fe2+ and Fe3+ in the octahedral sites. Fe3O4 have received considerable attention in various areas such as cancer therapy, drug targeting, enzyme immobilization catalysis, magnetic cell separation, magnetic refrigeration systems and super-paramagnetic materials. Fe3O4–ZnO nanostructures were synthesized via a surfactant-free ultrasonic reaction at room temperatures. The effect of various parameters such as temperature, time, and power on the size and morphology of the product was investigated. Alternating gradient force magnetometer shows that Fe3O4 nanoparticles exhibit super-paramagnetic behaviour at room temperature. For preparation of nanocomposite 1 g of Fe3O4 nanostructures were dispersed in 100 mL of distilled water. 0.25 g of Zn (NO3)2 and 20 mL of NH3 solution 1 M were then slowly added to the solution under ultrasonic irradiation. The product was centrifuged, washed with distilled water and dried in the air. The photocatalytic behaviour of Fe3O4–ZnO nanoparticles was evaluated using the degradation of a methyl orange aqueous solution under ultraviolet light irradiation. As time increased, more and more methyl orange was adsorbed on the nanoparticles catalyst, until the absorption peak vanish. The methyl orange concentration decreased rapidly with increasing UV-irradiation time.

Keywords: nanocomposite, ultrasonic, paramagnetic, photocatalytic

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Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan

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Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.

Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins

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Authors: Sihem Salmi Laouar, Khoudair Chabane, Rabah Laouar, Adrian J. Boyce et Anthony E. Fallick

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The solid mass of Essouabaa belongs paléogéography to the field téthysian and belonged to the area of the Mounts of Mellègue. This area was not saved by the oceanic-2 event anoxic (EAO-2) which was announced, over one short period, around the limit cénomanian-turonian. In the solid mass of Essouabba, the dominant sediments, pertaining to this period, are generally fine, dark, laminated and sometimes rolled deposits. They contain a rather rich planktonic microfaune, pyrite, and grains of phosphate, thus translating an environment rather deep and reducing rather deep and reducing. For targeting well the passage Cénomanian-Turonian (C-T) in the solid mass of Essouabaa, of the studies lithological and biostratigraphic were combined with the data of the isotopic analyses carbon and oxygen like with the contents of CaCO3. The got results indicate that this passage is marked by a biological event translated by the appearance of the "filaments" like by a positive excursion of the δ13C and δ18O. The cénomanian-turonian passage in the solid mass of Essouabaa represents a good example where during the oceanic event anoxic a facies with organic matter with contents of COT which can reach 1.36%. C E massive presents biostratigraphic and isotopic similarities with those obtained as well in the areas bordering (ex: Tunisia and Morocco) that throughout the world.

Keywords: limit cénomanian-turonian (C-T), COT, filaments, event anoxic 2 (EAO-2), stable isotopes, mounts of Mellègue, Algeria

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Authors: Lodgaard Eirin, Myklebust Odd, Eleftheriadis Ragnhild

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Continuous improvement is becoming increasingly a prerequisite for manufacturing companies to remain competitive in a global market. In addition, future survival and success will depend on the ability to manage the forthcoming digitalization transformation in the industry 4.0 era. Industry 4.0 promises substantially increased operational effectiveness, were all equipment are equipped with integrated processing and communication capabilities. Subsequently, the interplay of human and technology will evolve and influence the range of worker tasks and demands. Taking into account these changes, the concept of continuous improvement must evolve accordingly. Based on a case study from manufacturing industry, the purpose of this paper is to point out what the concept of continuous improvement will meet and has to take into considering when entering the 4th industrial revolution. In the past, continuous improvement has the focus on a culture of sustained improvement targeting the elimination of waste in all systems and processes of an organization by involving everyone. Today, it has to be evolved into the forthcoming digital transformation and the increased interplay of human and digital communication system to reach its full potential. One main findings of this study, is how digital communication systems will act as an enabler to strengthen the continuous improvement process, by moving from collaboration within individual teams to interconnection of teams along the product value chain. For academics and practitioners, it will help them to identify and prioritize their steps towards an industry 4.0 implementation integrated with focus on continuous improvement.

Keywords: continuous improvement, digital communication system, human-machine-interaction, industry 4.0, team perfomance

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Authors: Muhammad Munir, Riffat Mehboob, Samina Naeem, Muhammad Salman, Shehryar Ahmed, Irshad Hussain Qureshi, Tahira Murtaza Cheema, Ashraf Sultan, Akmal Laeeq, Nakhshab Choudhry, Asad Aslam Khan, Fridoon Jawad Ahmad

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A dengue outbreak in Lahore, Pakistan during 2011 was unprecedented in terms of severity and magnitude. This research aims to determine the serotype distribution of dengue virus during this outbreak and classify the patients demographically. 5ml of venous blood was drawn aseptically from 166 patients with dengue-like signs to test for the virus between the months of August to November 2011. The samples were sent to the CDC, Atlanta, Georgia for the purpose of molecular assays to determine their serotype. RT-PCR protocol was performed targeting at the 4 dengue serotypes. Out of 166 cases, dengue infection was detected with RT-PCR in 95 cases, all infected with same serotype DEN-2. 75% of positive cases were males while 25% were females. Most positive patients were in the age range of 16-30 years. 33% positive cases had accompanying bleeding. This is first study during the 2011 dengue epidemic in Lahore that reports DEN-2 as the only prevalent serotype. It also indicates that more infected patients were males, adults, within age range of 16-30 years, peaked in the month of November, Dengue hemorrhagic fever (DHF) is manifested more in females, Ravi town was heavily hit by dengue virus infection.

Keywords: dengue, serotypes, Pakistan, DEN 2, Lahore, demography, serotype distrbution, 2011 epidemic

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Authors: Kah Yan How, Peh Fern Ong, Keang Peng Song

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Porphyromonas gingivalis is a black-pigmented, anaerobic Gram-negative bacterium that is important in the progression of chronic and severe periodontitis. This organism has an essential requirement for iron, which is usually obtained from hemin, using specific membrane receptors, proteases, and lipoproteins. In this study, we report the characterization of a novel 24 kDa hemin-binding protein, HmuX, in P. gingivalis W50. The hmuX gene is 651 bp long which encodes for a 217 amino acid protein. HmuX was found to be identical at the C-terminus to the previously reported HmuY protein, differing by an additional 74 amino acids at the N-terminus. Recombinant HmuX demonstrated hemin-binding ability by LDS- PAGE and TMBZ staining. Sequence analysis of HmuX revealed a putative lipoprotein attachment site, suggesting its possible role as a lipoprotein. HmuX was also localized to the outer cell surface by transmission electron microscopy. Northern analysis showed hmuX to be transcribed as a single gene and that hmuX mRNA was tightly regulated by the availability of extra-cellular hemin. P. gingivalis isogenic mutant deficient in hmuX gene exhibited significant growth retardation under hemin-limited conditions. Taken together, these results suggest that HmuX is a hemin-binding lipoprotein, important in hemin utilization for the growth of P. gingivalis.

Keywords: Porphyromonas gingivalis, periodontal diseases, HmuX, protein characterization

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Authors: Hamidreza Jabal Ameli, Anahita Movahedi

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Purpose: In radionuclide therapy, radioactive atoms are coupled to monoclonal antibodies (mAbs) for treating cancer tumor while limiting radiation to healthy tissues. We know that tumoral and normal tissues are not equally sensitive to radiation. In fact, biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells should be taken account. For this reason, in this paper, we want to calculate biological effect dose (BED) inside tumoral area and healthy cells around tumors. Methods: In this study, deposited doses of a radionuclide, gold-198, inside cells lattice and surrounding healthy tissues were calculated with Monte Carlo method. The elemental compositions and density of malignant and healthy tissues were obtained from ICRU Report 44. For reaching to real condition of oxygen effects, the necrosis and hypoxia area inside tumors has been assessed. Results: With regard to linear-quadratic expression which was defined in Monte Carlo, results showed that a large amount of BED is deposited in the well-oxygenated part of the hypoxia area compared to necrosis area. Moreover, there is a significant difference between the curves of absorbed dose with BED and without BED.

Keywords: biological dose, monte carlo, hypoxia, radionuclide therapy

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Authors: Jinfeng Zhang, Chun-Sing Lee

Abstract:

The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed for improving their drug loading capacities (typically less than 10%) and reducing their potential systemic toxicity. So development of alternative self-carried nanodrug delivery strategies without using any inert carriers is highly desirable. In this study, we developed a self-carried theranostic curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environment, with drug loading capacity higher than 78 wt.%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescent “OFF-ON” activation and real-time monitoring of Cur molecule release, showing its potential for cancer diagnosis. In vitro and in vivo experiments clearly show that therapeutic efficacy of the PEGylated Cur NPs is much better than that of free Cur. This self-carried theranostic strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and diagnosis.

Keywords: drug delivery, in vitro and in vivo cancer therapy, real-time monitoring, self-carried

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Authors: Sotiroula Liasidou, Katerina Pericleous, Zanete Garanti,

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Traveling for religious and pilgrimage purposes consists of an early-stage motivation for the historical development of tourism. Sacred places have become important attractions for local and foreign visitors, and many countries invest in the development of religious and pilgrimage tourism. Cyprus has a rich tradition as an important place for the establishment and diffusion of the Christian Orthodox Religion (Greek). Being considered the ‘island of Saints’, Cyprus sets strong foundations to be recognised as a spiritual destination of devotion for visitors interested in discovering the roots and the spiritual essence of the Christian Orthodox Religion. The paper elucidates on bringing together the fact of whether tourism in sacred places affects spirituality and religiosity. Thus, the aim is to consider the perceptions of the main religious stakeholders, including monastery abbots, in relation to the development of religious tourism. The aim of the study is fulfilled by incorporating questionnaires targeting the responses of the involved religious key players and stakeholders. The results of the study are indicative and provide an understanding in terms of religious tourism as an important product by interpreting the stance of religious stakeholders. In general, religious leaders support tourism in religious sites and argue that spirituality and holiness can be maintained as long there is a policy that is followed both by religious and tourism policymakers. Undoubtedly, establishing Cyprus as a religious tourism destination would bring many economic and social benefits.

Keywords: religious tourism, pilgrimage, Cyprus, Christian Orthodox Religion, sacred places, monasteries

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Authors: Neveen Ali-Saleh Darawsha

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Exposure to community violence (CV) is alarmingly high and emphasizes negative consequences. The present study examines the rates and consequences of exposure to community violence, among Palestinian adolescents from Israel, age ranged 14-18. Specifically, it examines whether exposure to community violence is indirectly related to academic achievement through internalizing and externalizing symptoms among adolescents; and whether the indirect effects of exposure to CV and academic achievements will differ when the parents have different levels of psychological well-being. Method: Semi systematic random sample of 760 Palestinian adolescents in Israel, (320 boys, and 440 girls) filled out a self-administration questionnaire. Most of the adolescents had witnessed community violence during the last year and during their lifetime, and more than one third had directly experienced such violence during lifetime compared with 19.6% during the last year. Structural equation modeling was used to examine the indirect effects of exposure to CV and academic achievement. Results revealed that externalizing symptoms mediated the association between exposure to CV and academic achievement. There were no indirect effects through internalizing symptoms. Moreover, parental psychological well-being moderated the indirect effects between externalizing symptoms and academic achievements. Conclusion: Findings highlight the importance of targeting externalizing symptoms for adolescents that could improve their behaviors and also their academic achievements as well. limitations of the study, implications for the practice and recommendations for future research are discussed.

Keywords: community violence, witnessing violence, direct personal experiencing, academic achievement, psychological well-being, Palestinian adolescents

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Authors: Mohamed Muse Hassan

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Selling through the Internet is changing the norms of doing business globally. Today, selling and buying from the Internet is not only an option but the dominant form of shopping. But, this phenomenon is not thriving in the developing countries, mainly in Africa. Therefore, although previous studies focused on the e-retailers’ side, this study investigates the effect of consumer trust and online payment options on the awareness and perception of e-commerce in Africa. We developed a five-construct model and empirically tested the model by targeting professionals and college students who reside in Somalia. We employed structural equation modeling (SEM) technique for path analysis to probe answers for the variables under study. The main findings of the study show that there is significant evidence that online payment option impacts both the awareness level and perception of e-commerce in Somalia. Consumer trust was also found to determine both the awareness and perception of online shopping in the country. Moreover, the current global payment options available ignore local technologies popular in Africa. For example, the inclusion of a mobile payment option alone would make a big difference in Africa. The paper also determined that consumer trust toward online retailers is very low and this can be solved if consumers are given assurances for their financial transactions. The paper concludes that increased online payment options are needed in Somalia and, in Africa, in general. Limitations and further research suggestions are also included at the end of this paper.

Keywords: Africa, consumer trust, e-commerce, online payment

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Authors: Sanat K. Dash, Rama S. Verma, Sarit K. Das

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A logarithmic microfluidic shear device was designed and fabricated for cellular mechanotransduction studies. The device contains four cell culture chambers in which flow was modulated to achieve a logarithmic increment. Resistance values were optimized to make the device compact. The network of resistances was developed according to a unique combination of series and parallel resistances as found via optimization. Simulation results done in Ansys 16.1 matched the analytical calculations and showed the shear stress distribution at different inlet flow rates. Fabrication of the device was carried out using conventional photolithography and PDMS soft lithography. Flow profile was validated taking DI water as working fluid and measuring the volume collected at all four outlets. Volumes collected at the outlets were in accordance with the simulation results at inlet flow rates ranging from 1 ml/min to 0.1 ml/min. The device can exert fluid shear stresses ranging four orders of magnitude on the culture chamber walls which will cover shear stress values from interstitial flow to blood flow. This will allow studying cell behavior in the long physiological range of shear stress in a single run reducing number of experiments.

Keywords: microfluidics, mechanotransduction, fluid shear stress, physiological shear

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Authors: Ndidi Ofole

Abstract:

Ongoing Boko Haram crisis and instability in North-Eastern Nigeria has placed additional stress on academic resilience of female undergraduates who are already challenged by gender discrimination in educational opportunities. Students without resilience lack stress hardiness to cope with academic challenges. There is a limited study on academic resilience targeting this disadvantaged population in Nigeria. Consequently, survey research design was employed to investigate the contextual and personal factors that could predict academic resilience among female undergraduates in Boko Haram Neighbourhood in North-Eastern, Nigeria. Five hundred and thirty female students with age range of 18 to 24 years ( = 19.2; SD=6.9) were randomly drawn from 3 Universities in North-Eastern Nigeria. They responded to five instruments, namely; Academic Resilience scale (r=0.72); Social Support questionnaire (r=0. 64); Social Connectedness questionnaire (r=0.75); Self-Efficacy scale (r=0. 68) and Emotional Regulation questionnaire (r=78). Results showed that there was significant positive relationship between the four independent variables and academic resilience. The variables jointly contributed 5.9% variance in the prediction of academic resilience. In terms of magnitude, social support was most potent while self-efficacy was the least. It concluded that the factors considered in this study are academic resilience facilitators. The outcomes of the study have both theoretical and practical implications.

Keywords: academic resilience, emotional regulation, school connectedness, self-efficacy , social support

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