Search results for: constitutive expression

Authors: Armin Nabaei, M. Omair Ahmad, M. N. S. Swamy

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Many facial expression and emotion recognition methods in the traditional approaches of using LDA, PCA, and EBGM have been proposed. In recent years deep learning models have provided a unique platform addressing by automatically extracting the features for the detection of facial expression and emotions. However, deep networks require large training datasets to extract automatic features effectively. In this work, we propose an efficient emotion detection algorithm using face images when only small datasets are available for training. We design a deep network whose feature extraction capability is enhanced by utilizing several parallel modules between the input and output of the network, each focusing on the extraction of different types of coarse features with fined grained details to break the symmetry of produced information. In fact, we leverage long range dependencies, which is one of the main drawback of CNNs. We develop this work by introducing a Dynamic Soft-Margin SoftMax.The conventional SoftMax suffers from reaching to gold labels very soon, which take the model to over-fitting. Because it’s not able to determine adequately discriminant feature vectors for some variant class labels. We reduced the risk of over-fitting by using a dynamic shape of input tensor instead of static in SoftMax layer with specifying a desired Soft- Margin. In fact, it acts as a controller to how hard the model should work to push dissimilar embedding vectors apart. For the proposed Categorical Loss, by the objective of compacting the same class labels and separating different class labels in the normalized log domain.We select penalty for those predictions with high divergence from ground-truth labels.So, we shorten correct feature vectors and enlarge false prediction tensors, it means we assign more weights for those classes with conjunction to each other (namely, “hard labels to learn”). By doing this work, we constrain the model to generate more discriminate feature vectors for variant class labels. Finally, for the proposed optimizer, our focus is on solving weak convergence of Adam optimizer for a non-convex problem. Our noteworthy optimizer is working by an alternative updating gradient procedure with an exponential weighted moving average function for faster convergence and exploiting a weight decay method to help drastically reducing the learning rate near optima to reach the dominant local minimum. We demonstrate the superiority of our proposed work by surpassing the first rank of three widely used Facial Expression Recognition datasets with 93.30% on FER-2013, and 16% improvement compare to the first rank after 10 years, reaching to 90.73% on RAF-DB, and 100% k-fold average accuracy for CK+ dataset, and shown to provide a top performance to that provided by other networks, which require much larger training datasets.

Keywords: computer vision, facial expression recognition, machine learning, algorithms, depp learning, neural networks

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Authors: Ganesh K. Maurya, Reema Chaudhary, Neha Pandey, Hari S. Misra

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PprA, a pleiotropic protein participating in radioresistance, has been reported for its roles in DNA replication initiation, genome segregation, cell division and DNA repair in polyextremophile Deinococcus radiodurans. Interestingly, expression of deinococcal PprA in E. coli suppresses its growth by reducing the number of colony forming units and provide better resistance against γ-radiation than control. We employed different biochemical and cell biology studies using PprA and its DNA binding/polymerization mutants (K133E & W183R) in E. coli. Cells expressing wild type PprA or its K133E mutant showed reduction in the amount of genomic DNA as well as chromosome copy number in comparison to W183R mutant of PprA and control cells, which suggests the role of PprA protein in regulation of DNA replication initiation in E. coli. Further, E. coli cells expressing PprA or its mutants exhibited different impact on cell morphology than control. Expression of PprA or K133E mutant displayed a significant increase in cell length upto 5 folds while W183R mutant showed cell length similar to uninduced control cells. We checked the interaction of deinococcal PprA and its mutants with E. coli DnaA using Bacterial two-hybrid system and co-immunoprecipitation. We observed a functional interaction of EcDnaA with PprA and K133E mutant but not with W183R mutant of PprA. Further, PprA or K133E mutant has suppressed the ATPase activity of EcDnaA but W183R mutant of PprA failed to do so. These observations suggested that PprA protein regulates DNA replication initiation and cell morphology of surrogate E. coli.

Keywords: DNA replication, radioresistance, protein-protein interaction, cell morphology, ATPase activity

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Authors: Ainur Sharip, Jose E. Perez, Nouf Alsharif, Aldo I. M. Bandeas, Enzo D. Fabrizio, Timothy Ravasi, Jasmeen S. Merzaban, Jürgen Kosel

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Bone marrow-derived human mesenchymal stem cells (MSCs) are attractive candidates for tissue engineering and regenerative medicine, due to their ability to differentiate into osteoblasts, chondrocytes or adipocytes. Differentiation is influenced by biochemical and biophysical stimuli provided by the microenvironment of the cell. Thus, altering the mechanical characteristics of a cell culture scaffold can directly influence a cell’s microenvironment and lead to stem cell differentiation. Mesenchymal stem cells were cultured on densely packed, vertically aligned magnetic iron nanowires (NWs) and the effect of NWs on the cell cytoskeleton rearrangement and differentiation were studied. An electrochemical deposition method was employed to fabricate NWs into nanoporous alumina templates, followed by a partial release to reveal the NW array. This created a cell growth substrate with free-standing NWs. The Fe NWs possessed a length of 2-3 µm, with each NW having a diameter of 33 nm on average. Mechanical stimuli generated by the physical movement of these iron NWs, in response to a magnetic field, can stimulate osteogenic differentiation. Induction of osteogenesis was estimated using an osteogenic marker, osteopontin, and a reduction of stem cell markers, CD73 and CD105. MSCs were grown on the NWs, and fluorescent microscopy was employed to monitor the expression of markers. A magnetic field with an intensity of 250 mT and a frequency of 0.1 Hz was applied for 12 hours/day over a period of one week and two weeks. The magnetically activated substrate enhanced the osteogenic differentiation of the MSCs compared to the culture conditions without magnetic field. Quantification of the osteopontin signal revealed approximately a seven-fold increase in the expression of this protein after two weeks of culture. Immunostaining staining against CD73 and CD105 revealed the expression of antibodies at the earlier time point (two days) and a considerable reduction after one-week exposure to a magnetic field. Overall, these results demonstrate the application of a magnetic NW substrate in stimulating the osteogenic differentiation of MSCs. This method significantly decreases the time needed to induce osteogenic differentiation compared to commercial biochemical methods, such as osteogenic differentiation kits, that usually require more than two weeks. Contact-free stimulation of MSC differentiation using a magnetic field has potential uses in tissue engineering, regenerative medicine, and bone formation therapies.

Keywords: cell substrate, magnetic nanowire, mesenchymal stem cell, stem cell differentiation

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Authors: Yusuf Abubakar Mamud

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Highlighting the imperatives of local conflicts considering the dangerous dimensions of terrorism they are assuming in Africa has not attracted serious academic and political attention. The discourse about conflict in Africa was discussed within five identified conflict zones in the continent. The threats from these local conflicts are diverse and complex and the acts of terrorism in these local conflicts are driven by certain attitudes and behaviours linked to the African leadership. The paper examined and noted that the current conflict resolution model of the African Union (AU) was robust with requisite institutions to address the trends in local conflicts. However, it was observed that the AU peace and security framework lacked the requisite structural and technical capabilities to proactively address the drivers of local conflicts in Africa. It was found that the persistence of local conflicts in the African region may deny her the opportunities of achievement of the targets envisioned in the Sustainable Development Goals (SDGs). Consequently, the paper called on the international community to support Africa through provision of capacity. It urged the African leaders themselves to develop the political will to ensure that all issues concerning peace and security in the continent were guided by the provisions of the AU Constitutive Act. The need to strengthen the APRM in the light of the current trends in local conflicts was also highlighted.

Keywords: conflicts, local conflicts, terrorism, sustainable development

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Authors: Rehan Ali Shah, A. M. Siddiqui, T. Haroon

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Slip boundary value problem in wire coating analysis with heat transfer is examined. The fluid is assumed to be viscoelastic PTT (Phan-Thien and Tanner). The rheological constitutive equation of PTT fluid model simulates various polymer melts. Therefore, the current consequences are valuable in a number of realistic situations. Effects of slip parameter γ as well as εDec^2 (viscoelastic index) on the axial velocity, shear stress, normal stress, average velocity, volume flux, thickness of coated wire, shear stress, force on the total wire and temperature distribution profiles have been investigated. A new direction is explored to analyze the flow with the slip parameter. The slippage at the boundaries plays an important role in thickness of coated wire. It is noted that as the slip parameter increases the flow rate and thickness of coated wire increases while, temperature distribution decreases. The results reduce to no slip when the slip parameter is vanished. Furthermore, we can obtain the results for Maxwell and viscous model by setting ε and λ equal to zero respectively.

Keywords: wire coating, straight annular die, PTT fluid, heat transfer, slip boundary conditions

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Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

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Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari

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Cyperus rotendus rhizomes are used as traditional medicine, including Ayurveda in chronic liver diseases and hepatitis B. We investigated the in vitro hepatoprotective and anti-hepatitis B virus (HBV) potential of Cyperus rotundus rhizome organic and aqueous fractions. Of these, the n-butanol and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-injured HepG2 cells at 48 h. DCFH-toxicated cells were recovered to about 88% and 96%, upon treatment with n-butanol and aqueous fractions (200 g/ml), respectively compared to DCFH-only treated cells. Further, C. rotundus fractions were tested for anti-HBV activities by measuring the expression levels of viral antigens (HBsAg and HBeAg) in the HepG2.2.15 culture supernatants. At 48 h post-treatment, the ethyl acetate, n-butanol and aqueous fractions showed dose-dependent inhibition wherein at a higher dose (100 g/ml), HBsAg production was reduced to 60.27%, 46.87 and 42.76%, respectively. In a time-course study, HBsAg production was inhibited up to 50% and 40% by ethyl acetate and n-butanol fractions (100 g/ml), respectively on day 5. Three three active fractions were further subjected to time-dependent inhibition of HBeAg expression, an indirect measure of HBV active DNA replication. At day 5 post-treatment, ethyl acetate and n-butanol fractions downregulated HBV replication by 44.14% and 24.70%, respectively. In conclusion, our results showed very promising hepatoprotective and anti-HBV potential of C. rotendus tubers fractions in vitro. Our data could, therefore, provide the basis for the claimed traditional use of C. rotendus for jaundice and hepatitis.

Keywords: anti-hepatitis B, cyperus rotundus, hepatitis B virus, hepatoprotection

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: T. H. Young, S. J. Huang, Y. S. Chiu

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This paper investigates the parametric stability of an axially moving web subjected to nonuniform in-plane edge excitations on two opposite, simply-supported edges. The web is modeled as a viscoelastic plate whose constitutive relation obeys the Kelvin-Voigt model, and the in-plane edge excitations are expressed as the sum of a static tension and a periodical perturbation. Due to the in-plane edge excitations, the moving plate may bring about parametric instability under certain situations. First, the in-plane stresses of the plate due to the nonuniform edge excitations are determined by solving the in-plane forced vibration problem. Then, the dependence on the spatial coordinates in the equation of transverse motion is eliminated by the generalized Galerkin method, which results in a set of discretized system equations in time. Finally, the method of multiple scales is utilized to solve the set of system equations analytically if the periodical perturbation of the in-plane edge excitations is much smaller as compared with the static tension of the plate, from which the stability boundaries of the moving plate are obtained. Numerical results reveal that only combination resonances of the summed-type appear under the in-plane edge excitations considered in this work.

Keywords: axially moving viscoelastic plate, in-plane periodic excitation, nonuniformly distributed edge tension, dynamic stability

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Authors: Linette van der Merwe

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It is known that visual artists, performing artists, and literary artists have inspired each other since time immemorial. The enduring, symbiotic relationship between the various art genres is evident where words, colours, lines, and sounds act as metaphors, a physical separation of the transcendental reality of art. Simonides of Keos (c. 556-468 BC) confirmed this, stating that a poem is a talking picture, or, in a more modern expression, a picture is worth a thousand words. It can be seen as an ancient relationship, originating from the epigram (tombstone or artefact inscriptions), the carmen figuratum (figure poem), and the ekphrasis (a description in the form of a poem of a work of art). Visual artists, including Michelangelo, Leonardo da Vinci, and Goethe, wrote poems and songs. Goya, Degas, and Picasso are famous for their works of art and for trying their hands at poetry. Afrikaans writers whose fine art is often published together with their writing, as in the case of Andries Bezuidenhout, Breyten Breytenbach, Sheila Cussons, Hennie Meyer, Carina Stander, and Johan van Wyk, among others, are not a strange phenomenon either. Imitating one art form into another art form is a form of translation, transposition, contemplation, and discovery of artistic impressions, showing parallel interpretations rather than physical comparison. It is especially about the harmony that exists between the different art genres, i.e., a poem that describes a painting or a visual text that portrays a poem that becomes a translation, interpretation, and rediscovery of the verbal text, or rather, from the word text to the image text. Poetry-film, as a form of such a translation of the word text into an image text, can be considered a hybrid, transdisciplinary art form that connects poetry and film. Poetry-film is regarded as an intertwined entity of word, sound, and visual image. It is an attempt to transpose and transform a poem into a new artwork that makes the poem more accessible to people who are not necessarily open to the written word and will, in effect, attract a larger audience to a genre that usually has a limited market. Poetry-film is considered a creative expression of an inverted ekphrastic inspiration, a visual description, interpretation, and expression of a poem. Research also emphasises that animated poetry-film is not widely regarded as a genre of anything and is thus severely under-theorized. This paper will focus on Afrikaans animated poetry-films as a multimodal transposition of a poem text to an animated poetry film, with specific reference to animated poetry-films in Filmverse I (2014) and Filmverse II (2016).

Keywords: poetry film, animated poetry film, poetic metaphor, conceptual metaphor, monomodal metaphor, multimodal metaphor, semiotic metaphor, multimodality, metaphor analysis, target domain, source domain

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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Authors: Mostafa Jafarian Abyaneh, Khashayar Jafari, Vahab Toufigh

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The cost of experiments on different types of concrete has raised the demand for prediction of their behavior with numerical analysis. In this research, an advanced numerical model has been presented to predict the complete elastic-plastic behavior of polymer concrete (PC), high-strength concrete (HSC), high performance concrete (HPC) along with different steel fiber contents under uniaxial compression. The accuracy of the numerical response was satisfactory as compared to other conventional simple models such as Mohr-Coulomb and Drucker-Prager. In order to predict the complete elastic-plastic behavior of specimens including softening behavior, disturbed state concept (DSC) was implemented by nonlinear finite element analysis (NFEA) and hierarchical single surface (HISS) failure criterion, which is a failure surface without any singularity.

Keywords: disturbed state concept (DSC), hierarchical single surface (HISS) failure criterion, high performance concrete (HPC), high-strength concrete (HSC), nonlinear finite element analysis (NFEA), polymer concrete (PC), steel fibers, uniaxial compression test

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

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Authors: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: Ashima Sharma, Tapan K. Chaudhuri

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Human Serum Albumin (HSA) is one of the most demanded therapeutic protein with immense biotechnological applications. The current source of HSA is human blood plasma. Blood is a limited and an unsafe source as it possesses the risk of contamination by various blood derived pathogens. This issue led to exploitation of various hosts with the aim to obtain an alternative source for the production of the rHSA. But, till now no host has been proven to be effective commercially for rHSA production because of their respective limitations. Thus, there exists an indispensable need to promote non-animal derived rHSA production. Of all the host systems, Escherichia coli is one of the most convenient hosts which has contributed in the production of more than 30% of the FDA approved recombinant pharmaceuticals. E. coli grows rapidly and its culture reaches high cell density using inexpensive and simple substrates. The fermentation batch turnaround number for E. coli culture is 300 per year, which is far greater than any of the host systems available. Therefore, E. coli derived recombinant products have more economical potential as fermentation processes are cheaper compared to the other expression hosts available. Despite of all the mentioned advantages, E. coli had not been successfully adopted as a host for rHSA production. The major bottleneck in exploiting E. coli as a host for rHSA production was aggregation i.e. majority of the expressed recombinant protein was forming inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA form inclusion body is not preferred because it is tedious, time consuming, laborious and expensive. Because of this limitation, E. coli host system was neglected for rHSA production for last few decades. Considering the advantages of E. coli as a host, the present work has targeted E. coli as an alternate host for rHSA production through resolving the major issue of inclusion body formation associated with it. In the present study, we have developed a novel and innovative method for enhanced soluble and functional production of rHSA in E.coli (~60% of the total expressed rHSA in the soluble fraction) through modulation of the cellular growth, folding and environmental parameters, thereby leading to significantly improved and enhanced -expression levels as well as the functional and soluble proportion of the total expressed rHSA in the cytosolic fraction of the host. Therefore, in the present case we have filled in the gap in the literature, by exploiting the most well studied host system Escherichia coli which is of low cost, fast growing, scalable and ‘yet neglected’, for the enhancement of functional production of HSA- one of the most crucial biomolecule for clinical and biotechnological applications.

Keywords: enhanced functional production of rHSA in E. coli, recombinant human serum albumin, recombinant protein expression, recombinant protein processing

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Authors: Qingfang Guo

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Isodon rubescens is rich in a variety of terpenes such as oridonin. It has important medicinal value. MYB transcription factors are involved in the regulation of plant secondary metabolic pathways. The combined transcriptomics and metabolomics analysis revealed that IrMYB55 might be involved in the regulation of the synthesis of terpenes. The function of IrMYB55 was further verified by establishing of a genetic transformation system by CRISPR/Cas9. Obtaining a virus-mediated Isodon rubescens gene silencing material. The main research results are as follows: (1) Screening IrMYB which can regulate the synthesis of terpenes. Metabolomics and transcriptomics analyses of materials with high (TJ)-and low (FL)-content populations which revealed significant differences in terpene content and IrMYB55 expression. Correlation analysis showed that the expression level of IrMYB55 had a significant correlation with the content of terpenes. (2) Establishment of a genetic transformation system of Isodon rubescens. The IrPDS gene could be knocked out by injection of Isodon rubescens cotyledon, and the transformed material showed obvious albino phenotype. Subsequently, IrMYB55 conversion material was obtained by this method. (3) The IrMYB55 silencing material was obtained. Subcellular localization indicated that IrMYB55 was located in the nucleus, indicating that it might regulate the synthesis of terpenoids through transcription. In summary, IrMYB55 that may regulate the synthesis of oridonin was dug out from the transcriptome and metabolome data. In this study, a genetic transformation system of Isodon rubescens was successfully established. Further studies showed that IrMYB55 regulated the transcription level of genes related to the synthesis of terpenoids, thereby promoting the accumulation of oridonin.

Keywords: isodon rubescens, MYB, oridonin, CRISPR/Cas9

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Authors: Emre Bayamlıoğlu

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Apart from being the subject of neighboring rights when broadcasted on TV or of cinematographic work when fixed to a tangible medium including a hard drive, the copyright eligibility of a sports performance, and eventually the sporting event has once again given rise to controversy following the CJEU judgment in the Murphy case. Most of the arguments which deny copyright protection for sports performances focus on the fact that unlike movies, plays, television programs, or operas, athletic events are competitive and have no underlying script. The first part of the paper aims to explain that such rhetoric is rather weak simply for the fact that, several types of performances such as improvised musical or dramatic shows are still protected by copyright despite the fact that they are not based on a script. The second part argues that the core reason for the denial copyright protection was the functionality aiming certain practical results such as winning the game, scoring, eliminating an opponent, obstructing a shot and etc., but no scientific or artistic expression in whatsoever form. The paper further argues that expanding copyright protection to functional performances would give rise to unintended copyright claims by the athletes on tackles, shoots, passes, crosses etc. resulting with further restrictions on reporting and photographing of sporting events. The final part provides a policy analysis of the trend to broaden the scope of copyright to cover sports performances. It is argued that such expansion will clearly undermine the ratio legis of copyright laws since it will give rise to excessive commodification of information beyond the needs of a viable market economy. Therefore, remedies other than copyright protection such as unfair competition and unjust enrichment provides sufficient redress for the damages to be sustained by the investors of sporting events.

Keywords: copyright eligibility, idea-expression dichotomy, sports performance

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Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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Authors: Rayan B. M. Ameen, Ian P. Jones, Yu Lung Chiu

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Single alpha-beta colony micro-pillars have been manufactured from a polycrystalline commercial Ti-6Al-4V sample using Focused Ion Beam (FIB). Each pillar contained two alpha lamellae separated by a thin fillet of beta phase. A nano-indenter was then used to conduct uniaxial micro-compression tests on Ti alloy single crystals, using a diamond flat tip as a compression platen. By controlling the crystal orientation along the micro-pillar using Electron back scattering diffraction (EBSD) different slip systems have been selectively activated. The advantage of the micro-compression method over conventional mechanical testing techniques is the ability to localize a single crystal volume which is characterizable after deformation. By matching the stress-strain relations resulting from micro-compression experiments to TEM (Transmission Electron Microscopy) studies of slip transmission mechanisms through the α-β interfaces, some proper constitutive material parameters such as the role of these interfaces in determining yield, strain-hardening behaviour, initial dislocation density and the critical resolved shear stress are suggested.

Keywords: α/β-Ti alloy, focused ion beam, micro-mechanical test, nano-indentation, transmission electron diffraction, plastic flow

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Authors: Fereydoon Bondarian, Samira Shaygan

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Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

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Authors: Yi H. Wong, Li L. Chan, Chee O. Leong, Stephen Ambu, Joon W. Mak, Priyadashi S. Sahu

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Background: Acanthamoeba is a free-living opportunistic protist which is ubiquitously distributed in the environment. Virulent Acanthamoeba can cause fatal encephalitis in immunocompromised patients and potential blinding keratitis in immunocompetent contact lens wearers. Approximately 24 species have been identified but only the A. castellanii, A. polyphaga and A. culbertsoni are commonly associated with human infections. Until to date, the precise molecular basis for Acanthamoeba pathogenesis remains unclear. Previous studies reported that Acanthamoeba virulence can be diminished through prolonged axenic culture but revived through serial mouse passages. As no clear explanation on this reversible pathogenesis is established, hereby, we postulate that the epigenetic regulators, DNA-methyltransferases (DNMT) and histone-deacetylases (HDAC), could possibly be involved in granting the virulence plasticity of Acanthamoeba spp. Methods: Four rounds of mouse passages were conducted to revive the virulence potential of the virulence-attenuated Acanthamoeba castellanii strain (ATCC 50492). Briefly, each mouse (n=6/group) was inoculated intraperitoneally with Acanthamoebae cells (2x 105 trophozoites/mouse) and incubated for 2 months. Acanthamoebae cells were isolated from infected mouse organs by culture method and subjected to subsequent mouse passage. In vitro cytopathic, encystment and gelatinolytic assays were conducted to evaluate the virulence characteristics of Acanthamoebae isolates for each passage. PCR primers which targeted on the 2 members (DNMT1 and DNMT2) and 5 members (HDAC1 to 5) of the DNMT and HDAC gene families respectively were custom designed. Quantitative real-time PCR (qPCR) was performed to detect and quantify the relative expression of the two gene families in each Acanthamoeba isolates. Beta-tubulin of A. castellanii (Genbank accession no: XP_004353728) was included as housekeeping gene for data normalisation. PCR mixtures were also analyzed by electrophoresis for amplicons detection. All statistical analyses were performed using the paired one-tailed Student’s t test. Results: Our pathogenicity tests showed that the virulence-reactivated Acanthamoeba had a higher degree of cytopathic effect on vero cells, a better resistance to encystment challenge and a higher gelatinolytic activity which was catalysed by serine protease. qPCR assay showed that DNMT1 expression was significantly higher in the virulence-reactivated compared to the virulence-attenuated Acanthamoeba strain (p ≤ 0.01). The specificity of primers which targeted on DNMT1 was confirmed by sequence analysis of PCR amplicons, which showed a 97% similarity to the published DNA-methyltransferase gene of A. castellanii (GenBank accession no: XM_004332804.1). Out of the five primer pairs which targeted on the HDAC family genes, only HDAC4 expression was significantly difference between the two variant strains. In contrast to DNMT1, HDAC4 expression was much higher in the virulence-attenuated Acanthamoeba strain. Conclusion: Our mouse passages had successfully restored the virulence of the attenuated strain. Our findings suggested that DNA-methyltransferase (DNMT1) and histone deacetylase (HDAC4) expressions are associated with virulence potential of Acanthamoeba spp.

Keywords: acanthamoeba, DNA-methyltransferase, histone deacetylase, virulence-associated proteins

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Authors: Agumah N. B. Orji, M. U., Oru C. M., Ugbo, E. N., Onwuliri E. A Nwakaeze, E. A.,

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ERG11 gene has been reported to be one of the genes whose expression is responsible for resistance of Candida to various triazole drugs, which are first line treatment for candidiasis. This study was carried out to determine the prevalence of Triazole (Fluconazole and voriconazole) resistant Candida albicans expressing ERG11 gene from adult females in Abakaliki. Urine and vaginal swab samples were randomly collected from volunteers after obtaining their consent to participate in the study. A total of 565 adult females participated in the study. A total of 340 urine specimens and 288 vaginal swab specimens were collected. Direct wet mount technique, as well as culture in Trichomonas broth, were used to examine the urine and vaginal swab specimens for the presence of motile Trichomonads. The Trichomonas broth used was selective for both T. vaginalis and C. albicans. Broths that yielded budding yeast cells after microscopy were subcultured on to Sabouraud dextrose agar, after which Germ tube test was carried out to confirm the presence of C. albicans. Biochemical tests, including carbohydrate fermentation and urease utilization, were also performed. Antibiogram of C. albicans isolates obtained from this study was carried out using commercially available azole drugs. Fluconazole and voriconazole were selected as Triazole drugs used for this study. Nystatin was used as a tangential control. An MIC test was carried out with E-strips on some of the resistant C. albicans isolates A total of 6 isolates that resisted all the azole drugs were selected and screened for the presence of ERG11 gene using Reverse transcriptase polymerase chain reaction technique. The total prevalence recorded for C. albicans was 13.0%. Frequency was statistically higher in Pregnant (7.96%) than non pregnant (5.09%) volunteers (X2=0.94 at P=0.05). With respect to clinical samples, frequency was higher in vaginal swabs samples (7.96%) than Urine samples (5.09%) (X2=9.05 at P=0.05). Volunteers within the age group 26-30 years recorded the highest prevalence (4.46%), while those within the age group 36-40 years recorded the lowest at 1.27%(X2=4.34 at P=0.05). In pregnant female participants, the highest frequency was recorded with those in their 3rd trimester (4.14%), while lowest incidence was recorded for those in their first trimester (0.80%). Antibiogram results from this study showed that C. albicans isolates obtained from this study resisted Fluconazole (72%) more than Voriconazole (57%). Only one out of the six selected isolates yielded resistance in the MIC test. Results obtained from the RT-PCR showed that there was no expression of ERG11 gene among the fluconazole resistant isolates of C. albicans. Observed resistance may be due to other factors other than expression of ERG11 gene.

Keywords: candida, ERG11, triazole, nigeria

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Authors: Mianheng Lai, Johnny Ching Ming Ho, Hoat Joen Pam

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Concrete-filled-steel-tube (CFST) columns are becoming increasingly popular owing to the superior behavior contributed by the composite action. However, this composite action cannot be fully developed because of different dilation properties between steel tube and concrete. During initial compression, there will be de-bonding between the constitutive materials. As a result, the strength, initial stiffness and ductility of CFST columns reduce significantly. To resolve this problem, external confinement in the form of spirals is proposed to improve the interface bonding. In this paper, a total of 14CFST columns with high-strength as well as ultra-high-strength concrete in-filled were fabricated and tested under uni-axial compression. From the experimental results, it can be concluded that the proposed spirals can improve the strength, initial stiffness, ductility and the interface bonding condition of CFST columns by restraining the lateral expansion of steel tube and core concrete. Moreover, the failure modes of confined core concrete change due to the strong confinement provided by spirals.

Keywords: concrete-filled-steel-tube, confinement, failure mode, high-strength concrete, spirals

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Authors: Mustafa Sertçelik, Turan Çalban, Hacali Necefoğlu, Sabri Çolak

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In this study, Chevreul’s salt solubility and its dissolution kinetics in ammonium chloride solutions were investigated. Chevreul’s salt that we used in the studies was obtained by using the optimum conditions (ammonium sulphide concentration; 0,4 M, copper sulphate concentration; 0,25 M, temperature; 60°C, stirring speed; 600 rev/min, pH; 4 and reaction time; 15 mins) determined by T. Çalban et al. Chevreul’s salt solubility in ammonium chloride solutions and the kinetics of dissolution were investigated. The selected parameters that affect solubility were reaction temperature, concentration of ammonium chloride, stirring speed, and solid/liquid ratio. Correlation of experimental results had been achieved using linear regression implemented in the statistical package program statistica. The effect of parameters on Chevreul’s salt solubility was examined and integrated rate expression of dissolution rate was found using kinetic models in solid-liquid heterogeneous reactions. The results revealed that the dissolution rate of Chevreul’s salt was decreasing while temperature, concentration of ammonium chloride and stirring speed were increasing. On the other hand, dissolution rate was found to be decreasing with the increase of solid/liquid ratio. Based on result of the applications of the obtained experimental results to the kinetic models, we can deduce that Chevreul’s salt dissolution rate is controlled by diffusion through the ash (or product layer). Activation energy of the reaction of dissolution was found as 74.83 kJ/mol. The integrated rate expression along with the effects of parameters on Chevreul's salt solubility was found to be as follows: 1-3(1-X)2/3+2(1-X)= [2,96.1013.(CA)3,08 .(S/L)-038.(W)1,23 e-9001,2/T].t

Keywords: Chevreul's salt, copper, ammonium chloride, ammonium sulphide, dissolution kinetics

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Authors: Dwitya Elvira, Eryati Darwin

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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.

Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease

Procedia PDF Downloads 286

Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

Procedia PDF Downloads 166

Authors: Chu Wan-Loy, Kok Yih-Yih, Choong Siew-Ling

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The human health risks due to poor air quality caused by a wide array of microorganisms have attracted much interest. Airborne algae have been reported as early as 19th century and they can be found in the air of tropic and warm atmospheres. Airborne algae normally originate from water surfaces, soil, trees, buildings and rock surfaces. It is estimated that at least 2880 algal cells are inhaled per day by human. However, there are relatively little data published on airborne algae and its related adverse health effects except sporadic reports of algae associated clinical allergenicity. A collection of airborne algae cultures has been established following a recent survey on the occurrence of airborne algae in indoor and outdoor environments in Kuala Lumpur. The aim of this study was to investigate the allergenic potential of the isolated airborne green and blue-green algae, namely Scenedesmus sp., Cylindrospermum sp. and Hapalosiphon sp.. The suspensions of freeze-dried airborne algae were adminstered into balb-c mice model through intra-nasal route to determine their allergenic potential. Results showed that Scenedesmus sp. (1 mg/mL) increased the systemic Ig E levels in mice by 3-8 fold compared to pre-treatment. On the other hand, Cylindrospermum sp. and Hapalosiphon sp. at similar concentration caused the Ig E to increase by 2-4 fold. The potential of airborne algae causing Ig E mediated type 1 hypersensitivity was elucidated using other immunological markers such as cytokine interleukin (IL)- 4, 5, 6 and interferon-ɣ. When we compared the amount of interleukins in mouse serum between day 0 and day 53 (day of sacrifice), Hapalosiphon sp. (1mg/mL) increased the expression of IL4 and 6 by 8 fold while the Cylindrospermum sp. (1mg/mL) increased the expression of IL4 and IFɣ by 8 and 2 fold respectively. In conclusion, repeated exposure to the three selected airborne algae may stimulate the immune response and generate Ig E in a mouse model.

Keywords: airborne algae, respiratory, allergenic, immune response, Malaysia

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Authors: Ling-Lang Huang, Yih-Jer Wu

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Empathy is crucial for a patient-physician relationship and medical professionalism. Internet activity, gaming, or even addiction, have been more and more common among medical students. However, there’s been no report showing whether internet behavior has a substantial impact on empathy in medical students to our best knowledge. All year-2 medical students taking the optional course 'Narrative, Comprehension, and Communication' were enrolled. Internet behaviors are divided into two groups, 'internet users without online gaming (IU)' and 'internet users with online gaming (IG)', each group was further divided into 3 groups according to their average online retention time each day (< 2, 2 - 6, > 6 hours). Empathy was evaluated by the scores of the reports and humanities reflection after watching indicated movies, and by self-measured empathy questionnaire. All students taking the year-2 optional course 'Narrative, Comprehension, and Communication' were enrolled. As compared with students in the IU group, those in the IG group had significantly lower scores for the reports (81.3 ± 3.7 vs. 86.4 ± 5.1, P = 0.014). If further dividing the students into 5 groups (IU < 2, IU 2-6, IG < 2, IG 2 - 6, and IG > 6 hours), the scores were significantly and negatively correlated to online gaming with longer hours (r = -0.556, P = 0.006). However, there was no significant difference between IU and IG groups (33.0 ± 5.4 vs. 34.8 ± 3.2, P = n.s.), in terms of scores in the self-measured empathy questionnaire, neither was there any significant trend of scores along with longer online hours across the 5 groups (r = -0.164, P = n.s.). To date, there has been no evidence showing whether different internet behaviors (with or without online gaming) have distinct impacts on empathy. Although all of the medical students had a similarly good self-perception for empathy, our data suggested that online gaming did have a negative impact on their actual expression of empathy. Our observation has brought up an important issue for pondering: May IT- or gaming-assisted medical learning actually harm students’ empathy? In conclusion, this data suggests that long hours of online gaming harms expression of empathy, though all medics think themselves a person of high empathy.

Keywords: empathy. Internet, medical students, online gaming

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Authors: Mohsen Saleh Asheghabadi, Alireza Jafari Jebeli

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Increasing population growth requires more sustainable development of energy. This non-contaminated energy has an inexhaustible energy source. One of the vital parameters in such structures is the choice of foundation type. Suction caissons are now used extensively worldwide for offshore wind turbine. Considering the presence of a number of offshore wind farms in earthquake areas, the study of the seismic behavior of suction caisson is necessary for better design. In this paper, the results obtained from three suction caisson models with different diameter (D) and skirt length (L) in saturated sand were compared with centrifuge test results. All models are analyzed using 3D finite element (FE) method taking account of elasto-plastic Mohr–Coulomb constitutive model for soil which is available in the ABAQUS library. The earthquake load applied to the base of models with a maximum acceleration of 0.65g. The results showed that numerical method is in relative good agreement with centrifuge results. The settlement and rotation of foundation decrease by increasing the skirt length and foundation diameter. The sand soil outside the caisson is prone to liquefaction due to its low confinement.

Keywords: liquefaction, suction caisson foundation, offshore wind turbine, numerical analysis, seismic behavior

Procedia PDF Downloads 119

Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

Procedia PDF Downloads 124