Search results for: macrophage targeting

Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Musa Bala Zakari, Mark Button

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This paper explores the extent, nature, and characteristics of public sector corruption in Nigeria and the enhancement of the major anti-corruption initiatives (reforms), thereby providing insight into the types, forms and causes of corruption in Nigeria. This paper argues that attempts to devise and suggest effective anti-corruption reforms to control systemic corruption in Nigeria require identifying the most prevalent types of corruption targeted and tackling the fundamental country specific causes. It analyses two types of public sector corruption as it relates to Nigeria and the workings of its inefficient governance system. This paper concludes with the imperative of a collective action against corruption supported by considerable amount of domestic political will existing in a favourable policy context. In undertaking this, the paper draws upon publicly available documents, case laws review and semi-structured interviews conducted with various personnel working in the field of corruption in the dedicated anticorruption agencies, academics, and practitioners from other relevant institutions of accountability.

Keywords: corruption, development, good governance, public sector

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Authors: Afiqah Shafify Amran, Siti Aisyah Shamsudin, Nurul Yuziana Mohd Yusof

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Cadmium Sulphide (CdS) from group II-IV quantum dots with good optical properties was successfully synthesized by using the simple colloidal method. Capping them with ligand Polyethylinamine (PEI) alters the surface defect of CdS while, thioglycolic acid (TGA) was added to the reaction as a stabilizer. Due to their cytotoxicity, we decided to conjugate them with the protein cage nanoparticles. In this research, we used capsid of Cowpea Chlorotic Mottle Virus (CCMV) to package the CdS because they have the potential to serve in drug delivery, cell targeting and imaging. Adding Sodium Hydroxide (NaOH) changes the pH of the systems hence the isoelectric charge is adjusted. We have characterized and studied the morphology and the optical properties of CdS and CdS-CCMV by transmitted electron microscopic (TEM), UV-Vis spectroscopy, photoluminescence spectroscopy, UV lamp and Fourier transform infrared spectroscopy (FTIR), respectively. The results obtained suggest that the protein cage nanoparticles do not affect the optical properties of CdS.

Keywords: cadmium sulphide, cowpea chlorotic mottle virus, protein cage nanoparticles, quantum dots

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Camilla Trevor, Matthew K. Higgins, Andrea Gonzalez-Munoz, Mark Carrington

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Trypanosomiasis is a devastating disease affecting both humans and livestock in sub-Saharan Africa. The diseases are caused by infection with African trypanosomes, protozoa transmitted by tsetse flies. Treatment currently relies on the use of chemotherapeutics with ghastly side effects. Here, we describe the development of effective antibody-drug conjugates that target the T. brucei transferrin receptor. The receptor is essential for trypanosome growth in a mammalian host but there are approximately 12 variants of the transferrin receptor in the genome. Two of the most divergent variants were used to generate recombinant monoclonal immunoglobulin G using phage display and we identified cross-reactive antibodies that bind both variants using phage ELISA, fluorescence resonance energy transfer assays and surface plasmon resonance. Fluorescent antibodies were used to demonstrate uptake into trypanosomes in culture. Toxin-conjugated antibodies were effective at killing trypanosomes at sub-nanomolar concentrations. The approach of using antibody-drug conjugates has proven highly effective.

Keywords: antibody-drug conjugates, phage display, transferrin receptor, trypanosomes

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Authors: Obidimma Ezezika

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In light of the increasing importance of trust in development programs, the purpose of this study, was to identify how trust functions as an essential key determinant in successful innovation and technology development programs. Using projects in the agricultural sector as case studies, we determined how the concept of trust is understood. Our data collection relied on semi-structured, face-to-face interviews conducted as part of a larger study investigating the role of trust in development programs. Interview transcripts were analyzed to create a narrative on how trust is understood by the study’s participants and how trust functions in fostering innovation. We identified six themes and showed how trust plays an important factor in innovation. These themes included the practice of integrity and honesty; delivery of results in an accountable manner; capability and competency; sharing of the same objectives and interests; transparency about actions and intentions through clear communication; and the targeting of services toward the interests of the public. The results of this study can provide guidance on how to enhance implementation mechanisms and provide impetus for organizations to implement trust building activities in fostering effective innovation.

Keywords: trust, research, innovation, technology

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Authors: Emmanuel Uba, Lily Chimuanya, Maryam Tar

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Orthographic engineering is no longer the preserve of the Short Messaging Service (SMS), which is characterised by limited space. Such stylistic creativity or deviation is fast creeping into real-time messaging, popularly known as Instant Messaging (IM), despite the large number of characters allowed. This occurs at various linguistic levels: phonology, morphology, syntax, etc. Nigerians are not immune to this linguistic stylisation. This study investigates the phonological and meta-phonological conventions of the messages sent and received via WhatsApp by Nigerian graduates. This is ontological study of 250 instant messages collected from 98 graduates from different ethnic groups in Nigeria. The selection and analysis of the messages are based on figure and ground principle. The results reveal the use of accent stylisation, phoneme substitution, blending, consonantisation (a specialised form of deletion targeting vowels), numerophony (using a figure/number, usually 1-10, to represent a word or syllable that has the same sound) and phonetic respelling in the IMs sent by Nigerians. The study confirms the existence of linguistic creativity.

Keywords: figure and ground principle, instant messaging, linguistic stylisation, meta-phonology

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Authors: Natalia Khvorostianov, Larissa Remennick

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Recent immigrants seldom join the ranks of volunteers for various social causes. This gap reflects both material reasons (immigrants’ lower income and lack of free time) and cultural differences (value systems, religiosity, language barrier, attitudes towards host society, etc.). Immigrants from the former socialist countries are particularly averse to organized forms of volunteering for a host of reasons rooted in their past, including the memories of false or forced forms of collectivism imposed by the state. In this qualitative study, based on 21 semi-structured interviews, we explored the perceptions and practices of volunteer work among FSU immigrants - participants in one volunteering project run by an Israeli NGO for the benefit of elderly ex-Soviet immigrants. Our goal was to understand the motivations of immigrant volunteers and the role of volunteering in the processes of their own social and economic integration in their adopted country – Israel. The results indicate that most volunteers chose causes targeting fellow immigrants, their resettlement and well-being, and were motivated by the wish to build co-ethnic support network and overcome marginalization in the Israeli society. Other volunteers were driven by the need for self-actualization in the context of underemployment and occupational downgrading.

Keywords: FSU immigrants, integration, volunteering, participation, social capital

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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Authors: Kate Whitman, Zahra Murad, Joe Cox

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Digital piracy is costly to creative economies across the world. Anti-piracy messages can cause people to pirate more rather than less, suggesting the presence of psychological reactance. Gender differences in message reactance and the moderating impact of attitudes have not been explored. In this paper, we examine whether messages based on real-world anti-piracy campaigns cause reactance and whether this effect is explained by gender and attitudes. An experiment compares two threatening and one prosocial message against a control group, with changes in piracy intention from past behavior for digital TV/film analysed. The results suggest that the prosocial message is ineffective for both genders. However, the threatening messages have significantly opposing effects on men and women. One threatening message influences women to reduce their piracy intentions by over 50% and men to increase it by 18%. Gender effects are moderated by pre-existing attitudes, with men and women who report the most favorable attitudes towards piracy having the most polarised changes in piracy intentions. The results suggest that men and women process threatening messages differently and that the creative industries should take care when targeting their messages.

Keywords: piracy, reactance, persuasive-messages, TV/film, gender

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Authors: Valerii Dudin

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With the continuous increase in quantity and importance of the information surrounding our daily lives, it has become crucial to understand what makes information stand out and affect our point of view, regardless of the accuracy of the facts involved. Alaa Al-Aswany’s numerous works have been an inspiration for millions of his readers in Egypt and all across the Arab World. While highly factual, the author’s political essays are both lexically and stylistically rich; they also implement descriptive allusions and proverbs to support the presented opinions. We have undertaken an effort to explore the impact on the individual perception through these political works of the author. In this study, we have overviewed previously made research on similar subjects and through contextual, intertextual, linguistic and corpus analyses we have come to realize the presence of suggestive themes in these works, capable of shaping the reader’s perception regarding a certain topic, specifically targeting the reader’s emotional bias. The findings presented in the study will reveal an overview of such examples of suggestive elements used in the author’s works, as well as various new insights on what can be considered suggestive in the context of modern Arabic printed press.

Keywords: Alaa al-Aswany, cognitive linguistics, political essays, suggestion

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Authors: Afsaneh Ghorbanzadeh, Afshin Farahbakhsh, Zakieh Bayat

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The drug capsulation was used for release and targeted delivery in determined time, place and temperature or pH. The DOX nanocapsules were used to reduce and to minimize the unwanted side effects of drug. In this paper, the encapsulation methods of doxorubicin (DOX) and the labeling it by the magnetic core of iron (Fe3O4) has been studied. The Fe3O4 was conjugated with DOX via hydrazine bond. The solution was capsuled by the sensitive polymer of heat or pH such as chitosan-g-poly (N-isopropylacrylamide-co-N,N-dimethylacrylamide), dextran-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and mPEG-G2.5 PAMAM by hydrazine bond. The drug release was very slow at temperatures lower than 380°C. There was a rapid and controlled drug release at temperatures higher than 380°C. According to experiments, the use mPEG-G2.5PAMAM is the best method of DOX nanocapsules synthesis, because in this method, the drug delivery time to certain place is lower than other methods and the percentage of released drug is higher. The synthesized magnetic carrier system has potential applications in magnetic drug-targeting delivery and magnetic resonance imaging.

Keywords: drug carrier, drug release, doxorubicin, iron oxide NPs

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Authors: Marie-Josée Morneau

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A literacy-based approach, centred on the use of the language of instruction as a cognitive tool, can increase the L2 communication skills of French immersion students. Academic subject areas such as science and mathematics offer an authentic language learning context where students can become more proficient speakers while using specific vocabulary and language structures to learn, interact and communicate their reasoning, when provided the opportunities and guidance to do so. In this Canadian quasi-experimental study, the effects of teaching specific language elements during mathematic classes through literacy-based activities in Early French Immersion programming were compared between two Grade 7/8 groups: the experimental group, which received literacy-based teaching for a 6-week period, and the control group, which received regular teaching instruction. The results showed that the participants from the experimental group made more progress in their mathematical communication skills, which suggests that targeting L2 language as a cognitive tool can be beneficial to immersion learners who learn mathematic concepts and remind us that all L2 teachers are language teachers.

Keywords: mathematics, French immersion, literacy-based, oral communication, L2

Procedia PDF Downloads 47

Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

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In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

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Authors: Pablo Zoghbi-Manrique-de-Lara, Miguel A. Suárez-Acosta

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The goal of the present paper is to model two classic lines of research in which employees starred, organizational justice and citizenship behaviour (OCB), but that have never been studied together when targeting customers. The suggestion is made that a hotel’s fair treatment (in terms of distributive, procedural, and interactional justice) toward customers will be appreciated by the employees, who will reciprocate in kind by favouring the hotel with increased customer-oriented behaviours (COBs). Data were collected from 204 employees at eight upscale hotels in the Canary Islands (Spain). Unlike in the case of perceptions of distributive justice, results of structural equation modelling demonstrate that employees substantively react to interactional and procedural justice toward guests by engaging in customer-oriented behaviours (COBs). The findings offer new reasons why employees decide to engage in COBs, and they highlight potentially beneficial effects of fair treatment toward guests bring to hospitality through promoting COBs.

Keywords: hotel guests’ (mis) treatment, customer-oriented behaviours, employee citizenship, organizational justice, third-party observers, third-party intervention

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Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Mahmoud Mabrok, Channarong Rodkhum

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Flavobacterium columanre is one of the devastating pathogen that causes noticeable economic losses in freshwater cultured fish. Like other filamentous bacteria, F. columanre tends to aggregate and fluctuate to all kind of media, thus revealing obstacles in recognition of its colonies. Since the molecular typing is the only fundamental tool for rapid and precise detection of this pathgen. The present study developed a species-specific PCR assay based on cslA unique gene of F. columnare. The cslA gene sequences of 13 F. columnare, strains retrieved from gene bank database, were aligned to identify a conserved homologous segment prior to primers design. The new primers yielded amplicons of 287 bp from F. columnare strains but not from relevant or other pathogens, unlike to other published set that showed no specificity and cross-reactivity with F. indicum. The primers were sensitive and detected as few as 7 CFUs of bacteria and 3 pg of gDNA template. The sensitivity was reduced ten times when using tissue samples. These primers precisely defined all field isolates in a double-blind study, proposing their applicable use for field detection.

Keywords: Columnaris infection, cslA gene, Flavobacterium columnare, PCR

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Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

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Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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Authors: Hamide Özyürek, Metin Yılmaz

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Standard processes, similar and limited production lines, the production of high direct costs will be more accurate than the use of parts of the traditional cost systems in the literature. However, direct costs, overhead expenses, in turn, decreases the burden of increasingly sophisticated production facilities, a situation that led the researchers to look for the cost of traditional systems of alternative techniques. Variety cost management approaches for example Total quality management (TQM), just-in-time (JIT), benchmarking, kaizen costing, targeting cost, life cycle costs (LLC), activity-based costing (ABC) value engineering have been introduced. Management and cost applications have changed over the past decade and will continue to change. Modern cost systems can provide relevant and accurate cost information. These methods provide the decisions about customer, product and process improvement. The aim of study is to describe and explain the adoption and application of costing systems in SME. This purpose reports on a survey conducted during 2014 small and medium sized enterprises (SME) in Ankara. The survey results were evaluated using SPSS package program.

Keywords: modern costing systems, managerial accounting, cost accounting, costing

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Authors: Cosmin-Gabriel Porumb-Ghiurco, Dumitrana Fiț-Iordache, Szőke Árpád

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The literature incorporating geographical or tourist-geographical themes and explicit references to the Carpathian area is extremely abundant. Through this paper, we attempt to “undermine” the traditional, tourist-geographical approaches of the Carpathian Arch by targeting an aspect often regarded as marginal but which, if examined, even only empirically, takes the form of a vast problem with multidisciplinary vocation. Therefore, we propose a more extravagant yet pro-touristic approach to the Romanian Carpathian geo-space. Consequently, the explicit goal of this approach consists precisely in broadening the multidisciplinary, essentially geographic scope of the research, the vision and mental representation of the Carpathian area by advancing a lever that would symbolize a different kind of unification between geography and tourism on a more intimate, subtle, mythological and archetypal level. The spiritual and mercantile dimensions of the tourism field in general and of the local Carpathian tourism can meld harmoniously together in order to create a common territorial reality of referral and favorable perspectives for the consolidation of their symbiotic relationship.

Keywords: tourist image, mythical geography, collective imaginary, spiritual patrimony, Carpathians

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Authors: Benedict Okundaye, Patricia Tzortzopoulos, Yun Gao

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Scholars and international organisations have contended that developing nations lack the technical expertise, infrastructure, and ability to cope with or prepare for the neighbourhood’s sustainable development as Sustainable Development Goals, mainly targeting goal 11 unimpressive accomplishments. Both wealthy and impoverished communities are facing increasing issues due to rapid urbanisation and pandemics, particularly in Africa. The global neighbourhood challenges, especially in developing countries such as South Africa, include pollution poverty, energy poverty, digital poverty, environmental degradation, social exclusion, and socioeconomic inequalities. With the problematic international sustainability assessment tools lingering, few researchers have produced frameworks to engage the local contexts, but improvements are still required. This research anchors on developing a people-centred, flexible, and adaptable neighbourhood sustainability assessment framework that becomes a tool to assess the characteristics of neighbourhood sustainability in South Africa. The conceptual framework employs a variety of approaches, including broader dimensional factors, a closed-ended questionnaire, and statistical analysis to improve on and complement other existing frameworks.

Keywords: participation, development, inclusion, urbanism, cities, resilience

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Authors: Seo-Hee Kim, Kee-Won Kim, Seung-Hoon Kim

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The most important elements of a novel are the characters, events and background. The background represents the time, place and situation that character appears, and conveys event and atmosphere more realistically. If readers have the proper knowledge about background of novels, it may be helpful for understanding the atmosphere of a novel and choosing a novel that readers want to read. In this paper, we are targeting Korean historical novels because spatio-temporal background especially performs an important role in historical novels among the genre of Korean novels. To the best of our knowledge, we could not find previous study that was aimed at Korean novels. In this paper, we build a Korean historical national dictionary. Our dictionary has historical places and temple names of kings over many generations as well as currently existing spatial words or temporal words in Korean history. We also present a method for recognizing spatio-temporal background based on patterns of phrasal words in Korean sentences. Our rules utilize postposition for spatial background recognition and temple names for temporal background recognition. The knowledge of the recognized background can help readers to understand the flow of events and atmosphere, and can use to visualize the elements of novels.

Keywords: data mining, Korean historical novels, Korean linguistic feature, spatio-temporal background

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Authors: M. Moslehpour, S. Khorsandi

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As transition to widespread use of IPv6 addresses has gained momentum, it has been shown to be vulnerable to certain security attacks such as those targeting Neighbor Discovery Protocol (NDP) which provides the address resolution functionality in IPv6. To protect this protocol, Secure Neighbor Discovery (SEND) is introduced. This protocol uses Cryptographically Generated Address (CGA) and asymmetric cryptography as a defense against threats on integrity and identity of NDP. Although SEND protects NDP against attacks, it is computationally intensive due to Hash2 condition in CGA. To improve the CGA computation speed, we parallelized CGA generation process and used the available resources in a trusted network. Furthermore, we focused on the influence of the existence of malicious nodes on the overall load of un-malicious ones in the network. According to the evaluation results, malicious nodes have adverse impacts on the average CGA generation time and on the average number of tries. We utilized a Trust Management that is capable of detecting and isolating the malicious node to remove possible incentives for malicious behavior. We have demonstrated the effectiveness of the Trust Management System in detecting the malicious nodes and hence improving the overall system performance.

Keywords: CGA, ICMPv6, IPv6, malicious node, modifier, NDP, overall load, SEND, trust management

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Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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Authors: Richard Madanda, Paul Isaac Musasizi, Sandy Stevens Tickodri-Togboa, Doreen Orishaba, Victor Tumwine

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New vehicle concepts targeting specific geographical markets are designed to satisfy a unique set of road and load requirements. The KIIRA-EV SMACK (KES) hybrid vehicle is designed in Uganda for the East African market. The engine and generator added to the KES electric power train serve both as the range extender and the power assist. In this paper, the design consideration taken to achieve the proper management of the on-board power from the batteries and engine-generator based on the specific drive cycle are presented. To harness the fuel- efficiency benefits of the power train, a specific control philosophy operating the engine and generator at the most efficient speed- torque and speed-power regions is presented. By using a suitable model developed in MATLAB using Simulink and Stateflow, preliminary results show that the steady-state response of the vehicle for a particular hypothetical drive cycle mimicking the expected drive conditions in the city and highway traffic is sufficient.

Keywords: control strategy, drive cycle, hybrid vehicle, simulation

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Authors: Thomas Yeboah

Abstract:

In recent times, micro-finance programmes targeting women have become the central means of donor poverty alleviation strategies. In view of the renewed focus on post-Millennium Development Goals (MDGs) poverty reduction strategies, there is the likelihood that funding might increase in the next coming decades to support different initiatives by donor agencies. In this paper, we critically examine the role of microfinance in shaping gender relations and empowerment outcomes of women. It is widely argued that providing and reaching out to women with credit methodologies serves as a means of increasing women’s bargaining power and challenging existing gender subordination thereby releasing them from power structures which dominate their lives. This paper cautions this view and instead show that the mainstream argument surrounding microfinance and gender empowerment is much complex than what the popular rhetoric preaches. Drawing on empirical cases on microfinance literature, we argue that lack of systematic strategy to incorporate men and the wider socio-cultural dynamics within which women’s lives are embedded radically constraints the empowerment potential of microcredit programmes and in some context may lead to unintended consequences for women.

Keywords: microfinance, empowerment, women, men, gender relations

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Authors: Kulsoom S. Bughio, Naeem K. Janjua, Gordana Dermody, Leslie F. Sikos, Shamsul Islam

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The advancement in information and communication technologies (ICT) and wireless sensor networks have played a pivotal role in the design and development of real-time healthcare solutions, mainly targeting the elderly living in health-assistive smart homes. Such smart homes are equipped with sensor technologies to detect and record activities of daily living (ADL). This survey reviews and evaluates existing approaches and techniques based on real-time sensor-based modeling and reasoning in single-user and multi-user environments. It classifies the approaches into three main categories: learning-based, knowledge-based, and hybrid, and evaluates how they handle temporal relations, granularity, and uncertainty. The survey also highlights open challenges across various disciplines (including computer and information sciences and health sciences) to encourage interdisciplinary research for the detection and recognition of ADLs and discusses future directions.

Keywords: daily living activities, smart homes, single-user environment, multi-user environment

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Authors: Wen-Yu Lin, Yi-Ching Chung, Tzyy-Rong Jinn

Abstract:

It is well known that enterovirus 71 (EV71) causes recurring outbreaks of hand, foot and mouth disease (HFMD) and encephalitis leading to complications or death in young children. And, several HFMD of EV71 with high mortalities occurred in Asia countries, such as Malaysia (1997), Taiwan (1998) and China (2008). Thus, more effective antiviral drugs are needed to prevent or reduce EV71-related complications. As reported, interferon-α protects mice from lethal EV71 challenge by the modulation of innate immunity and then degrade enterovirus protease 3Cᵖʳᵒ. On the other side, pleconaril by targeting enterovirus VP1 protein and then block virus entry and attachment. Thus, the aim of this study was to evaluate the synergistic antiviral activity of interferon-α and pleconaril against enterovirus 71 infection. In a preliminary study showed that pleconaril at concentrations of 50, 100 and 300 µg/mL reduced EV71-induced CPE to 52.0 ± 2.5%, 40.2 ± 3.5% and 26.5 ± 1.5%, respectively, of that of the EV71-infected RD control cells (taken as 100%). Notably, 1000 IU/mL of interferon-α in combination with pleconaril at concentrations of 50, 100 and 300µg/mL suppressed EV71-induced CPE by 30.2 ± 3.8%, 16.5 ± 1.3% and 2.8 ± 2.0%, respectively, of that of the pleconaril alone treated with the infected RD cells. These results indicated that interferon-α 1000 IU/mL combination with pleconaril (50, 100 and 300µg/mL) inhibited EV71-induced CPE more effectively than treated with pleconaril alone in the infected RD cells.

Keywords: enterovirus 71, interferon-α, pleconaril, RD cells

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