Search results for: targeting antibodies

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: Ognen Kostovski, Svetozar Antovic, Rubens Jovanovic, Irena Kostovska, Nikola Jankulovski

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Introduction:Colorectal carcinoma (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The aim of study was to determine whether the expression of colorectal cancer stem cell markers CD133 and CD44 could be significant in prediction of clinically aggressive form of CRC. Materials and methods: Our study included ninety patients (n=90) with CRC. Patients were divided into two subgroups: with metatstatic CRC and non-metastatic CRC. Tumor samples were analyzed with standard histopathological methods, than was performed immunohistochemical analysis with monoclonal antibodies against CD133 and CD44 stem cell markers. Results: High coexpression of CD133 and CD44 was observed in 71.4% of patients with metastatic disease, compared to 37.9% in patients without metastases. Discordant expression of both markers was found in 8% of the subgroup with metastatic CRC, and in 13.4% of the subgroup without metastatic CRC. Statistical analyses showed a significant association of increased expression of CD133 and CD44 with the disease stage, T - category and N - nodal status. With multiple regression analysis the stage of disease was designate as a factor with the greatest statistically significant influence on expression of CD133 (p <0.0001) and CD44 (p <0.0001). Conclusion: Our results suggest that the coexpression of CD133 and CD44 have an important role in prediction of clinically aggressive form of CRC. Both stem cell markers can be routinely implemented in standard pathohistological diagnostics and can be useful markers for pre-therapeutic oncology screening.

Keywords: colorectal carcinoma, stem cells, CD133+, CD44+

Procedia PDF Downloads 126

Authors: Belaynesh Tsegay, Teklay Gebrecherkos, Atsebaha Gebrekidan Kahsay, Mahmud Abdulkader

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Background: Hepatitis B and C viruses are important health and socioeconomic problem across the globe, with a remarkable number of diseases and deaths in sub-Saharan African countries. The burden of hepatitis is unknown in the prison settings of Tigray. Therefore, we aimed to describe the seroprevalence and associated factors of hepatitis B and C viruses among prisoners in Tigray, Ethiopia. Methods: A cross-sectional study was carried out from February 2020 to May 2020 at the prison facilities of Tigray. Demographics and associated factors were collected from 315 prisoners prospectively. Five milliliters of blood were collected and tested using rapid tests kits of HBsAg (Zhejiang orient Gene Biotech Co., Ltd., China) and HCV antibodies (Volkan Kozmetik Sanayi Ve Ticaret Ltd. STI, Turkey). Positive samples were confirmed using ELISA (Beijing Wantai Biological Pharmacy Enterprise Co. Ltd). Data were analyzed using the SPSS version 20, and p<0.05 was considered statistically significant. Results: The overall seroprevalence of HBV and HCV were 25 (7.9%) and 1 (0.3%), respectively. The majority of hepatitis B viral infections were identified from the age groups of 18–25 years (10.7%) and unmarried prisoners (11.8%). Prisoners greater than 100 per cell (AOR=3.95, 95% CI=1.15–13.6, p=0.029) and with a history of alcohol consumption (AOR=3.01, 95% CI=1.17–7.74, p=0.022) were significantly associated with HBV infections. Conclusion: The seroprevalence of HBV among prisoners was nearly high or borderline, with a very low HCV prevalence. HBV was most prevalent among young adults, those housed with a large number of prisoners per cell, and those who had a history of alcohol consumption. This study recommends that there should be prison-focused intervention, including regular health education, with the emphasis on the mode of transmission and introducing HBV screening policy for prisoners, especially when they enter the prison.

Keywords: seroprevalence, HBV, HCV, prisoners, tigray

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Authors: Moussa Majed, Omar Yaser

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The main objective of this experiment was to study the impact of Probiotic compound on the specific immunity as the case study of infectious bursal disease. Total of 8000 one-day old Ross 108 broiler were randomly divided into two experimental groups; control group (4500 birds) and experimental group (3500 birds). Birds in two groups were reared under similar environmental conditions. Birds in control group received basal diets without probiotic whereas the birds in experimental one were fed basal diets supplemented with a commercial probiotic mixture) probiotic lacting k, which contains bacteria cells beyond to lactobacillus, Streptococcus and bifidobacterium genus that are isolated from gut microflora in healthy chickens(. The commercial probiotic were used according to the manufacturer instruction. 400 blood samples for each group were collected from wing vein every 5-7 days as interval period till 42 days old. Indirect Enzyme-Linked Immunosorbent Assay (ELISA) test was performed to detect the level of infectious bursal disease virus (IBDV) antibodies. The results clearly showed that the mean of immune titers was significantly (p= 0.03) higher in trail group than control one. The coefficient of variance percentages were 55% and 39% for control and trial groups respectively, this illustrates that homogeneity of immunity titers in the trail group was much better comparing with control group. The values of geometric means of titers in the control group and trial group were reported 3820 and 8133, respectively. The crude mortality rate in the experimental group was two times lower comparing with control group (14% and 28% respectively, p = 0.005

Keywords: probiotic, broiler chicken, infectious bursal disease, immunity, ELISA test

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Authors: Yahya Almurtadha, Mukhtar Ghaleb, Ahmed M. Shamsan Saleh

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The world witnessed a fierce attack from the Covid-19 virus, which affected public life socially, economically, healthily and psychologically. The world's governments tried to confront the pandemic by imposing a number of precautionary measures such as general closure, curfews and social distancing. Scientists have also made strenuous efforts to develop an effective vaccine to train the immune system to develop antibodies to combat the virus, thus reducing its symptoms and limiting its spread. Artificial intelligence, along with researchers and medical authorities, has accelerated the vaccine development process through big data processing and simulation. On the other hand, one of the most important negatives of the impact of Covid 19 was the state of anxiety and fear due to the blowout of rumors through social media, which prompted governments to try to reassure the public with the available means. This study aims to proposed using Sentiment Analysis (AKA Opinion Mining) and deep learning as efficient artificial intelligence techniques to work on retrieving the tweets of the public from Twitter and then analyze it automatically to extract their opinions, expression and feelings, negatively or positively, about the symptoms they may feel after vaccination. Sentiment analysis is characterized by its ability to access what the public post in social media within a record time and at a lower cost than traditional means such as questionnaires and interviews, not to mention the accuracy of the information as it comes from what the public expresses voluntarily.

Keywords: deep learning, opinion mining, natural language processing, sentiment analysis

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Authors: Muhammad Farhan Ul Moazzam, Tamkeen Urooj Paracha, Ghani Rahman, Byung Gul Lee, Nasir Farid, Adnan Arshad

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The novel coronavirus pandemic disease (COVID-19) affected the whole globe, though there is a lack of clinical studies and its epidemiological features. But as per the observation, it has been seen that most of the COVID-19 infected patients show mild to moderate symptoms, and they get better without any medical assistance due to a better immune system to generate antibodies against the novel coronavirus. In this study, the active cases, serious cases, recovered cases, deaths and total confirmed cases had been analyzed using the geospatial inverse distance weightage technique (IDW) within the time span of 2nd March to 3rd June 2020. As of 3rd June, the total number of COVID-19 cases in Italy were 231,238, total deaths 33,310, serious cases 350, recovered cases 158,951, and active cases were 39,177, which has been reported by the Ministry of Health, Italy. March 2nd-June 3rd, 2020 a sum of 231,238 cases has been reported in Italy out of which 38.68% cases reported in the Lombardia region with a death rate of 18%, which is high from its national mortality rate followed by Emilia-Romagna (14.89% deaths), Piemonte (12.68% deaths), and Vento (10% deaths). As per the total cases in the region, the highest number of recoveries has been observed in Umbria (92.52%), followed by Basilicata (87%), Valle d'Aosta (86.85%), and Trento (84.54%). The COVID-19 evolution in Italy has been particularly found in the major urban area, i.e., Rome, Milan, Naples, Bologna, and Florence. Geospatial technology played a vital role in this pandemic by tracking infected patient, active cases, and recovered cases. Geospatial techniques are very important in terms of monitoring and planning to control the pandemic spread in the country.

Keywords: COVID-19, public health, geospatial analysis, IDW, Italy

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Authors: Joel Ballesteros, Harriet Jane Caleja, Florian Del Mundo, Cherrie Pascual

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Diffraction-based sensing was utilized in the quantification of human ferritin in blood serum to provide an alternative to label-based immunoassays currently used in clinical diagnostics and researches. The diffraction intensity was measured by the diffractive optics technology or dotLab™ system. Two methods were evaluated in this study: direct immunoassay and direct sandwich immunoassay. In the direct immunoassay, human ferritin was captured by human ferritin antibodies immobilized on an avidin-coated sensor while the direct sandwich immunoassay had an additional step for the binding of a detector human ferritin antibody on the analyte complex. Both methods were repeatable with coefficient of variation values below 15%. The direct sandwich immunoassay had a linear response from 10 to 500 ng/mL which is wider than the 100-500 ng/mL of the direct immunoassay. The direct sandwich immunoassay also has a higher calibration sensitivity with value 0.002 Diffractive Intensity (ng mL-1)-1) compared to the 0.004 Diffractive Intensity (ng mL-1)-1 of the direct immunoassay. The limit of detection and limit of quantification values of the direct immunoassay were found to be 29 ng/mL and 98 ng/mL, respectively, while the direct sandwich immunoassay has a limit of detection (LOD) of 2.5 ng/mL and a limit of quantification (LOQ) of 8.2 ng/mL. In terms of accuracy, the direct immunoassay had a percent recovery of 88.8-93.0% in PBS while the direct sandwich immunoassay had 94.1 to 97.2%. Based on the results, the direct sandwich immunoassay is a better diffraction-based immunoassay in terms of accuracy, LOD, LOQ, linear range, and sensitivity. The direct sandwich immunoassay was utilized in the determination of human ferritin in blood serum and the results are validated by Chemiluminescent Magnetic Immunoassay (CMIA). The calculated Pearson correlation coefficient was 0.995 and the p-values of the paired-sample t-test were less than 0.5 which show that the results of the direct sandwich immunoassay was comparable to that of CMIA and could be utilized as an alternative analytical method.

Keywords: biosensor, diffraction, ferritin, immunoassay

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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 58

Authors: Sahar Essa, Hussain A. Safar, Raj Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications in immunologically immature and immunocompromised hosts. Effective CMV vaccines that help diminish CMV disease in transplant patients and avoid congenital infection are of great importance. Though the exact roles of defense mechanisms are unidentified, viral-specific antibodies and cytokine responses are known to be involved in controlling CMV infections. CMV envelope glycoprotein B (UL55/gB), matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. We immunized mice intraperitoneally with these five CMV-related proteins (commercial) for their ability to induce specific antibody responses (in-house immunoassay) and cytokine production (commercial assay) in a mouse model. We observed a significant CMV-antigen-specific antibody response to pp38 and pp65 (E/C ˃2.0, p˂0.001). Mice immunized with pp38 had significantly higher concentrations of GM-CSF, IFN-α, IL-2 IL-4, IL-5, and IL-17A (p˂0.05). Mice immunized with pp65 showed significantly higher concentrations of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF-α. Th1 to Th2 cytokines ratios revealed a Th1 cytokine bias in mice immunized with pp38, pp65, pp150, and gB. We suggest that stimulation with multiple CMV-related proteins, which include pp38, pp65, and gB antigens, will allow both humoral and cellular immune responses to be efficiently activated, thus serving as appropriate CMV antigens for future vaccines.

Keywords: cytomegalovirus, UL99/pp28, UL80a/pp38, UL83/pp65, UL32/pp150, UL55/gB, CMV-antigen-specific antibody, CMV antigen-specific cytokine responses

Procedia PDF Downloads 62

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

Procedia PDF Downloads 56

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

Procedia PDF Downloads 247

Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: S. Tebibel, C. Mechati, S. Messaoudi

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Algeria is currently experiencing the same rate of cancer progression as that registered these last years in the western countries. Colorectal cancer, constituting increasingly a major public health problem, is the most common form of cancer after breast and Neck-womb cancer at the woman and prostate cancer at the man. Our work is based on a retrospective study to determine the cases of colorectal cancer through eastern Algeria. Our goal is to carry out an epidemiological, histological and immune- histochemical study to investigate different techniques for the diagnosis of colorectal cancer and their interests and specific in detecting the disease. The study includes 110 patients (aged between 20 to 87 years) with colorectal cancer where the inclusions and exclusions criteria were established. In our study, colorectal cancer, expresses a male predominance, with a sex ratio of 1, 99 and the most affected age group is between 50 and 59 years. We noted that the colon cancer rate is higher than rectal cancer rate, whose frequencies are respectively 60,91 % and 39,09 %. In the series of colon cancer, the ADK lieberkunien is histological the most represented type, or 85,07 % of all cases. In contrast, the proportion of ADK mucinous (colloid mucous) is only 1,49% only. Well-differentiated ADKS, are very significant in our series, they represent 83,58 % of cases. Adenocarcinoma moderately and poorly differentiated, whose proportions are respectively 2,99 % and 0.05 %. For histological varieties of rectal ADK, we see in our workforce that ADK lieberkunien represent the most common histological form, or 76,74%, while the mucosal colloid is 13,95 %. Research of the mutation on the gene encoding K-ras, a major step in the targeted therapy of colorectal cancers, is underway in our study. Colorectal cancer is the subject of much promising research concern: the evaluation of new therapies (antiangiogenic monoclonal antibodies), the search for predictors of sensitivity to chemotherapy and new prognostic markers using techniques of molecular biology and proteomics.

Keywords: adenocarcinoma, age, colorectal cancer, epidemiology, histological section, sex

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Authors: Bernard L. Middleton, Susan P. Cosgrove

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There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Alternatives currently approved for the purposes of clinical administration includes antivirals and a reduced set of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. The tested 5CC were noted as being functional in the application of eliminating the DNA synthesis of herpes viral interferon (IFN) - induced cellular antiviral response. They were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. The activity of the 5CC was tested on RC-37 in vitro using an assay plaque reduction and in vivo against HSV-1 and HSV-2. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests were performed to evaluate the susceptibility of HSV-1 and HSV-2 to anti-herpetic drugs in Vero cells after virus entry. There were high-level markers of the 5CC virucidal activity in the viral suspension of HSV-1 and HSV-2. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. The results concluded the 5CC as being an effective treatment option for the herpes simplex virus.

Keywords: synergy pharmaceuticals, herpes treatment, herpes cure, synergy pharmaceuticals treatment

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Authors: Ruttayaporn Ngasaman, Saowakon Indouang, Usa Chethanond

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Leptospirosis is a public health concern zoonosis in Thailand. Human and animals are often infected by contact with contaminated water. The infected animals play an important role in leptospira infection for both human and other hosts via urine. In humans, it can cause a wide range of symptoms, some of which may present mild flu-like symptoms including fever, vomiting, and jaundice. Without treatment, Leptospirosis can lead to kidney damage, meningitis, liver failure, respiratory distress, and even death. The prevalence of leptospirosis in stray animals in Thailand is unknown. The aim of this study was to investigate leptospira infection in stray animals including dogs and cats in Songkhla province, Thailand. Total of 434 blood samples were collected from 370 stray dogs and 64 stray cats during the population control program from 2014 to 2018. Screening test using latex agglutination for the detection of antibodies against Leptospira interrogans in serum samples shows 29.26% (127/434) positive. There were 120 positive samples of stray dogs and 7 positive samples of stray cats. Detection by polymerase chain reaction specific to LipL32 gene of Leptospira interrogans showed 1.61% (7/434) positive. Stray cats (5/64) show higher prevalence than stray dogs (2/370). Although active infection was low detected, but seroprevalence was high. This result indicated that stray animals were not active infection during sample collection but they use to get infected or in a latent period of infection. They may act as a reservoir for domestic animals and human in which stay in the same environment. In order to prevent and reduce the risk of leptospira infection in a human, stray animals should be done health checking, vaccination, and disease treatment.

Keywords: leptospirosis, stray animals, risk reduction, Thailand

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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: 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: 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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